Article

Cause of portal or hepatic venous thrombosis in adults: The role of multiple concurrent factors

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Abstract

According to a recent hypothesis, venous thrombosis results from the concurrence of several factors. This hypothesis was assessed in patients with portal or hepatic venous thrombosis by simultaneously investigating most of the currently identified prothrombotic disorders, local precipitating factors, and other risk factors such as oral contraceptive use. Patients with a tumorous obstruction and patients with cirrhosis with portal vein thrombosis were excluded. The prothrombotic disorders that were investigated included classical and occult myeloproliferative disorders; antiphospholipid syndrome; protein C; protein S and antithrombin deficiency; factor V Leiden; factor II; and methylene-tetrahydrofolate-reductase gene mutations. We found 1 or several prothrombotic disorders and a local precipitating factor in 26 and 10 of the 36 patients with portal vein thrombosis, respectively; and in 28 and none of the 32 patients with hepatic vein thrombosis, respectively. We found a combination of prothrombotic disorders in 5 and 9 patients with portal and hepatic vein thrombosis, respectively, whereas such a combination is expected in less than 1% of asymptomatic subjects. Of the 10 patients with a local precipitating factor, 8 had a prothrombotic disorder. Of the 13 patients who use oral contraceptives, 10 had a prothrombotic disorder. We conclude that portal or hepatic venous thrombosis should be regarded as an index for 1 or several prothrombotic disorders, whether or not local precipitating factors or oral contraceptive use are found. Concurrence of prothrombotic disorders is more common than expected. Extensive investigation of prothrombotic disorders and anticoagulation should be considered in patients with portal or hepatic venous thrombosis.

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... A combination of two or more genetic or acquired risk factors is found in 26%-46% and 10-23% of patients with BCS or PVT, respectively. [3][4][5][6] Furthermore, 36% of patients with PVT and a local factor also have a general risk factor for thrombosis. 5,7 These results justify comprehensive investigations, even when predisposing or precipitating factors have already been identified (Table 1). ...
... Up to 74% of western women with BCS have been using oral contraceptive agents and a temporal link between pregnancy and BCS has been described. 3,4,33 Local or other general prothrombotic factors are commonly associated with pregnancy or oral contraceptives in women with BCS. Regarding PVT, exposure to female hormones does not appear to cause PVT, as illustrated by the absence of a female predominance among patients with PVT (contrary to BCS). ...
... 50 Only a few cases of anticoagulation interruption have been described in patients with BCS in whom the prothrombotic factor was treated. 3,51 However, there is no clear or sufficient argument currently to stop anticoagulation once BCS is stabilised and the causal factor adequately treated. Because of a high rate of heparin-induced thrombocytopenia, mainly observed with unfractionated heparin (15%), low-molecular-weight heparin (LMWH) is currently recommended. ...
Article
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Splanchnic vein thromboses include Budd-Chiari syndrome and portal vein thrombosis. These disorders have common characteristics: (i) they are rare diseases; and (ii) they can cause portal hypertension and its complications. Budd-Chiari syndrome and portal vein thrombosis in the absence of underlying liver disease share many risk factors, among which myeloproliferative neoplasms represent the most common; a rapid comprehensive workup for risk factors for thrombosis is needed in these patients. Long-term anticoagulation is indicated in most patients. Portal vein thrombosis can also develop in patients with cirrhosis and in patients with portosinusoidal vascular liver disease. The presence and nature of underlying liver disease impact the management of portal vein thrombosis. Indications for anticoagulation in patients with cirrhosis are growing, while transjugular intrahepatic portosystemic shunt (TIPSS) appears as a second-line option. Due to the rarity of these diseases, studies yielding high grade of evidence are scarce. However, collaborative studies have provided new insight into the management of these patients. This article focuses on the causes, diagnosis, and management of patients with Budd-Chiari syndrome, patients with portal vein thrombosis without underlying liver disease, patients with cirrhosis and nonmalignant portal vein thrombosis.
... Myeloproliferative neoplasm (MPN), including polycythemia vera, essential thrombocythemia, chronic idiopathic myelofibrosis, and unclassifiable type (MPN-U), is the most prominent cause of EHPVO with a prevalence of 15%-30% (3)(4)(5)(6)(7)(8)(9). The incidence of MPN is also rare with annual incidence rates for polycythemia vera, essential thrombocythemia, and chronic idiopathic myelofibrosis at 0.84, 1.03, and 0.47 per 100,000, respectively (10). ...
... All 3 MPN patients also continued anti-platelet agents under appropriate additional endoscopic treatment for with the pathogenesis of splenomegaly. MPN is reported to be the most significant factor for EHPVO (3)(4)(5)(6)(7)(8)(9). The original cause of EHPVO is based on thrombotic tendency; therefore, the association between MPN and increased risk of thrombosis should be considered in screening for EHPVO (15). ...
Article
Extrahepatic portal vein obstruction (EHPVO) is a rare disease with myeloproliferative neoplasm (MPN) as the most common cause. We report that hypersplenic hematologic changes in EHPVO might be eliminated by MPN. Through experience with splenectomy for variceal control with EHPVO, we suspected that spleen might mask MPN-induced thrombocytosis, and that MPN might have a significant influence on excessive thrombocytosis after splenectomy. To clarify the influence of MPN and spleen on platelet trends, we conducted a retrospective hospital database analysis, evaluating 8 EHPVO patients with splenectomy (2 males, 6 females; from 17 years to 64 years, mean 38.3 years). Three (37.5%) of 8 were diagnosed as MPN by JAK2V617F mutation. The perioperative serum platelet counts in EHPVO without MPN were 10.5, 35.4, and 36.6 (x10⁴/μL) preoperatively, after 1 week and 3 weeks, respectively. The platelet counts in EHPVO with MPN were 34.2, 86.4, and 137.0 (x10⁴/μL), respectively. Splenectomy and MPN showed positive interaction on platelet increasing with statistical significance. We also examined the spleen volume index (SpVI: splenic volume (cm³) / body surface area (m²) and postoperative platelet elevations ratio (PER: 3-week postoperative platelet counts / preoperative platelet counts). However, both SpVI and PER showed no significant difference with or without MPN. Histological examination revealed splenic congestion in all 8 EHPVO cases, and splenic extramedullary hematopoiesis in 2 of 3 MPN. In EHPVO with MPN, hypersplenism causes feigned normalization of platelet count by masking MPN-induced thrombocytosis; however, splenectomy unveils postoperative thrombocytosis. Spleen in EHPVO with MPN also participates in extramedullary hematopoiesis.
... The prevalence of PVT varies throughout the literature, and incidence rates have been increasing in recent years due, in part, to improved diagnostic imaging [138]. Historically, the prevalence of PVT was 1-16% [124,[139][140][141], but with more screening and improved diagnostics, PVT may be diagnosed in up to 35% of cases in some series [138,142]. It is important to note that the prevalence of PVT rises with the degree of liver damage, and with the development of hepatocellular carcinoma, incidence rates increase to 10% -40% [138,143,144]. ...
... First, the evolution of cirrhosis results in a stiff, fibrotic liver and these changes in the liver parenchyma increase the resistance to portal vein blood flow resulting in venous stasis, and increasing the propensity for the development of PVT [139,145,151]. A study by Zocco et al. [152] demonstrated that portal flow velocity is the most important predictive factor to the development of PVT and estimated that a flow of <15 cm/s on Doppler Ultrasound evaluation was associated with PVT. ...
Chapter
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Complications following lifesaving liver transplantation can be devastating and must be managed properly to optimize the patient and allograft survival. There are non-immune, non-infectious complications which present a severe risk to survival of both the patient and the allograft. These include primary graft non-function (PNF) and hepatic artery thrombosis (HAT). Other complications manifest less urgently but continue to represent potentially lethal consequences to both the patient and the hepatic allograft. These include vena cava outflow disruptions, portal venous outflow derangements, and portal vein thrombosis (PVT). Successful management of these complications is optimized with a multidisciplinary approach to the care of liver transplant recipients. We describe their definition, epidemiology, pathophysiology, related factors, presentation, operative and non-operative management, outcomes, and future directions of these potentially catastrophic complications.
... VTE is a disease caused by many factors 6 . Generally speaking, these risk factors include acquired, environmental and genetic possibility. ...
... When these risk factors are combined together, VTE may occur. Although viral hepatitis often does not lead to acute portal vein thrombosis, acute infection may be associated with an increased risk of transient VTE [6][7] . Various factors can lead to abnormal hemostasis, viral hepatitis can play an important role, and virus can down regulate the physiological anticoagulant mechanism, inhibit fibrinolysis and tissue factor mediated thrombin growth 8 . ...
Article
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Among the risk factors and underlying etiology of acute portal vein thrombosis, viral hepatitis is an extremely rare cause. We report a case of a young healthy 40-year-old male who was diagnosed with acute hepatitis A virus infection and presented with acute portal vein thrombosis. This article describes the possible pathophysiological mechanisms, clinical symptoms, and treatment of acute portal vein thrombosis in this patient. Based on this patient’s history and treatment, we encourage testing for hepatitis A serological markers in the emergency department in a population with recent hepatitis A exposure risk factors and concurrent unexplained acute portal thrombosis.
... Advances have been made in the field to identify the prothrombotic predisposition to thrombosis in a wide range of diseases including those of vascular beds and portal venous system. Several genetic polymorphisms of G20210A prothrombin and factor V Leiden gene mutations may be important factors in contributing to PVT (Denninger et al. 2000;Chamouard et al. 1999). A frequency of 48% to PVT was reported in myeloproliferative disorders (Valla and Condat 2000). ...
... An underlying cause of PVT is reported in 80% of patients while a low number of cases fall into idiopathic' PVT (Cardin et al. 1992). In those with known causes of PVT, the thrombophilic factors contribute almost 60% in them and the contribution of other non-local factors reported to be only 40% (Denninger et al. 2000). It is reported that local and systemic risk factors rarely lead to PVT. ...
Chapter
Cancer is the second leading cause of morbidity and mortality globally because it is usually detected at advanced stages. If detected early, deaths by cancer can be reduced and survival can be prolonged. Different types of cells possess unique molecular signatures and characteristics in particular conditions, which can be measured objectively and serve as the biomarker for that condition. Various biomolecules present in tissues, blood, and other body fluids may indicate the presence of cancer. Cancer biomarkers are useful tools for risk assessment, early detection, diagnosis, prognosis, and recurrence of cancer. Identification of reliable biomarkers can bring a deep understanding of carcinogenesis and help guide the clinicians in early detection and treatment of cancer. In the field of oncology, biomarker discovery has revolutionized the process of cancer treatment by focusing on the actionable targets in a cancer patient.KeywordsCancer, biomarkerEarly detectionDiagnosisPrecision medicineOncology
... They can be local (extrinsic compression by a tumoral or inflammatory process; iatrogenic), general (prothrombotic diseases, whether acquired or congenital), or infectious diseases responsible for pylephlebitis. However, portal thrombosis remains an undetermined cause in 50% of the cases [2]. ...
Article
Portal cavernoma corresponds to the abnormal development of a venous network whose caliber is initially microscopic, with hepatopetal portal blood flow. It is a consequence of chronic portal thrombosis in a healthy or slightly fibrous liver. The causes are essentially those of portal thrombosis. However, portal thrombosis remains an undetermined cause in 50% of the cases. The clinical manifestations of cavernoma reflect extrahepatic portal hypertension and are exceptionally biliary. The diagnosis of portal cavernoma is radiological. Ultrasound Doppler and CT confirmed the diagnosis. MRI offers a better analysis of biliary impact. The treatment is essentially medically based on anticoagulants. Recording to surgery was reserved for complications.
... [5]. Individual genetic pre-disposition for hypercoagulability plays an important role in the initiation of thromboembolic events [52,53]. The assessment and treatment of hypercoagulability can benefit from the use of VET devices as stated by Zamper et al. in 2017 [54]. ...
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Liver transplantation is a complex surgical procedure in which various forms of coagulation dysfunction can occur, including perioperative hypercoagulability. The hemostasis balance in liver graft recipients with end-stage liver disease can shift to thrombosis or haemorrhage, depending on the associated risk factors and clinical conditions. Hypercoagulability can result in serious complications such as thromboembolism, which can affect the vessels of the newly transplanted liver graft. Standard coagulation tests (SCTs), such as prothrombin time and activated partial thromboplastin time (aPTT), have a poor ability to diagnose and monitor an early stage of hypercoagulability. Recent studies demonstrated that viscoelastic hemostatic elastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), are promising alternative tools for diagnosing hypercoagulability disorders. VETs measure clotting and clot formation time, clot strength (maximum clot firmness), fibrin and platelet contribution to clot firmness, and fibrinolysis, which makes them more sensitive in identifying liver graft recipients at risk for thrombosis as compared with SCTs. However, developing evidence-based guidelines for the prophylaxis and treatment of hypercoagulability based on VET results is still needed.
... Etiologically, PVT can occur due to underlying malignancy, infection, use of oral contraceptives, acute pancreatitis, pregnancy, Liver disease, or coagulopathies [ 6 ]. Pro-coagulative states leading to PVT can either be acquired due to myeloproliferative disorders, antiphospholipid syndrome, and Paroxysmal Nocturnal Hemoglobinuria (PNH) [ 4 ,6 ] or inherited due to mutations in Prothrombin, anti-thrombin, protein C, protein S, or Factor V [ 8 ]. ...
Article
Full-text available
Protein S and C deficiency is a rare inherited thrombophilia that predisposes individuals to a hypercoagulable state, leading to clot formation in various locations, such as the deep veins of the legs, cerebral veins, and rarely the portal vein. We present the case of a 21-year-old male who came to the ER with hematemesis and melena secondary to chronic portal vein thrombosis (PVT) without any evidence of cirrhosis. Diagnostic investigations, including ultrasonography and computed tomography, confirmed the presence of thrombosis and cavernous transformation of the portal vein, splenic vein thrombosis, and splenomegaly. Coagulation profiling revealed diminished Protein S and C levels, thus confirming the diagnosis of a combined Protein S and C deficiency. Management involved indefinite anticoagulant therapy with direct oral anticoagulants to mitigate thromboembolic risks associated with the inherited thrombophilia. This case underscores the importance of considering rare coagulation disorders in young patients with unexplained thrombotic events, emphasizing the need for a comprehensive diagnostic approach and timely therapeutic interventions to minimize morbidity and mortality.
... Denninger et al, based on their study of 36 patients with PVT, found that this condition was associated with one or more thrombophilic states in 26 out of 36 patients. They recommended screening for prothrombotic states in all cases of PVT, irrespective of other local predisposing factors or OCP use [10]. Hence, the multidisciplinary team concluded that this patient warranted a full thrombophilia study. ...
Article
Full-text available
Infection with SARS-CoV-2 has been shown to predispose to thromboembolic events. The risk of such thromboses further increases in those with underlying inherited or acquired prothrombotic states. The authors present a 30-year-old lady who developed acute abdominal pain, three days after recovery from a mild COVID-19 infection. She was also using oral contraceptive pills. Laboratory investigations revealed elevated inflammatory markers, and a contrast-enhanced abdominal CT scan demonstrated portal vein thrombosis (PVT). Due to the unusual site of thrombosis, a thrombophilia screen was performed, which detected a heterozygous Factor V Leiden mutation (FVL). Thus, her PVT was attributed three simultaneous risk factors, namely COVID-19 infection, OCP use and FVL mutation. She was initiated on anti-coagulation, with which she improved significantly. In patients presenting with thromboses at uncommon sites, investigation for evidence of recent Covid-19 infection and screening for inherited and acquired thrombophilia should be considered, while discontinuing any offending medications.
... Ruling out coagulation disorders is necessary for the diagnosis of BCS secondary to tumor thrombosis [8]. JAK2 mutation testing for myeloproliferative disorders can assist in ruling those out [9]. Imaging with modalities such as CT/MRI with vascular contrast is typically preferred for BCS [10]; however, they may reveal filling defects and not the nature of the tissue causing obstruction. ...
Article
Full-text available
Budd-Chiari syndrome (BCS) is a rare constellation of conditions due to obstruction of venous flow from anatomical levels ranging from the hepatic veins to the confluence of the inferior vena cava (IVC) and right atrium. The resulting retrograde flow of blood leads to hepatomegaly, ascites, and liver failure among other features. Our case highlights the clinical features, diagnostic challenges, and management of a patient with a tumor thrombus from a metastatic prostate adenocarcinoma in a 67-year-old male leading to BCS. This patient, with a past history of prostate adenocarcinoma and aortic valve replacement on chronic warfarin anticoagulation, presented with acutely worsening abdominal pain and a distended abdomen, and imaging revealed an IVC filling defect. Subsequent imaging with a piflufolastat prostate-specific PET showing increased uptake in the IVC elucidated the diagnosis of tumor thrombosis. Management considerations include aggressive therapy and optimization of quality of life. The patient was offered both options, and options including surgical shunting, bypasses, and anticoagulation were discussed. After shared decision-making, the patient and family opted to choose the pathway of palliative radiation and anticoagulation.
... Indeed, the absence of controlled prospective studies examining the risk-benefit profile of long-term anticoagulation in preventing re-thrombosis in chronic portal NNPVT remains a notable gap. While retrospective studies hint at its effectiveness in reducing new thrombotic episodes [14,[22][23][24] and potentially enhancing survival without an increase in the risk of bleeding [22,[25][26][27][28], there are also conflicting reports [16,29]. Furthermore, these studies have not differentiated outcomes based on the presence or absence of underlying prothrombotic factors in patients. ...
Article
Full-text available
Transjugular intrahepatic portosystemic shunt (TIPS) emerges as a key treatment for portal hypertension (PH) complications. While international guidelines provide clear indications for its use in cirrhosis, empirical knowledge is notably scarcer in non-cirrhotic PH, particularly in nonmalignant noncirrhotic portal vein thrombosis (NNPVT) and in patients with portosinusoidal vascular disorder (PSVD). Patients afflicted by these rare diseases exhibit distinct clinical profiles compared to their cirrhotic counterparts, often characterized by a younger age, predominantly preserved hepatic functionality even in cases of severe PH, and a higher propensity for extensive splanchnic thrombosis, which intricately complicates TIPS placement, posing unique challenges for its creation. The objective of this review is to synthesize existing literature on the effectiveness, safety, specific indications, and clinical outcomes of TIPS in adult patients with NNPVT or PSVD, focusing also on the technical challenges of TIPS insertion in the presence of portal cavernoma.
... Кроме того, в структуре ве нозных тромбозов при ИП гораздо чаще (до 10 %) по сравнению со здоровой популяцией наблюдаются тромбозы абдоминальных сосудов (воротной и пече ночных вен), симптоматика которых сложна для ди агностики, особенно когда такой тромбоз становится первым клиническим проявлением ранее не диагнос тированной ИП. В группе пациентов с тромбозами воротной и печеночных вен без явной предшествовав шей причины МПН как причину тромбоза выявляют у 31-53 % больных, при этом более часто это проис ходит у молодых пациентов [22][23][24][25][26]. В случае отсутст вия явной причины (карцинома или цирроз печени) тромбоза абдоминальных вен необходимо проведение скринингового исследования на мутацию JAK2V617F и другие драйверные мутации МПН. ...
Article
Polycythemia vera is a disease known since ancient times, however, until recent decades, diagnosis was carried out by exclusion, and therapy was symptomatic. The discovery of the pathogenetic role of mutations in the Janus kinase II gene has led to the possibility of establishing a diagnosis based not only on morphology, but also on genetic verification and to the development of directed targeted therapy, which is much more effective than previously used methods. The introduction of molecular genetic screening led to the need for a differential diagnosis with familial erythrocytosis, and the lessons of the coronavirus pandemic revealed the presence in the population of a significant proportion of patients with erythrocytosis due to the carriage of gene polymorphisms associated with familial hemochromatosis. The article presents our own personalized algorithms for the diagnosis and treatment of polycythemia vera and the results of their use, demonstrating the possibility of a two-fold reduction in the incidence of thrombosis and an increase in overall survival.
... Variable Gender (Male/Female) Age at initial symptom mean ± SD (range) BMI kg/m2 mean ± SD WBC (×10 3 /μL) mean ± SD RBC (×10 6 /μL) mean ± SD Platelet (×10 4 /μL) mean ± SD Antithrombin III % (80-120) mean ± SD Protein S % (64-149) mean ± SD Protein C % (64-146) mean ± SD D-dimer ug/mL (< 0. (MPN-U), is the most frequent underlying prothrombotic factor for EHPVO with a reported prevalence of 15-30% (12,(16)(17)(18)(19)(20). In the West, MPN has been reported in 58% of patients with EHPVO of unknown etiology, and 57% of these go on to develop an overt MPN during follow up (20). ...
Article
Extrahepatic portal vein obstruction (EHPVO) is a rare disease. Most EHPVO patients are usually referred to a gastroenterologist for intestinal bleeding and hypersplenic thrombocytopenia; however, hypercoagulative diseases may be occult in these patients and require anticoagulation. The purpose of this study was to elucidate the clinical characteristics of EHPVO. We conducted a retrospective analysis of the hospital database, evaluating the medical records of 15 patients (7 males, 8 females, mean age of onset 42.0 years, range 5–74 years). Thirteen of 15 EHPVO patients (86.7%) had intestinal varices. These included 10 esophageal (66.7%), 12 gastric (80.0%), and 6 ectopic varices (40.0%). Nine (60.0%) of 15 had a history of intestinal bleeding. Regarding comorbidities, 5 of 15 (33.3%) suffered from vascular diseases, including acute myocardial infarction, cerebral infarction, pulmonary embolism, Budd–Chiari syndrome, and mesenteric vein thrombosis. The former 3 vascular commodities manifested at less than 32 years of age. Four patients (26.7%) with JAK2V617F mutation were diagnosed as myeloproliferative neoplasm (MPN). 72.3% of EHPVO patients without MPN experienced thrombocytopenic state. No EHPVO patients with MPN experienced thrombo-leukocytopenia. The elevation of white blood cell and platelet counts, and decrease of protein S were seen in EHPVO with MPN, compared with EHPVO without MPN. EHPVO is frequently associated with underlying hypercoagulative factors, causing a dilemma between thrombotic complications and portal hypertensive bleeding. Most EHPVO patients experience an evident thrombocytopenic state due to severe hypersplenism; however, hypersplenic hematologic changes are eliminated in EHPVO with MPN. MPN should be suspected in EHPVO patients negative for thrombo-leukocytopenia.
... По отношение на хормоналните фактори, бременността и приемът на орални контрацептиви са свързани с БКС, относно ТПВ такава връзка не е доказана [2,[16][17]. ...
Article
Full-text available
Abstract Aim: Myeloproliferative neoplasias (MPNs) are a heterogeneous group of clonal diseases of hematopoietic stem cells characterized by increased proliferation of cells of the myeloid lineage in the bone marrow (BM). Ph-negative MPNs are the most common risk factor for vein thrombosis (VLT), including Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT). A number of studies have addressed the role of all etiologic and risk factors for VLT, including acquired prothrombotic conditions, hereditary thrombophilia, and local disease. The present communication describes a rare clinical case of a female patient with 3 risk factors for BCS: Ph-neg. MPN caused by acquired JAK2V617F mutation, inherited coagulation disorder, factor V Leiden mutation, and use of hormonal contraception. Material and methods: The diagnostic-therapeutic algorithm for the specific patient exactly follows the current opinions on behavior in this condition, including the evaluation of all possible prothrombotic risk factors. Results: The patient continues his regular follow-up by a gastroenterologist and a hematologist, maintaining a good quality of life with no new thrombotic events and normal hematological parameters. Conclusion: The presented clinical case confirms the role of routine screening for MPN in TVL. Screening for congenital thrombophilia is warranted regardless of the patient’s JAK2 status because of the likelihood of a multifactorial genesis of thrombosis in this condition, which on in turn necessitates the application of a different mechanism of antithrombotic action.
... These rates, which range from 4.4% to 15% in people with cirrhosis, considerably increase and represent around 5%-10% of all instances of portal hypertension [4]. Local variables account for 10%-50% of instances with prothrombotic disorders, which appear in 22%-70% of those without cirrhosis [3][4][5] and frequently involve numerous contributory factors [6]. ...
Article
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A disorder known as portal venous thrombosis (PVT) is characterized by a partial or total obstruction of the portal vein. Although PVT is somewhat uncommon, liver illness is frequently linked to it. Cirrhosis, carcinoma of the liver, myeloproliferative neoplasms, other malignancies, the use of oral contraceptives, intestinal infections, and genetic hypercoagulable illnesses are typical risk factors. In this case report, we discuss the case of a young male patient who had PVT as a result of a protein C deficit. The patient first had abdominal distention due to ascites, and the diagnosis of portal vein thrombosis was later confirmed by a triphasic computed tomography (CT) scan and Doppler ultrasonography. Anticoagulant medications were successfully administered to treat the patient. The importance of identifying PVT in patients with hypercoagulable diseases and the efficacy of anticoagulant therapy in such circumstances are both highlighted by this case.
... По отношение на хормоналните фактори, бременността и приемът на орални контрацептиви са свързани с БКС, относно ТПВ такава връзка не е доказана [2,[16][17]. ...
Article
Full-text available
Цел: Миелопролиферативните неоплазии (МПН) са хетерогенна група клонални заболявания на хемопоетичните стволови клетки, характеризиращи се с повишена пролиферация на клетки от миелоидния ред в костния мозък (КM). Ph-негативните MПН са най-честият рисков фактор за тромбоза на вена лиеналис (ТВЛ), включваща синдром на Бъд-Киари (БКС) и тромбоза на порталната вена (ТПВ). Редица проучвания разглеждат ролята на различните етиологични и рискови фактори за ТВЛ, включващи придобити протромботични състояния, наследствена тромбофилия и локални заболявания. Настоящото съобщение описва рядко срещан клиничен случай на пациентка с 3 рискови фактора за БКС: Ph-нег. МПН, причинена от придобита мутация JAK2V617F, наследствено нарушение на кръвосъсирването, фактор V Leiden мутация, и употреба на хормонална контрацепция. Материал и методи: Диагностично-терапевтичният алгоритъм при конкретната пациентка прецизно следва актуалните препоръки за поведение при това състояние, включващо и оценка на всички възможни протромботични рискови фактори. Резултати: Пациентката продължава своето регулярно проследяване от гастроентеролог и хематолог, поддържайки добро качество на живот без нови тромботични инциденти и нормални хематологични показатели. Заключение: Представеният клиничен случай потвърждава ролята на рутинния скрининг за МПН при ТВЛ. Откроява необходимост от извършване на скрининг за вродена тромбофилия, независимо от JAK2 статуса на пациента, поради вероятността за мултифакторна генеза на тромбообразуване при тези състояния, които от своя страна налагат прилагането на различни по механизъм на действие антитромботични терапии.
... As other studies reported, even before LT, patients with advanced liver diseases and PVT may not necessarily have a worse outcome, except for malignant thrombosis. 86,87 An important role in the natural history of PVT is also played by the systemic inflammation. Some studies recently investigated the link between the inflammatory cytokines such as TNF-alpha and IL-6 and the risk for PVT, setting these biomarkers as independent predictors for the PVT. ...
Article
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Purpose This study aimed to explore inflammatory biomarkers, stool’s functional bacterial groups and their possible link to portal vein thrombosis (PVT) in patients with liver cirrhosis (LC). Materials and Methods An observational study of 300 participants: 200 inhospital cirrhotic patients, who met inclusion criteria, equally assigned into two groups, based on the presence or absence of PVT and 100 healthy controls was carried out. Results The PVT group displayed significant differences related to older age, cigarettes smoking history, emergency admission, higher Child-Pugh score, metabolic related disorders and nonalcoholic fatty liver disease, as well as non-obstructive aspects, with chronic thrombi. The PVT group exhibited significant differences related to biomarkers such as tumor necrosis factor (TNF)-alpha, C-reactive protein (CRP), D-dimers (D-D), as well as gut overall dysbiosis (DB) and alteration of different functional bacterial groups of the gut microbiota. Strong positive correlations were observed between PVT severity, and TNF-alpha, CRP, D-D as well as lipopolysaccharide (LPS) positive bacteria. Esophageal varices, age and abdominal pain were independent predictors for PVT severity as well as CRP, TNF-alpha and D-D. Conclusion Patients with LC and PVT displayed elevation of TNF-alpha, CRP, D-D alterations of the functional gut microbiota, as well as several morphological and clinical particularities. Although the LPS positive gut microbiota was linked to inflammatory biomarkers and PVT severity, it was not proven to be an independent predictor of the PVT severity like CRP, TNF-alpha and D-D.
... This condition could lead to three main complications, such as small bowel ischemia, ischemic hepatitis, and gastrointestinal bleeding [9]. PVT could be categorized into four groups: thrombosis confined to the portal vein beyond the confluence of the splenic and SMV, extension of the thrombus into the SMV but with patent mesenteric vessels, diffuse thrombosis of the splanchnic venous system but with large collaterals, and extensive splanchnic venous thrombosis but with fine collaterals [10]. Our patient developed acute thrombosis of the portal vein and SMV with signs of ischemic colitis. ...
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Protein C (PC) is an essential vitamin K-dependent protein that regulates thrombosis and hemostasis in the body. A mutation in the PROC gene on chromosome 2q14.3 results in PC deficiency. The clinical presentation of PC deficiency can vary, ranging from a single vein thrombosis to disseminated intravascular coagulation, purpura fulminans, or even life-threatening complications such as sepsis. Here, we present a case of a 37-year-old female who was found to have acute portal vein thrombosis as an initial presentation of PC deficiency. She presented to the hospital with acute onset of abdominal pain associated with nausea, blood-streaked emesis, and bloody bowel movement.
... For patients without a clear history of PA intake, we classify them as BCS group if hepatic vein occlusion is detected by imaging methods. On the other hand, it is recognized that BCS-HV is often complicated by thrombophilia, the main causes of which are underlying hereditary and acquired hematological disorders [26,27]. The younger age of onset in patients with hematologic diseases may partly explain why BCS-HV patients are generally younger on average. ...
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(1) Background: Hepatic venous occlusion type of Budd–Chiari syndrome (BCS-HV) and pyrrolizidine alkaloid-induced hepatic sinusoidal obstructive syndrome (PA-HSOS), share similar clinical features, and imaging findings, leading to misdiagnoses; (2) Methods: We retrospectively analyzed 139 patients with BCS-HV and 257 with PA-HSOS admitted to six university-affiliated hospitals. We contrasted the two groups by clinical manifestations, laboratory tests, and imaging features for the most valuable distinguishing indicators.; (3) Results: The mean patient age in BCS-HV is younger than that in PA-HSOS (p < 0.05). In BCS-HV, the prevalence of hepatic vein collateral circulation of hepatic veins, enlarged caudate lobe of the liver, and early liver enhancement nodules were 73.90%, 47.70%, and 8.46%, respectively; none of the PA-HSOS patients exhibited these features (p < 0.05). DUS showed that 86.29% (107/124) of patients with BCS-HV showed occlusion of the hepatic vein, while CT or MRI showed that only 4.55%(5/110) patients had this manifestation (p < 0.001). Collateral circulation of hepatic veins was visible in 70.97% (88/124) of BCS-HV patients on DUS, while only 4.55% (5/110) were visible on CT or MRI (p < 0.001); (4) Conclusions: In addition to an established history of PA-containing plant exposure, local hepatic vein stenosis and the presence of collateral circulation of hepatic veins are the most important differential imaging features of these two diseases. However, these important imaging features may be missed by enhanced CT or MRI, leading to an incorrect diagnosis.
... Knowledge about these key points might be suggestive, not sufficient, of BCS diagnosis. Treatments administered by clinicians must put into account not only the obstruction by itself, but also its possible underlying causes: MPNs, e.g., PV, ET, PMF [63]; History of hereditary or acquired thrombogenic disorders [64]; Use of oral contraceptives [65,66]; Paroxysmal nocturnal hemoglobinuria [67]; Status and history of recent pregnancy [68,69]; History of hepatocellular carcinoma [70]; Chronic liver disease, remained unexplained after exclusion of alcoholism, chronic viral hepatitis B or C, autoimmunity, iron overload, Wilson's disease and alpha-1 antitrypsin deficiency [71]; and other possible risk factors towards thrombosis or obstruction. ...
... Ÿ In the restricted analysis, we found a combination of local (54%) and systemic risk factors (26%). Ÿ Denninger et al. [9] reported a higher incidence of systemic factors (72%). Ÿ The typical presentation of acute PVT was abdominal pain, splenomegaly, fever and ascites, while the presentation of chronic PVT was abdominal pain and splenomegaly together with gastrointestinal haemorrhages and ascites. ...
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Background: The portal vein is formed by the conuence of the splenic and superior mesenteric veins. Occlusion of the portal vein by thrombus (portal vein thrombosis [PVT]) typically occurs in patients with cirrhosis and/or prothrombotic disorders/ pancreatitis. Patients with acute PVT have the sudden onset of portal venous occlusion due to thrombus. Patients with acute PVT have not yet developed features of chronic PVT, such as collateral circulation (e.g., cavernous portal transformation) or portal hypertension. Chronic PVT develops when acute doesn't resolve with formation of collaterals. In patients with suspected acute PVT, we typically obtain a contrast-enhanced abdominal computed tomography (CECT) to conrm the diagnosis, evaluate for predisposing conditions (eg, intra-abdominal infection), assess the extent of the thrombosis and the anatomy of collaterals, and detect evidence of intestinal infarction. Doppler and MRI are other alternative imaging modalities. The primary management of acute portal vein thrombosis (PVT) is anticoagulation and, when possible, treatment of predisposing condition. The goal of anticoagulation is to prevent extension of the clot and to allow for recanalization, so that intestinal infarction and portal hypertension do not develop. Unlike chronic PVT, where the role of anticoagulation in patients with cirrhosis is unclear, studies suggest anticoagulation for acute PVT is benecial for patients with cirrhosis. However, because patients with cirrhosis may have esophageal varices, we typically screen for varices prior to initiating anticoagulation. 60 cases of extrahepatic portal vein thrombosis or intrahepatic Methods: portal vein thrombosis were included. All registered diagnoses were based on either ultrasound with Doppler, CT-angiography or MRI. In our study, Ris Results: k factors were established in 24 cases (80%). When including all risk factors, 16 cases (53.3%) had local risk factor, and 8 cases (26.6%) had a systemic risk factor. Anatomical location was in 26 cases (86%)extrahepatic, (14%) intrahepatic. In addition, patients with extrahepatic PVT also had intrahepatic thrombosis (38%) and/or in the splenic vein (23%). 66% had oesophageal varices, 53% gastric varices, 46% portal hypertensive gastropathy, 26% variceal haemorrhage, and 40% ascites. Most patients had a combination of local and systemic risk Conclusion: factors for PVT. Partial/ complete recanalization is more in patients treated with anticoagulation therapy, and that regression of varices was more in patients who were treated with active endoscopy combined with beta blockers.
... Doppler ultrasonography results were comparable in PVT and other patients. Denninger et al. [13] found a mixed etiology for BCS in 25% patients. Mohanty et al, [14] reported that approximately 26% BCS were caused by the FVLM as a most prevalent risk factor. ...
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Background and Aim: Thrombosis of the portal vein or obstruction of the hepatic venous outflow tract is the cause of portal vein thrombosis (PVT) and Budd-Chiari syndrome (BCS). Patients with PVT may experience a shorter survival rate compared to those without. The present study aimed to determine the portal vein thrombosis occurrence in Budd-Chiari syndrome patients. Patients and Methods: This cross-sectional study was conducted on 46 Budd-Chiari syndrome patients in Gastroenterology department of DHQ Teaching Hospital and Mufti Mahmood Memorial Hospital, Dera Ismail Khan from November 2021 to October 2022. Written informed consent was taken from each individual. Doppler ultrasonography (colored-pulsed) was used to confirm the PVT and BCS cases. Clinical data, laboratory findings, and radiological data were recorded. SPSS version 26 was used for data analysis. Results: The overall mean age of the BCS patients was 28.34±4.6 years. The prevalence of portal vein thrombosis in BCS patients was 12.8% (n=6). Of the total cases, the incidence of chronic and acute BCS presentation was 42 (91.3%) and 4 (8.7%) respectively. The most prevalent symptoms of BCS were abdominal pain and abdominal enlargement in 38 (82.6%) and 41 (89.1%) respectively. Hepatomegaly and ascites were most prevalent clinical signs found in 36 (78.3%) and 37 (80.4%) respectively. The incidence of esophageal varices, gastric extension, and fundal varices were 32 (69.6%), 4 (8.7%), and 2 (4.3%) respectively. About 21 (45.7%) cases had Portal hypertensive gastropathy (PHG). Conclusion: A higher incidence of PVT was observed in the present study than previously reported. Sociodemographic data and underlying etiology of BCS were not significantly different between patients with and without PVT. Those with PVT were more likely to experience hepatic tenderness, increased white blood cells, and increased direct bilirubin. PVT and other patients had similar Doppler ultrasound findings. Keywords: Portal vein thrombosis, Prevalence, Budd-Chiari syndrome
... The ligation of the gastroepiploic and short gastric vessels, resulting in gastric and splenic venous reflux near the splenic vein, could potentially initiate thrombosis, and the thermal effect of energy devices used for ligation can damage the splenic vein via mechanical or thermal effects [1,9,22,23]; 3. ...
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Activated protein C (APC) is a serine protease with potent anticoagulant properties, which is formed in blood on the endothelium from an inactive precursor. During normal haemostasis, APC limits clot formation by proteolytic inactivation of factors Va and VIIIa (ref. 2). To do this efficiently the enzyme needs a nonenzymatic cofactor, protein S (ref. 3). Recently it was found that the anticoagulant response to APC (APC resistance) was very weak in the plasma of 21% of unselected consecutive patients with thrombosis and about 50% of selected patients with a personal or family history of thrombosis; moreover, 5% of healthy individuals show APC resistance, which is associated with a sevenfold increase in the risk for deep vein thrombosis. Here we demonstrate that the phenotype of APC resistance is associated with heterozygosity or homozygosity for a single point mutation in the factor V gene (at nucleotide position 1,691, G-->A substitution) which predicts the synthesis of a factor V molecule (FV Q506, or FV Leiden) that is not properly inactivated by APC. The allelic frequency of the mutation in the Dutch population is approximately 2% and is at least tenfold higher than that of all other known genetic risk factors for thrombosis (protein C (ref. 8), protein S (ref. 9), antithrombin10 deficiency) together.
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Background: A mutation in the prothrombin ger (G→A 20210 ) has been associated with higher plasma prothrombin levels and an increased tendency for venous thrombosis. Objective: To determine whether the prothrombi A 20210 allele is independently associated with the occu rence of venous thrombosis. Design: Case-control study. Setting: Two thrombosis centers in southern Italy. Patients: 281 consecutive patients with venous thrombosis confirmed by objective tests and 850 controls. Measurements: Medical history was collected on standardized questionnaires. The presence of prothrombi G→A 20210 and factor V Leiden mutations was determine by polymerase chain reaction. The presence of anticoagulant factors and prothrombin activity was determined b tests of function. Results: In 150 controls, increased prothrombin activil (P < 0.001) was associated with the prothrombin A 2021 allele. This allele was more frequent in patients than i controls (8.01% compared with 2.29%; P < 0.001) and wa associated with an increased risk for thrombosis (odc ratio, 3.88 [95% Cl, 2.23 to 6.74]). The increased prevalenc of this allele was independent of the presence of the factc V Leiden mutation. After adjustment for sex, age, arterial thrombosis, and factor V Leiden mutation, the risk was sti significantly elevated (odds ratio, 3.13 [Cl, 1.89 to 5.21] Moreover, the overall prevalence of inherited coagulatio abnormalities was significantly higher in patients wit thrombosis of the lower extremities than in patients wit thrombosis of the upper extremities (odds ratio, 3.77 [C 1.10 to 12.93]). Fourteen patients carried both the prc thrombin G→A 20210 and factor V Leiden mutations. Conclusions: The prothrombin A 20210 allele is indeper dently associated with the occurrence of venous thrombc sis, particularly in patients with a history of thrombosis c the lower extremities.
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The protein C anticoagulant pathway is of major importance in maintaining vascular patency. Resistance to the key enzyme of this system, activated protein C (APC), is a recently discovered congenital defect of the protein C system. This genetic defect is present in 20% to 60% of venous thrombosis patients, making it by far the most common known pathogenetic risk factor of thrombosis. APC resistance is due to a single point mutation in the factor V gene (G to A at nucleotide position 1691) that predicts the replacement of arginine(506) by glutamine. This is associated with the loss of one of three APC cleavage sites in factor Va, one of the substrates for APC, and hypercoagulability. The identification of APC resistance as an additional genetic risk factor in a large proportion of symptomatic protein C- and protein S-deficient families has provided evidence that thrombosis is a polygenetic disease. Thus, several genetic defects act in concert with environmental factors in the pathogenesis of venous thromboembolism.
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The pathogenesis of portal hypertension arising in patients with myeloproliferative disorders has been difficult to understand because liver biopsy findings often show minimal changes. It has been suggested that increased splenic blood flow, hepatic infiltration with hematopoietic cells or sinusoidal fibrosis may be important. We have reviewed the autopsy findings and clinical histories of 97 patients with polycythemia vera and 48 patients with agnogenic myeloid metaplasia collected from three institutions and from the Polycythemia Vera Study Group. Cirrhosis was present in seven patients, one of whom had bleeding varices. Esophageal varices were present clinically in 10 patients without cirrhosis (seven polycythemia and three agnogenic myeloid metaplasia). All of these patients had lesions in small or medium-sized portal veins and four had stenosis of the extrahepatic portal vein with histology compatible with organized thrombi. Nodular regenerative hyperplasia occurred in 14.6% and correlated closely with the presence of portal vein lesions. Thirty patients had > 500 ml of ascites, seven of these patients also had varices and six of them had hepatic vein thrombosis. Ascites also correlated with hepatic vein disease confined to small intrahepatic branches. No correlation was seen between hepatic hematopoietic infiltration and signs of portal hypertension. We conclude that esophageal varices are common and are almost always associated with portal vein lesions visible by light microscopy. These portal vein lesions, and the secondary effects of nodular regenerative hyperplasia and portal hypertension, are most likely a result of portal vein thrombosis in patients with myeloproliferative disorders. (HEPATOLOGY 1990;12:1166-1174).
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Sixty-six SLE patients were studied for the presence of lupus type circulating anticoagulant. Forty-nine percent of them showed activity of this anticoagulant. The sensitivity of various coagulation tests was compared. Recalcification time was found to be the most sensitive screening test and the kaolin clotting time mixture test, the best for determining the presence of the anticoagulant. Tissue thromboplastin inhibition test detected only half of the patients in whom the anticoagulant was found by recalcification time and kaolin clotting time mixture test. APTT, using 2 different reagents, resulted in 73% and 52% false negatives. A numerical index for determining the presence of the anticoagulant and its quantitative evaluation is suggested. The association between thromboembolic events, recurrent abortions and the different coagulation tests is shown.
Article
In a prospective study of 33 adults with portal vein thrombosis unrelated to a liver tumor, we have assessed the prevalence of primary myeloproliferative disorders using conventional criteria and cultures of bone marrow progenitor cells. A primary myeloproliferative disorder was documented in 14 patients investigated at the time of recognition of portal vein thrombosis. Among these 14 patients, the main clue to the presence of the myeloproliferative disorder was (a) the observation of suggestive abnormalities of peripheral blood cell counts in 4 patients; (b) characteristic findings at bone marrow biopsy or determination of total red cell volume in 3 patients; and (c) formation of "spontaneous" erythroid colonies in cultures of bone marrow progenitor cells in erythropoietin-poor medium in 7 patients. In 2 other patients, agnogenic myeloid metaplasia with myelosclerosis of apparently recent onset developed 5 yr after recognition of portal vein thrombosis. In conclusion, primary myeloproliferative disorders--in a full-blown or latent form, or at an early stage--are a major cause of portal vein thrombosis.
Article
We assessed the prevalence of overt and latent primary myeloproliferative disorders in hepatic vein thrombosis. Cultures of bone marrow or peripheral blood mononuclear cells were done in 20 patients with Budd-Chiari syndrome. Erythroid colony formation in the absence of erythropoietin, which is a reliable indicator for a primary myeloproliferative disorder, was seen in 16 patients in whom Budd-Chiari syndrome was due to hepatic vein thrombosis, including 13 women aged 18 to 45 years. Among these 16 patients, the conventional criteria for the diagnosis of a primary myeloproliferative disorder were met in only 2. Primary myeloproliferative disorder, often without peripheral blood changes, is a major cause of hepatic vein thrombosis in young women.
Article
The myeloproliferative disorders, including polycythaemia rubra vera, arise as a result of a single-cell mutation. A characteristic of the abnormal haemopoietic clone is that it can form erythroid colonies in vitro in the absence of added erythropoietin. Such endogenous erythroid clones were consistently found in two of seven patients with peripheral vascular disease. These two patients had mean platelet counts of 600 X 10(9)/l and 630 X 10(9)/l. Culture of blood and bone-marrow cells from patients with raised platelet counts secondary to a variety of other disorders failed to yield such colonies. The presence of endogenous erythroid clones provides early evidence of a myeloproliferative disorder.
Article
In a prospective study of 22 patients with non-tumorous Budd-Chiari syndrome, four were found to have the antiphospholipid syndrome with no other cause of hepatic vein thrombosis. All four patients were young women. The antiphospholipid syndrome was secondary to systemic lupus in one case, to a "lupus-like disease" in another, and apparently primary in the remaining two cases. Two patients died. The other two are in good health on chronic oral anticoagulation. In our experience, the antiphospholipid syndrome is a frequent cause, after myeloproliferative disorders, of non-tumorous Budd-Chiari syndrome. In such patients, long-term anticoagulation may prevent recurrence or extension of thrombosis.
Article
Several physiological antithrombotic proteins--including antithrombin, protein C, protein S, tissue factor pathway inhibitor, and components of the fibrinolytic system--act as inhibitors at strategic sites in the coagulation cascade to maintain normal blood fluidity under normal circumstances. The molecular basis of specific inherited hypercoagulable states has been recently elucidated. With the description of resistance to activated protein C, which is the commonest coagulation defect associated with thrombophilia, a specific primary hypercoagulable state can be identified in over 50% of patients with thrombophilia. Although the prevalence in the normal population of some "prothrombotic" mutations is remarkably high, most affected individuals do not have clinical thrombotic complications, so it is likely that clinically apparent hypercoagulable states result from multigene interactions, and that clinical episodes of thrombosis are precipitated by acquired prothrombotic insults in patients with an inherited predisposition to thrombosis.
Article
To assess the contribution of naturally occurring portal-systemic shunts to the coagulopathy of patients with liver disease, we studied laboratory parameters of hemostasis in 20 adult patients with extrahepatic portal hypertension, secondary to portal vein thrombosis, that had resulted in variceal bleeding. All extrahepatic portal hypertension patients had normal liver function and histological appearance. None had any evidence of preexisting coagulation disorders, and none had bled or undergone sclerotherapy in the 6 mo before study. Age- and gender-matched groups of 20 healthy individuals and 20 stable patients with cirrhosis and portal hypertension who had a history of variceal bleeding served as controls. Both patient groups had thrombocytopenia consistent with hypersplenism and portal hypertension. Prothrombin international normalized ratio (extrahepatic portal hypertension, 1.3 +/- 0.12; cirrhosis, 1.7 +/- 0.2; control, 1.02 +/- 0.06; p < 0.05) and partial thromboplastin time ratios (extrahepatic portal hypertension, 1.12 +/- 0.1; cirrhosis, 1.26 +/- 0.2; controls, 1.01 +/- 0.03; p < 0.05) were significantly prolonged in both patient groups. Extrahepatic portal hypertension and cirrhotic patient groups had significantly increased levels of serum total fibrin(ogen)-related antigen (extrahepatic portal hypertension, 818 +/- 150 ng/ml; cirrhosis, 454 +/- 52 ng/ml; controls, 124 +/- 7.3 ng/ml; p < 0.05), fibrin monomer (extrahepatic portal hypertension, 168.8 +/- 16.9 ng/ml; cirrhosis, 115.6 +/- 11.1 ng/ml; controls, 19.7 +/- 0.4 ng/ml; p < 0.05) and D-dimer (extrahepatic portal hypertension, 118 +/- 9.6 ng/ml; cirrhosis, 129 +/- 10 ng/ml; controls, 53.2 +/- 1.6 ng/ml; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Obstruction of the main hepatic veins or suprahepatic inferior vena cava is caused mainly by thrombosis or its fibrous sequela. One or several underlying thrombogenic disorders are usually present, the most common of which is an overt or occult primary myeloproliferative disorder. The major complications are ascites and gastrointestinal bleeding. A sizeable proportion of the cases are asymptomatic. Diagnosis is usually made at ultrasound or magnetic resonance imaging when collateral veno-venous circulation or endoluminal hepatic venous material are demonstrated. Natural history is poorly known. Overall, mortality is high in the early phase of the disease but once the acute episode is terminated, prognosis is good. Treatment includes anticoagulation to prevent recurrence or extension of thrombosis, nonspecific measures to control ascites and gastrointestinal bleeding, and procedures aiming to restore hepatic blood outflow. Portal-caval shunts are preferred when possible. In patients with obstructed inferior vena cava, the first choice is percutaneous angioplasty, and the second choice is portal-systemic shunts with the right atrium or superior vena caval circulation. Transplantation is proposed for patients with severe liver failure.
Article
Obstructive lesion of the hepatic portion of the inferior vena cava is common in Nepal. The clinical data on 150 patients who were seen at the Liver Unit, Bir Hospital, Kathmandu, in three years from 1990 to 1992 were analysed. Although the majority of patients were over 20 years of age, 25 patients were below 10 years of age; there were more males than females in this study. This disease accounted for 17% of 866 patients with chronic liver disease and for nearly one quarter of 267 biopsies performed on this patient group during the same period. Obstructive lesions of the inferior vena cava seem to be more common among poor people with malnutrition. Clinically, our patient group could be divided into acute (n = 27), subacute (n = 43) and chronic (n = 80) cases. The important clinical features are hepatomegaly and/or ascites and, in chronic cases, prominent dilated superficial veins over the body trunk with cephalad flow. Ultrasound is the most helpful diagnostic procedure, especially in subacute and chronic cases, as it frequently demonstrates caval obstruction, thrombosis, dilated hepatic veins and intrahepatic collaterals. Diagnosis is confirmed by cavography, which shows a caval obstruction of varying lengths at the cavo-atrial junction or a marked narrowing of the hepatic portion of the vena cava. In subacute and chronic cases cavography also demonstrates collateral veins, such as the ascending lumbar, hemiazygos and azygos that drain into the superior vena cava. Chronic cases had periods of exacerbation often associated with bacterial infection. The aetiology of inferior vena cava obstruction at its hepatic portion is not known, but there seems to be a frequent association of bacterial infection with the disease.
Article
We have examined the prothrombin gene as a candidate gene for venous thrombosis in selected patients with a documented familial history of venous thrombophilia. All the exons and the 5'- and 3'-UT region of the prothrombin gene were analyzed by polymerase chain reaction and direct sequencing in 28 probands. Except for known polymorphic sites, no deviations were found in the coding regions and the 5'-UT region. Only one nucleotide change (a G to A transition) at position 20210 was identified in the sequence of the 3'-UT region. Eighteen percent of the patients had the 20210 AG genotype, as compared with 1% of a group of healthy controls (100 subjects). In a population-based case-control study, the 20210 A allele was identified as a common allele (allele frequency, 1.2%; 95% confidence interval, 0.5% to 1.8%), which increased the risk of venous thrombosis almost threefold {odds ratio, 2.8; 95% confidence interval, 1.4 to 5.6}. The risk of thrombosis increased for all ages and both sexes. An association was found between the presence of the 20210 A allele and elevated prothrombin levels. Most individuals (87%) with the 20210 A allele are in the highest quartile of plasma prothrombin levels (> 1.15 U/mL). Elevated prothrombin itself also was found to be a risk factor for venous thrombosis.
Article
PV is a myeloproliferative disorder characterized by an elevated hematocrit and red blood cell mass. In vitro hematopoietic culture systems have been used extensively to characterize the cellular defect in PV. Erythroid progenitor cells from PV patients exhibit characteristic endogenous erythroid colony growth in serum-containing semisolid culture medium. These endogenous erythroid colonies can be used as a diagnostic tool to distinguish PV from other myeloproliferative disorders and secondary erythrocytosis. Both EPO independence and exquisite EPO sensitivity are mechanism which have been proposed to explain the growth of endogenous colonies. In contrast with normal erythroid progenitor cells which have both high and low affinity EPO-R, PV erythroid cells have only low affinity EPO-R, Molecular analyses did not reveal mutations in the PV EPO-R. These findings have failed to clarify the role of EPO in the etiology of PV. PV hematopoietic progenitor cells also exhibit increased sensitivity to the hematopoietic growth factors GM-CSF, IL-3, and SCF. As with EPO-R studies, examination of IL-3 and SCF receptors on PV erythroid cells has not identified mechanisms underlying the observed increased sensitivities to these hematopoietic growth factors. The recent development of a truly serum-free culture system has led to the observation that PV progenitor cells are more than 100-fold more sensitive to IGF-1 than are normal progenitor cells. In addition, the IGF-1 receptor on PV progenitor cells exhibits increased basal phosphorylation and a hypersensitivity and hyperresponsiveness to IGF-1 with respect to tyrosine phosphorylation. Thus in PV, hypersensitivity to several hematopoietic growth factors may result in hyperproliferation of hematopoietic cells. This hypersensitivity ma be due to a defective intracellular mechanism common to these hematopoietic growth factors.
Article
In contrast with the well-recognized membranous obstruction of the inferior vena cava, short-length hepatic vein stenoses are not well-recognized causes of hepatic venous outflow block. The aim of this study was to ascertain the prevalence, causes, manifestations, and outcome of short-length hepatic vein stenoses. We performed a retrospective study of patients with short-length hepatic vein stenosis among 86 patients with hepatic venous outflow block who were seen between 1970 and 1992. There were 25 patients with short-length hepatic vein stenosis. A thrombogenic condition was identified in 14 patients (56%). The lesions of the accompanying hepatic veins in these patients were variable (short-length stenoses, thromboses, or nonspecific changes) and similar to that seen in patients without short-length hepatic vein stenosis. In 3 necropsied cases, the venous lesions were suggestive of fibrous sequela of prior thromboses. In patients with short-length hepatic vein stenosis, splenomegaly (28% vs. 55%, P < .05) and hypersplenism were significantly less common; serum transaminase (P < .001) and creatinine levels (P < .02) were lower, prothrombin was higher (P < .001), and 5-year survival was significantly better (Kaplan-Meier estimates: 80% vs. 50%, P < .05). In patients with hepatic venous outflow block, short-length hepatic vein stenosis is a common lesion that appears to be the sequela of localized thrombosis. Long-term anticoagulation and percutaneous angioplasty (with or without stenting) are potentially applicable in these lesions. The long-term results of these treatments merit further evaluation.
Article
The factor V Leiden (FVL) mutation has been shown to be the most frequent cause of hereditary thrombophilia. The prevalence of the mutation in patients with Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT) has not been fully elucidated. To investigate the association between the FVL mutation and BCS and PVT. Thirty patients with BCS, 32 patients with PVT, and a control group of 54 patients with liver disorders and no history of thrombosis. The factor V gene was analysed for the presence of the FVL mutation by a polymerase chain reaction (PCR) technique. The presence of the mutation was confirmed by DNA sequencing. Seven (23%) patients with BCS, one (3%) patient with PVT, and three (6%) patients in the control group were identified as having the FVL mutation. There of the BCS patients had coexisting hypercoagulable states. The prevalence of the FVL mutation was significantly higher in patients with BCS compared with patients with PVT and controls (p < 0.04). The FVL mutation was the second most common aetiology associated with BCS. The FVL mutation is an important factor in the pathogenesis of BCS and screening for the disorder must be included in the investigation of patients presenting with this condition. In contrast, the FVL mutation is not a major predisposing factor in the pathogenesis of PVT.
Article
Budd-Chiari syndrome is a severe disease characterized by occlusion of large hepatic veins leading to death if untreated. Using the classical criteria for the diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (IMF), overt PV was the underlying cause in about 10% of the cases and ET or IMF in only a very few. Using spontaneous endogenous erythroid colony (EEC) formation in vitro and/or bone marrow biopsies, a primary myeloproliferative disorder (PMD) was present in 78% of the patients with apparently idiopathic Budd-Chiari syndrome and in about half of the patients with portal, splenic, and/or mesenteric vein thrombosis. The diagnoses in 40 reported cases with hepatic vein thrombosis and spontaneous EEC were overt PV in 25 and latent unclassified PMD in 15 patients. The diagnoses of 40 reported cases with splanchnic vein thrombosis and spontaneous EEC were overt PV in 12, ET in 2, IMF in 2, and latent unclassified PMD with the presence of EEC in 24 patients. Thrombocytosis as a manifestation of myeloproliferative disease was recorded in 34 of 80 (42.5%) patients with spontaneous EEC and Budd-Chiari syndrome or portal vein thrombosis. Thrombocythemia was present in 15 of 41 patients with a proven and in 19 of 39 patients with a latent myeloproliferative disorder. Patients with hepatic vein or splanchnic vein thrombosis associated with a PMD are predominantly females younger than 45. It is concluded that both spontaneous EEC and histopathology from bone marrow biopsy provide specific information as sensitive clues to the diagnosis of all variants of overt and latent myeloproliferative disorders. The association of hepatic and splanchnic vein thrombosis and PMD is not fully understood. Therapeutic options of Budd-Chiari syndrome include anticoagulation with heparin, fibrinolysis followed by oral anticoagulation, and appropriate treatment of the underlying PMD. In case of failure, invasive options include local procedures such as angioplasty or stenting, venous decompression by portal-systemic shunts, or liver transplantation.
Article
A mutation in the prothrombin gene (G-->A20210) has been associated with higher plasma prothrombin levels and an increased tendency for venous thrombosis. To determine whether the prothrombin A20210 allele is independently associated with the occurrence of venous thrombosis. Case-control study. Two thrombosis centers in southern Italy. Patients: 281 consecutive patients with venous thrombosis confirmed by objective tests and 850 controls. Medical history was collected on standardized questionnaires. The presence of prothrombin G-->A2020 and factor V Leiden mutations was determined by polymerase chain reaction. The presence of anticoagulant factors and prothrombin activity was determined by tests of function. In 150 controls, increased prothrombin activity (P < 0.001) was associated with the prothrombin A20210 allele. This allele was more frequent in patients than in controls (8.01% compared with 2.29%; P < 0.001) and was associated with an increased risk for thrombosis (odds ratio, 3.88 [95% CI, 2.23 to 6.74]). The increased prevalence of this allele was independent of the presence of the factor V Leiden mutation. After adjustment for sex, age, arterial thrombosis, and factor V Leiden mutation, the risk was still significantly elevated (odds ratio, 3.13 [CI, 1.89 to 5.21]). Moreover, the overall prevalence of inherited coagulation abnormalities was significantly higher in patients with thrombosis of the lower extremities than in patients with thrombosis of the upper extremities (odds ratio, 3.77 [CI, 1.10 to 12.93]). Fourteen patients carried both the prothrombin G-->A20210 and factor V Leiden mutations. The prothrombin A20210 allele is independently associated with the occurrence of venous thrombosis, particularly in patients with a history of thrombosis of the lower extremities.
Article
Despite extensive investigations of portal vein thrombosis, no underlying cause is identifiable in up to 30% of patients. A recently described mutation of the prothrombin gene at nucleotide position 20210 is associated with history of venous thrombosis and was assessed in this study. We compared the frequency of factor II G20210A and factor V G1691A (factor V Leiden) mutations in 10 patients with idiopathic portal vein thrombosis, 10 patients with nonidiopathic portal vein thrombosis, 60 patients with deep vein thrombosis of the legs, and 42 control subjects. The frequency of factor II G20210A mutation was increased in patients with idiopathic portal vein thrombosis (40.0%; confidence interval, 3.1%-76.9%) compared with controls (4.8%; confidence interval, 0%-11.5%) or patients with nonidiopathic portal vein thrombosis or deep vein thrombosis (P = 0.0001). In contrast, the frequency of the factor V G1691A mutation was similar in subjects with portal vein thrombosis and in controls but was increased in patients with deep vein thrombosis (P = 0.0001). The factor II G20210A mutation is frequent in patients with idiopathic portal vein thrombosis and should therefore be assessed under this circumstance.
Hepatic venous outflow blockBudd Chiari syndrome'') due to short-length hepatic vein stenoses (''hepatic vein webs'')
  • D Valla
  • A Hadengue
  • M Younsi
  • N Azar
  • G Zeitoun
  • Molas G Boudet Mj
Valla D, Hadengue A, El Younsi M, Azar N, Zeitoun G, Boudet MJ, Molas G, et al. Hepatic venous outflow block (''Budd Chiari syndrome'') due to short-length hepatic vein stenoses (''hepatic vein webs''). HEPATOLOGY 1997;25:814-819.
From the 1 Laboratoire d'Hé et d'Immunologie, 2 Service d'Hé Clinique, and 4 Service d'Hé and Laboratoire d'Hé Splanchnique et de Biologie Vasculaire
  • Abbreviation
  • Mthfr
Abbreviation: MTHFR, methylene-tetrahydrofolate reductase. From the 1 Laboratoire d'Hé et d'Immunologie, 2 Service d'Hé Clinique, and 4 Service d'Hé and Laboratoire d'Hé Splanchnique et de Biologie Vasculaire, Hô pital Beaujon, Clichy, France; and 3 Laboratoire d'hé, Hô pital Raymond Poincarré, Garches, France. Received May 25, 1999; accepted December 10, 1999. Supported by Délé a ` la recherche clinique de l'Assistance publique, Hô pitaux de Paris (CRC 930507).
Essential thrombocythemia
  • H Iland
  • J Laszlo
  • Murphy
  • Wasserman
  • Berk Pd Lr
  • Berlin
Iland H, Laszlo J, Murphy S: Essential thrombocythemia. In: Wasserman LR, Berk PD, Berlin NI, eds. Polycythemia Vera and the Myeloprolifera-tive Disorders. Philadelphia: WB Saunders, 1995;293-310.
Classification of the polycythemias and initial clinical features in polycythemia vera
  • Berlin Ni Wasserman
  • Berk Pd Lr
  • Berlin
Berlin NI: Classification of the polycythemias and initial clinical features in polycythemia vera. In: Wasserman LR, Berk PD, Berlin NI, eds. Polycythemia Vera and the Myeloproliferative Disorders. Philadelphia: WB Saunders, 1995;22-30.
Polycythemia Vera and the Myeloproliferative Disorders
  • Berlin NI
Hepatic venous outflow block (“Budd Chiari syndrome”) due to short-length hepatic vein stenoses (“hepatic vein webs”)
  • Valla