Deep vein thrombosis and pulmonary embolism in cirrhotic patients:Systematic review

Patients with liver cirrhosis were traditionally believed to be protected against development of blood clots.Lately,studies have shown that these patients may probably be at an increased risk of venous thrombotic complications.Although the hemostatic changes in the chronic liver disease patients and the factors that may predict bleeding vs thrombotic complications remains an area of active research,it is believed that the coagulation cascade is delicately balanced in these patients because of parallel reduced hepatic synthesis of pro and anticoagulant factors.Thrombotic state in cirrhotic patients is responsible for not only portal or non-portal thrombosis[deep vein thrombosis(DVT)and pulmonary embolism(PE)];it has also been associated with progression of liver fibrosis.The use of anticoagulants in cirrhosis patients is a challenging,and often a scary situation.This review summarizes the current literature on the prevalence of venous thrombosis(DVT and PE),risk factors and safety of prophylactic and therapeutic anticoagulation in patients with chronic liver disease.     

Thrombosis of the Portal Venous System in Cirrhotic vs. Non-Cirrhotic Patients

Introduction and aim. Thrombosis is a vascular disorder of the liver often associated with significant morbidity and mortality. Cirrhosis is a predisposing factor for portal venous system thrombosis. The aim of this study is to determine differences between cirrhotics and non-cirrhotics that develop thrombosis in portal venous system and to evaluate if cirrhosis severity is related to the development of portal venous system thrombosis.Material and methods. We studied patients diagnosed with portal venous system thrombosis using contrast-enhanced computed tomography scan and doppler ultrasound at Medica Sur Hospital from 2012 to 2017. They were categorized into two groups; cirrhotics and non-cirrhotics. We assessed the hepatic function by Child-Pugh score and model for end-stage liver disease.Results. 67 patients with portal venous system thrombosis (25 with non-cirrhotic liver and 42 with cirrhosis) were included. The mean age (± SD) was 65 ± 9.5 years in cirrhotic group and 57 ± 13.2 years (p = 0.009) in noncirrhotic group. Comparing non-cirrhotics and cirrhotics, 8 non-cirrhotic patients showed evidence of extra-hepatic inflammatory conditions, while in the cirrhotic group no inflammatory conditions were found (p < 0.001). 27 (64.29%) cirrhotic patients had thrombosis in the portal vein, while only 9 cases (36%) were found in non-cirrhotics (p = 0.02).Conclusions. In cirrhotic patients, hepatocellular carcinoma and cirrhosis were the strongest risk factors to develop portal venous system thrombosis. In contrast, extrahepatic inflammatory conditions were main risk factors associated in non-cirrhotics. Moreover, the portal vein was the most frequent site of thrombosis in both groups.     

Direct oral anticoagulant administration in cirrhotic patients with portal vein thrombosis: What is the evidence?

In recent years, the traditional concept that cirrhosis-related coagulopathy is an acquired bleeding disorder has evolved. Currently, it is known that in cirrhotic patients, the hemostatic system is rebalanced, which involves coagulation factors, fibrinolysis and platelets. These alterations disrupt homeostasis, skewing it toward a procoagulant state, which can lead to thromboembolic manifestations, especially when hemodynamic and endothelial factors co-occur, such as in the portal vein system in cirrhosis. Portal vein thrombosis is a common complication of advanced liver cirrhosis that negatively affects the course of liver disease, prognosis of cirrhotic patients and success of liver transplantation. It is still debated whether portal vein thrombosis is the cause or the consequence of worsening liver function. Anticoagulant therapy is the mainstay treatment for acute symptomatic portal vein thrombosis. In chronic portal vein thrombosis, the role of anticoagulant therapy is still unclear. Traditional anticoagulants, vitamin K antagonists and low-molecular-weight heparin are standard-of-care treatments for portal vein thrombosis. In the last ten years, direct oral anticoagulants have been approved for the prophylaxis and treatment of many thromboembolic-related diseases, but evidence on their use in cirrhotic patients is very limited. The aim of this review was to summarize the evidence about the safety and effectiveness of direct oral anticoagulants for treating portal vein thrombosis in cirrhotic patients.     

Activated platelets in paroxysmal nocturnal haemoglobinuria

Summary. One of the major causes of morbidity and mortality in paroxysmal nocturnal haemoglobinuria (PNH) is venous thrombosis. We have studied fibrinolysis, coagulation and platelets in 11 patients with PNH in an attempt to identify the possible mechanism(s) of thrombosis in PNH. In this study we did not identify any fibrinolytic defects, evidence of coagulation activation, nor reduction in coagulation inhibitors. In contrast, in this cohort of 11 PNH patients we have identified varying degrees of platelet activation as defined by the surface expression of activation dependent proteins and the binding of adhesive proteins to the platelet surface. The thrombotic events in PNH usually occur in the venous system. Our studies and previous experimental studies suggest that anti-platelet therapy may be efficacious in reducing the incidence and severity of venous thrombosis in PNH.     

Splanchnic and Extrasplanchnic Thrombosis in Cirrhosis: Prophylaxis vs Treatment

Venous thromboembolism (deep vein thrombosis and pulmonary embolism) and portal vein thrombosis (PVT) occur in up to 6.3 % and 15.9 % of patients with cirrhosis, respectively. There is recent evidence that a procoagulable prothrombotic state is related to cirrhosis despite the reduced levels of many coagulation factors, and decreased platelet counts. Indeed, (i) the combination of high levels of factor VIII, with low levels of protein C and antithrombin induces a procoagulant state in vitro; while (ii) increased levels of von Willebrand factor and decreased ADAMTS 13 activity can compensate for decreased platelet counts. PVT is partial in a majority of patients in whom it develops and may spontaneously resolve in some of them. Although PVT is associated with features of more severe liver disease, it is uncertain whether it plays a causal role in the decompensation of cirrhosis. In patients listed for liver transplantation, PVT may make the procedure difficult or impossible. Pre-transplant PVT is associated with increased post-transplant mortality rates. Studies evaluating clinical outcome of anticoagulation therapy for splanchnic or extrasplanchnic venous thrombosis are scarce. Anticoagulation therapy, given to patients with cirrhosis of intermediate severity before PVT occurrence, in prophylactic doses, appears to decrease decompensation and mortality rate. Interestingly, this improvement is out of proportion of the prophylaxis of extrahepatic portal vein thrombosis. The risk of bleeding does not seem to be increased in patients with cirrhosis receiving anticoagulation therapy, once prophylaxis for bleeding related to portal hypertension has been implemented. Overall, the room for anticoagulation therapy is probably larger than previously recognized, and may be of particular benefit in patients without portal vein thrombosis. However, clinical trials remain to be done before the benefit risk ratio of anticoagulation therapy is properly evaluated.     

Therapeutic and clinical aspects of portal vein thrombosis in patients with cirrhosis

Portal vein thrombosis(PVT) is a frequent complication in cirrhosis, particularly in advanced stages of the disease. As for general venous thromboembolism, risk factors for PVT are slow blood flow, vessel wall damage and hypercoagulability, all features of advanced cirrhosis. Actually, the old dogma of a hemorrhagic tendency in cirrhosis has been challenged by new laboratory tools and the clinical evidence that venous thrombosis also occurs in cirrhosis. The impaired hepatic synthesis of both pro- and anticoagulants leads to a rebalanced hemostasis, more liable to be tipped towards thrombosis or even bleeding. Conventional anticoagulant drugs(low molecular weight heparin or vitamin K antagonists) may be used in cirrhosis patients with PVT, particularly in those eligible for liver transplantation, to prevent thrombosis progression thus permitting/facilitating liver transplant. However, several doubts exist on the level of anticoagulation achieved as estimated by coagulation tests, on the efficacy of treatment monitoring and on the correct timing for discontinuation in non-transplant candidates, while in transplant candidates there is expert consensus on continuing anticoagulation until transplantation. The recent introduction of direct acting oral anticoagulant drugs(DOACs) in other clinical settings generates much interest on their possible application in patients with cirrhosis and PVT. However, DOACs were not evaluated yet in patients with liver disease and cannot be recommended for the present time.     

Deep venous thrombosis and pulmonary emboli: etiology, medical treatment, and prophylaxis

Risk factors for venous thrombosis include conditions leading to venous stasis, hypercoagulable states, and trauma to veins. The most important factor is venous stasis. Both extrinsic and intrinsic coagulation pathways are intimately involved in the thrombotic process. In recent years, the importance in thrombus formation of the endothelium, platelet products, the fibrinolytic system, and inhibitors of clotting mechanisms has been discovered. Deficiencies of proteins that normally protect against venous thrombosis have been found. Heparin therapy with subsequent warfarin therapy is still the primary treatment for deep venous thrombosis or pulmonary emboli. Fibrinolytic agents lyse pulmonary emboli but are not as effective in deep venous thrombosis. The incidence of serious bleeding complications has hampered the use of fibrinolytic agents except in emergency situations. Even the newer agents, which act more specifically on thrombi instead of on plasma factors, are associated with a similar incidence of hemorrhagic events. Dextrans are a suitable alternative for treatment of deep venous thrombosis when heparin cannot be used. In the prophylaxis of deep venous thrombosis, minidose heparin (5,000 U every 8 hours subcutaneously) is effective, safe, and convenient in most situations. Heparin-dihydroergotamine, dextran, or warfarin can also be used. Aspirin has been disappointing. In orthopaedic surgery, minidose heparin is not protective; large pulmonary emboli may be prevented by starting warfarin therapy at the time of surgery or by daily dextran infusions. Finally, recent studies have shown that lower doses of warfarin than previously recommended are protective against recurrent venous thrombosis and have a reduced risk of hemorrhagic complications.     

Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis

BACKGROUND/AIMS: Portal vein thrombosis in patients with liver cirrhosis is usually associated to hepatocellular carcinoma. Clinical presentation of non-neoplastic portal vein thrombosis (PVT) in cirrhotic patients has not been specifically studied and risk factors of PVT in this group of patients are still poorly understood. METHODS: We studied all patients with PVT and liver cirrhosis admitted to our Unit from January 1998 to December 2002. They were paired (by gender, age and Child-Pugh score) to a group of cirrhotic patients without PVT and screened for acquired and inherited thrombophilic risk factors. These factors together with the site of thrombosis and the severity of the liver disease were correlated to the clinical presentation of PVT. RESULTS: Out of a total of 701 cirrhotic patients admitted to our hospital and routinely screened with Doppler ultrasound, 79 (11.2%) were found to have PVT. Of these, 34 (43%) were asymptomatic and 45 (57%) were symptomatic (31 presented with portal hypertensive bleed and 14 with abdominal pain, 10 of whom had intestinal infarction). Mesenteric vein involvement was never asymptomatic and lead to intestinal ischemia or infarction. Most patients were in class Child-Pugh B and C. Among thrombophilic risk factors studied only the mutation 20210 of the prothrombin gene resulted independently associated to PVT. CONCLUSIONS: Portal vein thrombosis may be completely asymptomatic in patients with liver cirrhosis; however in more than half of cases presents with life-threatening complications such as gastrointestinal haemorrhage and intestinal infarction. Cirrhotic patients with PVT usually have an advanced liver disease and the presence of the mutation 20210 of the prothrombin gene increases more than fivefold the risk of PVT.     

Should we give thromboprophylaxis to patients with liver cirrhosis and coagulopathy?

Patients with liver cirrhosis are characterized by decreased synthesis of both pro- and anticoagulant factors, and recently there has been evidence of normal generation of thrombin resulting in a near normal haemostatic balance. Although it is generally recognized that bleeding is the most common clinical manifestation as a result of decreased platelet function and number, diminished clotting factors and excessive fibrinolysis, hypercoagulability may play an under recognized but important role in many aspects of chronic liver disease. In fact, they can encounter thrombotic complications such as portal vein thrombosis, occlusion of small intrahepatic vein branches and deep vein thrombosis (DVT). In particular, patients with cirrhosis appear to have a higher incidence of unprovoked DVT and pulmonary embolism (PE) compared with the general population. In dedicated studies, the incidence of DVT/PE ranges from 0.5% to 1.9%, similar to patients without comorbidities, but lower than patients with other chronic diseases (i.e, renal or heart disease). Surprisingly, standard coagulation laboratory parameters are not associated with a risk of developing DVT/PE; however, with multivariate analysis, serum albumin level was independently associated with the occurrence of thrombosis. Moreover, patients with chronic liver disease share the same risk factors as the general population for DVT/PE, and specifically, liver resection can unbalance the haemostatic equilibrium towards a hypercoagulable state. Current guidelines on antithrombotic prophylaxis do not specifically comment on the cirrhotic population as a result of the perceived risk of bleeding complications but the cirrhotic patient should not be considered as an auto-anticoagulated patient. Therefore, thromboprophylaxis should be recommended in patients with liver cirrhosis at least when exposed to high-risk conditions for thrombotic complications. Low molecular weight heparins (LWMHs) seem to be relatively safe in this group of patients; however, when important risk factors for bleeding are present, graduated compression stockings or intermittent pneumatic compression should be considered.     

Antiphospholipid antibodies are related to portal vein thrombosis in patients with liver cirrhosis

The pathogenesis of portal vein thrombosis (PVT) in cirrhotic liver patients is not known. PVT has been related to liver dysfunction, neoplasm, hemodynamic factors, and hypercoagulability states. PVT has been reported in patients with antiphospholipid syndrome without liver cirrhosis. Our aim was to find the role of antiphospholipid antibodies (APAs) and coagulation inhibitors in PVT in patients with liver cirrhosis. We present a case-controlled study, matched by age, liver function, and etiology, to discover the role of APAs and anticoagulant protein activity in PVT in cirrhotic patients. We studied 30 cirrhotic patients: 6 of 10 (60%) patients with PVT were APA-positive, whereas only 2 of 20 (10%) in the cirrhotic control group were APA-positive (p < 0.005). Low serum levels of protein C, protein S antithrombin III, and plasminogen were found in cirrhotic patients; and, no differences were found between patients with and without PVT. Significantly lower protein S and antithrombin III levels were found in patients with Child-Pugh class C. Therefore, APAs were related to PVT in cirrhotic patients; but, a lower concentration of coagulation inhibitors was associated with liver dysfunction alone.     

肝硬化患者血浆凝血因子的研究

目的：系列检测50例肝硬化患者血浆凝血因子，分代偿期与失代偿期两组，并分别探索其临床意义。方法：凝血因子抗原测定采取火箭电泳法，凝血因子活性测定采取一期凝血法或发色底物法。结果：除凝血因子Ⅶ活性升高外，其余各凝血因子的抗原性与活性均呈不同程度的降低，其中失代偿期因子Ⅴ与纤维蛋白原的降低显著，结论：因子Ⅴ降低见于肝硬化失代偿期，其降低表明病情恶化与预后不良。     

Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis

The prevalence and pathogenesis of portal vein thrombosis (PVT) in patients with cirrhosis without hepatocellular carcinoma are not clearly defined. The role of thrombophilic genetic factors is well established in other venous thrombotic diseases, as well as in noncirrhotic portal thrombosis. Recently, new, inherited thrombophilic disorders (factor V Leiden [FVL], mutation G20210A of prothrombin [PTHR A(20210)], and mutation TT677 of methylenetetrahydrofolate reductase [MTHFR C677-->T]) have been identified and associated with increased risk of venous thrombosis. The aim of our study was to investigate the role of these thrombophilic disorders in the pathogenesis of PVT in cirrhotic patients. Twenty-three cirrhotic patients with PVT and 40 cirrhotics without PVT were included. A group of 184 patients with deep vein thrombosis (DVT) and 431 healthy persons served as controls. The FVL, PTHR A(20210), and MTHFR C(677)-->T genotypes were identified by a polymerase chain reaction and restriction analysis. The frequencies of FVL, PTHR A(20210) mutation, and homozygous MTHFR C(677)-->T were 13%, 34.8%, and 43.5% in cirrhotic patients with PVT and 7.5%, 2.5%, and 5% in cirrhotic patients without PVT, respectively. Five patients in the former group had associated defects. A thrombophilic genotype was detected in 69.5% of the patients with PVT. Identification of this high-risk group may have implications in patients who are candidates for major surgery or liver transplantation, and may influence the duration of oral anticoagulation.     

The coagulopathy of chronic liver disease: Is there a causal relationship with bleeding? Yes

Variceal hemorrhage is a major cause of death in patients with cirrhosis. Much still could be performed in clinical practice to reduce the risk for bleeding in cirrhotic patients and accurate predictive rules should be provided for early recognition of high-risk patients. Liver cirrhosis patients present a complex hemostatic dysfunction with prolongation of bleeding time, chronic coagulation activation, and secondary hyperfibrinolysis. Therefore, liver failure determines an acquired coagulopathy that has been considered to be one potential underlying mechanism of bleeding. Endotoxemia may play a pivotal role in activating clotting system in portal and systemic circulation and it could represent a common mechanism accounting for portal vein thrombosis, systemic hyperfibrinolysis and eventually gastrointestinal bleeding. Nevertheless, clinical trials should also be planned to investigate the causal relationship between acquired coagulopathy and bleeding in patients with chronic liver disease.     

Anticoagulation for the treatment of thrombotic complications in patients with cirrhosis

Cirrhotic patients can develop thrombotic complications, which in this group of patients occur with a greater frequency than in the general population. Portal vein thrombosis (PVT) is the most common thrombotic phenomenon, although deep venous thrombosis and pulmonary embolism can also occur. Risk factors for thrombosis include inherited and acquired deficiency of factors involved in anticoagulation mechanisms, venous stasis of the portal vein owing to architectural derangement of the liver and possibly local factors related to the endothelium. Clinical manifestations of PVT range from asymptomatic disease to a life‐threatening complication, and although it is no longer considered an absolute contraindication for liver transplant, its presence may require challenging surgical techniques, which entail greater morbidity. Anticoagulation therapy is henceforth an important strategy to treat cirrhotic patients with PVT, although experience in this group of patients is limited. Vitamin K antagonists and low‐molecular‐weight heparin have been used successfully, achieving recanalization of the thrombosed vessel in patients with cirrhosis; however, the precise drug regimen management and monitoring has not be fully explored in this group of patients.     

Thromboprophylaxis in the cancer patient

Thrombosis is a common complication in patients with malignant disease resulting from tumour elaboration of procoagulants and subsequent activation of intravascular coagulation. Cancer therapies (operation, chemotherapy and the use of central venous lines) further heighten the risk of thrombosis. The risk of thrombosis in cancer operations is of sufficient magnitude to necessitate routine thromboprophylaxis, for which low-dose unfractionated heparin or the low-molecular-weight heparins (LMWHs) have been proven effective and safe. Thrombotic complications with chemotherapy have been extensively described in women receiving either adjuvant or palliative cytotoxic or hormonal therapy for breast carcinoma. The problems are common, but of all the suitable prophylactic modalities available, only oral anticoagulants have been evaluated for this indication. Thrombosis complicates the use of central venous catheters in the cancer patient and both low-dose warfarin and LMWHs are effective in protecting against line-associated thrombi. Recent evidence from the retrospective analyses of randomized studies comparing unfractionated heparin and LMWH in the treatment of deep vein thrombosis have shown a striking mortality reduction among cancer patients who received LMWH. The use of LMWHs to prolong survival in patients with advanced malignant disease is currently the subject of a prospective, randomized, placebo-controlled study.     

Inherited thrombotic disorders: An update

Significant advances in identification of etiologies of inherited thrombosis have been recently reported. A point mutation in coagulation factor V (factor V Leiden) results in resistance to activated protein C and probably represents the most common genetic risk factor for venous thrombosis. A metabolic disorder, homocysteinemia, is now known to be an important risk factor for both arterial and venous thrombosis. Many patients with recurrent thrombosis will have more than one genetic risk factor identified. Recognition of these new disorders should permit a diagnosis to be achieved in at least half of patients evaluated for inherited thrombosis. Am. J. Hematol. 54:53–60, 1997 © 1997 Wiley-Liss, Inc.     

Impact of portal vein thrombosis on the efficacy of endoscopic variceal band ligation

BackgroundInfluence of portal vein thrombosis on efficacy of endoscopic variceal banding in patients with cirrhosis or extrahepatic portal vein obstruction has never been evaluated. Aim of the study was to assess influence of thrombosis on rate and time to eradication in cirrhosis and extrahepatic portal vein obstruction undergoing banding, compared to cirrhotic patients without thrombosis.MethodsRetrospective analysis of 235 consecutive patients (192 with cirrhosis without thrombosis, 22 cirrhosis and thrombosis and 21 extrahepatic portal vein obstruction) who underwent banding. Banding was performed every 2–3 weeks until eradication; endoscopic follow-up was performed at 1, 3, 6 months, then annually.ResultsEradication was achieved in 233 patients. Median time to eradication in cirrhotic patients with portal vein thrombosis vs. cirrhotic patients without thrombosis was 50.9 days (12–440) vs. 43.4 days (13–489.4); log-rank: 0.04; patients with extrahepatic portal vein obstruction vs. cirrhotic patients without thrombosis 63.9 days (31–321.6) vs. 43.4 days (13.0–489.4); log-rank: 0.008. Thrombosis was shown to be the only risk factor for longer time to eradication.ConclusionsPortal vein thrombosis per se appears to be the cause of a longer time to achieve eradication of varices but, once eradication is achieved, it does not influence their recurrence.     

Coagulopathy and transfusion therapy in pediatric liver transplantation

Bleeding and coagulopathy are critical issues complicating pediatric liver transplantation and contributing to morbidity and mortality in the cirrhotic child. The complexity of coagulopathy in the pediatric patient is illustrated by the interaction between three basic models. The first model, "developmental hemostasis", demonstrates how a different balance between pro- and anticoagulation factors leads to a normal hemostatic capacity in the pediatric patient at various ages. The second, the "cell based model of coagulation", takes into account the interaction between plasma proteins and cells. In the last, the concept of "rebalanced coagulation" highlights how the reduction of both pro- and anticoagulation factors leads to a normal, although unstable, coagulation profile. This new concept has led to the development of novel techniques used to analyze the coagulation capacity of whole blood for all patients. For example, viscoelastic methodologies are increasingly used on adult patients to test hemostatic capacity and to guide transfusion protocols. However, results are often confounding or have limited impact on morbidity and mortality. Moreover, data from pediatric patients remain inadequate. In addition, several interventions have been proposed to limit blood loss during transplantation, including the use of antifibrinolytic drugs and surgical techniques, such as the piggyback and lowering the central venous pressure during the hepatic dissection phase. The rationale for the use of these interventions is quite solid and has led to their incorporation into clinical practice; yet few of them have been rigorously tested in adults, let alone in children. Finally, the postoperative period in pediatric cohorts of patients has been characterized by an enhanced risk of hepatic vessel thrombosis. Thrombosis in fact remains the primary cause of early graft failure and re-transplantation within the first 30 d following surgery, and it occurs despite prolongation of standard coagulation assays. Data, however, are currently lacking regarding the use of anti-aggregation/anticoagulation therapies and how to best monitor for thrombosis in the early postoperative period in pediatric patients. Therefore, further studies are necessary to elucidate the interaction between the development of the coagulation system and cirrhosis in children. Moreover, strategies to optimize blood transfusion and anticoagulation must be tested specifically in pediatric patients. In conclusion, data from the adult world can be translated with difficulty into the pediatric field as indication for transplantation, baseline pathologies and levels of pro- and anticoagulation factors are not comparable between the two populations.     

Anti-platelet and anti-thrombotic approaches in patients undergoing percutaneous coronary intervention.

Over the past three decades, there has been a tremendous increase in the use of percutaneous coronary interventions (PCI) for the treatment of patients with atherosclerotic coronary artery disease. However, PCI causes disruption of atherosclerotic plaque and denudation of the endothelium, leading to stimulation of platelet aggregation and activation of the coagulation cascade. Therefore, anti-platelet and anti-thrombotic agents have a pivotal role as adjuncts before, during and after PCI, in order to minimize the risk of procedural ischemic complications, such as myocardial infarction, stent thrombosis, and various degrees of myonecrosis. The current article presents a comprehensive review of the evolution of current anti-platelet and anticoagulation regimens used in the setting of PCI. It starts with a summary of the current perspective of the coagulation process along with platelet activation and aggregation. The review then focuses specifically on individual anti-platelet and anti-thrombotic drugs including their mechanism of action and the scientific evidence which led to their use in PCI. Finally, we present summary recommendations from the AHA/ACC guidelines for individual anticoagulant and anti-platelet regimens given peri-PCI.     

Therapy insight: Vascular complications in patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) is associated with an increased risk of vascular complications. The most important of these complications are arterial and venous thromboembolism, which represent a significant cause of morbidity and mortality in IBD patients. Recent data suggest that thromboembolism is a disease-specific extraintestinal manifestation of IBD. The most common thrombotic manifestations in IBD are deep vein thrombosis of the leg and pulmonary emboli. It has been suggested that disease activity and the extent of colonic localization are correlated with the risk of developing thromboembolism. The occurrence of thrombosis in patients with IBD is partially attributed to the existing hypercoagulable state in IBD. Both coagulation and fibrinolysis are activated in patients with IBD; this is especially true for those with active disease. The most common risk factors for thrombophilia in IBD patients with venous thromboembolism are Leiden mutation in the gene encoding factor V, hyperhomocysteinemia, and antiphospholipid antibodies. The main genetic defects that have been established as risk factors for venous thrombosis are rather uncommon in IBD, but when present increase the risk of thromboembolism. Screening for coagulation defects seems justified only in IBD patients with a history of thrombosis or a family history of venous thromboembolic events. Antithrombotic treatment of IBD patients with venous thromboembolism is similar to that of thrombotic non-IBD patients.