Clinical Application of Thrombin Generation: A Deeper Reflection of Plasmatic Haemostasis of Ventricular Assist Device Recipients

Objectives: Precise monitoring of haemostasis is of utmost importance in ventricular assist device recipients. In clinical routine thromboplastin time (PTT) and international normalized ratio (INR) are used for evaluation of coagulation capacity and adjustment of anticoagulation therapy. In detail, PTT represents endogenous homeostasis and INR represents the exogenous homeostasis but both only reflect 2 percentage of the total plasmatic thrombin generation. During the past decade alternative methodological approaches were designed to address the total thrombin generation (TG) as a measure for true plasmatic coagulation. The present study aimed to investigate the course of thrombin generation in VAD recipients in intensive care unit. Furthermore, the study reveals a more detailed few of the disturbed haemostasis and its correlation with bleeding and thromboembolism events.

Methods: Thrombin generation was measured in platelet-poor (PPP) and platelet rich plasma (PRP) from 20 healthy controls and 15 left ventricular assist device (LVAD) recipients 4 weeks postoperatively over a period of 10 days. Samples were taken 4 times per day, while this was done only once per day in healthy controls. Clinical data including clotting tests (partial thromboplastin time, prothrombin time and its derived measures of international normalized ratio) were also collected at the same time points.

Results: Analyzing PRP, endogenous thrombin potential (ETP) was significant different (p < 0.001) comparing LVAD recipients (AUC: 1046 ± 149 nmol/l*min) and controls (AUC: 2601 ± 320 nmol/l*min) regarding peak thrombin (110.5 ± 32 nmol/l; 242.9 ± 48.1 nmol/l), lag time (4.5 ± 1.1 minute; 3.1 ± 0.5 minute) and time to thrombin peak (15.2 ± 2.1 minute; 7.2 ± 1.9 minute). Three recipients showed bleeding events (1–15 days). Additionally, there was no significant difference in thrombin generation comparing PPP versus PRP in LVAD recipients, indicating diminished platelet function. Additionally, no correlation between PTT or prothrombin time and bleeding events was observed, while ETP was significantly down-regulated (−75± 3% of controls) in LVAD recipients.

Conclusion: Monitoring of TG identify bleeding events in LVAD recipients and have a prognostic value. Moreover, the PPP/PRP ratio displayed physiological dysfunction of platelet.