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Immune thrombocytopenic purpura in pregnancy
Abstract
This review assesses the need for revision of the present guidelines for immune thrombocytopenic purpura in pregnancy based on evidence-based data from published articles of relevance.
The American Society of Hematology (ASH) and British Committee for Standards in Haematology (BCSH) guidelines indicate that at platelet counts below 70,000 or 80,000/microl, respectively, causes of thrombocytopenia other than gestational thrombocytopenia should be considered. The ASH guidelines indicate that for severe thrombocytopenia or thrombocytopenic bleeding in the third trimester, intravenous immunoglobulin is an appropriate first-line agent. No consensus was reached concerning the use of intravenous immunoglobulin or corticosteroids as first-line therapy at other gestational periods. Splenectomy is considered acceptable for patients with refractory immune thrombocytopenic purpura and severe thrombocytopenia with bleeding only in the second trimester. Laparoscopic splenectomy can be safely performed during pregnancy. The BCSH guidelines are consistent with contemporary practice in recommending that the mode of delivery of a pregnant patient with immune thrombocytopenic purpura should be determined based on maternal indications. Screening of articles published since the formulation of the BCSH guidelines in 2003 did not reveal new data that would lead to significant revisions in the guidelines.
Though outdated in some aspects, the ASH and BCSH guidelines still provide a useful framework for management of pregnant patients with immune thrombocytopenic purpura.
... [5] As in the nonpregnant patients, the diagnosis of ITP in pregnant women is a clinical one. [6] Since there are no diagnostic tests to confirm ITP, the diagnosis of ITP in pregnancy is made by exclusion of secondary causes of thrombocytopenia, such as gestational thrombocytopenia, preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome. Antibody testing for ITP utilizing the monoclonal antibody-specific immobilization of platelet antigens assay in pregnant women is unnecessary for lack of diagnostic specificity. ...
... [9] Furthermore, maternal circulating antiplatelet antibodies did not correlate with neonatal thrombocytopenia. [6] Similarly, as in nonpregnant individuals, bone marrow examination is not recommended for diagnosis of ITP. [6,10] Kasai et al. found that gestational thrombocytopenia with platelet counts of <10 × 10 9 /L is common in twin pregnancies, [11] which suggests that twin pregnancy complicated by ITP will experience much lower platelet counts than singleton pregnancy with ITP. ...
... [6] Similarly, as in nonpregnant individuals, bone marrow examination is not recommended for diagnosis of ITP. [6,10] Kasai et al. found that gestational thrombocytopenia with platelet counts of <10 × 10 9 /L is common in twin pregnancies, [11] which suggests that twin pregnancy complicated by ITP will experience much lower platelet counts than singleton pregnancy with ITP. In the present paper, our patient presented with severe thrombocytopenia as early as in the first trimester of her twin pregnancy whereas her first childbirth was uneventful. ...
Idiopathic thrombocytopenic purpura (ITP) is an acquired thrombocytopenia without other clear cause of thrombocytopenia. It is not common in a singleton pregnancy and less common in twin pregnancy. We report a 33-year-old ITP pluripara whose first pregnancy was uneventful. She carried twin pregnancy, complicated by recurrent very low platelets, and gave birth to preterm twins. This patient received multiple courses of intravenous immunoglobulin (IVIG) and showed a significant platelet count improvement with IVIG therapy.
... АД -артериальное давление ГКС -глюкокортикостероиды ГТ -гестационная тромбоцитопения ЕТСО 2 -концентрация СО 2 в конце выдоха ИТП -иммунная тромбоцитопеническая пурпура СЭ -спленэктомия ЭКО -экстракорпоральное оплодотворение IgG -иммуноглобулин G GP -гликопротеины HELLP-синдром -гемолиз (Hemolysis), повышение активности ферментов печени (Elevated Liver enzymes) и тромбоцитопения (Lоw Platelet соunt) ческая тромбоцитопеническая пурпура, гемолитико-уремический синдром, гепатиты, врожденная тромбоцитопения, прием лекарственных препаратов, дефицитов фолатов, острый лейкоз, апластическая анемия, малярия [6,7]. Тромбоцитопения менее 150·10 9 /л встречается у 6-15% беременных, среди них у 74,7% легкая форма тромбоцитопении, у 17,9% умеренная и у 7,4% тяжелая форма [3,6]. ...
... АД -артериальное давление ГКС -глюкокортикостероиды ГТ -гестационная тромбоцитопения ЕТСО 2 -концентрация СО 2 в конце выдоха ИТП -иммунная тромбоцитопеническая пурпура СЭ -спленэктомия ЭКО -экстракорпоральное оплодотворение IgG -иммуноглобулин G GP -гликопротеины HELLP-синдром -гемолиз (Hemolysis), повышение активности ферментов печени (Elevated Liver enzymes) и тромбоцитопения (Lоw Platelet соunt) ческая тромбоцитопеническая пурпура, гемолитико-уремический синдром, гепатиты, врожденная тромбоцитопения, прием лекарственных препаратов, дефицитов фолатов, острый лейкоз, апластическая анемия, малярия [6,7]. Тромбоцитопения менее 150·10 9 /л встречается у 6-15% беременных, среди них у 74,7% легкая форма тромбоцитопении, у 17,9% умеренная и у 7,4% тяжелая форма [3,6]. Если исключить случаи тромбоцитопении, обусловленные приемом лекарственных препаратов, то ее общая частота составляет 5,1% [7]. ...
... ИТП встречается значительно реже ГТ и наблюдается у 0,01-0,02% беременных, составляя от 2 до 5,6% всех случаев тромбоцитопении у беременных [4,6]. Для ИТП характерны более глубокая тромбоцитопения -менее (50-100)·10 9 /л, появление тромбоцитопении на ранних сроках гестации либо тромбоцитопения в анамнезе, отсутствие других системных заболеваний или воздействия лекарственных препаратов, вызывающих тромбоцитопению, отсутствие спленомегалии. ...
The paper describes 4 cases of laparoscopic splenectomy in pregnant women with immune thrombocytopenic purpura. No complications of surgery were noted in all the patients. The postoperative period was marked by sustained clinical and hematological remission that made it possible to discontinue prednisolone therapy and to ensure an uncomplicated course of pregnancy and labor.
... It is suggested that platelet count should be over 20,000/mm 3 in patients who do not have and delivery indication, over 50,000/mm 3 for vaginal delivery and over 80,000/ mm 3 for cesarean. [17] For medical treatment, intravenous immunoglobulin (IVIg) which has similar effects, oral corticosteroids or both are used and splenectomy is applied in cases who do not respond to treatment. Excess weight gaining, triggering gestational diabetes, increase in bone loss, hypertension and fetal congenital anomaly risks may appear due to corticosteroid treatment at preg-nancy. ...
... Therefore, IVIg treatment may be preferred instead of corticosteroid treatment. [17] Webert et al. [18] emphasized in their studies where retrospective analysis was performed for 92 pregnants with ITP that 68.9% of cases did not need treatment while Won et al. [19] reported that they applied treatment on 61.3% of cases in order to increase platelet count. In our study, prednisolone treatment was applied to 15 cases (57.6%). ...
... The natural course of platelet counts in neonates of mothers with ITP describes a platelet nadir at postnatal day 3-5, after which platelets will stabilize or rise spontaneously [1,3,12,17,18]. However, the optimal postnatal treatment for severe neonatal thrombocytopenia is not evident and includes IVIG, platelet transfusions and/or prednisone [2,4,6,7,15,[19][20][21]. Evidence on the neonatal outcome, risk factors and optimal management is scarce due to lack of studies. ...
... We can conclude that despite severe neonatal thrombocytopenia due to maternal ITP during pregnancy was fairly high in our series, severe bleeding manifestations were rare. As platelet nadir is seen within the first 7 days postpartum, bleeding risks are the highest in the first week, and daily platelet count control is necessary until a stable or rising safe platelet count above 50 9 10 9 /l is observed (as advised in guidelines) [20,24,28]. In addition should each individual case be evaluated precisely, to determine whether daily platelet count measurement is really necessary or once in 2 days will suffice. ...
Pregnant women with Idiopathic thrombocytopenic purpura (ITP) can deliver neonates with severe thrombocytopenia. Clear evidence declaring the pathophysiological cause of this neonatal thrombocytopenia is lacking, as antiplatelet antibodies are not always detectable in maternal serum. Severe neonatal thrombocytopenia below 50 × 109/l is reported in 8–13% of the neonates from mothers with ITP and intracranial haemorrhage (ICH) in 0–2·9%. Evidence about the optimal postnatal treatment is scarce. Our objective was to evaluate the outcome and management in neonates with passive ITP.
All neonates from mothers with ITP born between 1980 and 2011 were included. Platelet counts during the first 10 days, presence of ICH and postnatal treatment were recorded. Maternal characteristics were analysed as possible risk factors for severe neonatal thrombocytopenia.
Sixty-seven neonates were included. Severe thrombocytopenia (<50 × 109/l) occurred in 20/67 (29·9%) neonates. In three neonates, platelet count rose spontaneously, 18 neonates were treated (one with persistent moderate thrombocytopenia) with the following: platelet transfusions (3), prednisone (2), intravenous immunoglobulin (IVIG) (1), platelet transfusions and IVIG (11), platelet transfusion and prednisone (1). Recurrence of low platelet counts after transfusions was commonly seen. Risk factors for severe neonatal thrombocytopenia were a previous sibling with severe thrombocytopenia and low maternal platelet nadir during pregnancy.
In this cohort, severe neonatal thrombocytopenia occurs more frequently than previously reported. To maintain a platelet count above 50 × 109/l, often multiple transfusions and IVIG are required. Multiple transfusions may be avoided by starting IVIG, when platelet count falls below 50 × 109/l after the first platelet transfusion.
... Severe bleeding in the form of mucosal bleed in genitourinary or gastrointestinal tract, epistaxis may occur below 10 9 10 9 /l counts. Management of these patients is based on guidelines given by American Society of Haematology (ASH) [6] which are recently reviewed and observed to be effective [4,9]. The indications to treat a parturient with thrombocytopenia are based on risk of haemorrhage and summarized in Table 2 [3,4,6,10]. ...
... ITP Patients who fail to respond to standard medical line of treatment are termed as non-responder and are defined as a platelet count \30 9 10 9 or a less then two fold increase in platelet count from baseline or the presence of bleeding [4]. For these patients, splenectomy is considered appropriate treatment modality [1,4,6,9,10]. During pregnancy, splenectomy should ideally be performed in second trimester as it is associated with premature labour in first trimester and is technically difficult in third trimester [1,3,4,6,10,11]. ...
We report anaesthesia management of a parturient with severe thrombocytopenia secondary to immune thrombocytopenic purpura (ITP). Her platelet count remained around 3 × 10/l in spite of optimum medical therapy and hence was posted for splenectomy combined with caesarean section. Anaesthesia implications of severe thrombocytopenia comprises risk of central nervous system bleeding, perioperative haemorrhage causing placental hypoperfusion and foetal hypoxia, risk of trauma to compromised airway and risk of epidural haematoma. The purpose of this paper is to discuss the risk factors associated, different management strategies and also to review the literature in an attempt to ameliorate the anaesthesiologist in perioperative management of these cases.
... Stanowi 65-80% wszystkich przypadków małopłytkowości związanej z ciążą [2,6]. Najczęściej pojawia się w trzecim trymestrze ciąży [7]. Warto zwrócić uwagę na moment obniżenia liczby trombocytów. ...
Thrombocytopenia in pregnancy is the second most common hematological disorder with the incidence rate between 6.6–11.6%. Thrombocytopenia in pregnancy usually occurs in the third trimester of pregnancy and usu-
ally disappears after labour. However, low platelet count can also occur in life-threatening illnesses e.g. HELLP syndrome, DIC and HUS. Differentiation between gestational thrombocytopenia and immune thrombocytopenic purpura (ITP) is the basis for correct diagnosis and implementation of appropriate treatment.
ITP is manifested in approximately 1:1000 to 1:10,000 pregnant women and is defined as an immune disorder in which isolated reduction in the number of platelets drops below 100,000/μL. Differentiation between gestational thrombocytopenia and ITP is not easy due to the fact that many, if not all of the characteristics of gestational thrombocytopenia coincide with mild immune thrombocytopenia. If ITP is mild and the platelet count is above 70,000/μL it is impossible to distinguish it from gestational thrombocytopenia. Treatment is not necessary and the differentiation between gestational thrombocytopenia and ITP is not relevant. ITP is more likely to occur if thrombocytopenia is diagnosed in early pregnancy or if the platelet count is less than 50,000/μL. Indications for treatment of patient with ITP include: the occurrence of symptomatic haemorrhagic diathesis, low platelet count — less than 20,000–30,000/μL and the necessity to increase platelet count to the values required to perform medical procedures. Drugs used primarily in the treatment of ITP in early stages of pregnancy are glucocorticoids (prednisone), intravenous immunoglobulin and anti-D immunoglobulin. The biggest concerns of
potential interventions come in the time of labour. During the childbirth thrombocytopenia in pregnancy is the most dangerous for woman due to the risk of haemorrhage. Both vaginal and elective caesarean delivery are considered to be safe when platelet counts is higher than 50,000/μL. If necessary, it is indicated to administer corticosteroids or intravenous immunoglobulin. It has been recommended that the mode of delivery should be guided by obstetric indications. There is no accurate predictor of fetal thrombocytopenia. The correlation between maternal and neonatal platelet count is low. Currently the best predictor of neonatal thrombocytopenia is thrombocytopenia which occurred in child’s older siblings. Fetal mortality rate, after labour complicated by ITP, is estimated at 1–2%.
Key words: thrombocytopenia, pregnancy, approach, treatment
... Las limitaciones generales de la esplenectomía laparoscópica son cada vez más restringidas. Ni la obesidad [22] ni el embarazo [23] parecen ser factores limitantes. La edad avanzada, aunque no es una contraindicación para la esplenectomía laparoscópica, parece ser un factor de riesgo de complicaciones postoperatorias. ...
Resumen
Con el auge de la laparoscopia y el aumento del interés por las conductas conservadoras, la cirugía de los bazos no traumáticos ha evolucionado de forma considerable y las indicaciones para la cirugía mínimamente invasiva han seguido progresando. Los «bazos pequeños» son intervenidos preferentemente por laparoscopia. Las principales indicaciones son las hemopatías benignas (púrpura trombocitopénica inmunitaria [PTI], anemia hemolítica autoinmunitaria [AHAI], etc.). Las hemopatías malignas (linfomas, leucemia linfocítica crónica, síndromes mieloproliferativos, etc.) también se pueden tratar por laparoscopia, cuando no existe una esplenomegalia masiva asociada; en este caso, la laparotomía conserva su lugar. Más recientemente, la cirugía mínimamente invasiva, con monotrocar o asistida por robot, ha sido propuesta en las indicaciones para la laparoscopia. En el caso de un tumor esplénico focal, la esplenectomía parcial, preferiblemente por laparoscopia, debe discutirse. Aquí se desarrollan las diferentes técnicas, resultados, complicaciones y consecuencias quirúrgicas de las esplenectomías. Se detallan las técnicas y los tiempos de intervención específicos de las esplenectomías totales o parciales, por laparoscopia o laparotomía.
... Le limitazioni generali alla splenectomia laparoscopica sono sempre più limitate. Né obesità [22] , né gravidanza [23] sembrano essere fattori limitanti. L'età avanzata, sebbene non sia una controindicazione alla splenectomia laparoscopica, sembra essere un fattore di rischio per le complicanze postoperatorie ed è piuttosto la condizione generale apprezzata dal punteggio dell'American Society of Anesthesiologists (ASA) che deve guidare l'indicazione e l'approccio [24] . ...
Riassunto
Con il boom della laparoscopia e il guadagno d’interesse per gli atteggiamenti conservatori, la chirurgia delle milze non traumatiche si è evoluta considerevolmente e le indicazioni della chirurgia mini-invasiva hanno continuato a crescere. Le “piccole milze” sono, ora, preferibilmente operate in laparoscopia. Le principali indicazioni sono le emopatie benigne (porpora trombocitopenica immunologica [PTI], anemia emolitica autoimmune [AEAI], ecc.). Anche le emopatie maligne (linfomi, leucemia linfocitica cronica, sindromi mieloproliferative, ecc.) possono essere gestite mediante laparoscopia, quando non vi è una splenomegalia massiva associata, nel qual caso la laparotomia mantiene, naturalmente, il suo posto. Più recentemente, è stata proposta la chirurgia minimamente invasiva, mediante monotrocar, o robot-assistita, nelle indicazioni per la laparoscopia. Di fronte a un tumore splenico focale, deve, ormai, essere discussa la splenectomia parziale, preferibilmente mediante laparoscopia. Le diverse tecniche, i risultati, le complicanze e le sequele operatorie delle splenectomie sono qui esposte. Descriviamo in dettaglio le tecniche e i tempi operatori specifici della splenectomia totale o parziale, mediante laparoscopia o laparotomia.
... Since LSCS had to be performed platelet transfusion was done as per British guidelines. Platelet count of >80,000/mm 3 is recommended for epidural anesthesia by the British committee for the standards in hematology [10]. The count that was aimed in our patients was 50,000/mm 3 for vaginal delivery and 80,000/mm 3 for LSCS. ...
... Its use during the rest of pregnancy warrants caution due to definite, dose-dependent, increased risk of gestational diabetes, weight gain, hypertension, intrauterine growth restriction (IUGR), bone loss, preterm labor, preterm birth [23] and possibly placental abruption. Furthermore, the use of several medications like vinca alkaloids, danazol and cyclophosphamide used in resistant cases is contraindicated during first trimester for fear of potential teratogenicity [35]. The use of these agents during the rest of pregnancy is linked to IUGR, impaired hematopoiesis and developmental delay [36]. ...
Thrombocytopenia (TCP) is a common medical finding in obstetric population at term. The majority of new-onset TCP cases are mild, asymptomatic and diagnosed accidentally on routine antenatal screening. The most common causes at term are gestational thrombocytopenia (GT), preeclampsia/HELLP syndrome and immune-mediated thrombocytopenia (ITP). Preeclampsia/HELLP syndrome is accompanied with well-defined clinical characteristics and specific laboratory findings, while the other two are usually asymptomatic and are impossible to distinguish from one another. We encountered a case of new-onset TCP at 40 weeks gestation with negative history and a platelet count of 33 × 10⁹/L, yet, who had a fast spontaneous postpartum recovery. Her second pregnancy was also complicated by TCP of 77 × 10⁹/L at 37 weeks gestation. The newborn platelet count was normal in both instances. She was considered to have GT after a lapse of 4 years, being consistently healthy with normal platelet counts. After excluding other serious causes of severe new-onset TCP at term, management should be oriented towards securing hemostasis in preparation for delivery without wasting precious time and resources trying to discern between GT and ITP.
J Hematol. 2016;5(4):142-150
doi: https://doi.org/10.14740/jh308w
... Maternal thrombocytopenia may variably influence fetal thrombocytopenia and could stem from a pre-existing disease state such as idiopathic thrombocytopenic purpura [47], autoimmune diseases such as systemic lupus erythematosis or thrombotic thrombocytopenic purpura [30], gestational or incidental thrombocytopenia [41,334] or disorders acquired during pregnancy (viral or bacterial sepsis, disseminated intravascular coagulation or preeclampsia. [335][ Figure 3] A normal maternal platelet account associated with an otherwise healthy and well appearing term newborn infant with thrombocytopenia, should prompt a diagnosis of alloimmune disease. If neonatal alloimmune thrombocytopenia is suspected, then identification of the maternal human platelet alloantigen (HPA) antibody and phenotyping/genotyping of the parents for a potential platelet incompatibility is necessary to confirm the diagnosis. ...
Neonatal thrombocytopenia is defined as a platelet count of less than 150 x 10 9/L. Approximately 15% of healthy infants will have a platelet count of 100-150 x 109/L. Neonates with platelet counts of less than 100 x 109/L, require investigation. Thrombocytopenia is a risk factor for significant hemorrhage, adverse neurodevelopmental outcome and mortality. Early signs and symptoms may include petechiae and mucosal bleeding. The first step in investigating neonatal thrombocytopenia is to check the maternal platelet count. If this is abnormal screening should be initiated for maternal diseases such as immune thrombocytopenia (ITP), systemic lupus erythematosis (SLE) or hyperthyroidism. If maternal platelets are normal, neonatal alloimmune thrombocytopenia (NAIT) or other neonatal disorders should be explored. The etiology of known neonatal disorders that result in thrombocytopenia generally include one of four categories: increased platelet consumption, decreased platelet production, increased destruction or a variable combination of the three mechanisms. The pathophysiology of increased platelet consumption encompasses a wide spectrum of conditions such as disseminated intravascular coagulopathy (DIC), thrombosis, hemangioma, polycythemia, intrauterine growth restriction (IUGR), or may occur following an exchange transfusion. Conversely, decreased platelet production is usually due to aplastic anemia, leukemia, neuroblastoma or other congenitally acquired syndromes. Asphyxia and metabolic disorders are generally ascribed to combined mechanisms. The etiology of thrombocytopenia may also be related to the time of occurrence. Early-onset or fetal thrombocytopenia is often associated with placental insufficiency. This form of thrombocytopenia is generally benign and is associated with a spontaneous recovery in the absence of other complications such as sepsis. Thrombocytopenia diagnosed less than 72 hours of birth may be due to NAIT or ITP and congenital infections, while aneuploidy or congenital/inherited thrombocytopenias should also be considered as part of the differential diagnosis. Late onset thrombocytopenia develops rapidly and is almost always a result of underlying sepsis or necrotizing enterocolitis (NEC). The platelet nadir is reached within 24-48 hours, and is followed by a slow recovery with treatment over 1-2 weeks. Other less common causes include: inherited disorders (Bernard-Soulier syndrome, May-Hegglin anomaly, and Type II Vonwillebrand disease), bone marrow disorders (i.e. congenital leukemia, Langerhan's cell histiocytosis, neuroblastoma), or giant hemangioma. The primary steps in the management of neonatal thrombocytopenia are: identification of the most likely cause of the thrombocytopenia, management specifically tailored to the cause as in NAIT, and appropriate administration of platelet transfusions. While a safe lower limit to trigger a platelet transfusion has not been defined, prophylactic platelet transfusion is normally considered for a platelet count of less than 30 x 109/L, and less than 50 x 109/L for a very sick or premature infant. There are currently no evidence-based guidelines for the management of neonatal thrombocytopenia, and these are urgently needed to properly assess appropriate indications for platelet transfusion, the dose and schedule of administration, as well as the short and long term therapeutic effects of the strategy.
... The BCSH guidelines are consistent with contemporary practice in recommending that the mode of delivery of a pregnant patient with ITP should be determined based on maternal indications. 47 Mothers with ITP require monitoring during pregnancy and may require intervention with agents to raise the platelet count. For most women, however, pregnancy is uncomplicated and even those with severe thrombocytopenia during pregnancy have good outcomes. ...
Immune thrombocytopenia (ITP) is an acquired autoimmune disorder defined by isolated thrombocytopenia and the exclusion of other causes of thrombocytopenia.Although the underlying pathophysiology of ITP has been known for more than five decades, therapy has remained empirical. ITP guidelines were published by the American Society of Hematology 15 years ago (updated in 2011) and the British Committee for Standards in Hematology 8 years ago. The primary treatment goal is to prevent severe bleeding rather than achieve normal platelet counts. Nowadays, new therapeutic agents have changed strategies for ITP treatment. In this review,we discuss criteria for treatment, the role of splenectomy and other treatment options along with their side effects, and the treatment of ITP during pregnancy. Erişkin İmmun Trombositopeni ve Tedavisi: Derleme İmmün trombositopeni (İTP) diğer trombositopeni yapan nedenlerin olmaması ve izole trombositopeni ile seyreden edinilmiş otoimmün hastalıktır. İTP'nın patofizyolojisi 50 yıldan daha uzun süredir bilinmesine rağmen tedavi empirik olarak kalmıştır. İTP kılavuzu 15 yıl önce Amerikan Hematoloji Derneği(2011 de güncellenmiştir) ve 8 yıl önce de Hematoloji Standartları İngiliz Komitesi tarafından yayınlanmıştır. Tedavinin başlıca amacı normal platelet sayısına ulaşıncaya kadar ciddi kanamayı engellemektir. Günümüzde İTP'de yeni ilaçlarla tedavi stratejileri değişti. Bu derlemede erişkin İTP'de tedavi kriterlerini, tedavi yaklaşımlarını, splenektominin rolünü, yan etkileri ile birlikte diğer tedavi seçeneklerini ve gebelikteki İTP'nın tedavisini tartıştık.
... In alcuni casi l'ITP può esordire in gravidanza, mentre i casi con preesistente diagnosi di ITP possono rimanere quiescenti o peggiorare o ricadere durante la gravidanza. Questi ultimi richiedono minor trattamento rispetto ai nuovi casi 17 . Il meccanismo patogenetico noto da tempo, comune all'ITP non in gravidanza, prevede la produzione di autoanticorpi di tipo IgG diretti contro glicoproteine (GP) piastriniche (principalmente GP IIb/IIIa e GP Ib/IX) con successiva fagocitosi delle piastrine opsonizzate da parte dei macrofagi splenici; il meccanismo prevede l'interazione dei linfociti B produttori di autoanticorpi con i linfociti T-helper (Th1) produttori di interleuchine stimolati da peptidi piastrinici processati da cellule presentanti l'antigene. ...
Riassunto Le principali malattie ematologiche che posso-no complicare una gravidanza sono rappresenta-te dall'anemia e dalla piastrinopenia. Le cause più comuni di anemia in gravidanza, definita dalla WHO come un valore di emoglobina al di sotto di 11 g/dL, comprendono i deficit di fattori nutri-zionali (ferro, folati e vitamina B12), l'insufficien-za midollare, le malattie emolitiche (malaria, fal-cemia), la perdita cronica di sangue (parassitosi) e le neoplasie sottostanti. La più frequente è la carenza di ferro, che può diventare un serio pro-blema in quanto incrementa significativamente i rischi per la madre (parto prematuro, stanchezza, ridotte prestazioni mentali e fisiche, disturbi car-diovascolari, mortalità, necessità di trasfusioni post-partum) e per il feto (basso peso alla nasci-ta, ritardo mentale, rischio di sviluppare carenza di ferro nei primi 4 mesi di vita). Durante la gravi-danza c'è un'espansione della massa eritrocitaria e in misura minore del volume plasmatico mater-no in accordo alla crescita dell'unità feto placen-tare. La conseguenza è un'emodiluizione fisiolo-gica di significato ancora controverso e un'aumen-tata richiesta di ferro con deplezione fisiologica dei depositi che vanno considerati per un corret-to work-up diagnostico. In tale situazione è più attendibile valutare lo stato di deplezione ferrica con il recettore solubile della transferrina piutto-sto che con la ferritina. La piastrinopenia interes-sa circa il 10% di tutte le gravidanze. Può presen-tarsi in forma isolata e spesso clinicamente beni-gna o associata a disordini sistemici, con una si-gnificativa morbidità, sia specifici della gravidan-za (preeclampsia, HELLP syndrome) che non spe-cifici (microangiopatie trombotiche, LES, CID, anticorpi antifosfolipidi, infezioni virali). La for-ma più comune è la piastrinopenia gestazionale o incidentale, forma benigna con valori piastrinici solitamente non inferiori alle 100.000/µ µ µ µ µL che va differenziata dalla porpora trombocitopenica im-mune e dalla fisiologica e modesta riduzione del conteggio piastrinico che si verifica solitamente nel terzo trimestre di gravidanza.
... 5 Splenectomy during pregnancy was previously regarded as a high-risk procedure for the mother and the fetus, 1 but nowadays with safe surgical techniques and improved neonatal care it is considered a second-line therapeutic option for refractory ITP during pregnancy. [1][2][3][4][5] Tables 1 and 2 show the cases of ITP where splenectomy was carried out as a second-line therapy during the antenatal period or the caesarean section, respectively. ...
Immune thrombocytopenic purpura (ITP) complicates 1-2/10 000 pregnancies and accounts for 5% of cases of pregnancy-associated thrombocytopenia. Corticosteroids and intravenous immunoglobulin remain the first-line therapy in pregnancy, and a majority of pregnant women respond to this conventional therapy. Other cytotoxic and immunosuppressive agents used for treatment in non-pregnant patients, for example, danazol, cyclophosphamide, vinca alkaloids and azathioprine, are potential teratogens and cannot be administered during pregnancy. For pregnant women with ITP who fail to respond to medical management and are at a significant risk of haemorrhage due to thrombocytopenia, splenectomy may be considered as an option. We report two cases of splenectomy during pregnancy for refractory ITP. In one patient, it was carried out at 24 weeks, and in the second patient it was carried out during the caesarean section. Splenectomy as a second-line option in cases of refractory severe ITP in pregnancy is discussed.
... La durée de vie de ces cellules (dix fois plus petites qu'un globule rouge) dépourvues de noyau est d'environ une dizaine de jours, 10 % d'entre elles sont renouvelées chaque jour à partir des mégacaryocytes. De faç on physiologique, le nombre des plaquettes chute de 10 % au cours de la grossesse [1]. Dans une importante série scandinave de plus de 4000 grossesses [2], 7 % des femmes avaient moins de 150 × 10 9 /L plaquettes en fin de grossesse et 1 % moins de 100 × 10 9 /L. ...
The occurrence of thrombocytopenia during pregnancy is frequent (about 10%). Etiologies of thrombocytopenia are dominated by the gestational thrombocytopenia (>75%), which requires no exploration and no specific treatment; it usually occurs during the last trimester of pregnancy and corrects itself spontaneously after delivery. Other etiologies are: (1) immune thrombocytopenia (ITP) either primary or associated with other pathologies; ITP may appear early in the first trimester of pregnancy, (2) thrombotic microangiopathy syndromes, and (3) obstetric thrombocytopenia: eclampsia and HELLP syndrome (hemolysis elevated liver enzymes, and low platelet count). Treatment of pre-eclampsia and HELLP syndrome is based on resuscitative measures and symptomatic fetal extraction that will be discussed according to the term and severity of the case. The treatment of microangiopathy is based on resuscitation and plasma exchange. For ITP, no specific action is needed during pregnancy and only symptomatic patients with a platelet count less than 30×10(9)/L must receive a treatment. It is important to prepare the childbirth that can be vaginally except if there is an obstetric contraindication. A platelet count of 50×10(9)/L is required for the delivery, and of 75×10(9)/L in case of spinal anesthesia. Treatment implies a short course of corticosteroids associated with infusion of immunoglobulins in the most severe forms or in case of steroids resistance. There is a risk of neonatal thrombocytopenia requiring a control of the blood count for the baby at birth and within 5 days, newborns have to be treated if the platelet count is less than 20×10(9)/L.
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... In this patient, a platelet count of 82 ϫ 10 9 /L early in the second trimester requires further evaluation. 10 A mild congenital thrombocytopenia that worsens during pregnancy cannot be excluded without prior records or testing of other family members, which should be pursued, especially because some of these disorders are associated with platelet dysfunction. Our patient reported that none of the male family members had platelet disorders. ...
A mild thrombocytopenia is relatively frequent during pregnancy and has generally no consequences for either the mother or the fetus. Although representing no threat in the majority of patients, thrombocytopenia may result from a range of pathologic conditions requiring closer monitoring and possible therapy. Two clinical scenarios are particularly relevant for their prevalence and the issues relating to their management. The first is the presence of isolated thrombocytopenia and the differential diagnosis between primary immune thrombocytopenia and gestational thrombocytopenia. The second is thrombocytopenia associated with preeclampsia and its look-alikes and their distinction from thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome. In this review we describe a systematic approach to the diagnosis and treatment of these disease entities using a case presentation format. Our discussion will include the antenatal and perinatal management of both the mother and fetus.
Since it was first reported in 1991, laparoscopic splenectomy (LS) has been extensively performed in clinical practices worldwide. Over the past three decades, it has addressed more and more indications, covering almost all diseases in need of splenectomy by virtue of ever-improving surgical skills. Therefore, LS has been widely accepted as the “standard procedure” of splenectomy [1, 2].
The study of the pathogenesis of thrombocytopenia during pregnancy remains a very important problem, since hemostatic abnormalities continue to occupy one of the leading places among the causes of infertility, miscarriage and a large number of perinatal complications. Pregnant women with thrombocytopenia constitute a risk group for the development of bleeding events and thrombotic complications during pregnancy, in childbirth, and in the postpartum period. This article reviews literature data on the pathogenic causes of thrombocytopenia during pregnancy and on the main methods of treatment of the disease.
Introduction:
Immune thrombocytopenia (ITP) complicates 1–2 cases/10,000 pregnancies in India. Management of these patients is a challenge as it is associated with potential risks of maternal bleeding episodes and neonatal alloimmune thrombocytopenia (NAITP).
Objective:
To study the maternal and fetal/neonatal outcome of pregnancy in Indian patients with ITP and identify the risk factors for NAITP.
Materials and Methods:
In this retrospective study, all ITP patients with pregnancy who were diagnosed and treated at our center over 8 years (2010–2018) were evaluated for their hematological, obstetrical, and fetal outcomes.
Results:
Twenty-nine pregnancies in 27 ITP patients were studied. The mean interval between the diagnosis of ITP and each pregnancy was 29 ± 14.9 months. The mean baseline platelet count was 0.18 ± 0.05 X 109/L. Twenty-seven (93.1%) cases were treated with oral prednisolone. Twenty deliveries (69.0%) were vaginal and 9 (31.0%) deliveries were by cesarean section. There were no major bleeding episodes during pregnancy or delivery.
The mean neonatal platelet count was 1.23 ± 0.58 × 109/L at birth. NAITP was seen in 3 (3.5%) neonates. No bleeds or intracranial hemorrhages were observed. Only maternal platelet count < 50 X 109/L at delivery showed a statistical correlation with NAITP (p = 0.022). There was no positive correlation between NAITP and the duration of maternal ITP, the timing of ITP onset, or type of treatment. Conclusion:
Successful outcome of pregnancies in ITP patients is possible, and the risk of maternal bleeding and NAITP is low.
Thrombocytopenia is a common finding in pregnancy. Establishing the diagnosis of immune thrombocytopenia (ITP) in a pregnant patient is similar to doing so in a nonpregnant patient, except that the evaluation must specifically rule out other disorders of pregnancy associated with low platelet counts that present different risks to the mother and fetus and may require alternate distinct therapy. Many of the same treatment modalities are used to manage the pregnant patient with ITP, but others have not been determined to be safe for the fetus, are limited to a particular gestational period, or side effects may be more problematic during pregnancy. The therapeutic objective differs from that in chronic ITP in the adult because many pregnant patients recover or improve spontaneously after delivery and therefore maintenance of a safe platelet count, rather than prolonged remission, is the goal. Thrombocytopenia may the limit choices of anesthesia, but does not guide mode of delivery, and the fetus is rarely severely affected at birth. Patients should be advised that a history of ITP or ITP in a previous pregnancy is not a contraindication to future pregnancies and that, with proper management and monitoring, positive outcomes can be expected in the majority of patients.
Cambridge Core - Obstetrics and Gynecology, Reproductive Medicine - High-Risk Pregnancy - edited by David James
Objective:
We reviewed outcomes of 52 pregnancies in 45 women with immune thrombocytopenic purpura who delivered at Auckland Hospital with an antenatal platelet count of <100 × 109/L.
Outcome measures:
Primary outcomes were maternal platelet count at delivery and treatment response. Secondary outcomes included post-partum haemorrhage (PPH).
Results:
Most women had thrombocytopenia at delivery. Treatment with prednisone was given in 14 (27%) pregnancies with responses considered safe for delivery in 11 pregnancies (79%). Women in eight pregnancies also received intravenous immunoglobulin; in five pregnancies (63%) a platelet response acceptable for delivery was achieved.Seventeen pregnancies (33%) were complicated by a PPH ≥500 mL. Ten pregnancies (19%) were complicated by a PPH ≥1000 mL. PPH was reported in all women with a platelet count <50 × 109/L at delivery.
Conclusions:
There were no antenatal bleeding complications but PPH was common among women with platelet counts <50 × 109/L at the time of birth.
Most of thrombocytopenic pregnant women present mild decrease of platelet counts and have favorable outcome. However, small portion of these cases can show moderate to severe thrombocytopenia and may increase the risk of bleeding during delivery. We investigated the prevalence, causes, and outcomes of pregnancies complicated by moderate to severe thrombocytopenia. We reviewed medical records of pregnant women who were diagnosed with moderate to severe thrombocytopenia (<100 × 10⁹/L) during their pregnancies. A total of 4822 deliveries were performed and 26 patients (0.54%) with moderate to severe thrombocytopenia were identified. The most common cause of moderate to severe thrombocytopenia was immune thrombocytopenia (ITP) (42.3%), followed by gestational thrombocytopenia (GT) (34.6%). Compared to GT, ITP showed lower platelet counts at presentation (52.4 × 10⁹/L vs. 80.5 × 10⁹/L, P = 0.041). Patients with GT could conduct successful delivery without specific management, and patients with ITP showed favorable delivery outcomes with adequate treatment. In conclusion, the incidence of moderate to severe thrombocytopenia during pregnancy was very low and most common causes were ITP and GT. Patients with moderate to severe thrombocytopenia could have favorable delivery outcomes with adequate treatment.
Thrombocytopenia is a common hematologic problem in pregnant women. The most common cause of thrombocytopenia is gestational thrombocytopenia, which is usually mild, is not associated with bleeding or neonatal thrombocytopenia, and resolves spontaneously postpartum. Gestational thrombocytopenia, however, may be hard to discern from immune thrombocytopenia (ITP), another cause of isolated thrombocytopenia during pregnancy, although thrombocytopenia due to ITP is often more severe and occurs earlier in pregnancy. Preeclampsia is the most common medical disorder of pregnancy and is associated with a constellation of symptoms including hypertension and proteinuria; thrombocytopenia is generally mild, but reflects the severity of underlying preeclampsia. The syndrome of hemolysis, elevated liver enzymes and low platelets (HELLP) is thought by some to be a variant of preeclampsia as it shares some manifestations but also displays unique ones, particularly liver involvement and microangiopathic hemolytic anemia. HELLP may be difficult to discern from primary thrombotic microangiopathies such as thrombotic thrombocytopenic purpura (TTP) and the atypical hemolytic uremic syndrome (aHUS), which are not unique to pregnancy but occur with increased frequency in this setting. Accurate diagnosis of the cause of thrombocytopenia during pregnancy is important, as treatment varies depending on the etiology. Careful consideration of the timing of onset of thrombocytopenia, and associated hematologic and other manifestations, needs to be considered in the differential diagnosis. Though thrombocytopenic disorders may severely compromise the outcomes of some pregnancies, prompt diagnosis and appropriate therapy often lead to successful pregnancy outcomes.
Introduction: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by autoantibody production against platelets, increased platelet destruction, and, in some cases, impaired thrombopoiesis. The majority of affected patients have significant bleeding risks due to low platelet counts and require treatment. The etiology of ITP is an immunological labyrinth. Currently available treatment options are usually not only nonspecific, but are also associated with some risks.
Areas covered: Several useful drugs for the treatment of ITP are currently available. Furthermore, ongoing trials with new drugs and preclinical development of additional drugs may help to improve and determine their value.
Expert opinion: ITP is a heterogeneous complex requiring individualized treatment. None of the available drugs are specific, nor are they invariably safe and effective. Thus, the need for specific therapy is evident.
Pregnant women face hemostatic challenges during labor and delivery. However, a subset of this population will additionally face an increased risk of thromboembolic events secondary to inherited or acquired risk factors during the prepartum or postpartum period. Pregnancy itself, because of changes in the coagulation cascade and anatomic factors, represents a state of heighted risk for clotting events. Who should receive anticoagulants, at what dose, and for how long are frequent issues that arise when dealing with a patient at increased risk for thromboembolism during pregnancy. Another common hematologic condition during pregnancy is thrombocytopenia which frequently can be categorized as a benign, gestational thrombocytopenia, but other more serious conditions such as idiopathic thrombocytopenia purpura or thrombotic thrombocytopenic purpura should be considered. Here we discuss the risk of vascular thromboembolism in various inherited and acquired thrombophilias and their management during pregnancy as well as the differential diagnosis of thrombocytopenia in the pregnant woman with discussion on the management.
Thrombocytopenia is one of the most frequently encountered hematological disorders and occurs as a consequence of numerous pathophysiological mechanisms. One of the more common causes of thrombocytopenia is “immune thrombocytopenia” (ITP). Landmark studies on this disease performed more than 50 years ago demonstrated an important role for antibody-mediated platelet destruction in ITP (Harrington et al. 1951). Subsequent studies have revealed that bone marrow megakaryocytes are also affected by platelet autoantibodies (McMillan et al. 2004; Nugent et al. 2009) and that T cells may also contribute to platelet destruction and inhibit platelet production by megakaryocytes (Cines et al. 2009a; Semple and Provan 2012). As with other thrombocytopenic disorders, ITP may occur as a primary syndrome or may be secondary to underlying infectious, autoimmune, or malignant disorders (Cines et al. 2009a; Rodeghiero et al. 2009).
The management of idiopathic thrombocytopenic purpura (ITP) during pregnancy can be challenging. The diagnosis and distinction between gestational thrombocytopenia and ITP is important and requires assessment of the timing and degree of thrombocytopenia. Exclusion of thrombocytopenia of another origin and of secondary causes of ITP is also vital before embarking on treatment, and current therapeutic options are discussed in this chapter. The mode of delivery should be dictated by obstetric indications and not related to the platelet count. Fetal blood sampling is not recommended as the incidence of neonatal bleeding remains low, but a cord-derived blood count should be taken at birth. In babies who are thrombocytopenic, intravenous immunoglobulin treatment is recommended and counts should be repeated daily until normalization of the platelet count.
The management of immune thrombocytopenic purpura (ITP) during pregnancy can be challenging. The diagnosis and distinction between gestational thrombocytopenia and ITP is important and requires assessment of the timing and degree of thrombocytopenia. Exclusion of thrombocytopenia of another origin and of secondary causes of ITP is also vital before embarking on treatment, and current therapeutic options are discussed in this chapter. The mode of delivery should be based on obstetric indications. Fetal scalp blood sampling is not recommended as the incidence of neonatal bleeding remains low, but an umbilical cord-derived blood count should be taken at birth. In babies who are thrombocytopenic, intravenous immunoglobulin treatment is recommended and platelet counts should be repeated daily until normalized.
The research group for studies of idiopathic thrombocytopenic purpura (ITP) has developed clinical recommendations for the diagnosis and treatment of this disease. The aim of the recommendations is standardization of the diagnostic and therapeutic approaches in Russia. The current methodological approaches proceed from the conclusive medicine philosophy and are based on the recommendations of the Russian Expert Council for the diagnosis and therapy of patients with primary immune thrombocytopenia and the experience gained in the treatment of ITP patients (primary immune thrombocytopenia) in Russia, as well as on recommendations of the International Working Group for studies of primary immune thrombocytopenia, decisions of the International Consensus on ITP diagnosis and therapy, and recommendations of the European and American Societies of Hematologists for ITP studies. The recommendations are developed by the multicenter research group for ITP studies. Working groups from 8 leading institutions of Russia contributed to the development of clinical recommendations.
The major hematological malignancies affecting pregnancy are anaemia and thrombocytopenia. The most common causes of anaemia in pregnancy, defined by WHO as hemoglobin concentration below 11 g/dL, are nutritional deficiency (iron, folate and vit. B12), bone marrow failure, hemolytic diseases (malaria, sickle cell disease), chronic blood loss (parasites) and underlying neoplasm. The main causes iron deficiency which can become a severe problem because it significantly increases the risks for the mother (premature birth, tiredness, reduced mental and physical performance, cardiovascular disease, mortality, transfusion requirement post-partum) and the fetus (low birth weight, mental retardation and risk of developing iron deficiency during the first four months of life). During pregnancy, there is an expansion of red cell mass and to a lesser extent in plasma volume according to maternal fetal placental unit growth. The result is a physiological hemodilution of still controversial meaning and increased demand for iron with depletion of deposits which should be considered for a proper diagnostic workup. In this situation, it is more reliable to assess the state of iron depletion with soluble transferrin receptor ra ther than ferritin. Thrombocytopenia affects approximately 10% of all pregnancies. It can occur alone and often clinically benign form or associated with systemic disorders, with significant morbidity, both specific to pregnancy (preeclampsia, HELLP syndrome) that non-specific diseases (thrombotic microangiopathy, LES, CID, antiphospholipid antibodies, viral infections). The most common form is gestational thrombocytopenia, or incidental benign form with platelet count usually not lower than 100.000/μL, which should be differentiated from immune thrombocytopenic purpura and the physiological and modest reduction in platelet count that usually occurs in the third trimester of pregnancy.
Haematological disorders of pregnancy are common reasons for hospital visits. Iron-deficiency anemia is a public health problem. Pregnant women are among the high-risk population. Thrombocytopenia affects 6-10% of all pregnancies. Thrombocytopenia in pregnant women may often be associated with other abnormalities, such as hypertension, microangiopathic hemolytic anemia and elevated hepatic enzymes, but may also occur in isolation. Pregnancy-related venous thromboembolism is one of the risk factors that increase maternal mortality and morbidity. In this review, hematological disorders of pregnancy are discussed.
Bleeding disorders in pregnancy may be inherited or acquired. While not all bleeding disorders are pregnancy specific, the hemostatic stressors of pregnancy can unmask the diagnosis. Bleeding disorders in pregnancy may be inherited or acquired and can manifest as disorders of primary and secondary hemostasis. This chapter will discuss the impact of the physiologic changes of pregnancy on hemostasis, as well as diagnostic and therapeutic options.
Immune thrombocytopenia (ITP) is not infrequently encountered during reproductive years with an estimated incidence of 0.1-1 per 1000 pregnancies. An international consensus group recently re-defined ITP and outlined standardized response criteria and up-to-date investigation and management. The pathogenesis encompasses autoantibody platelet destruction and immune-mediated decreased platelet production. Maternal antibodies may cross the placenta and have the potential to cause fetal and/or neonatal thrombocytopenia. The diagnosis and subsequent management of ITP in pregnancy requires a multidisciplinary approach involving the midwife, obstetrician, haematologist and anaesthetist. Women with ITP diagnosed prior to pregnancy should receive preconception counselling to outline potential treatments and provide information regarding expected maternal and neonatal outcome. Management prior to 36 weeks aims to avoid treatment in the absence of bleeding and ensure an acceptable platelet count for planned procedures. At 34-36 weeks, women are generally reviewed to consider whether a tailored course of treatment is required in preparation for delivery. Further research is required to determine a suitable platelet count for neuraxial anaesthesia. The mode of delivery should be guided by obstetric indication. It is pertinent to consider both the risk of maternal bleeding and thrombosis in maternal ITP. The risk of neonatal intracranial haemorrhage in association with ITP is less than 1%. Postpartum a cord blood platelet count should be checked. Additional management is dependent upon the neonatal platelet count. Data collection using the new standardized terminology should provide robust comparable epidemiological data regarding ITP in pregnancy.
Thrombocytopenia during pregnancy is quite common. Evaluation of blood counts of pregnant women has shown that thrombocytopenia is the second most common haematological problem in pregnancy, after anaemia. While mostly thrombocytopenia has no consequences for either the mother or the foetus, in some cases it is associated with substantial maternal and/or neonatal morbidity and mortality. It may result from a number of diverse aetiologies. Adequate knowledge of these causes will help the clinicians in making proper diagnosis and management of thrombocytopenia in pregnancy. The evaluation of thrombocytopenia is essential to rule out any systemic disorders that may affect pregnancy management as thrombocytopenia can present as an isolated finding or in combination with underlying conditions. In this concise review, we have provided the overview of thrombocytopenia diagnosed during pregnancy.
Immune Thrombocytopenia, or ITP, has been recognized as a clinical entity for centuries, and the importance of humoral mechanisms in the pathophysiology of ITP has been recognized for decades. Despite the long history of the syndrome, progress in understanding its epidemiology and management has been hindered by inconsistencies in nomenclature and classification schema together with the inherent heterogeneity in characteristics of global populations and ITP-associated disorders. In the past decade, great strides have been made in devising a common language for caregivers and investigators alike through standardization definitions and outcome measures, while new tools have become available for management of its clinical manifestations. In 2009, an International Working Group presented proposed standards for definitions, classification criteria, and outcome measures. The American Society of Hematology adopted these standards in 2011, including them in that body's guideline for immune thrombocytopenia. Despite the progress made so far, 20(th) century interventions such as corticosteroids and IVIg remain the mainstay of therapy. However, advances in treatment have led to the introduction of targeted therapies for select patients with chronic disease. In this paper, we review aspects of the epidemiology and pathophysiology of ITP and discuss the recent changes to guidelines for nomenclature, diagnosis, and treatment.
Con la comparsa della laparoscopia e l’aumento dell’interesse per le tecniche conservative, la chirurgia non traumatologica della milza è considerevolmente cambiata e le indicazioni alla chirurgia mini-invasiva non hanno smesso di aumentare. Le emopatie benigne (porpora trombocitopenica immunologica, anemia emolitica autoimmune ecc.) rappresentano la maggior parte delle indicazioni odierne. Tenuto conto delle dimensioni normali della milza, essa deve essere oramai operata in laparoscopia. Le emopatie maligne (linfomi, leucemia linfoide cronica, sindromi mieloproliferative ecc.) possono anch’esse essere operate in laparoscopia, ma per queste indicazioni, nelle quali la splenomegalia può essere di tipo maggiore, la laparotomia conserva un ruolo elettivo. In caso infine di tumore splenico focale, deve essere presa in esame la splenectomia parziale, preferenzialmente laparoscopica. Verranno di seguito discusse le diverse tecniche, i risultati, le complicazioni e le sequele delle splenectomie, esponendo dettagliatamente le tecniche o i tempi operatori specifici alle splenectomie in laparotomia o in laparoscopia. Verranno descritte le tecniche della splenectomia parziale o totale per l’accesso mini-invasivo alla milza.
La aparición de la laparoscopia ha cambiado considerablemente la cirugía de los bazos no traumáticos. Desde entonces, las indicaciones de la cirugía mínimamente invasiva se han extendido sin cesar. La mayor parte de las indicaciones actuales corresponde a hemopatías benignas (púrpura trombocitopénica inmunológica, anemia hemolítica autoinmunitaria, etc.), en las que el tamaño normal del bazo posibilita la intervención laparoscópica. Las hemopatías malignas (linfomas, leucemia linfoide crónica, síndromes mieloproliferativos, etc.) también pueden operarse por laparoscopia. Sin embargo, cuando se trata de grandes esplenomegalias, la laparotomía sigue siendo la técnica de elección. En los tumores esplénicos focales cabe evaluar la pertinencia de una esplenectomía parcial, preferentemente laparoscópica. El presente artículo expone las diversas técnicas, los resultados, las complicaciones y los aspectos postoperatorios de las esplenectomías. Se detallan las técnicas y las fases quirúrgicas específicas de las esplenectomías por laparotomía y por laparoscopia; además, se distinguen las intervenciones parciales de las totales.
Idiopathic thrombocytopenic purpura is an autoimmune disorder characterized by a low platelet count. Onset usually occurs during adolescence with episodes of cutaneous and mucosal bleeding. Thrombocytopenia during pregnancy is associated with many diseases, of which idiopathic thrombocytopenic purpura is the most common in the first trimester. The need for treatment will depend on the platelet count and whether there is bleeding. At the end of pregnancy, however, whether delivery is vaginal or by cesarean, more aggressive therapeutic measures are required. Anesthetic management in this type of patient will be determined by coagulation status and platelet count, and local or regional anesthesia may be contraindicated. We report the case of a pregnant woman with idiopathic thrombocytopenic purpura who was admitted to the emergency department of our hospital with suspected preeclampsia.
The consensus document on the diagnosis, treatment and monitoring of primary immune thrombocytopenia was developed in 2010 by specialists with recognized expertise in this disease under the auspices of the Spanish Society of Hematology and Hemotherapy and the Spanish Society of Pediatric Hematology and Oncology, with the aim to adapt to Spain the recommendations of the recently published international consensus documents. The decision to start treatment is based on bleeding manifestations and platelet count (<20×10(9)/L). The first-line treatment is corticosteroids, albeit for a limited period of 4-6 weeks. The addition of intravenous immunoglobulin is reserved to patients with severe bleeding. Splenectomy is the most effective second-line treatment. For patients refractory to splenectomy and those with contraindications or patient refusal, the new thrombopoietic agents are the drugs of choice due to their efficacy and excellent safety profile. The other treatment options have highly variable response rates, and the absence of controlled studies does not allow to establish clear recommendations. Monitoring should be individualized. In patients without active treatment, blood counts are recommended every 3-6 months, and the patient should be instructed to consult in case of bleeding, surgery or invasive procedure and pregnancy. In most of the pediatric population, the disease tends to spontaneous remission. High-dose corticosteroids in short course and intravenous immunoglobulin are the treatment of choice. Second- and further-line treatments should be monitored in specialized centers.
Copyright © 2011 Elsevier España, S.L. All rights reserved.
Abstract Objectives: The purpose was to correlate use of regional analgesia/anasthesia among women with different degrees of thrombocytopenia relative to women with normal platelet counts, and note maternal and neonatal outcome, and mode of delivery. Methods: A case-control paradigm was developed based on women who delivered during 2007-2011 with platelet counts ≤80,000/mm(3). For each women in this 'severe' thrombocytopenic group, an age- and parity-matched control was found who delivered a singleton within the same year but whose platelets were either 81,000-150,000/mm(3) ('moderate' thrombocytopenia) or ≥151,000/mm(3) (normal platelet counts). Results: 168 women were identified for each group; mean maternal age (28.4 years), mean gravidity (4.3), mean parity (3.7), mean gestational age (39.2 weeks), and mean birth weight (3283grams) were comparable. However, only in the severe thrombocytopenic women were there very early preterm deliveries, lowest birth weight, lowest Apgar scores, the greatest number with serious post-partum hemorrhage (>500ml); use of regional analgesia/anesthesia was lowest, and percent cesarean sections highest. Conclusions: This study highlights potential for adverse maternal outcome of post-partum hemorrhage and adverse neonatal outcomes of prematurity, low birth weight, and low Apgar scores (but not neonatal death), and limited regional analgesia/anesthesia in women who present at delivery with severe (≤80,000/mm(3)) thrombocytopenia. Keywords: Apgar scores, delivery, blood products, maternal outcome, neonatal outcome, regional analgesia/anesthesia, thrombocytopenia.
Thrombocytopenia is a common finding in pregnancy. Establishing the diagnosis of immune thrombocytopenia (ITP) in a pregnant patient is similar to doing so in a nonpregnant patient, except that the evaluation must specifically rule out other disorders of pregnancy associated with low platelet counts that present different risks to the mother and fetus and may require alternate distinct therapy. Many of the same treatment modalities are used to manage the pregnant patient with ITP, but others have not been determined to be safe for the fetus, are limited to a particular gestational period, or side effects may be more problematic during pregnancy. The therapeutic objective differs from that in chronic ITP in the adult because many pregnant patients recover or improve spontaneously after delivery and therefore maintenance of a safe platelet count, rather than prolonged remission, is the goal. Thrombocytopenia may the limit choices of anesthesia, but does not guide mode of delivery, and the fetus is rarely severely affected at birth. Patients should be advised that a history of ITP or ITP in a previous pregnancy is not a contraindication to future pregnancies and that, with proper management and monitoring, positive outcomes can be expected in the majority of patients.
There is no standard treatment for refractory idiopathic thrombocytopenic purpu- ra (ITP) that occurs during pregnancy.We report the case of a patient with chronic ITP during pregnancy; the condition was refractory to steroids, intravenous im- munoglobulin, high dose anti-D, and vincristine. The patient underwent cesarean section for maternal indications and developed postpartum hemorrhage, which was treated successfully with recombinant factor VIIa. KeyWords: cesarean section, intravenous immunoglobulin, high dose anti-D, intravenous vincristine, recombinant factor VIIa (Novo Seven), refractory idiopathic thrombocytopenic purpura.
Immune thrombocytopenia (ITP) is an autoimmune disorder that leads to premature destruction of antibody-coated platelets. This study evaluated perinatal outcome and medications used for pregnancies complicated by ITP.
Medical records of 132 pregnancies belonged to 125 parturients with ITP who delivered between March 2001 and January 2011 were reviewed. Cases were included if diagnosed before pregnancy or if their platelet counts (PCs) were less than 80,000/µL during pregnancy without any other cause. Maternal and fetal outcomes were compared.
Fifty six mothers (42.1%) had PC<50,000, 18 women (13.5%) developed preeclampsia and 15 (11.3%) were diabetics. Corticosteroid was used for120 cases (90.9%) and intravenous immunoglobulin for 14 women (10.5%). PCs of 114 neonates were available in the charts and 84 (83.2%) had PC>150,000/µL. Three neonates (2.3%) had PC<50 000, 31 neonates (23.3%) had preterm births and 32 (24.1%) needed NICU admissions. Fifty seven cases of ITP (43.2%) were diagnosed before pregnancy and 75 (56.8%) were diagnosed during pregnancy. There were 2 intrauterine fetal deaths and higher NICU admissions, 20 (34.48%) versus 12 (16%) in the first group (p=0.01).
Perinatal outcome of pregnancies with ITP is generally good. However neonates born from parturients with chronic ITP needed more NICU admissions.
The optimal management of immune thrombocytopenic purpura during pregnancy remains controversial because the risk of severe neonatal thrombocytopenia remains uncertain. We studied the outcome of the index pregnancy in 162 women with a presumptive diagnosis of immune thrombocytopenic purpura to determine the frequency of neonatal thrombocytopenia and to determine whether neonatal risk could be predicted antenatally by history or platelet-antibody testing.
Two maternal characteristics were identified as predicting a low risk of severe neonatal thrombocytopenia: the absence of a history of immune thrombocytopenic purpura before pregnancy, and the absence of circulating platelet antibodies in the women who did have a history of the condition. Eighteen of 88 neonates (20 percent; 95 percent confidence interval, 13 to 30 percent) born to women with a history of immune thrombocytopenic purpura had severe thrombocytopenia (platelet count less than 50 x 10(9) per liter at birth), as compared with 0 of 74 (0 percent; 95 percent confidence interval, 0 to 5 percent) born to women first noted to have thrombocytopenia during pregnancy (P less than 0.0001). Among the women with a history of immune thrombocytopenic purpura, 18 of 70 neonates (26 percent; 95 percent confidence interval, 16 to 38 percent) born to those with circulating platelet antibodies had severe thrombocytopenia, as compared with 0 of 18 infants (0 percent; 95 percent confidence interval, 0 to 18.5 percent) born to those without circulating antibodies (P less than 0.02). Thus, the risk of severe neonatal thrombocytopenia in the offspring of women without a history of immune thrombocytopenic purpura before pregnancy and of women with a history of the condition in whom circulating platelet antibodies are not detected was 0 percent (95 percent confidence intervals, 0 to 5 and 0 to 18.5 percent, respectively).
The absence of a history of immune thrombocytopenic purpura or the presence of negative results on circulating-antibody testing in pregnant women indicates a minimal risk of severe neonatal thrombocytopenia in their offspring.
Idiopathic thrombocytopenic purpura (ITP) is a condition that often develops in young women and, consequently, physicians should frequently manage and monitor pregnant patients with this disorder.
We reviewed the charts of 30 women with chronic ITP delivered in 31 pregnancies from January 1995 to December 2003.
Fifteen patients were diagnosed with ITP before pregnancy and sixteen patients were diagnosed during pregnancy. The mean platelet counts before pregnancy, during pregnancy, and at delivery were 70,040/mm3, 83,960/mm3, and 62,680/mm3, respectively. The symptoms of hemostatic impairment were not noted in most of the pregnancies (77%, 24/31). During pregnancy and at delivery, most of the women (61%, 19/31) received various kinds of treatment to raise platelet counts. At delivery, the most commonly used therapy was platelet transfusion (48.4%, 15/31). Seven pregnancies (22.6%) were treated with corticosteroids during pregnancy and at delivery. Five pregnancies (16.1%) were treated with IV IgG during pregnancy and at delivery. Fifteen deliveries (51.7%) were performed by cesarean section and fourteen (48.3%) with vaginal delivery. Bleeding was uncommon at delivery. There were no cases of infants with any clinical signs of hemorrhage.
Our current results suggest that ITP in pregnancy can proceed safely with low hemorrhagic risk in both infants and mothers, and that mothers with ITP can deliver healthy infants without serious hemorrhagic complications.
Numerous studies have examined the outcomes of infants born to mothers with idiopathic thrombocytopenic purpura (ITP). Fewer studies have discussed the morbidity of obstetric patients with ITP. We describe a retrospective study of 92 women with ITP during 119 pregnancies over an 11-year period. Most women had thrombocytopenia during pregnancy. At delivery, women in 98 pregnancies (89%) had platelet counts lower than 150 x 109/L; most had mild to moderate thrombocytopenia. For many, the pregnancy was uneventful; however, women had moderate to severe bleeding in 25 pregnancies (21.5%). Women in 37 pregnancies (31.1%) required treatment to increase platelet counts. During delivery, 44 women (37.3%) received epidural analgesia without complications, with most having a platelet count between 50 and 149 x 109/L. Most deliveries (82.4%) were vaginal. Bleeding was uncommon at delivery. Infant platelet counts at birth ranged from 12 to 436 x 109/L; 25.2% of infants had platelet counts lower than 150 x 109/L, and 9% had platelet counts lower than 50 x 109/L. Eighteen infants (14.6%) required treatment for hemostatic impairment. Two fetal deaths occurred. One was caused by hemorrhage. ITP in pregnancy carries a low risk, but mothers and infants may require therapy to raise their platelet counts.
Thrombocytopenia detected during pregnancy addresses the issue of its mechanism and of the possible occurrence of neonatal thrombocytopenia. To further investigate these issues, 50 women referred to us because of thrombocytopenia detected during pregnancy (platelet count, <150 × 109/L), were extensively studied, as well as their offspring. Among these thrombocytopenic women, we used the threshold of 70 × 109/L to differentiate between mild and severe thrombocytopenia. Whatever the severity of thrombocytopenia, we found biological features of an autoimmune disorder in 48% of the women, and chronic thrombocytopenia in 55%. A familial thrombocytopenia was evidenced in 1 case. These 50 women gave birth to 63 neonates, among whom 24 were thrombocytopenic, either at birth or during the first week of life. Neonatal thrombocytopenia could only be predicted in multiparous women, on the basis of previous neonatal thrombocytopenia in older siblings, and/or when maternal platelet life span study, performed before pregnancy, had evidenced an autoimmune thrombocytopenia (AITP)-like profile. These results suggest that, in case of pregnancy-associated thrombocytopenia, familial and immunological studies, combined with postdelivery iterative platelet counts, should be performed to properly characterize the thrombocytopenia. Moreover, the platelet count of the neonate should be carefully assessed at birth and during the following days, a platelet life span study should be performed after delivery in the mother, because these two parameters are likely to bring valuable information regarding the forthcoming pregnancies and the risk of neonatal thrombocytopenia.
To study the association between maternal drug use in early pregnancy and orofacial cleft in the infant.
Register analysis based on prospectively collected information.Patients: All delivered women in Sweden July 1, 1995, through December 31, 2001.
Presence of orofacial cleft in infant.
Prospective information on maternal drug use during the first trimester, as reported in early pregnancy, was studied in 1142 infants with orofacial clefts, isolated or with other malformations, excluding chromosome anomalies. Any drug use was not associated with clefts (odds ratio [OR] = 0.98, 95% confidence interval [95% CI] = 0.85 to 1.13), with isolated clefts (OR = 0.92) with isolated median cleft palate (OR = 1.03, 95% CI = 0.79 to 1.36) or with isolated cleft lip with or without cleft palate (OR = 0.86, 95% CI = 0.71 to 1.05). Reported use of multivitamins, folic acid, or B(12) was not associated with a decrease in orofacial cleft risk (OR = 1.00, 95% CI = 0.63 to 1.52). ORs above 2 were seen for some drugs: sulfasalazine, naproxen, and anticonvulsants, but only a few exposed cases occurred. An association between glucocorticoid use and infant cleft was indicated and seemed to be strongest for median cleft palate.
Maternal drug use seems to play only a small role for the origin of orofacial clefts, at least in Sweden.
Idiopathic thrombocytopenic purpura and pregnancy are commonly associated. In this article we describe our experience in the management of 61 infants born to 50 mothers with confirmed idiopathic thrombocytopenic purpura. The focus was the neonatal cord platelet count, the parameter of greatest interest to obstetricians. None of the 61 infants had morbidity or mortality as a consequence of the thrombocytopenia. Only three of 61 infants (4.9%) had a cord platelet count that was less than 50 x 10(9) per liter. Although 66% of the infants had a further fall in the platelet count after birth, in all the thrombocytopenia could readily be corrected. Neither maternal platelet count, maternal treatment with corticosteroids, maternal platelet-associated immunoglobulin G level, nor maternal splenectomy could be used to predict neonatal thrombocytopenia. Fetal scalp platelet sampling was likely to lead to an erroneous decision. The rareness of a poor neonatal outcome raises the question of whether obstetric interventions are justified for every pregnant patient with idiopathic thrombocytopenic purpura.
To determine the efficacy of antenatal low dose oral betamethasone in preventing neonatal thrombocytopenia and/or bleeding in infants of mothers with idiopathic thrombocytopenic purpura (ITP).
Hospital department of obstetrics and gynaecology, referral centre.
41 pregnancies in 38 women were randomized. The results of 13 pregnancies were considered non-assessable. The final analysis involved 14 in the betamethasone group and 14 in the non-treatment group. All fulfilled the criteria for ITP.
The treated group received 1.5 mg betamethasone orally per day, from day 259 till day 273 and 1 mg from day 273 till delivery.
Effects of treatment were assessed in terms of maternal platelet counts after the first trimester and neonatal platelet counts at birth and the first week of life and neonatal bleeding episodes.
There were no significant differences in neonatal platelet counts at birth. Two infants in the betamethasone group and one in the untreated group had a severe thrombocytopenia either at birth or during the first week of life (less than 50 x 10(9)/l). Seven infants in the betamethasone group and six in the non-treatment group had a mild thrombocytopenia. The overall frequency of neonatal thrombocytopenia was similar: 64% in the betamethasone group and 57% in the untreated group (95% CI of the true difference: -43.5% to +29.5%). There was also no significant difference in neonatal bleeding episodes.
Low-dose betamethasone in pregnant women with ITP does not prevent thrombocytopenia or bleeding in their newborn infants.
Thrombocytopenia occurred in 513 (7.6%) of 6715 consecutive deliveries that occurred in our hospital over a 3-year interval. The patients with thrombocytopenia could be divided into three groups. The largest group (65.1%) consisted of healthy women whose thrombocytopenia was incidentally detected. The next group of patients (13.1%) was composed of healthy women who had an obstetric or medical condition such as diabetes or premature labor. No mother or infant in either group had excessive bleeding, and no infant had a cord platelet count less than 50 x 10(9) per liter. The last group (21%) was composed of hypertensive patients and patients with immune thrombocytopenia. Two infants in this group had cord platelet counts less than 50 x 10(9) per liter, but neither had bleeding. This study indicates that incidental thrombocytopenia in an otherwise well woman at term is the most frequent type of thrombocytopenia and poses no apparent risk for mother or infant at delivery.
The unexpected discovery of thrombocytopenia in an asymptomatic pregnant woman--often considered to be equivalent to the diagnosis of idiopathic thrombocytopenic purpura--leads to a variety of interventions, including delivery by cesarean section. However, the actual risk to mothers and their infants posed by incidentally noted thrombocytopenia is not known. To investigate this issue, we performed a prospective study of a group of normal women who delivered at our medical center and their infants during a period of one year. Of the 2263 women who delivered during the year, 1357 were considered to be normal. One hundred twelve of the women (8.3 percent) had mild thrombocytopenia (range of platelet counts, 97 to 150 x 10(9) per liter). The thrombocytopenia had no discernible clinical effect on the women or their infants. The frequency of thrombocytopenia in babies born to this group of women was not appreciably different from that in babies born to the other normal patients who did not have thrombocytopenia, and none of the infants of women with thrombocytopenia had a platelet count of less than 100 x 10(9) per liter. This study demonstrates that the frequency of mild thrombocytopenia is high in normal pregnant women at term and that the thrombocytopenia appears to have no adverse effect on either the mothers or their infants. To perform obstetrical interventions such as cesarean section because of thrombocytopenia in these mothers is not justified.
Thirty-nine pregnant women with idiopathic thrombocytopenic purpura (ITP) were studied in order to evaluate the influence of therapies for maternal ITP on fetal passive immune thrombocytopenia (PIT). Neonatal platelet counts were also compared with platelet counts, amount of PAIgG, and presence of circulating antiplatelet antibody in maternal blood. Eight of 41 neonates (19.5%) presented PIT without neonatal mortality. A higher incidence of PIT was observed in women with prior splenectomy than in women without splenectomy (66.7% vs 11.4%). Neither a therapeutic effect nor an increased risk of PIT was observed with steroids or gammaglobulin administration. No correlation was found between neonatal platelet counts and maternal platelet counts or maternal PAIgG, while positive cases for circulating antiplatelet antibody assay presented a higher incidence of PIT than negative cases. Additionally, a higher incidence of PIT was observed in women with a history of previous PIT than in women with a history of normal delivery. Prior splenectomy, presence of antiplatelet antibody in maternal blood, and a history of previous PIT seem to be risk factors for fetal PIT.
Twenty-nine of 27,662 pregnant women had autoimmune thrombocytopenia at the time of delivery at King Khalid University Hospital over 6 years starting June 1986. Twenty-six had idiopathic thrombocytopenic purpura (ITP), gave birth to 33 infants, of which 22 were by spontaneous vaginal delivery, eight by lower segment cesarean section, and two by forceps. Fourteen (44%) of the 32 living infants had platelets less than 150 x 10(9)/L and four (12.5%) had severe thrombocytopenia (platelets less than 50 x 10(9)/L). The mothers' platelets of less than 50 x 10(9)/L at delivery were found to be predictive of thrombocytopenia in their infants (P < 0.027), compared with mothers' platelet of more than 50 x 10(9)/L. Maternal treatment with prednisone did not seem to have significant effect on infants' platelets (P < 0.89). All infants with severe thrombocytopenia (less than 50 x 10(9)/L) at birth had ultrasound done and were found to be normal. We conclude that: (1) steroid given to pregnant women with ITP does not increase infants' platelet counts, (2) severe thrombocytopenia in the mothers (platelet counts less than 50 x 10(9)/L) is highly predictive of thrombocytopenia in their infants; (3) cesarean section should be limited to the mother with severe thrombocytopenia if fetal scalp platelets are less than 50 x 10(9)/L.
Neonates with severe thrombocytopenia can have bleeding leading to death or lifelong residual defects. The predictors, frequency, and consequences of fetal thrombocytopenia are not known, nor is it known if there are maternal clinical features that could predict fetal thrombocytopenia.
We conducted a seven-year cross-sectional study in which platelet counts were determined in newborns' umbilical-cord blood and blood obtained from their mothers at consecutive deliveries in one obstetrical unit. The relations of the umbilical-cord platelet count to maternal risk factors were determined.
Platelet counts were determined in blood samples from 15,471 mothers and 15,932 newborn infants. The cord-blood platelet count was less than 50,000 per cubic millimeter in 19 infants (0.12 percent; 95 percent confidence interval, 0.07 to 0.19 percent), whereas the platelet count was less than 150,000 per cubic millimeter in 6.6 percent of the mothers (95 percent confidence interval, 6.2 to 7.0 percent). One infant among those born to 756 mothers with incidental thrombocytopenia, 5 infants among those born to 1414 mothers with hypertension, and 4 infants among those born to 46 mothers with idiopathic thrombocytopenic purpura had cord-blood platelet counts between 20,000 and 50,000 per cubic millimeter. Only 6 infants (0.04 percent; 95 percent confidence interval, 0.01 to 0.08 percent) had cord-blood platelet counts of less than 20,000 per cubic millimeter; all their mothers were among the 18 whose 19 fetuses were at risk for neonatal alloimmune thrombocytopenia. Two of these infants had in utero intracranial hemorrhage. In addition, 3 infants born to these 18 women had cord-blood platelet counts between 20,000 and 50,000 per cubic millimeter; there was 1 stillbirth due to intracranial hemorrhage.
Moderate-to-severe fetal thrombocytopenia is a rare event. The only severely affected neonates with morbidity or mortality due to this condition are those born to mothers with antiplatelet alloantibodies.
To examine the incidence and significance of complications related to percutaneous fetal blood sampling, we reviewed all the articles published in the English literature on this procedure. Risks of complications and adverse outcomes depend mainly on the gestational age at the time of the procedure, the operator's experience, and the indication for the procedure. To determine the incidence of fetal losses, we pooled the data from series with > 100 cases. After exclusion of cases where some fetal pathologic condition was present, we determined the incidence of adverse outcomes in a low-risk population. In this population fetal blood sampling performed by an experienced operator carries about a 1.4% risk of fetal loss before 28 weeks' gestation and a 1.4% risk of perinatal death (after 28 weeks).
To determine the type of recurrent pregnancy loss associated with antiphospholipid antibodies.
This was a retrospective analysis of women who had two or more pregnancy losses and who were tested for antiphospholipid antibodies. The specific type of pregnancy losses were determined in patients with and without antiphospholipid antibodies.
In our highly selected referral population, 76 of 366 women (21%) tested positive for lupus anticoagulant or anticardiolipin antibodies of 20 or more immunoglobulin-G phospholipid antibody units. Pregnancy loss occurred in 280 of 333 (84%) prior pregnancies in women with and 1240 of 1479 (84%) without antiphospholipid antibodies. However, 50% of pregnancy losses in women with antiphospholipid antibodies were fetal deaths, compared with less than 15% in women who were antiphospholipid antibody-negative. More than 80% of women with antiphospholipid antibodies had at least one fetal death, compared with less than 25% of women without (P < .001). The specificity of fetal death for the presence of antiphospholipid antibodies in patients with recurrent pregnancy loss was 76%. In contrast, two or more early first-trimester losses without fetal death had a specificity of only 6% for antiphospholipid antibodies.
Fetal death is more characteristic of the type of loss experienced by patients with recurrent pregnancy loss than early first-trimester pregnancy loss in women with antiphospholipid antibodies.
The antenatal and intrapartum management of women with autoimmune thrombocytopenia is controversial. The current approach emphasizes an effort to identify maternal characteristics predictive of severe neonatal thrombocytopenia or to measure fetal platelet counts and perform cesarean section in patients considered to be at risk for neonatal intracranial hemorrhage. In the current study we review our experience with maternal autoimmune thrombocytopenia and neonatal outcome.
Fifty-five pregnancies with autoimmune thrombocytopenia over a 10-year period in three major medical centers in San Diego, California, were evaluated. Maternal characteristics and neonatal outcomes were assessed and compared with those in other recent reports. Data were submitted to Fisher's exact (two-tailed), chi2, and Student t tests, with linear regression performed to analyze the association between variables.
Maternal characteristics including platelet count, presence of antiplatelet antibody, antecedent history of autoimmune thrombocytopenia, and corticosteroid therapy were not predictive of severe neonatal thrombocytopenia. Maternal history of splenectomy was significantly correlated with fetal platelet counts <50 x 10(9)/L (odds ratio 5.63; 95% confidence interval 2.2 to 14.3). There were four neonates with severe neonatal thrombocytopenia (8%), and one who was delivered by cesarean section had intracranial hemorrhage.
These findings, combined with others in the literature, confirm that severe neonatal thrombocytopenia is an infrequent complication of maternal autoimmune thrombocytopenia and is not reliably predicted by maternal characteristics. Intracranial hemorrhage is also a rare event and is not related to mode of delivery. Cesarean section should be reserved for obstetric indications only.
Regional anesthesia is a popular form of pain relief for the management of labor and delivery. Thrombocytopenia is considered a relative contraindication to the administration of regional anesthesia. Some authorities have recommended that an epidural anesthetic be withheld if the platelet count is <100,000 mm(-3). For the period of March 1993 through February 1996, we reviewed the charts of all parturients who had a platelet count <100,000 mm(-3) during the peripartum period. Eighty women met this criterion. Of these 80, 30 had an epidural anesthetic placed when the platelet count was <100,000 mm(-3) (range 69,000-98,000 mm(-3)), 22 had an epidural anesthetic placed with a platelet count >100,000 mm(-3) that subsequently decreased below 100,000 mm(-3), and 28 did not receive a regional anesthetic. We found no documentation of any neurologic complications in the medical records. We conclude that regional anesthesia should not necessarily be withheld when the platelet count is <100,000 mm(-3).
This study was designed to estimate the predictive value of the first neonatal platelet count for the second neonate in women with immune thrombocytopenic purpura (ITP).
Data of 34 patients, repeatedly pregnant while they had ITP, were prospectively collected in two study centers between 1984 and 1995. The main outcome measure was neonatal thrombocytopenia.
Early neonatal platelet counts (i.e., umbilical cord count or count during the first 24 hours of life) between siblings were correlated (r = .73; 95% confidence interval (CI) for the correlation coefficient 0.52, 0.86). Severe thrombocytopenia (less than 50 x 10(9)/L) at birth did not occur in any of the 27 siblings of infants with birth platelet levels above 50 x 10(9)/L. Also the second sibling's nadir neonatal platelet counts during the first 2 weeks of life were correlated with those of the first sibling (r = .76; 95% CI for the correlation coefficient 0.58, 0.88). In those cases in which the first sibling had a lowest platelet count above 100 x 10(9)/L (n = 19), the second sibling never became thrombocytopenic.
The platelet count of the first sibling can be used to counsel women with ITP, and may be helpful in their management.
Thrombocytopenia detected during pregnancy addresses the issue of its mechanism and of the possible occurrence of neonatal thrombocytopenia. To further investigate these issues, 50 women referred to us because of thrombocytopenia detected during pregnancy (platelet count, <150 x 10(9)/L), were extensively studied, as well as their offspring. Among these thrombocytopenic women, we used the threshold of 70 x 10(9)/L to differentiate between mild and severe thrombocytopenia. Whatever the severity of thrombocytopenia, we found biological features of an autoimmune disorder in 48% of the women, and chronic thrombocytopenia in 55%. A familial thrombocytopenia was evidenced in 1 case. These 50 women gave birth to 63 neonates, among whom 24 were thrombocytopenic, either at birth or during the first week of life. Neonatal thrombocytopenia could only be predicted in multiparous women, on the basis of previous neonatal thrombocytopenia in older siblings, and/or when maternal platelet life span study, performed before pregnancy, had evidenced an autoimmune thrombocytopenia (AITP)-like profile. These results suggest that, in case of pregnancy-associated thrombocytopenia, familial and immunological studies, combined with postdelivery iterative platelet counts, should be performed to properly characterize the thrombocytopenia. Moreover, the platelet count of the neonate should be carefully assessed at birth and during the following days, a platelet life span study should be performed after delivery in the mother, because these two parameters are likely to bring valuable information regarding the forthcoming pregnancies and the risk of neonatal thrombocytopenia.
To determine the incidence of maternal antiplatelet antibodies in cases of thrombocytopenia during pregnancy, using the monoclonal antibody-specific immobilization of platelet antigens assay; and to assess the usefulness of this assay for predicting risk of neonatal thrombocytopenia.
A total of 6770 pregnant women were included in the study, and the monoclonal antibody-specific immobilization of platelet antigens assay was done when platelet counts were less than 150 x 10(9)/L. Platelet counts were determined in 6103 newborns.
The incidence of maternal thrombocytopenia was 11.6% (95% confidence interval [CI] 10.8, 12.4). Among newborns, 1.3% (95% CI 0.5, 2.7) born to thrombocytopenic mothers were thrombocytopenic, compared with 0.4% (95% CI 0.2, 0.6) born to nonthrombocytopenic women. Antiplatelet antibodies were detected in 37 (8.6%) of 430 thrombocytopenic women; autoantibodies were detected in 28 cases (circulating or bound to platelets), alloantibodies in eight cases, and an association of alloantibodies and autoantibodies in one case. The positive and negative likelihood ratios for predicting neonatal thrombocytopenia were 4.6 and 0.7, respectively.
The monoclonal antibody-specific immobilization of platelet antigens assay did not predict the risk of neonatal thrombocytopenia in an unselected population of thrombocytopenic pregnant women.
The aim of the study was to determine how perinatologists in the United States manage the care of women with immune thrombocytopenic purpura with respect to mode of delivery. Study Design: US members of the Society of Perinatal Obstetricians were surveyed with a 4-question questionnaire. Two mailings were sent. Questions 1 and 2 asked for a response regarding the perinatal management of delivery for women with chronic immune thrombocytopenic purpura and new-onset disease. The options were cordocentesis or fetal scalp blood sampling and cesarean delivery if the platelet count was <50,000 cells/microL, cesarean delivery if the maternal platelet count was <50,000 cells/microL, cesarean delivery of all women with immune thrombocytopenic purpura, and trial of labor without determining fetal platelet count. The third question asked for an opinion on whether cesarean delivery was protective against intracranial hemorrhage in cases of immune thrombocytopenic purpura. The fourth question asked whether the practitioner was in academic or private practice or both.
Among the 1596 perinatologists surveyed, there were 940 informative responses (58.9%). Most would allow a trial of labor for women with chronic (59.0%) or new-onset (66.6%) immune thrombocytopenic purpura. In cases of chronic immune thrombocytopenic purpura, 31.0% of those responding would perform an invasive procedure to determine fetal platelet count, followed by cesarean delivery if this count was <50, 000 cells/microL. In cases of new-onset immune thrombocytopenic purpura, 25.4% would do so. Of the respondents, 11.8% reportedly considered cesarean delivery protective against intracranial hemorrhage, whereas 56.6% did not and 31.6% were unsure.
The management of women with immune thrombocytopenic purpura remains controversial in the United States. Approximately two thirds of perinatologists would allow a trial of labor without a procedure to determine fetal platelet count. Most physicians surveyed did not consider cesarean delivery to be protective against intracranial hemorrhage.
To assess the safety of a new platelet count threshold for the definition of maternal thrombocytopenia late in pregnancy.
A platelet count was performed in 6770 pregnant women late in pregnancy and in 6103 of their newborns as well as in a control group of 287 age-matched nonpregnant healthy women.
The prevalence of maternal thrombocytopenia (platelet count less than 150 x 10(9)/L) was 11.6%. The mean platelet counts (248 compared with 213 x 10(9)/L) and 2.5th percentile (164 compared with 116 x 10(9)/L) were significantly higher in healthy nonpregnant women than in pregnant women. Among thrombocytopenic pregnant women, 621 (79%) had platelet counts between 116 and 149 x 10(9)/L; none (0%; 95% confidence interval 0, 0.6) had complications related to thrombocytopenia, and none of their newborns had severe thrombocytopenia (platelet count less than 20 x 10(9)/L).
In healthy pregnant women, a platelet count over 115 x 10(9)/L late in pregnancy does not require further investigation during pregnancy and may be considered a safe threshold.
Thrombocytopenia is a common problem during pregnancy and often inappropriately managed. This study aimed to assess the prevalence and causes of maternal thrombocytopenia at term with special attention to immune mechanisms of thrombocytopenia and the need for assessing fetal risks.
We conducted a 1-year population-based surveillance study involving 4,382 fullterm (at least 37 weeks' gestation) women (83.8% of the study population) and their infants from the city of Helsinki. Maternal and cord platelet counts were performed at delivery. Immune studies were performed if maternal platelet counts were less than 100 x 10(9)/l; 95% confidence intervals (CIs) were calculated from the binomial distribution.
A total of 317 women (7.3%; 95% CI 6.5, 8.1) had platelet counts of less than 150 x 10(9)/l. Most cases (81%) of maternal thrombocytopenia at term were due to gestational thrombocytopenia, which had no impact on either the mother or the fetus unless associated with some other medical or obstetric disorder. Other causes of thrombocytopenia were preeclampsia (16%) and idiopathic thrombocytopenic purpura (ITP) (3%). There was no association between maternal and fetal platelet counts: of the infants born to thrombocytopenic mothers, 2.1%, had thrombocytopenia in the cord blood, which did not differ significantly from the 2.0% of thrombocytopenic infants born to non-thrombocytopenic mothers.
Women with gestational thrombocytopenia do not require alteration of their treatment. Fetal blood sampling is not considered necessary when thrombocytopenia is discovered unexpectedly at term.
To determine whether Myocet (liposome-encapsulated doxorubicin; The Liposome Company, Elan Corporation, Princeton, NJ) in combination with cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing comparable antitumor efficacy in first-line treatment of metastatic breast cancer (MBC).
Two hundred ninety-seven patients with MBC and no prior chemotherapy for metastatic disease were randomized to receive either 60 mg/m(2) of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg/m(2) of cyclophosphamide (C), every 3 weeks until disease progression or unacceptable toxicity. Cardiotoxicity was defined by reductions in left-ventricular ejection fraction, assessed by serial multigated radionuclide angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization criteria), time to progression, and survival.
Six percent of MC patients versus 21% (including five cases of CHF) of AC patients developed cardiotoxicity (P =.0002). Median cumulative doxorubicin dose at onset was more than 2,220 mg/m(2) for MC versus 480 mg/m(2) for AC (P =.0001, hazard ratio, 5.04). MC patients also experienced less grade 4 neutropenia. Antitumor efficacy of MC versus AC was comparable: objective response rates, 43% versus 43%; median time to progression, 5.1% versus 5.5 months; median time to treatment failure, 4.6 versus 4.4 months; and median survival, 19 versus 16 months.
Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.
Study 2 did not provide sufficient confirmation that the anticancer efficacy associated with doxorubicin is preserved by using Myocet. Even though the response rates for the two treatment arms were the same (26%), this study was inadequately powered to exclude the possibility that Myocet was less effective than doxorubicin. The sample size was calculated based on the erroneous assumption that these doxorubicin moieties would produce higher response rates. The trial’s regulatory goal was to prove that the response rate with Myocet was at least 75% of that with doxorubicin (ie, that the lower bound of the 95% CI for the ratio of response rates [doxorubicin/Myocet] was at least 0.75). Because the lower bound of the CI was 0.62, this study only supported the conclusion that the Myocet response rate was at least 62% of the doxorubicin response rates. In addition, a trend toward inferior survival in the Myocet arm compared with the doxorubicin arm was noted (median survival, 14.6 months v 20.1 months, respectively; P = .07). The FDA multivariate analysis correcting for imbalances in prognostic factors demonstrated a significant survival difference (P = .03). ODAC voted (nine to two) to recommend against approval of this drug for the first line of treatment of MBC.
Idiopathic thrombocytopenic purpura (ITP) occurs more commonly in young women during the reproductive years. To obtain information for management of ITP in pregnancy, we performed a nationwide retrospective survey. Findings from a total of 284 pregnant women with ITP and their 286 newborn infants were available for analysis. The bleeding tendency at delivery was managed chiefly with corticosteroid, intravenous high-dose gamma-globulin, and platelet transfusion. Maternal complications occurred in 77 cases (27.1%) and were frequently seen in cases with poor control of ITP. Neonatal abnormalities, which were not influenced by the clinical state of the mother, occurred at a frequency of 17.8%. Thrombocytopenia in neonates occurred in 48 cases (22.4%), and bleeding tendency was found in 16 cases (6.3%) without severe bleeding. Prediction of thrombocytopenia in neonates was difficult. However, infants from splenectomized mothers with well-controlled ITP showed thrombocytopenia more frequently than those from nonsplenectomized mothers. Mothers treated with steroids at doses greater than 15 mg/day showed a high frequency of maternal complications and fetal abnormal body weight. These observations will be useful in the management of pregnant women with ITP and their infants.
Idiopathic thrombocytopaenic purpura (ITP) is a common haematological disorder in young women. The management of ITP in pregnancy is controversial, particularly with regards to the mode of delivery. To date, there is no systematic study of the outcome of these pregnancies in Singapore.
To study the outcomes of pregnancies in Asian women with a proven diagnosis of ITP.
Retrospective study of 27 pregnancies in 18 women managed at the Singapore General Hospital from 1 January 1994 to 30 June 2001.
The mean age of the women was 30 years (range, 20 to 41 years) and the mean parity was 1 (range, 0 to 3). Thrombocytopaenia (platelet count < 150 x 10(9)/L) occurred in 18 pregnancies (67%). There were 3 first trimester missed abortions (11%), 1 termination of pregnancy (4%), 1 stillbirth (4%) and 22 livebirths (81%) in this series. The mode of delivery was spontaneous vaginal in 14 women (64%), vacuum extraction in 2 women (9%), elective caesarean section in 5 women (23%) and emergency caesarean section in 1 woman (4%). All liveborn neonates were delivered in good condition at term. Neonatal thrombocytopaenia occurred in 4 neonates (18%). Two neonates had cord platelet counts of less than 50 x 10(9)/L and 1 required therapy with corticosteroids and intravenous immune globulins. No bleeding complications occurred in any of the neonates.
Our experience supports the increasingly prevalent practice of managing pregnancies in women with ITP with a conservative approach to investigations and treatment. Caesarean sections should be performed for obstetric indications only, given the rarity of bleeding complications in the offspring of these women and the lack of evidence to support its role in the prevention of neonatal intracranial haemorrhage.
Thrombocytopenia in pregnant women may result from a number of diverse etiologies. While some of these are not associated with adverse pregnancy outcomes, others are associated with substantial maternal and/or neonatal morbidity and mortality. However, specific therapies, if instituted promptly, may significantly improve the outcomes of affected patients and their offspring. Since the clinical features of many of these disorders often overlap, identifying a specific cause of thrombocytopenia in a pregnant patient may be difficult. However, through familiarity with the more common clinical and laboratory features of each of these disorders, accurate diagnosis may be achieved, and appropriate treatment instituted in most cases. In this review, we discuss the differential diagnosis of the more common causes of pregnancy-associated thrombocytopenia, and provide an overview of approaches to hematologic management.
This pilot study assessed the safety and efficacy of intravenous anti-D in eight Rh(D)-positive women with immune thrombocytopenic purpura (ITP) during the second and third trimesters of pregnancy. The median pretreatment platelet count was 28 x 109/l. The patients received one to seven anti-D infusions at a mean dose of 62.7 micro g/kg, and the response rate to anti-D was 75%. A haemoglobin decrease of > 2.0 g/dl occurred only once. Fetal hydrops was not identified by ultrasonography. The direct antiglobulin test was positive in three out of seven Rh+ newborns, none of whom was anaemic or jaundiced. Anti-D is effective and appears to be safe for both mother and fetus.
The possible association between oral cleft in the newborn and maternal exposure to corticoids during pregnancy is still controversial. The aim of this study was to test this association by a case-control analysis using the large multicentric MADRE database.
The MADRE database is a collection of information on malformed infants with a history of maternal first-trimester drug exposure. Nine malformation registries participate in the data collection. Cases were defined as infants presenting with a cleft palate or cleft lip, and exposure was defined by the use of corticosteroids during the first trimester of pregnancy.
After 12 years of data collection, the database includes data on 11,150 malformed infants. A slight association is observed between exposure to corticoids for systemic use and the occurrence of cleft lip with or without cleft palate (OR, 2.59; 95% CI, 1.18-5.67).
If the observed association is real, an interpretation is suggested, based on a likely interaction between corticosteroids and environmental dioxins. It is indeed possible that human fetuses may become sensitive to the teratogenic effect of corticosteroids when they are exposed in utero to environmental pesticides as well.
The optimal treatment of non-Hodgkin's lymphoma (NHL) during pregnancy is currently undefined. The potential teratogenic effects of conventional chemotherapy preclude its use during the first trimester of pregnancy. We report the case of a pregnant woman with relapsed indolent follicular NHL who was treated with rituximab (unintentionally) during the first trimester. The treatment stabilised the disease. Following an uncomplicated pregnancy, a healthy child was born at full term and careful haematological and immunological monitoring has revealed no adverse effects resulting from exposure to rituximab. Data of using rituximab during pregnancy are scarce, but the present case shows that rituximab may be one option for treatment of NHL in early pregnancy.
Immune thrombocytopenic purpura (ITP) is a condition with potential hazard during pregnancy for both mother and fetus if platelet concentrations fall below a critical level. This report describes the use of laparoscopic splenectomy following unsuccessful medical management.
A 35-year-old primigravid woman with systemic lupus erythematosis (SLE) developed ITP several years before becoming pregnant. She was treated early in pregnancy with high-dose oral prednisone and weekly intravenous immunoglobulin (IVIG) alternating with anti-D immune globulin, but laparoscopic splenectomy was indicated at 20 weeks' gestation because of thrombocytopenia. Following surgery, she continued prednisone and intermittent IVIG therapy until spontaneous delivery at 34 weeks' gestation. A small accessory spleen was identified postpartum by nuclear medicine scan. Satisfactory platelet concentrations were maintained postpartum using danazol and prednisone.
Laparoscopic splenectomy is a therapeutic option for women with ITP during pregnancy that fails to respond to medical management.
The use of azathioprine (AZA) in the treatment of autoimmune diseases during pregnancy are believed to be relatively safe, particularly taking into account the potential risks for mother and fetus should the underlying disease become active due to withdrawal of this thiopurine. However, essential evidence on the safety of AZA use during pregnancy is lacking. The determination of the intrauterine exposure to maternal AZA use may provide additional and crucial insights into the safety and teratogenicity of this drug.
We describe three patients with Crohn's disease and autoimmune hepatitis who were treated with AZA throughout all trimesters of their pregnancies. Thiopurine metabolites (6-thioguaninenucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP)) were measured in the red blood cells (RBC) of mother and infant directly after delivery.
The 6-TGN concentration was slightly lower in the RBC of the infant than the mother. No 6-MMP could be detected in the infant.
The placenta forms a (relative) barrier to AZA and its metabolites. Intrauterine exposure to 6-TGN may be minimized by careful therapeutic drug monitoring of the mother during pregnancy.
- Burrows
- Christiaens