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Thrombogenicity of Prothrombin Complex Concentrates

https://doi.org/10.1016/S0049-3848(99)00079-1Get rights and content

Abstract

Thrombogenicity of factor IX complex or prothrombin complex concentrates (PCC) is a well-acknowledged problem. The exact incidence is unknown but has decreased with the improvement of the quality of coagulation factor concentrates and a more judicious use of these products. The clinical spectrum of thrombogenicity ranges from superficial thrombophlebitis, deep-vein thrombosis and pulmonary embolism, and arterial thrombosis to disseminated intravascular coagulation. Several risk factors have been identified: (a) predisposing clinical factors (underlying disease and clinical condition), (b) therapy factors (dosing, concomitant therapy and drug interactions), and (c) quality of the PCC used. It is generally assumed that the risk of thromboembolic adverse effects is greater in patients with acquired disorders of hemostasis than in patients with inherited coagulation factor deficiencies. In hemophilia B, clinical conditions with an increased risk include large muscle hematomas, immobilization, surgery (especially orthopedic surgery), and liver disease. In acquired disorders of hemostasis, a prethrombotic state can be assumed in all patients where an indication for PCC concentrates is considered. Liver disease and/or antithrombin deficiency are considered as major risk factors. Therapy factors with an increased risk include large, repetitive doses of PCC. It is assumed that heparin and, in the case of antithrombin deficiency, antithrombin substitution decrease the incidence of thromboembolic adverse effects. Heparin neutralisation with protamine and aprotinin therapy may be additional risk factors. The declining incidence and the recent cluster of fatal thromboembolic adverse events in Germany with one brand of PCC is strong evidence for the crucial role of the quality of PCC in the occurrence of thromboembolic adverse effects.

Section snippets

Incidence and Clinical Spectrum

In 1973, a Task Force of the ICTH was established to investigate these adverse effects. In the first report on thromboembolic complications after PCC, 20 patients with liver disease were mentioned; 18 developed disseminated intravascular coagulation (DIC) and two patients developed pulmonary embolism. Complications after surgery were reported in 12 hemophilia B patients; pulmonary embolism was observed in six patients, thrombosis or phlebitis in three, and in addition one case each of

Risk Factors

Based on the above-mentioned reports, animal experiments, and in vitro data, it seems reasonable to postulate three major variables determining the risk of thrombogenicity: (a) predisposing factors, (b) therapy factors, and (c) quality of the PCC used.

Predisposing factors may be divided into the patient's underlying disease and the current clinical condition. It should be stressed that thromboembolic events occur even in the most severe inherited bleeding disorders after administration of PCCs,

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