Reference values for hemostatic parameters

The development from a promising innovative haemostasis test to a clinical diagnostic device is a long procedure. A very important step in this development is to determine the distribution of the test outcomes in healthy volunteers, who are representative for the general population. Synapse Research Institute has done several of those reference studies to determine the reference ranges of thrombin generation and of a flow cytometry based platelet activation test (PACT). 


Reference values for calibrated thrombin generation

Thrombin generation in plasma and whole blood has been used as a research tool in the field of thrombosis and hemostasis. There is substantial evidence that thrombin generation can be used to elucidate coagulation mechanisms, investigate hemorrhagic coagulopathies, 

predict the risk of (recurrent) thrombosis, and to monitor hemostatic and antithrombotic therapy. Thrombin generation has not reached clinical application, partly due to lack of reference values.

1. Bloemen S, Huskens D, Konings J, Kremers R, Miszta A, de Laat B, Kelchtermans H. Interindividual variability and normal ranges of whole blood and plasma thrombin generation. JALM. 2017 Sept; 2 (2): 150 -164.

Reference values for flow cytometry based platelet activation

We developed a user-friendly, reliable and quick flow cytometric based assay to determine platelet function in whole blood. Our assay uses three different platelet agonists (TRAP, CRP and ADP) and two platelet activation markers (αIIbβ3 receptor activation and P-selectin expression). For clinical applicability of hemostatic tests, it is of great importance to determine reference values in healthy individuals. Therefore, we determined references ranges for thrombin generation in platelet poor plasma (PPP), platelet rich plasma (PRP) and whole blood and for whole blood platelet function in 129 healthy individuals according to CLSI (Clinical & Laboratory Standards Institute) guidelines.

The assessment of platelet (dys)function is of crucial relevance in several clinical settings, including monitoring the response to antiplatelet treatment, evaluation of perioperative haemostasis, transfusion medicine and identification of bleeding disorders. The current gold standard to test platelet function for the diagnosis of bleeding disorders is light transmission aggregometry (LTA). However, LTA is laborious, relatively insensitive to small changes in platelet function and the outcome is affected by haemolysis and an abnormal platelet count. Additionally, the test is poorly standardized, consumes large blood volumes and requires skilled technicians in specialized laboratories. 

2. Huskens D, Sang Y, Konings J, van der Vorm L, de Laat B, Kelchtermans H, Roest M. Standardization and reference ranges for whole blood platelet function measurements using a flow cytometric platelet activation test. PLoS One. 2018 Feb 1;13(2):e0192079.