Comparison of Thrombin Generation Assay With Conventional Coagulation Tests in Evaluation of Bleeding Risk in Patients With Rare Bleeding Disorders

Abstract

Based on the premise that the capacity of plasma to generate thrombin in vitro is a comprehensive and precise functional test of the clotting system, we designed a cross-sectional, single-center study involving 83 patients with rare bleeding disorders (RBDs) to compare the usefulness of the thrombin generation (TG) assay versus conventional tests including prothrombin time (PT) and activated partial thromboplastin time (aPTT) in predicting bleeding risk in patients with RBD in southern Iran. The TG parameters consisted of endogenous thrombin potential, lag time, peak, time to peak (ttPeak), and start tail. The area under the receiver-operating characteristic (ROC) curve showed statistically significant associations between bleeding risk and lag time, ttPeak, and start tail. We determined cutoff values for these 3 TG parameters and obtained a negative predictive value of 86% to 90% in patients with RBD who had a bleeding score (BS) ≤13. The ROC curves for the association of PT and aPTT with BS did not indicate any significant association. Correlation analysis supported the results of ROC curve analysis, only lag time, ttPeak, and start tail showed significant positive correlations with BS (P < .05). Disease severity based on plasma factor activity was significantly associated with prolonged lag time and ttPeak and with prolonged PT (P <.05). We suggest that TG assay is a potentially more useful tool for predicting the bleeding risk in patients with RBD. However, the small sample size in different RBD subgroups precluded subgroup analysis. Prospective multicenter studies with larger numbers of patients are therefore advisable.

Increased thrombin generation in splanchnic vein thrombosis is related to the presence of liver cirrhosis and not to the thrombotic event

“…lagtime and ttpeak, indicating that it is mainly the amount of produced thrombin that is important for the hypercoagulability. This could be potentially important when assessing the bleeding risk, for example during invasive procedures, as prolonged lagtime has been associated with increased bleeding risk in patients with factor deficiencies [27]; however, this has not been studied in patients with liver disease.…”

Evaluation of Thrombin Generation Assay in Patients With Hemophilia

“…Also, bleeding tendency was shown to become more prominent when TG decreases by more than 20% of the normal range. 11,13,17,18 Surprisingly all TG parameters except ETP showed this significant pattern in patients with mild hemophilia compared with those of healthy individuals as well. However, we should consider the small number of patients with mild hemophilia in our population (n ¼ 5).…”

Systematic Analysis of Bleeding Phenotype in PT-VWD Compared to Type 2B VWD Using an Electronic Bleeding Questionnaire

“…[32][33][34] In addition, little information is available with respect to correlating BS with other parameters such as age or laboratory data. One study that used the condensed MCMDM-1VWD questionnaire showed a strong inverse correlation between BS and VWF:Ag in type 1 VWD.…”