Hyperfibrinogenemia as a cause of prolonged thrombin clotting time.

Abstract

Recognized causes of a prolonged thrombin clotting time (TCT) include a decreased plasma fibrinogen level, dysfibrinogenemia, paraproteinemia, heparin contamination, elevated levels of fibrin degradation products, and liver failure. We have frequently seen patients with an isolated prolonged TCT in the absence of any of these conditions and without obvious clinical impact. During a previous evaluation of hyperfibrinogenemia, we noted a surprisingly high incidence of prolonged TCT, prompting this evaluation of hyperfibrinogenemia as a possible cause. In our prospective study nine patients had a TCT more than 3 seconds longer than a matched control subject's TCT, with simultaneously normal prothrombin and activated partial thromboplastin times. Eight patients had fibrinogen levels more than 100 mg/dl above the control level (range 383 to 1,223 mg/dl). Only one patient's prolonged TCT could be explained on the basis of elevated levels of fibrin degradation products. In vitro studies in both a purified fibrinogen system and in plasma confirmed a delay in TCT with increasing initial fibrinogen concentrations. Kinetic measurements demonstrated a slowing of the normal initial increase in turbidity seen upon the addition of thrombin. Possible explanations include binding of thrombin to fibrin, or interference with fibrin assembly by excess fibrinogen. Regardless of the kinetic explanation, isolated prolongations of TCT due to hyperfibrinogenemia appear to be of minimal clinical significance.