The significance of the MTHFR C677T/A1298C combination polymorphism in deep vein thrombosis: a case report.

A 37-year-old woman came to the emergency room with abdominal pain and nausea for about three weeks. She had no known risk factors for venous thromboembolism other than taking oral contraceptives as a regular medication. Computerized tomography (CT) revealed thrombosis of the portal, superior mesenteric, and spleen veins. Tests for thrombophilia were negative, except for the presence of heterozygosity for the methylenetetrahydrofolate reductase mutation (mthfr) gene. Homocysteine ​​and folic acid levels were normal. Anticoagulation started. CT follow-up after eight months showed a cavernous transformation of the portal vein.

an introduction

Portal vein thrombosis (PVT) occurs when there is obstruction of the portal vein with or without extension of the splenic or superior mesenteric veins. It is responsible for about 5-10% of cases of portal hypertension. Symptoms often depend on the location and size of the clot. Vein thrombosis can result from malignancy, thrombotic conditions such as thrombosis, pregnancy, hormone replacement/oral contraceptives, myeloproliferative disorders, and autoimmune diseases. [1]. Mutation in methylenetetrahydrofolate reductase (mthfrThe gene is the most common cause of a moderate increase in homocysteine [2]. The amino acid causes endothelial dysfunction, activates the coagulation system, and inhibits the fibrinolytic system [3]. Half the case of a 37-year-old woman presenting with abdominal pain associated with PVT and mthfr The C677T/A1298C polymorphism combined with normal homocysteine ​​levels.

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A 37-year-old Caucasian woman appeared in the emergency room with nausea and abdominal pain. The pain started three weeks ago as epigastric pain and progressed to spreading abdominal pain with increasing intensity to 7/10, without relief after analgesics. She had no other symptoms. She had no comorbidities. Her usual medication has been estrogen-progestin oral contraceptives for 20 years. She had an active lifestyle. You have not consumed alcohol, tobacco, or any other type of drug use. She had no family history of thromboembolic events. The patient appeared to be distressed by abdominal pain. Her blood pressure was 122/74 mm Hg, pulse rate 95 bpm, respiratory rate 26 bpm, and temperature 36.1°C. Abdominal palpation was mildly painful in the upper quadrants, with no other noticeable signs on physical examination. Blood tests had no noticeable changes. Abdominal ultrasound showed mesenteric, splenic, and upper portal thrombosis and CT angiography confirmed the thrombotic event and excluded other changes (Fig. 1).

They were inserted and coagulated with enoxaparin 1 mg/kg every 12 hours. Endoscopy and colonoscopy, chest CT scan, mammography, ultrasonography of the breast, neck, thyroid, and myelography were performed without any suspicious results. Serological marker tests for hepatitis B, hepatitis C, and HIV were negative. Genetic testing showed normal genotypes for factor V Leiden and prothrombin, and a heterozygous mutation in the heterozygote. mthfr C677T / A1298C. Antithrombin and protein C and S activity were normal. No lupus anticoagulants were detected and anticardiolipin and B-glycoprotein antibodies were negative; The homocysteine ​​level was 7 μmol/L (reference range 4–12) and folic acid was normal. She was discharged with a prescription for warfarin. Eight months after her discharge from hospital, she was asymptomatic and a CT scan showed a cavernous shift in the portal vein.


The portal vein results from the confluence of the mesenteric and upper spleen veins and drains directly into the liver [4]. PVT is observed in 0.6-16% of patients with cirrhosis and is responsible for 5-10% of all cases of portal hypertension. Acute PVT usually causes abdominal pain and the physical findings are not noticeable, except in the case of intra-abdominal inflammation, intestinal infarction, or perforation. Venous thromboembolism is a multifactorial disease caused by the interaction of genetic factors with environmental factors [1]. Use of birth control pills may cause blood clots by increasing levels of clotting factors and decreasing levels of clotting inhibitors [5]. Furthermore, combined oral contraceptives, containing ethinyl estradiol and progesterone, have a greater effect in women with hereditary thrombosis (antithrombin deficiency, protein C and protein S deficiency, factor V Leiden mutation, and prothrombin G20210A mutation) [6]. mthfr Variants are also associated with an increased risk of venous thromboembolism. MTHFR is an important enzyme in the remethylation pathway of homocysteine ​​metabolism and molecular defects can lead to deficiency of the enzyme, and thus to hyperhomocysteinemia, which is associated with an increased risk of venous thromboembolism. [2]. The amino acid causes endothelial dysfunction, activates the coagulation system, and inhibits the fibrinolytic system [3]. On the other hand, there is evidence of a co-mutation in heterozygosity for both C677T and A1298C from mthfr The gene is associated with venous thromboembolism even without hyperhomocysteinemia [7]. Anticoagulation is the mainstay of PVT therapy, unless contraindicated, to enable portal vein re-canalization and prevent portal hypertension. [8]. Portal hypertension is a complication of PVT and its consequences include ascites and esophageal varices. The portal vein is expected to be recanalized for up to six months and the mesenteric and splenic veins up to 12 months of follow-up. Therefore, anticoagulant therapy should be given for at least six months and a CT scan should be performed to assess re-canalization of the portal venous system after 6-12 months of follow-up. If effective portal re-canalization does not occur, the collateral veins dilate and become tortuous (cavernous shunt of the portal vein) [9].


This case report indicates that carriers of a co-mutation in heterozygosity for C677T and A1298C from mthfr A gene who uses oral contraceptives is more likely to develop venous thromboembolism. More studies are needed to assess the relationship between inherited thrombophilia, including MTFR Genotype, use of oral contraceptives that could potentiate their thrombolytic effect. Genetic testing may be important to assess clotting risks before you start using oral contraceptives.

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