Monitoring plasma heparin concentration in a patient with antiphospholipid syndrome

Abstract

Antiphospholipid syndrome (APS) is an acquired thrombophilia characterized by the occurrence of arterial and venous events as well as recurrent miscarriages [1, 2]. In the revised classification criteria for APS, lupus anticoagulant (LAC), anti-cardiolipin antibody (aCL), and anti-b2 glycoprotein-I antibody (ab2GPI) have been utilized as laboratory criteria [1]. Concerning the LAC assay, prolongation of a phospholipid-dependent clotting time such as activated partial thromboplastin time (aPTT) has been commonly used as a screening test [3]. Once patients are diagnosed as having APS, they are recommended to receive prolonged antithrombotic therapy, especially with warfarin [4, 5]. We encountered a patient with APS who could not receive oral warfarin because of malabsorption, and it was also difficult to perform conventional therapeutic monitoring of the heparin dosage using aPTT because of the baseline prolongation of aPTT due to LAC. A 63-year-old female who had a history of recurrent miscarriages was admitted to our hospital because of severe abdominal pain on September 19, 2009. Radiologic examination revealed an arterial thrombus at the trunk of the superior mesenteric artery (SMA), and she was treated with intravenous urokinase and unfractionated heparin. However, 2 days later, she complained of severe abdominal pain again. She underwent emergent laparotomy and was diagnosed with extended intestinal necrosis ranging from the upper jejunum to transverse colon. Therefore, she received surgical resection of the necrotizing intestine followed by colostomy and common hepatic artery bypass grafting. Her abdominal pain resolved, but she became dependent on parenteral nutrition due to malabsorption as a result of short bowel syndrome after extended enterocolectomy. Intravenous heparin was continued until postoperative day (POD) 13 to prevent graft occlusion. aPTT (PTT-LA , Sysmex, Kobe, Japan, normal range 24.2–34.1 s.) was prolonged to more than 100 s. even after withdrawing anticoagulation with heparin. On POD 23, she was positive for LAC on the phospholipid-dependent coagulation test using the diluted Russell viper venom time (dRVVT; Gradipore , MBL, Nagoya, Japan) (Table 1). Both aCL and b2GPI dependent aCL (aCL/b2GPI) showed significantly high titers of [120 U/mL (normal range \ 10 U/mL) and 71.6 U/mL (normal range \ 3.5 U/mL), respectively, in her T. Inaba (&) N. Fujita Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan e-mail: inaba178@koto.kpu-m.ac.jp