Mesenteric venous thrombosis in a patient with congenital afibrinogenemia and diffuse peritonitis

Abstract

Congenital afibrinogenemia is a rare autosomal recessive hemorrhagic disorder, and thrombotic complications occurring spontaneously or after infusion of fibrinogencontaining preparations have been reported in afibrinogenemic patients [1]. We report a case of mesenteric venous thrombosis due to fibrinogen replacement in a patient with congenital afibrinogenemia. A 19-year-old male with congenital afibrinogenemia had previously undergone uneventful surgical procedures for splenic rupture, intracranial bleeding, and mandibular abscess (2002) with preoperative supplement of fibrinogen concentrate. He was urgently admitted to the Critical Care Medical Center and diagnosed with diffuse peritonitis in 2003. After prophylactic administration of ten units of fresh-frozen plasma (FFP), resection of the small intestine was performed. Numerous thromboses were detected in the mesenteric veins of the resected specimen. The color of the remaining small intestine darkened during wound closure and mesenteric circulation worsened. Continuous infusion of unfractionated heparin (Novo Heparin 1000, Mochida Pharmaceutical Co., Japan) at 500 units/h was initiated following a 2000-unit bolus. The following day, massive resection of the small intestine, leaving only 60 cm of small intestine, was performed due to necrosis identified during a second-look operation. In 2004, emergency surgery was performed for adhesive intestinal obstruction without hemostatic complications by prophylactic administration of fibrinogen concentrate and unfractionated heparin. Perioperative laboratory data from 2002, 2003, and 2004 are shown in Table 1. In 2002, data revealed undetectable plasma fibrinogen levels by the functional assay, undetectable prothrombin time (PT) and activated partial thromboplastin time (APTT), and thrombocytosis. Supplementation with 9000 mg of fibrinogen raised fibrinogen levels to 1.91 g/l and normalized PT and APTT. In 2003, fibrinogen levels, PT, APTT, and platelet count after preoperative administration of ten units of FFP were approximately the same as in 2002. However, excessively high levels of hemostatic and inflammatory markers preoperatively indicated a hypercoagulable and inflammatory state. While perioperative heparin infusion in the first operation suppressed levels of hemostatic markers, the levels of those in the second-look operation were still above normal range. In 2004, preoperative tests again showed undetectable plasma fibrinogen level and PT, but APTT was normal. Values for all hemostatic markers, WBC, and C-reactive protein (CRP) were markedly elevated compared to reference ranges, but platelet count was normal. Supplementation with fibrinogen concentrate and intraoperative heparin administration resulted in a plasma fibrinogen concentration of 1.03 g/l and an APTT of 44.7 s. Fibrinogen level measured using both functional and immunological assays was 0.1 g/l at 5 days after administration of 1000 mg of fibrinogen concentrate. Prothrombin activation increases and increased thrombin generation has been observed in afibrinogenemia [2]. Thrombin represents a potent activator of platelets and platelet aggregation [3]. Tefferi et al. [4] reported marked thrombocytosis occurring in 22.0% of postsplenectomy patients. Furthermore, Remijn et al. [1] showed that the absence of fibrinogen results in large but loosely packed platelet aggregates and suggested that afibrinogenemic patients could be at risk for thrombosis. Thus, hypercoagulable states due to increased prothrombin activation and platelet aggregation may exist in our patient. Compensative reaction for severe intestinal inflammation and/or heparin-induced thrombocytopenia [5] may have been considerable for the reduced platelet count in 2004, Y. Takasugi (*) . Y. Shiokawa . R. Kajikawa . J. Oh . Y. Koga Department of Anesthesiology, Kinki University School of Medicine, 377-2 Ono-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan e-mail: yoshihiro.takasugi@nifty.com Tel.: +81-72-3660221 Fax: +81-72-3660206