Venous thromboembolism and hyperhomocysteinemia as first manifestation of pernicious anemia


Introduction

Hyperhomocysteinemia has been suspected of favoring thrombosis. Several case–control studies and even a meta-analysis have confirmed a link between venous thrombosis and hyperhomocysteinemia. Homocysteine is due to genetic and acquired factors (poor diet in folate and vitamin B12, older age, renal impairment, thyroid diseases, and malignancies) induced by the intake and the concentrations of vitamin B9 or B12 in the majority of cases.

Case Report

A 34-year-old Moroccan man was admitted to our intensive care unit because of dyspnea. He had been under treatment for psychosis for 3 years. His physical examination was normal. There was no physical sign of thrombophlebitis. 

Diagnosis

Chest radiographs and an electrocardiogram were unremarkable. His hemoglobin was 9 g/dl; his mean corpuscular volume was 120 μm3. His prothrombin time, partial thromboplastin time, and fibrinogen level were normal. A spiral computed tomography scan of his chest revealed bilateral pulmonary embolism. There was no clinical or biological evidence of neoplasia, Behçet disease, antiphospholipid syndrome, or systemic lupus.

He also had a normal platelet count, normal protein C and protein S levels, and normal antithrombin III function. Genetic testing for factor V Leiden and factor II mutation was negative. His plasma homocysteine level was 50 μmol/l (normal < 16) and cobalamin plasma level was measured at 60 pg/ml (normal > 120).

His folate plasma level was normal. Antibodies to intrinsic factor were positive. Bone marrow aspiration with biopsy showed megaloblastosis. An endoscopy revealed atrophic gastritis.

Treatment

Treatment included orally administered anticoagulation therapy and cobalamin supplementation, initially parenteral. After a 1-year follow-up period, he remained free of psychiatric disorders and thrombotic events. His hemoglobin and homocysteine plasma levels were within normal range.

Discussion

The three first cases, the diagnostic of pernicious anemia was suspected and then confirmed on the basis of the biological findings: macrocytosis, cobalamin deficiency, bone marrow aspiration with biopsy, gastric atrophy, and intrinsic factor antibodies. But we had tested for cobalamin deficiency and then for hyperhomocysteinemia because she had psychiatric disorders and a history of ischemic myocardial stroke.All patients presented with severe clinical manifestations at admission. All of our patients had very high levels of plasma homocysteine (50 to 200 μmol/l). The hyperhomocysteinemia secondary to pernicious anemia may explain the thrombosis in our observations. Also, all of our cases had no other risk factors for vascular thrombosis: no clinical or biological evidence of neoplasia, Behçet disease, antiphospholipid syndrome, thrombophilic abnormality, or systemic lupus.After vitamin supplementation, the biological abnormalities disappeared and the follow-up was free of vascular thrombotic events in all patients with a median follow-up of 3 years.The case is original in that psychiatric manifestations and pulmonary embolism were the first manifestations of hyperhomocysteinemia-related pernicious anemia. After vitamin B12 supplementation, his clinical and biological abnormalities disappeared.

Keywords

Homocysteine Pernicious anemia Venous thrombosis Cobalamin

Author : W. Ammouri et.al