Esophageal Variceal Bleed, an Unusual Presentation of Factor V Leiden Thrombophilia
Authors: Shan Ul Abedin Muhammad , Batool Izza 
Published: December 2024

Introduction: Factor V Leiden is an inherited blood clotting disorder due to change in factor V protein in the coagulation cascade, increasing risk of thromboembolism. We present a case of 27-year-old female who initially had esophageal variceal bleed with workup showed portal hypertension and splenomegaly, leading to diagnosis of right portal vein thrombosis and factor V Leiden thrombophilia.
Case Presentation: A 27-year-old female with no significant past medical history presented at her age of 21 years with multiple episodes of hematemesis with endoscopy showed grade III varices with band ligation done twice. Blood workup showed platelets 90000/ uL and hemoglobin (Hb) 7.9.g/dL. It was attributed to recent bleeding events. Computed tomography (CT) of abdomen showed dilated portal vein and splenomegaly suggestive of portal hypertension. Further workup was mostly unremarkable including albumin 4.7 g/dL, ceruloplasmin 21 mg/dL, anti-trypsin 1.3 G/L, ALT 41 U/L, AST 30 U/L, ALP 59 U/L, GGT 59 U/L, total bilirubin 1.86 mg/dL, direct bilirubin 0.57, INR 1.1, ferritin 33.1 ng/mL and ANA negative. She lost to follow up for certain years but established care with gastroenterologist in 2023. Blood counts on two different occasions showed platelets to be 40000 and 66000/uL, though Hb improved to 13 g/dl. Office endoscopy showed grade II esophageal varices, which were banded again. CT liver dynamic showed right portal vein thrombosis, mild common bile duct dilation and chronic liver disease related changes with upper abdominal collaterals. She was referred to hematology for thrombophilia workup. Extensive workup included protein S 65.6%, protein C 74.9%, AT III 77%, factor VIII 139%, LDH 155 UL, retic count 1.3 %. The results were negative for lupus anticoagulant, anti-cardiolipin IgG/M, Anti-B2GP IgG/IgM and PNH (paroxysmal nocturnal hemoglobinuria) flow cytometry. Genetic testing for PT 20210 mutation, JAK (V617F) and factor II (prothrombin gene) was negative but came positive for factor V Leiden (homozygous). She was started on carvedilol 3.125 mg and low dose Eliquis 2.5 mg twice a day due to high risk for bleeding.
Discussion: Factor V Leiden (FVL) results from a point mutation in the F5 gene, which encodes the factor V protein in the coagulation cascade. FVL renders factor V insensitive to the actions of activated protein C (aPC). As a result, FVL variants are at increased risk of venous thromboembolism (VTE). An association between FVL and arterial thromboembolism remains controversial and is likely to be relatively small. FVL can be detected by genetic testing or a functional coagulation test for aPC resistance. A heterozygous mutation puts 3-7-fold increased risk of thrombosis, while homozygous mutation has risk increased up to 50-100-fold. FVL is one of most common thrombophilia increasing risk of Budd-Chiari syndrome. In contrast, the FVL mutation is not a major predisposing factor of portal vein thrombosis (PVT). Our case report is one of few cases of factor V Leiden causing portal vein thrombosis. Chronic portal vein thrombosis leads to development of portal hypertension and venous collaterals. There are few cases of esophageal variceal bleed and rare of jejunal bleed.
The management of VTE with heterozygous factor V Leiden mutation is same as in general population. We generally do not start anticoagulation in asymptomatic individuals who are homozygous for FVL. However, indefinite anticoagulation is warranted in cases with life threatening VTE or at unusual sites like portal or mesenteric thrombosis. High risk individuals including first-degree relatives and pregnant females need consideration and discussion with their hematologist. There is no consensus on management of recurrent esophageal bleed on the basis of thrombophilia complicated with PVT. Sequential endoscopic therapy combined with anticoagulant appears to be effective and safe. A study by Kouides et al showed that apixaban has equivalent efficacy in prevention of recurrent VTE but decreased risk of major and minor bleeding events compared with rivaroxaban. Our patient was started on lower dose Eliquis 2.5 mg twice a day due to high risk for esophageal bleed.
Conclusion: Factor V thrombophilia is a rare cause of poral vein thrombosis. Complications can include esophageal variceal bleed and other sequalae of portal hypertension. Multidisciplinary approach is required for individual case including decision about anticoagulation.