[Show abstract][Hide abstract] ABSTRACT: In recent decades, the association between a hypercoagulable state and its causes and adverse pregnancy outcome, in particular recurrent pregnancy loss (RPL) has been studied extensively. Although the first studies were focused only on the association between thrombophilia and RPL, subsequent studies underlined also a potential role of antithrombotic treatment to prevent vascular complication such as venous thromboembolism (VTE) during pregnancy. Thromboprophylaxis should be considered also for pregnant subjects carriers of molecular thrombophilia or that previously experienced VTE, in order to prevent VTE during pregnancy, while antithrombotic treatment for VTE should be performed during all pregnant periods.
Full-text · Article · Mar 2010 · Hematology Research and Reviews
[Show abstract][Hide abstract] ABSTRACT: Emerging data seem to be available also on the role of active thromboprophylaxis with heparin and pregnancy outcome. In the last decades we found many data concerning the association between a hypercoagulable state and its causes and adverse pregnancy outcome, in particular recurrent pregnancy loss (RPL). First studies which focused on the association between thrombophilia and RPL underlined the role of reduced clotting inhibitors and RPL, and subsequent studies underlined a pathogenetic role of gene variant associated to hypercoagulable state in the occurrence of RPL. On the other hand, acquired thrombophilic abnormalities as antiphipsholipid syndrome are a well known cause of RPL and should be considered for a screening. These data are relevant because recent studies suggested a role of an extensive thromprophilaxis in women with RPL that should be addressed only in case of known thrombophilia and high risk of venous thromboembolism.
Thrombophilia; Recurrent pregnancy loss; Factor V Leiden; Hyperhomocysteinemia; Antiphospholipid antibodies; PAI 4G\4G
Full-text · Article · Feb 2010 · Journal of Clinical Medicine Research
[Show abstract][Hide abstract] ABSTRACT: The aim of this observational preliminary trial was to estimate the association between the most common polymorphism of LH (LH-beta variant: v-betaLH), with different profiles of ovarian response to recombinant human FSH (rhFSH). A total of 60 normogonadotrophic patients undergoing a gonadotrophin-releasing hormone analogue long down-regulation protocol followed by stimulation with recombinant human FSH (rhFSH) for IVF/intracytoplasmic sperm injection, and in whom at least five oocytes were retrieved were retrospectively included. On the basis of the total rhFSH consumption, patients were divided into three groups: Group A: 22 women requiring a cumulative dose of rhFSH >3500 IU; Group B: 15 patients requiring 2000-3500 IU; Group C (control): 23 women requiring <2000 IU. The presence of v-betaLH was evaluated using specific immunoassays. Peak oestradiol concentrations were significantly lower in Group A when compared with both groups B (P < 0.05) and C (P < 0.001). Group A had a significantly lower (P < 0.05) number of oocytes retrieved (7.3 +/- 1.5, 11.7 +/- 2.4 and 14.7 +/- 4.1 in the three groups, respectively). Seven carriers (31.8%) of v-betaLH were found in Group A, whereas only one variant (6.7%) was observed in Group B; no variant was detected in Group C. These preliminary results suggest that v-betaLH is more frequent in women with ovarian resistance to rhFSH.
No preview · Article · Dec 2009 · Reproductive biomedicine online
[Show abstract][Hide abstract] ABSTRACT: Recurrent fetal loss (RPL) is one of the most common cause of sterility. Several studies identified thrombophilia as the principal cause of recurrent pregnancy loss. However, reported studies often do not evaluate other causes of miscarriages in their inclusion and exclusion criteria. So the aim of our study was to investigate the role of inherited thrombophilia in patients with RPL and without other causes of RPL.
Patients with 2 or more first trimester abortion or with 1 or more late pregnancy loss were considered for this study. In order to evaluate the causes of RPL we looked for chromosomal, endocrine, chronic inflammatory, and infectious alterations. 90 patients affected by unexplained RPL were enrolled and tested for hemostatic alterations. These women were tested for inherited and/or acquired thrombophilia by MTHFR C677T gene polymorphism, factor V Leiden gene polymorphism, PTHRA20210G gene polymorphism, protein S deficiency, protein C deficiency, antithrombin III deficiency, lupus anticoagulant, and anticardiolipin antibodies Ig G and Ig M.
Acquired and/or inherited thrombophilia are strongly associated with RPL when other common causes of miscarriage were excluded. 78% of tested women showed hemostatic abnormalities. Several women with combined thrombophilic defects were also identified by our data.
After a thorough evaluation of other causes of miscarriage women affected by RPL should be tested for thrombophilia. Our data demonstrated 78% of women with one or combined thrombophilic conditions. Differences with previous studies should be related to difference in the inclusion and exclusion criteria and ethnic background. Because these patients often also show a hypercoagulable state, it an antithrombotic treatment before and during pregnancy may improve their clinical outcome (ie, secondary prevention of miscarriage and primary thromboprophylaxis).
Full-text · Article · Jan 2009 · Targets & therapy
[Show abstract][Hide abstract] ABSTRACT: In the last decades we found many data concerning the association between a hypercoagulable state and its causes and adverse pregnancy outcome, in particular recurrent pregnancy loss (RPL). Although first studies were focused only on the association between thrombophilia and RPL, subsequent studies underlined also a potential role of antithrombotic treatment to prevent vascular complication such as venous thromboembolism (VTE) during pregnancy. Now, emerging data seem to be available also on the role of active thromboprophylaxis with heparin and pregnancy outcome. This review will be focused on the recent knowledge between thrombophilia, hypercoagulable state, RPL, VTE and future perspectives.
Full-text · Article · Feb 2007 · Clinical laboratory
[Show abstract][Hide abstract] ABSTRACT: Hyperhomocysteinemia has been described as a risk factor for unexplained recurrent pregnancy loss. Increased levels of homocysteine may be due to inadequate dietary intake of folate and vitamin B12 and inherited defects within the methionine-homocysteine pathway such as MTHFR C677T gene polymorphism. However, the association between hyperhomocysteinemia and sterility problems have been underlined only for recurrent pregnancy loss while a relationship between hyperhomocysteinemia and female sterility is still matter of discussion.
This study sought to find out a possible relationship between sterility (primary sterility or secondary sterility due to recurrent pregnancy loss) and homocysteine metabolism.
We selected 20 patients with recurrent pregnancy loss, 20 patients with unexplained female sterility and 20 healthy women as control group. Several whole blood samples were collected by venipuncture. Firstly homocysteinemia and other related variables were tested (i.e. folate and vitamin B12 levels); thereafter DNA was extracted by a further whole blood sample collected in EDTA in order to screen MTHFR C677T gene polymorphism. Statistical analysis was performed by chi square test; differences were considered to be significant if p < 0.05.
The median fasting total plasma homocysteine concentration was 19.2 +/- 6.14 microM for patients with recurrent pregnancy loss, while was 21.05 +/- 8.78 microM for patients with unexplained sterility, vs 7.85 +/- 3.31 microM of control group (p < 0.05). Fifteen patients with unexplained female sterility showed MTHFR C677T homozigosity vs 17 with recurrent pregnancy loss and 3 in the control group (p < 0.05). On the other hand no significant differences were found in the levels of vitamin B 12 in the three groups, while reduced folate concentrations were found in women with unexplained female sterility and recurrent pregnancy loss (p < 0.05 vs control group.
MTHFR C677T gene polymorphism is frequent in the studied populations. These data raise questions on the role of the homocysteine metabolism in sterility problems. Even though increased homocysteine (i.e. > 15 microM) and MTHFR C677T homozigosity have already been described as risk factors for recurrent pregnancy loss, few studies evaluated their role in women with unexplained sterility. Further studies on larger series are needed to better understand the role of homocysteine metabolism, including folate metabolism, in this clinical setting.
Full-text · Article · Feb 2007 · Thrombosis Journal
[Show abstract][Hide abstract] ABSTRACT: Mesenteric venous thrombosis (MVT) is an unusual site of deep venous thrombosis. Little is known about risk factors of MVT, but available data seem to confirm a pathogenetic role of acquired thrombotic risk factors as well as inherited thrombotic risk factors. However, few cases on the association of MVT with oral contraceptive use have been described. We here report a case of MVT in a woman on oral contraception with fine and complete resolution after a fast diagnosis with abdominal ultrasound imaging and prompt therapy based on low molecular weight heparin.
No preview · Article · Feb 2007 · Clinical laboratory
[Show abstract][Hide abstract] ABSTRACT: Antiphospholipid syndrome (APS) has been often associated to RPL since 1980 and some reports in the Literature rarely described antibodies to factor XII in patients with APS.
We report the case history of 34-year-old caucasian women with recurrent fetal loss and persistent prolonged activated partial thromboplastin time. Haemostatic tests revealed persistent light decrease of clotting factor XII with normal values of IgG and IgM anticardiolipin antibodies and transient positivity for lupus anticoagulant (LA). Few reports in the Literature described antibodies to factor XII in patient with antiphospholipid syndrome (APS) and transient LA. So, once other causes of RPL were excluded, the patient was diagnosed an unusual form of APS associated to antibodies to factor XII, reduced factor XII plasma levels, transient LA and prolonged activated partial thromboplastin time.
We suggest to consider also antibodies directed to clotting factors (e.g. factor XII in our case) as second step of thrombophilia screening in RPL, in particular if a persistent prolonged aPTT is present without an apparent cause.
Full-text · Article · Feb 2005 · Journal of Translational Medicine
[Show abstract][Hide abstract] ABSTRACT: D-dimer is considered a marker of hypercoagulable state and of endogenous fibrinolysis, so increased d-dimer is detectable in patients affected by thrombosis. Yet, several studies showed that also infertility, in particular secondary infertility due to recurrent fetal losses, has been often related to thrombotic events, in particular in women carrying thrombotic risk factors such as inherited thrombophilia (MTHFRC677T, PTHRA20210G, Factor V Leiden polimorphisms and/or inhAfter this screening we selected 39erited protein C, protein S, AT III deficiency) or acquired thrombophilia (primary antiphospholipid syndrome, acquired protein C, protein S, AT III deficiency, drugs induced thrombophilia). However, because its high predictive negative value in case of suspected thrombosis, increased d-dimer has been often associated to subclinical thrombophilia. The aim of this study is to investigate the role of d-dimer as first marker of thrombophilia in women affected by unexplained infertility and subsequently to search the cause of increased d-dimer, such as inherited and/or acquired thrombophilia.
Patients and Methods
We selected 79 patients with unexplained primary or secondary infertility. We excluded 40 patients affected by hydrosalpinx, uterine fibroids, uterine malformations, endocrinological and immunological diseases, luteal insufficiency, cytogenetical alterations. All remaining 39 patients were tested for d-dimer and divided in two groups: the patients of group A (25 patients) showed increased plasma d-dimer, in group B were included 14 patients with normal plasma level of d-dimer. After this step all 39 patients were screened for MTHFRC677T, PTHRA20210G, Factor V Leiden polimorphisms, protein C, protein S, AT III, anticardiolipin IgM and IgG, lupus anticoagulant. In the control group were included 15 age matched women without sterility problems referred to our outpatient's section of vascular medicine for suspected deep venous thrombosis.
Statistical analysis was based on χ2 test, differences were considered to be significant if p < 0.05.
D-dimer was increased in 25/39 and 20/25 showed inherited/acquired thrombophilia while patients with normal d-dimer showed inherited/acquired thrombophilia in 7/14 (p: < 0.05, s).
D-dimer is a well known marker of hypercoagulable state, in particular its high predictive negative value in case of suspected thrombosis has been recognised by several reports. Yet, increased d-dimer has been identified also for subclinical thrombophilia besides for vascular thrombosis. Our data, in fact, for the first time suggest an interesting role of d-dimer to identify women affected by unexplained primary or secondary infertility and thrombophilia. So, probably there is a role for d-dimer in these subjects for its predictive positive value. Of course, further data on large based population are needed to confirm our results, because these findings may speed up a diagnostic screening in these patients also for a good cost/effectiveness of this test.
Full-text · Article · Nov 2004 · Journal of Translational Medicine
[Show abstract][Hide abstract] ABSTRACT: Cancer related thrombophilia is often present in oncological patients. Lot of reports, in fact, described an increased incidence of thromboembolic events not only in the first stage of the disease, but also during cancer related treatment. Breast cancer patients, in fact, receive also an endocrine treatment based on an antiestrogenic drug tamoxifen and tamoxifen has been often investigated because of a potential additional action toward thrombophilia, but this action has been not confirmed by other reports. In this study the authors showed not only the hypercoagulable state present in women receiving a chemoendocrine therapy based on cyclophosphamide, methotrexate, fluorouracil and tamoxifen, but also a specific reduction in free S protein, a physiological anticoagulant protein. This could explain the increased incidence of thromboembolic complications in women receiving this treatment and could suggest a thromboprophylaxis of these patients.
[Show abstract][Hide abstract] ABSTRACT: Alteration of haemostasis are common during oncological disease and thromboembolic complications have been recognized as one of the most common cause of morbidity and mortality of these patients. This study was designed to identify thrombophilic markers in cancer patients affected by solid tumors, in order to prevent thrombotic events. We studied 52 patients with gastrointestinal and breast cancer (24 males and 28 females, mean age 51 ± 6 years) and 42 health subjects (15 males and 27 females, 49 ± 7 years) as control group. We measured prothrombin time, activated partial thromboplastin time, fibrinogen, vitamin K dependent clotting factors (i.e. II, VII, IX, X), natural clotting inhibitors, activated protein C resistance, prothrombin 1 + 2 fragment and d-dimer in all subjects. We found a significant increase in plasma levels of prothrombin 1 + 2 fragment of cancer patients compared with control subjects and d-dimer plasma levels were increased in 89% of cancer patients compared with control subjects. In conclusion we can assert that cancer patients with solid tumors are at risk for thrombotic event as demonstrated by increased concentrations of prothrombin 1 + 2 fragment and d-dimer. In particular, prothrombin 1 + 2 fragment showed a sensibility better than d-dimer in the identification of cancer-related thrombophilia. However, a screening of these markers of hypercoagulable state could help to prevent a thrombotic event in cancer patients if just interpreted.
[Show abstract][Hide abstract] ABSTRACT: The implantation rate after either in vitro fertilization (IVF) of intracytoplasmatic sperm injection (ICSI) is still low. The implantation mechanism are wide-ranging and still not completely understood. Impaired uterine perfusion, coagulative disorders and alloimmunity may alter this process. Low dose aspirin (LDA) can improve the tissue perfusion reducing the platelet aggregation and vasoconstriction. Prednisone (Pdn) administration, modifying the citokyne synthesis, may favour the TH-2 response, associated with normal reproductive outcome. In addition, both drugs were successfully used in women with recurrent abortion affected by autoimmune conditions or primary coagulative disorders. The aim of this study was to investigate into the efficacy of the administration of LDA plus Low-Dose Pdn (LDP) in patients with no autoimmune condition undergoing their first cycle of ICSI. One-hundred-eighty-one women were randomly allocated in two groups. Group A patients (n=94) received progesterone 50 mg/die and Pdn 5 mg/die plus aspirin 100 mg/die starting from the day of occyte retrieval. Eighty-seven patients, matched for age and body mass index (Group B) received only progesterone 50 mg/die. Implantation and pregnancy rates were similar in the two groups (14.6 vs 12.8 and 35.1 vs 36.8, respectively). Eight twins and 3 triplets were achieved in the group A. In group B, 4 twins and 1 triplet were registered. Two patients in group A (6.1%) and 9 in group B (28.1%) had an abortion (P<0.05). It is concluded that LDA plus LDP administration, starting from the day of oocyte retrieval onward, may be effective in reducing the abortion rate in patients with no autoimmune conditions undergoing ICSI.
No preview · Article · Jan 2002 · Giornale Italiano di Ostetricia e Ginecologia