Budd-Chiari syndrome and activated protein C resistance

Copyright 0 European Association for the Study of the Liver 1996

Journal of Hepatology 1996; 24: 246248 Printed in Denmark All rights reserved

Journal of Hepatology ISSN 0168-8278

Correspondence

Budd-Chiari syndrome aud activated protein C resistance To the Editor: A defect in the anticoagulant response to activated protein C (APC) is a recently identified hereditary mechanism of thrombophilia (1) linked to a single point mutation in the factor V gene (2). We report a case of Budd-Chiari syndrome associated with APC resistance and a myeloproliferative disorder. A 21-year-old man was admitted in February 1995 with a 2-month history of abdominal pain, weakness, and swelling. Physical examination showed hepatosplenomegaly, jaundice, ascites, and peripheral oedema. Total bilirubin was 40 pmolll, aspartate aminotransferase 80 U/I gammaglutamyl transpeptidase 241 U/I, alkaline phosphatases 257 U/l, and prothrombin ratio 55%, with factor V 43%. Hepatic Doppler ultrasonography, magnetic resonance imaging, and liver histology demonstrated Budd-Chiari syndrome, with occluded hepatic veins. Red cells were 6.7~10’*/1, haemoglobin 16.5 gidl, packed cell volume 54%, white cells 10x 109/1, and platelets 438x 109/1. Red cell mass was increased to 40 ml/kg, vitamin B12 to 1550 rig/l and leukocyte alkaline phosphatase score to 65. Serum erythropoietin was 5.9 mUI/ml (normal 4-16). Bone-marrow biopsy was hypercellular with an increased number and polymorphism of megakaryocytes. There was no myelofibrosis. These results were consistent with myeloproliferative disease. Thrombophilia screening showed 61% protein C, 100% protein S, 95% antithrombin III, and negative lupus anticoagulant. The APC resistance test ratio was uninformative because of increased activated partial thromboplastin time. Polymerase chain reaction genomic DNA analysis (2) indicated heterozygosity for factor V 4506 mutation. Although there was no familial history of thrombosis, the patient’s father presented APC resistance, as determined by the APC-dependent prolongation of the activated partial thromboplastin time, and he was also heterozygous for the factor V 4506 mutation. The patient was discharged on a low-sodium diet, with venesection, and chemotherapy with pipobroman. One month later, the prothrombin ratio reached 6.5%, and the patient was treated with vitamin K antagonists. Although myeloproliferative disorders are the most common aetiology of Budd-Chiari syndrome, deficiencies in antithrombin III, protein C, protein S, and lupus anticoagulant have also been incriminated. APC resistance seems to be the most prevalent cause of throm-

bophilia, since it is detected in 2&30% of patients with unexplained thromboembolism, compared with 2-5% of healthy individuals (1). Recently, two cases of Budd-Chiari syndrome were reported, in which APC resistance was associated with protein S deficiency (3) or myeloproliferative disease (4). However, one case of portal thrombosis associated with APC resistance and with no other aetiology, suggests that APC resistance can be implicated in this pathology (5). Our case

underlines the possibility of multifactorial aetiology in Budd-Chiari syndrome and suggests that screening for APC resistance may be justified in all patients with Budd-Chiari syndrome or portal thrombosis, even if another predisposing factor has already been identified. For patients with APC resistance, long-term anticoagulant therapy and familial screening for APC resistance may be warranted. Pierre Mambrini, Dominique Mallet, The&e O’Callaghan, Gerard Sebahoun, Jacques Salducci and Jean Charles Grimaud Department of Gastroenterology, Department of Hematology, North Hospital, 13915 Marseille Cedex 20, France

References 1. Svensson

2.

3.

4. 5.

PJ, Dahlback B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-22. Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, De Ronde H. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7. Denninger MH, Beldjord K, Durand F, Denie C, Valla D, Guillin MC. Budd-Chiari syndrome and factor V Leiden mutation. Lancet 1995; 345: 52556. Mahmoud AEA, Wilde JT, Elias E. Budd-Chiari syndrome and factor V Leiden mutation. Lancet 1995; 345: 526. Levoir D, Aubertin JM, Bejanin H, Bloch F, Alhenc Gelas M, Aiach M, Petite JP Une nouvelle cause htreditaire de thrombose portale: la mutation Arg 506 par Gln dans le gene

du facteur

V Gastroenterol

Clin Biol 1995; 19: A 108 (abstr).

Spontaneously reversible extensive portal vein thrombosis after gallbladder puncture during transjugular liver biopsy To the Editor: The incidence of portal vein thrombosis (PVT) varies widely from 0.6 to 21% in cirrhosis (1) and is usually related to the presence of hepatoma, decreased portal blood flow, or a local inflammatory state (2). It has never been described in the setting of a transjugular liver biopsy. We report a case of extensive PVT after such a procedure. A 45-year-old, alcoholic man was admitted to our hospital on 23

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January 1995 for repeated variceal hemorrhage. He had clinical evidence of cirrhosis, with a Child-Pugh score of 10115, but an otherwise unremarkable medical history. His temperature was 38”C, and blood pressure was 130/80 mmHg with a regular heart rate of 70/min. He had grade 2 hepatic encephalopathy. Cardiac auscultation was normal and crackles were heard at the left lung base. Non-tense ascites was present, and the abdomen was supple with normal bowel sounds