English

Abstract

To investigate wheather cancer patients during and following chemotherapy with short activated partial thromboplastin times (aPTTs) have increased thrombin generation and are at increased risk for thromboembolism, this prospective study was designed. Routine coagulation specimens of such patients were screened for the presence of short or normal aPTT for 5-month period, and, accordingly, 250 specimens were collected. Prothrombin fragment F1+2 (F1+2) was measured to evaluate thrombin activation, and a second aPTT was performed with a different reagent. Clinical history were obtained from medical records after conclusion of sample collection. 6 to12months later, patients were questioned on thromboembolic events during the previous 18 months by questionnaire. F1+2 and the incidence of venous thromboses were elevated significantly in the short aPTT group. Patients with acute bleeding had short aPTTs, but 36% of these also had thromboembolic events during the 18 months proximal to blood collection. These findings were confirmed with the second aPTT reagent. Patients with short aPTTs have increased thrombin generation and are at increased risk for thromboembolism, mainly venous thromboses, despite the fact that a short aPTT can occur in the acute setting of bleeding. INTRODUCTION: The prothrombin time (PT) and the activated partial thromboplastin time (aPTT) are routine coagulation tests used to assess the coagulation system in a clinical setting. Numerous factor deficiencies are known to prolong the respective screening test result and can be related to bleeding; (1) however, prolongation of the aPTT may be related to a hypercoagulable state if a lupus anticoagulant is present.(2) A clinically relevant decrease in the activity of clotting factors usually related to the prolongation of one of the respective routine screening test results. By analogy, shortened clotting times could, therefore, be the expression of a hypercoagulable state. Earlier studies have found some evidence that short aPTTs are related to a higher incidence of throm- boembolic disorders. (3, 4) These findings have been disputed, and there is some suggestion in the literature that short aPTTs occur during bleeding episodes. (5, 6) Nowadays, molecular markers of activation processes in the coagulation and fibrinolytic system have become widely available for use in the specialized clinical laboratory. Prothrombin fragment F1+2 is cleaved from prothrombin on activation by factor Xa in amounts equimolar to the thrombin generated. (7) Consequently, F1+2 levels have been shown to reliably measure the amount of prothrombin activation and, thus, thrombin generation. (8) The purposes of the present study were to evaluate the hypothesis that in cancer patients