Risk factors of thrombosis in abdominal veins

AIM： To estimate the prevalence of inherited and acquired thrombophilic risk factors in patients with abdominal venous thrombosis and to compare the risk factor profiles between Budd-Chiari syndromes （BCS） and splanchnic vein thrombosis （SVT）.
METHODS： In this retrospective study, 36 patients with abdominal venous thrombosis were studied. The patients were divided into Budd-Chiari group （hepatic vein, IVC thrombosis） and splanchnic venous thrombosis group （portal, splenic, superior mesenteric veins） based on the veins involved. Hereditary and acquired thrombophilic risk factors were evaluated in all patients.
RESULTS： Twenty patients had SVT, 14 had BCS, and 2 had mixed venous thrombosis. Ten patients （28%） had hereditary and 10 patients （28%） acquired thrombophilic risk factors. The acquired risk factors were significantly more common in the SVT group （SVT vs BCS： 45% vs 7%, χ^2= 5.7, P = 0.02） while hereditary risk factors did not show significant differences between the two groups （SVT vs BCS： 25% vs 36%, χ^2 = 0.46, P = 0.7）. Multiple risk factors were present in one （7%） patient with BCS and in 3 patients （15%） with SVT. No risk factors were identified in 57% of patients with BCS and in 45% of patients with SVT.
CONCLUSION： Hereditary and acquired risk factors play an important role in the etiopathogenesis of abdominal venous thrombosis. Acquired risk factors are significantly more common in SVT patients while hereditary factors are similar in both groups.     

Venous thrombosis at unusual sites and the role of thrombophilia

Thrombophilia includes multiple inherited and acquired risk factors that determine a shift in the balance of procoagulant and anticoagulant factors promoting hypercoagulability, which is associated with an increased risk of venous thromboembolism (VTE). VTE is characterized by more common clinical manifestations, such as deep vein thrombosis of the lower limbs or pulmonary embolism, and less common clinical manifestations affecting cerebral, splanchnic, upper limbs, and retinal veins. The role of inherited thrombophilia in the pathogenesis of VTE at unusual sites is better established in cerebral vein thrombosis, but its role is less clear in splanchnic, upper limbs, and retinal vein thrombosis, in which acquired risk factors such as malignancy, central venous catheters, or systemic diseases also are frequently involved. The complex interactions between different inherited and acquired thrombophilic risk factors and their relationship with endothelium may be considered the pathophysiologic key of underlying phenotypic manifestations of thrombosis. The understanding of these mechanisms might facilitate diagnosis with appropriate investigations and improve therapeutic decision making.     

The role of thrombophilia in splanchnic vein thrombosis

In the last few years, the mechanistic role of thrombophilia due to hypercoagulability and of clonal disorders of hemopoiesis such as chromosome Philadelphia-negative chronic myeloproliferative disorders has been increasingly recognized in primary splanchnic vein thrombosis. As in deep venous thrombosis of the lower limbs, the frequent finding of several prothrombotic disorders in the same individual has led to the concept of primary splanchnic vein thrombosis as a multifactorial disease. Significant progress has been made in determining the molecular bases of inherited thrombophilia, and particularly in the identification of molecular markers of clonal disease in the so-called occult or latent myeloproliferative disorders. In this review article, the authors discuss the current knowledge on the role of thrombophilia in extrahepatic portal vein obstruction and in the Budd-Chiari syndrome, two of the most clinically relevant splanchnic vein thromboses.     

Acute splanchnic vein thrombosis in patients with COVID-19: A systematic review

There is increasing evidence that coronavirus disease 2019 (COVID-19) is associated with a significant risk of venous thromboembolism. While information are mainly available for deep vein thrombosis of the lower limb and pulmonary embolism, scarce data exist regarding acute splanchnic vein thrombosis (SVT) in this setting. PubMed, EMBASE and Google Scholar English-language articles published up to 30 January 2021 on SVT in COVID-19 were searched. Overall, 21 articles reporting equal number of patients were identified. 15 subjects presented with portal vein thrombosis, 11 with mesenteric vein thrombosis, four with splenic vein thrombosis, and two with Budd-Chiari syndrome. Male sex was prevalent (15 patients), and median age was 43 years (range 26–79 years). Three patients had a history of liver disease, while no subject had known myeloproliferative syndrome. Clinical presentation included mainly gastrointestinal symptoms. Anticoagulation was started in 16 patients. Three patients underwent bowel resection. Ten subjects developed gastric or bowel ischemia, seven of whom underwent bowel resection, and four died after SVT diagnosis.Although rare, SVT should be seen as a complication of COVID-19. Patients with severe gastrointestinal symptoms should be screened for SVT, as rapid recognition and correct management are essential to improve the outcome of these patients.     

Splanchnic vein thrombosis: clinical presentation,risk factors and treatment

The term splanchnic vein thrombosis encompasses Budd-Chiari syndrome (BCS), extrahepatic portal vein obstruction (EHPVO), and mesenteric vein thrombosis; the simultaneous involvement of additional regions is frequent, and clinical presentations and risk factors may be shared. The annual incidence of BCS and isolated mesenteric vein thrombosis is less than one per million individuals, while the incidence of EHPVO is about four per million; autopsy studies, however, suggest higher numbers. Current advances in non-invasive vascular imaging allow for the identification of chronic or asymptomatic forms. Risk factors can be local or systemic. A local precipitating factor is rare in BCS, while it is common in patients with portal vein thrombosis. Chronic myeloproliferative neoplasms (MPN) are the leading systemic cause of splanchnic vein thrombosis, and are diagnosed in half the BCS patients and one-third of the EHPVO patients. The molecular marker JAK2 V617F is detectable in a large majority of patients with overt MPN, and up to 40% of patients without overt MPN. Inherited thrombophilia is present in at least one-third of the patients, and the factor V Leiden or the prothrombin G20210A mutations are the most common mutations found in BCS or EHPVO patients, respectively. Multiple factors are present in approximately one-third of the patients with BCS and two-thirds of the patients with portal vein thrombosis. Immediate anticoagulation with heparin is used to treat patients acutely. Upon clinical deterioration, catheter-directed thrombolysis or transjugular intrahepatic portosystemic shunt is used in conjunction with anticoagulation. Long-term oral anticoagulation with vitamin K-antagonists (VKA) is recommended in all BCS patients, and in the patients with a permanent prothrombotic state associated with an unprovoked EHPVO. In patients with an unprovoked EHPVO and no prothrombotic conditions, or in those with a provoked EHPVO, anticoagulant treatment is recommended for a minimum of 3–6 months.     

Pulmonary embolism and deep vein thrombosis

Pulmonary embolism is the third most common cause of death from cardiovascular disease after heart attack and stroke. Sequelae occurring after venous thromboembolism include chronic thromboembolic pulmonary hypertension and post-thrombotic syndrome. Venous thromboembolism and atherothrombosis share common risk factors and the common pathophysiological characteristics of inflammation, hypercoagulability, and endothelial injury. Clinical probability assessment helps to identify patients with low clinical probability for whom the diagnosis of venous thromboembolism can be excluded solely with a negative result from a plasma D-dimer test. The diagnosis is usually confirmed with compression ultrasound showing deep vein thrombosis or with chest CT showing pulmonary embolism. Most patients with venous thromboembolism will respond to anticoagulation, which is the foundation of treatment. Patients with pulmonary embolism should undergo risk stratification to establish whether they will benefit from the addition of advanced treatment, such as thrombolysis or embolectomy. Several novel oral anticoagulant drugs are in development. These drugs, which could replace vitamin K antagonists and heparins in many patients, are prescribed in fixed doses and do not need any coagulation monitoring in the laboratory. Although rigorous clinical trials have reported the effectiveness and safety of pharmacological prevention with low, fixed doses of anticoagulant drugs, prophylaxis remains underused in patients admitted to hospital at moderate risk and high risk for venous thromboembolism. In this Seminar, we discuss pulmonary embolism and deep vein thrombosis of the legs.     

The postoperative splenic/portal vein thrombosis after splenectomy and its prevention--an unresolved issue

Patients undergoing splenectomy have an increased risk of splenic/portal vein thrombosis. We used several databases to identify publications dealing with this risk and analyzed incidence, risk factors and outcome. The risk of splenic portal vein thrombosis has been addressed in prospective and retrospective randomized or non-randomized studies. All studies combined, the overall risk is 3.3%. Risk factors are big spleens (i.e. myeloproliferative disorders) and hereditary hemolytic anemias, whereas the risk is low in autoimmune thrombocytopenia and trauma. The incidence is approximately the same in laparoscopic and open splenectomy. The median time from splenectomy to symptomatic splenic vein thrombosis is 8-12 days. Postoperative antithrombotic prophylaxis ranged from no prophylaxis to heparin for seven days or longer. Treatment of symptomatic splenic vein thrombosis with heparin and warfarin leads to complete resolution of thrombosis in 67%, to partial resolution in 13%, but persistent occlusion, portal hypertension or cavernoma occurred in 20%.The long-term outcome of treatment failures is unknown. Well-designed randomized studies on the prophylaxis of venous thromboembolism after splenectomy are urgently needed.     

Portal venous thrombosis after umbilical vein catheterization.

PURPOSE: Portal vein thrombosis has been associated with umbilical venous catheterization. This prospective study was done to determine the incidence of neonatal portal venous thrombosis associated with catheterization of the umbilical vein . METHODS: Neonates who had undergone umbilical vein catheterization for exchange transfusion between March 2003 and March 2004 in Children's Hospital of Tabriz, Iran, were included. Doppler ultrasonography was performed within 1-2 weeks after the removal of the catheter. In the cases with portal venous thrombosis, subsequent serial ultrasonography was performed at intervals of every 1-2 months until clot resolution. Risk factors, if any were identified and correlated with catheter-related thrombi. RESULTS: Ultrasonography detected clinically silent portal venous thrombosis in 17 (34%) of 50 neonates. Follow-up ultrasonography was available in 13 of 17 babies, and revealed complete or partial resolution in all the cases. Sepsis was identified as a significant risk factor (p < 0.001). CONCLUSION: Umbilical venous catheter-associated thrombosis is common, and spontaneous resolution occurs in most cases.     

Primary antiphospholipid syndrome presented with portal vein thrombosis]

Antiphospholipid Antibody Syndrome (APS) is defined by arterial and venous thrombosis, recurrent spontaneous abortions and thrombocytopenia associated with persistence of antiphospholipid antibodies. Thrombosis may involve virtually all arterial or venous sites, but deep vein thrombosis of the lower limbs are the most common; however, unusual thrombi that involve the portal vein have been described. We report females with documented portal vein thrombosis and primary APS. The treatment of these patients is difficult because of the risk of bleeding and the recurrent thrombosis if they don't receive appropriate long-term anticoagulant therapy.     

Traveler's thrombosis

It is pathophysiologically conceivable that prolonged sitting in a tight space (e.g., in airplane or other transport vehicle) may lead to leg vein thrombosis. The association between the incidence of venous thromboembolism and long travel has not been sufficiently documented but seems probable. However, this association is only weak and the incidence of symptomatic thromboembolism much lower than the impression given by the recent publicity. In a healthy person, the risk of suffering a clinically relevant leg vein thrombosis solely because of a flight is extreme low. In persons with risk factors for venous thromboembolism, the flight represents an additional, as yet not quantifiable risk. This risk increases with the duration of the travel. The most important cause of thrombosis during long journeys seems to be venostasis due to relative immobilization. It is not clear whether flight travel represents a higher risk of thrombosis compared to other transport vehicles with comparable duration and immobilization. Until more exact information becomes available, it seems reasonable to recommend simple isometric and isotonic leg exercises during long travel. More aggressive measures must be considered for persons with risk factors for thromboembolism, but these measures should be individualized.     

Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study

OBJECTIVE: To assess the potential impact of controlling risk factors on the incidence of venous thromboembolism by estimating the population attributable risk (defined as the percentage of all cases of a disease in a population that can be "attributed" to a risk factor) for deep vein thrombosis and pulmonary embolism associated with venous thromboembolism risk factors. METHODS: Using data from a population-based, nested, case-control study of the 625 Olmsted County, Minnesota, residents with a definite first lifetime deep vein thrombosis or pulmonary embolism diagnosed during the 15-year period 1976 to 1990 and 625 unaffected Olmsted County residents matched for age and sex, we developed a conditional logistic regression model appropriate to the matched case-control study design and then estimated attributable risk for the risk factors individually and collectively. RESULTS: Fifty-nine percent of the cases of venous thromboembolism in the community could be attributed to institutionalization (current or recent hospitalization or nursing home residence). Hospitalization for surgery (24%) and for medical illness (22%) accounted for a similar proportion of the cases, while nursing home residence accounted for 13%. The individual attributable risk estimates for malignant neoplasm, trauma, congestive heart failure, central venous catheter or pacemaker placement, neurological disease with extremity paresis, and superficial vein thrombosis were 18%, 12%, 10%, 9%, 7%, and 5%, respectively. Together, the 8 risk factors accounted for 74% of disease occurrence. CONCLUSIONS: Factors associated with institutionalization independently account for more than 50% of all cases of venous thromboembolism in the community. Greater emphasis should be placed on prophylaxis for hospitalized medical patients. Other recognized risk factors account for about 25% of all cases of venous thromboembolism, while the remaining 25% of cases are idiopathic.     

Clinical presentations,risk factors,treatment and outcomes in patients with splanchnic vein thrombosis: a single-center experience

Splanchnic vein thrombosis (SVT) is an uncommon form of venous thrombosis. Management can be challenging due to underlying conditions, increased bleeding risk, and lack of evidence from clinical trials. We sought to characterize the presentation and management of patients with SVT at a large tertiary hospital. A total of 43 patients’ electronic medical records were reviewed. Median age at diagnosis was 43 (18–71). Sixteen patients had isolated portal vein thrombosis (37.2 %), and 16 (37.2 %) had thrombosis involving multiple splanchnic veins. Abdominal pain was the most common clinical presentation (67.4 %). Thrombophilia was present in 18 patients (41.9 %), nine had underlying liver disease (20.9 %) and seven had inflammatory bowel disease (16.3 %). Thirty-nine (90.7 %) patients were treated with anticoagulation, and 11(25.6 %) of these patients underwent interventional procedures. Thirty (69.8 %) patients remained on indefinite anticoagulation. Results of follow-up imaging at least 1 month after diagnosis were available for 29 patients; imaging showed chronic, stable thrombosis in 14 patients (48.3 %), resolution of thrombosis in 13 patients (44.8 %) and asymptomatic progression in two patients (6.9 %). Recurrent thrombosis occurred in four patients (9.3 %). Major bleeding occurred in eight patients who received anticoagulation (18.6 %), including fatal subdural hematoma in one patient. In this cohort of patients managed by hematologists and gastroenterologists, the majority of patients were treated with anticoagulation. Interventional procedures were higher than in previously reported series. Our study strongly supports the interdisciplinary management of splanchnic venous thrombosis.     

Etiology and portal vein thrombosis in Budd-Chiari syndrome

AIM： To research the etiology, portal vein thrombosis and other features of Budd-Chiari syndrome （BCS） patients prospectively.
METHODS： A total of 75 patients （40 female, 35 male） who were diagnosed between January 2002 and July 2004 as having BCS were studied prospectively. Findings from on physical examination, ultrasonography, duplex ultrasonography and venography were analyzed. Hemogram and blood chemistry were studied at the time of diagnosis and on each hospital visit. Bone marrow examination and immune phenotyping were performed by a hematologist when necessary. Protein C, S, antithrombin Ⅲ, activated protein C resistance, and anticardiolipin antibodies, antinuclear antibodies, and anti ds-DNA were studied twice. The presence of ascite, esophageal varices, and portal thrombosis were evaluated at admission and on every visit.
RESULTS： At least one etiological factor was determined in 54 （72%） of the patients. The etiology could not be defined in 21 （28%） patients. One etiological factor was found in 39, 2 factors in 14 and 3 factors in 1 patient. The most common cause was the web （16%）, the second was Hydatid disease （11%）, the third was Behcet’s disease （9%）. Portal vein thrombosis was present in 11 patients and at least one etiology was identified in 9 of them （82%）.
CONCLUSION： Behcet’s disease and hydatid disease are more prominent etiological factors in Turkey than in other countries. Patients with web have an excellent response to treatment without signs of portal veinthrombosis while patients having thrombofilic factors more than one are prone to develop portal vein thrombosis with worse clinical outcome.     

Splanchnic vein thrombosis in severe acute pancreatitis: a 2-year, single-institution experience

ObjectivesThis study aimed to determine current practice in the management and outcome of splanchnic vein thrombosis complicating acute pancreatitis (AP).MethodsAn audit of prospectively collected data for all patients presenting with AP was conducted. Patients with splanchnic vein thrombosis were grouped according to vessel involvement and whether or not systemic anticoagulation was administered.ResultsOf 127 consecutive patients admitted with AP, 20 had splanchnic venous thrombosis; in all cases the thrombosis was associated with a severe attack of AP. Involvement of the splenic vein (SV), portal vein (PV) and superior mesenteric vein (SMV) was observed in 14, 10 and three patients, respectively. Involvement of more than one vessel was observed in six patients (SV and PV in four patients; SMV and SV in one patient; all three veins in one patient). Thromboses were colocalized with collections in 19 patients. Only four patients received systemic anticoagulation. Resolution of thrombosis was observed in six patients over a median of 77 days. No significant differences were observed in recanalization rates following anticoagulation (P= 0.076). No complications associated with systemic anticoagulation occurred. One patient developed liver failure associated with progressive PV thrombosis and one patient died.ConclusionsSplanchnic vein thrombosis is a relatively common observation in severe AP and is associated with pancreatic necrosis and peripancreatic collections. Recanalization is observed in almost a third of patients, irrespective of whether or not they receive systemic anticoagulation.     

Splanchnic vein thrombosis in myeloproliferative neoplasms

Splanchnic vein thrombosis (SVT) is one of the most important complications of myeloproliferative neoplasms (MPN). Although MPN are common causes of SVT, the pathophysiological mechanisms underlying this predisposition, their epidemiology and natural history are not fully understood. Studies have concentrated on the generalized prothrombotic environment generated by MPN and their relationship with abnormal blood counts, thereby furthering our knowledge of arterial and venous thrombosis in this population. In contrast, there are few studies that have specifically addressed SVT in the context of MPN. Recent research has demonstrated in patients with MPN the existence of factors increasing the risk of SVT such as the presence of the JAK2 V617F mutation and its 46/1 haplotype. Features unique to the circulating blood cells, splanchnic vasculature and surrounding micro‐environment in patients with MPN have been described. There are also abnormalities in local haemodynamics, haemostatic molecules, the spleen, and splanchnic endothelial and endothelial progenitor cells. This review considers these important advances and discusses the contribution of individual anomalies that lead to the development of SVT in both the pre‐neoplastic and overt stage of MPN. Clinical issues relating to epidemiology, recurrence and survival in these patients have also been reviewed and their results discussed.     

Deep vein and isolated calf muscle vein thrombosis following long-haul flights: pilot study.

The risk of venous thromboembolism associated with long-haul flights is the subject of controversy. In a prospective, controlled study, we examined 160 passengers before and after return from a long-haul flight and 160 age-matched and sex-matched, non-travelling volunteers using venous compression ultrasound. Deep vein thrombosis was not observed in either group. Isolated calf muscle vein thrombosis (ICMVT) was present in 4/160 (2.5%) flight passengers and in 1/160 (0.6%) controls. All subjects with ICMVT were clinically asymptomatic, and ICMVT was located in the soleal muscle veins in all four subjects. Three of the four passengers with ICMVT had other risk factors for thrombosis.     

Portal vein thrombosis, cirrhosis, and liver transplantation

Portal vein thrombosis is not uncommon in candidates for transplantation. Partial thrombosis is more common than complete thrombosis. Despite careful screening at evaluation, a number of patients are still found with previously unrecognized thrombosis per-operatively. The objective is to recanalize the portal vein or, if recanalization is not achievable, to prevent the extension of the thrombus so that a splanchnic vein can be used as the inflow vessel to restore physiological blood flow to the allograft. Anticoagulation during waiting time and transjugular intrahepatic portosystemic shunt (TIPS) are two options to achieve these goals. TIPS may achieve recanalization in patients with complete portal vein thrombosis. However, a marked impairment in liver function, which is a characteristic feature of most candidates for transplantation, may be a contraindication for TIPS. Importantly, the MELD score is artificially increased by the administration of vitamin K antagonists due to prolonged INR. When patency of the portal vein and/or superior mesenteric vein is not achieved, only non-anatomical techniques (renoportal anastomosis or cavoportal hemitransposition) can be performed. These techniques, which do not fully reverse portal hypertension, are associated with higher morbidity and mortality risks. Multivisceral transplantation including the liver and small bowel needs to be evaluated. In the absence of prothrombotic states that may persist after transplantation, there is no evidence that pre-transplant portal vein thrombosis justifies long term anticoagulation post-transplantation, provided portal flow has been restored through conventional end-to-end portal anastomosis.     

Superficial vein thrombosis: risk factors, diagnosis, and treatment

Superficial vein thrombosis (SVT) is a very common disease even though its incidence has never been assessed properly. Until recently, the literature on this topic has been relatively poor, old, and with numerous methodologic drawbacks, probably because this disease was considered benign and trivial. However, the recent recognition of a frequent association with concomitant venous thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary embolism [PE]) and the risk of subsequent VTE complications in patients with isolated SVT has revived interest and has encouraged new clinical research. SVT and VTE share many common predisposing risk factors. Even if varicose veins represent the main cause of SVT, several underlying conditions (e.g., malignancy, thrombophilia, autoimmune diseases) should be sought, especially in idiopathic, migrant, or recurrent SVT of nonvaricose vein patients. The diagnosis is made in a clinical setting but ultrasonography is useful to identify concomitant asymptomatic DVT. Many medical and surgical treatments have been suggested to relieve local symptoms and signs, prevent recurrences, and limit the VTE risk of SVT, but the evidence coming from the limited number of prospective randomized studies does not allow strong recommendations on the optimal treatment of SVT.     

Superficial vein thrombosis: risk factors,diagnosis, and treatment

Superficial vein thrombosis (SVT) risk factors are close to those of venous thromboembolism (VTE). Diagnosis is made in a clinical setting but ultrasonography is useful to eliminate concomitant deep vein thrombosis (DVT). For SVT of the lower limbs, which is the main location, varicose veins represent the principal cause but underlying conditions (e.g.: autoimmune diseases, malignancy or thrombophilia) must be sought in idiopathic, migrant or recurrent SVT and in the absence of varicose veins. Concomitant DVT and pulmonary embolism can occur in approximately 15% and 5% respectively. Historical treatments consist of anti-inflammatory agents plus elastic stockings and, in case of varicose veins, thrombectomy and stripping. Other treatments (anticoagulants, vein ligation) were assessed to limit the VTE risk. A one-month prophylactic dose of low molecular weight heparin plus elastic stockings could be the appropriate strategy in most cases. Other studies are needed before definitive conclusions can be drawn.