Short Activated Partial Thromboplastin Times Are Related to Increased Thrombin Generation and an Increased Risk for Thromboembolism

Abstract

This prospective study was designed to investigate whether patients with short activated partial thromboplastin times (aPTTs) have increased thrombin generation and are at increased risk for thromboembolism. During a 4-month period, routine coagulation specimens were screened for the presence of a short or normal aPTT, 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. Diagnoses were obtained from medical records after conclusion of sample collection. Five to 9 months later, patients were questioned on thromboembolic events during the previous 18 months by questionnaire and telephone interview. F1 + 2 and the incidence of venous thromboses were elevated significantly in the short aPTT group. Unexpectedly, 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.

A shortened activated partial thromboplastin time is associated with the risk of venous thromboembolism

“…These results are biologically plausible because shortened APTTs have been associated with high levels of biochemical markers of thrombin generation and fibrin deposition such as prothrombin fragment 1 ϩ 2, thrombin-antithrombin complex, and D-dimer, 15,16 as well as with a poor prognosis for thrombosis and mortality in patients admitted over time to a general medical center. 17 Furthermore, the APTT is a global test responsive to the plasma levels of coagulation factors of the contact (factor XII, prekallikrein, and high-molecular-weight kininogen) intrinsic (factor XI, VIII, IX) and common (factor X, V, II and fibrinogen) pathways of blood coagulation.…”

Abnormally Short Activated Partial Thromboplastin Times Are Related to Elevated Plasma Levels of TAT, F1+2, D-Dimer and FVIII:C

“…One prospective clinical study found that a short APTT is related to a 10-fold increased incidence of thromboembolic events [8]. A recent prospective study demonstrated ten Boekel/Bartels First aid 91 45 50 50 Cardiology 22 11 8 8 Intensive care unit 40 20 21 21 Neurology 8 4 2 2 Internal medicine 18 9 14 14 Oncology 2 1 0 0 Others 21 10 5 5 that patients with short APTTs are at increased risk for thromboembolism, in particular venous thrombosis (odds ratio: 5.4) [9]. Reddy et al [10] reported that approximately 25% of patients with short APTTs will develop thrombotic events within 1 year after detection, whereas in the control group the incidence was less than 3%.…”

Improved Stability of Proline-Derived Direct Thrombin Inhibitors through Hydroxyl to Heterocycle Replacement

“…10 Both dabigatran (1) and compound 2 were found to exhibit good functional activity in this coagulation assay in human plasma (2 × APTT = 0.63 and 0.23 μM, respectively). Compound 10 possessed anticlotting activity (2 × APTT = 6.9 μM) roughly 10-fold less potent than dabigatran.…”