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      Development of acquired factor V inhibitor after treatment with ceftazidime: a case report and review of the literature

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          Abstract

          We report the case of a 59-year-old Chinese man who showed an asymptomatic coagulation factor V deficiency pattern after second intravenous treatment with ceftazidime. Normal pooled plasma failed to correct the abnormalities in a mixing test, and the presence of factor V inhibitor was confirmed by the Bethesda method. The coagulopathy was not corrected by transfusion of fresh frozen plasma and prothrombin complex concentrate, but rather by treatment with prednisone and withdrawal of dubious drugs. The findings reported here should prompt clinicians to watch for drug-induced coagulation factor deficiency.

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          Most cited references 13

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          How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults.

          The prothrombin time (PT) and activated partial thromboplastin time (APTT) are among the most commonly ordered coagulation tests. In 2005, more than 140,000 PT and more than 95,000 APTT tests were performed at Mayo Clinic. The most common indications for ordering these tests include anticoagulant monitoring, initial evaluation of hemorrhage, and, although not generally indicated, routine preoperative screening. In addition, the bleeding time (BT) test, which is infrequently performed, is still available in certain institutions. Abnormal results from these tests (prolonged PT, APTT, and BT), especially from tests conducted for initial evaluation of hemorrhage or for preoperative screening, may pose a diagnostic dilemma to the nonhematologist. We review the essential factors affecting test results; provide a practical approach to the evaluation of a prolonged PT, APTT, and BT; and offer suggestions on which reflexive tests are appropriate and when to consider a subspecialty consultation.
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            Acquired factor V inhibitor. A problem-based systematic review.

            Acquired factor V(FV) inhibitors as a rare bleeding disorder, poses a formidable challenge to treating physicians with limited evidence to guide its management. We systematically reviewed our experience in Singapore and the published literature to determine possible answers to clinical questions formulated on the manifestation and best management of non-bovine thrombin and non-congenital acquired FV inhibitors. The incidence in Singapore was 0.09 cases per million person years (3 cases over 10 years). Seventy-three other cases meeting pre-defined search criteria were found in the published literature. Bleeding occurred in 68.4% of these patients, with mucous membranes being the most common site. Intracranial and retroperitoneal bleeds carried the highest mortality. The mortality rate from bleeding was 12%. There was a tendency for FV levels and PT/aPTT prolongation to predict bleeding but not the inhibitor level. No consistently effective haemostatic agent could be determined, but platelet transfusion should probably be the first line therapy. Among bleeding patients, inhibitors tended to disappear faster with inhibitor elimination therapy (IET) compared to without IET (60 vs. 150 days, p=0.299). IET made no significant difference among non-bleeding patients (p=0.511) and is thus recommended for bleeding patients or those with high bleeding risk. Steroids as single agent IET was effective in the majority of patients. Logical management approaches may be drawn but are limited by small sample size, heterogeneity of reports, and potential publication bias. The inception of a comprehensive registry will provide more reliable data that may verify our findings.
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              Acquired FV inhibitors: a needless iatrogenic complication of bovine thrombin exposure.

              FV inhibitors are a largely preventable iatrogenic coagulopathy in which the frequency is increasing in clinical practice. Three cases associated with our institution are reported. A systematic review of the MEDLINE database was performed, and reference lists were reviewed to identify relevant publications. One hundred twenty-six cases of FV inhibitors have been reported in the world's literature. Eighty-seven have been reported in the last decade, of which two thirds are due to exposure to bovine thrombin. Bovine thrombin-associated FV antibodies develop in 40 to 66 percent of cardiac surgery patients and in 20 percent of neurosurgery patients. Thirty-three percent of reported patients developed bleeding complications. Inhibitors persisted on average 2.3 months. Standard coagulation assays do not reliably predict clinical manifestations. Multimodality therapy, including immunosuppression, is useful for treatment of symptomatic patients. FV inhibitors are a common complication of bovine thrombin exposure that can have devastating clinical consequences. Transfusion medicine specialists and hematologists can play a critical role in reducing the incidence of FV inhibitors by educating the medical community about safer alternative fibrin sealants.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2015
                24 April 2015
                : 9
                : 2395-2398
                Affiliations
                [1 ]Department of Hematology, PLA 100th Hospital, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
                [2 ]Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
                Author notes
                Correspondence: Hong-shi Shen, Department of Hematology, PLA 100th Hospital, 53 Wuqueqiao Street, Suzhou 215006, People’s Republic of China, Tel +86 512 6506 3541, Fax +86 512 6506 3541, Email shs10@ 123456163.com
                Zhao-yue Wang, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, People’s Republic of China, Tel +86 512 6778 0872, Fax +86 512 6511 3556, Email zwang11@ 123456sina.com
                Article
                dddt-9-2395
                10.2147/DDDT.S68682
                4422287
                25987837
                © 2015 Cui et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Case Report

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