Arterial thrombosis and the role of thrombophilia

Thrombophilia is a prominent risk factor for venous thromboembolism. The role of thrombophilia in determining the risk of arterial thrombotic events is less well defined. In this review, we summarize the existing literature on the relationship between thrombophilic defects and the risk of arterial thrombosis, in particular myocardial infarction and stroke. The six defects reviewed are the factor V Leiden mutation, the prothrombin G20210A mutation, protein C deficiency, protein S deficiency, antithrombin deficiency, and the antiphospholipid syndrome. We observed that substantial evidence supports an association between the presence of the antiphospholipid syndrome and the risk of myocardial infarction, particularly among people in whom the atherosclerotic burden is low. The literature contains no solid evidence to support an important relationship between the other thrombophilic defects reviewed and the risk of arterial thrombosis. We conclude that thrombophilia screening in unselected patient populations with myocardial infarction or ischemic stroke is not justified.     

Next-generation sequencing in the diagnosis of non-cirrhotic splanchnic vein thrombosis

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Hypercoagulability and hypofibrinolysis and risk of deep vein thrombosis and splanchnic vein thrombosis: similarities and differences

In this review, we provide an overview of the risk factors for venous thromboembolism, focusing on hypercoagulability and hypofibrinolysis. In the first part of this review, we discuss the risk factors for commonly occurring venous thrombosis, in particular deep vein thrombosis and pulmonary embolism. In the second part, we provide an overview of the risk factors for the Budd-Chiari syndrome and portal vein thrombosis. These are rare, life-threatening forms of venous thromboembolism located in the splanchnic veins. There are many similarities in the risk profiles of patients with common venous thrombosis and splanchnic vein thrombosis. Inherited thrombophilia and hypofibrinolysis increase the risk of both common venous thrombosis and splanchnic vein thrombosis. However, there are also apparent differences. Myeloproliferative neoplasms and paroxysmal nocturnal hemoglobinuria have a remarkably high frequency in patients with thrombosis at these unusual sites but are rarely seen in patients with common venous thrombosis. There are also clear differences in the underlying risk factors for Budd-Chiari syndrome and for portal vein thrombosis, suggesting site specificity of thrombosis even within the splanchnic venous system. These clear differences in underlying risk factors provide leads for further research on the site specificity of venous thrombosis and the development of thrombosis at these distinct sites.     

Thrombophilia differences in splanchnic vein thrombosis and lower extremity deep venous thrombosis in North America

Background

The utility of thrombophilia testing in patients with splanchnic vein thrombosis (SpVT) has not previously been rigorously evaluated. The purpose of this study was to characterize differences in the prevalence of thrombophilia in patients with SpVT involving portal (PVT), mesenteric (MVT), splenic (SVT), or hepatic (HVT) veins in isolation or with multisegmental (M-SpVT) involvement compared to patients with lower extremity deep vein thrombosis (DVT).

Methods

An inception cohort of patients with incident SpVT was identified for whom comprehensive thrombophilia testing was performed between 1995 and 2005 and compared to DVT controls.

Results

341 patients with SpVT (mean age 50 ± 16 years, 53 % women) including isolated PVT (n = 112), MVT (n = 67), HVT (n = 22), SVT (n = 11), and M-SpVT (n = 129) involvement and 3621 DVT controls (mean age 55 ± 16 years, 56 % women) had comprehensive thrombophilia testing. The prevalence of abnormal results was similar for SpVT (24.6 %) and DVT (25.9 %) patients. “Strong” thrombophilias were more prevalent among SpVT patients (12.3 vs. 8.5 %, p = 0.0168). Patients with splenic (45.5 %) and mesenteric (41.8 %) thrombosis had the highest thrombophilia prevalence. Protein S deficiency was more common in SpVT patients (3.5 vs. 0.9 %, p < 0.001). In contrast, FV Leiden was more prevalent among DVT patients (15.8 vs. 10.9 %, p = 0.0497).

Conclusion

The prevalence of selected thrombophilia factors differ comparing SpVT and DVT patients. The prevalence is particularly high for patients with splenic and mesenteric vein thrombosis. Whereby the finding of strong thrombophilia impacts duration of anticoagulant therapy, such testing is warranted in the evaluation of patients with unprovoked SpVT.     

Inherited thrombophilia is associated with deep vein thrombosis in a Colombian population

The development of venous thromboembolism is influenced by a variety of genetic and environmental risk factors. A few studies have ascertained whether thrombophilic defects are risk factors for venous thromboembolism in Latin American populations with a variable degree of admixture, such as the Colombian population. To address this issue, we conducted a case-control study involving 100 consecutive patients with deep vein thrombosis and 114 healthy controls from the Hospital Universitario San Vicente de Paúl, Medellín, Colombia. Activated protein C resistance (APC resistance) was detected in 25/99 patients vs. 6/114 controls (OR = 6.08, 95% CI = 2.23-17.47). Ten of 100 patients carried the factor V Leiden mutation vs. 1/114 controls (OR = 12.56, 95% CI = 1.61-267). APC resistance was associated with the factor V Leiden mutation in only 10/25 patients. The prothrombin G20210A mutation was found in 4/100 patients, but none of the controls (P < 0.05). There was no significant difference in the proportion of homozygous carriers of methylenetetrahydrofolate reductase C677T variant among patients and controls. In conclusion, in our studied population, factor V Leiden, APC resistance, and prothrombin G20210A were associated with an increased risk of deep vein thrombosis. However, the frequencies of these thrombophilic defects and of APC resistance associated with factor V Leiden was lower than the corresponding frequencies previously reported for Caucasian populations. Further study is required to assess the influence of ethnicity on thrombophilia.     

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.     

Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms

Splanchnic vein thrombosis (SVT) is one of the vascular complications of myeloproliferative neoplasms (MPN). We designed a phase 2 clinical trial to evaluate safety and efficacy of ruxolitinib in reducing splenomegaly and improving disease‐related symptoms in patients with MPN‐associated SVT. Patients diagnosed with myelofibrosis (12 cases), polycythemia vera (5 cases) and essential thrombocythemia (4 cases) received ruxolitinib for 24 weeks in the core study period. Spleen volume was assessed by magnetic resonance imaging (MRI) and splanchnic vein circulation by echo‐Doppler analysis. Nineteen patients carried JAK2V617F, one had MPLW515L, and one CALRL367fs*46 mutation. Eighteen patients had spleno‐portal‐mesenteric thrombosis, two had Budd–Chiari syndrome, and one had both sites involved; 16 patients had esophageal varices. Ruxolitinib was well tolerated with hematological toxicities consistent with those of patients without SVT and no hemorrhagic adverse events were recorded. After 24 weeks of treatment, spleen volume reduction ≥35% by MRI was achieved by 6/21 (29%) patients, and a ≥50% spleen length reduction by palpation at any time up to week 24 was obtained by 13/21 (62%) patients. At week 72, 8 of the 13 (62%) patients maintained the spleen response by palpation. No significant effect of treatment on esophageal varices or in splanchnic circulation was observed. MPN‐related symptoms, evaluated by MPN‐symptom assessment form (SAF) TSS questionnaire, improved significantly during the first 4 weeks and remained stable up to week 24. In conclusion, this trial shows that ruxolitinib is safe in patients with MPN‐associated SVT, and effective in reducing spleen size and disease‐related symptoms.     

Predicting the clinical manifestations in necrotizing acute pancreatitis patients with splanchnic vein thrombosis

BackgroundSplanchnic venous thrombosis (SVT) is a relatively rare but important complication of necrotizing acute pancreatitis (NAP). Clinical manifestations and severity of this complication in different patients vary greatly, ranging from mild abdominal discomfort even asymptomatic to lethal gastrorrhagia or hepatic failure. The aim of the present study was to develop a model to predict the clinical manifestations of SVT in NAP patients.MethodsThis retrospective cohort study was conducted in the surgical intensive care unit (SICU) of Jinling Hospital. Patients with the presence of both pancreatic necrosis and SVT were selected for possible inclusion. Both univariate and multivariate logistic regression analyses were applied using 12 indices including age, gender, Acute Physiology and Chronic Health Evaluation II scores (APACHE II), CRP(C - reactive protein) levels, etc to assess potential predictors for symptomatic pancreatic splanchnic venous thrombosis (PSVT) in this cohort. A prognostic nomogram was also applied to develop an easy-to-use prediction model.ResultsA total of 104 patients with necrotizing acute pancreatitis (NAP) and splanchnic vein thrombosis (SVT) from January 2012 to December 2013 were enrolled for analysis. A quarter of study subjects (26 of 104, 25%) developed variable symptomatic manifestations including variceal bleeding, persistent ascites and enteral nutrition (EN) intolerance during the disease course. In the multivariable regression model, the following factors were found to be associated with the occurrence of symptomatic SVT: Balthazar's computed tomography (CT) score (OR = 1.818; 95% CI: 1.251–2.641; P = 0.002), intra-abdominal pressure (IAP) (OR = 1.172; 95% CI: 1.001–1.251; P = 0.043 and presence of SMVT (OR = 6.946; 95% CI: 2.290–21.074; P = 0.001). A prediction model incorporating these factors demonstrated an area under the receiver operating characteristic curve of 0.842.ConclusionsBalthazar's CT score, IAP and SMVT are predictors of symptomatic SVT in NAP patients. The nomogram we conducted can be used as an easy-to-use risk stratification tool in either clinical practice or future studies.     

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.     

Natural history of polycythemia vera and essential thrombocythemia presenting with splanchnic vein thrombosis

Annals of Hematology - Patients with polycythemia vera (PV) or essential thrombocythemia (ET) presenting with splanchnic vein thrombosis (SVT) might have a specific clinico-biological profile. To...     

Hyperhomocysteinemia and the methylene tetrahydrofolate reductase C677T mutation in splanchnic vein thrombosis

Introduction: The role that hyperhomocysteinemia (HH) and the C677T mutation in 5,10‐methylenetetrahydrofolate reductase (MTHFR) play in splanchnic vein thrombosis (SVT) remains unclear due to this unusual thrombotic location. Objective: To analyse the possible association of HH with the C677T mutation in the MTHFR gene in SVT. Material and methods: We determined homocysteine levels and the C677T MTHFR mutation, along with classical cardiovascular risk factors, in 48 patients with SVT (18 Budd‐Chiari syndrome, 11 mesenteric vein thrombosis, 19 portal vein thrombosis) and 84 controls. Results: In the univariate analysis, patients with SVT showed statistically higher homocysteine levels (P = 0.044). After adjusting for total cholesterol, differences disappeared (P = 0.256). However, no differences in homocysteine levels were observed when comparing the three SVT types (P = 0.199), even after adjusting for age and total cholesterol (P = 0.095). In addition, the prevalence of the TT genotype was no different when controls were compared with patients with SVT (P = 0.253) or with SVT subtypes (P = 0.885). No association was found between HH (>15 μm ) and the TT genotype in cases (P = 0.404), controls (P = 0.178), or in the different SVT subtypes (P = 0.495). Conclusions: Our results suggest that HH and the homozygous genotype in the MTHFR C677T mutation do not seem to play a role in SVT development.