Abstract Number: PB0387
Meeting: ISTH 2020 Congress
Background: In the protein C pathway, thrombin binds to thrombomodulin resulting in the activation of protein C (PC). Activated PC together with its cofactor protein S then inactivates coagulation factors Va and VIIIa. Patients with a PC deficiency have an increased risk of thrombosis.
Aims: Evaluation of platelet and coagulation responses of PC deficient patients in a whole blood flow perfusion assay.
Methods: Patients and corresponding control subjects were obtained from the screening program for familial thrombophilia at the University Hospital of Padua. Hematological parameters and von Willebrand factor (VWF) antigen levels were determined, as well as thrombin generation. Using GPVI-dependent microfluidics, recalcified whole blood was perfused at 1000 s-1 over microspots of collagen with(out) tissue factor (TF). Multicolor fluorescence microscopy was used to assess kinetics of platelet adhesion and activation, followed by fibrin formation.
Results: Platelet counts and VWF levels were all in the normal ranges. Whole blood perfusion revealed a remarkable decrease in platelet activation, aggregation, thrombus formation and contraction in 10 out of 14 PC deficient patients, in comparison to controls. In contrast, shear-dependent platelet adhesion was unaffected, suggesting an adhesion-independent platelet defect. In the presence of TF, platelet-dependent fibrin formation was reduced as well in the same 10 patients. In vitro inhibition of the protein C pathway did not lower the platelet parameters in control blood samples. Thrombin generation profiles in TF-triggered patients´ platelet-poor plasmas were normal.
Conclusions: Our findings collectively point to in situ platelet desensitization in a substantial fraction of patients with inherited protein C deficiency. The result is a partial impairment of thrombus and secondary fibrin formation in whole-blood flow. Such desensitization might be compensatory for the prothrombotic phenotype of the patients.
To cite this abstract in AMA style:Brouns SLN, Tullemans BME, Perrella G, Bulato C, Campello E, Spiezia L, van Geffen JP, Kuijpers MJE, van Oerle R, Spronk HMH, Castoldi E, van der Meijden PEJ, Simioni P, Heemskerk JWM. Paradoxical Platelet Inhibitory Effect of Protein C Deficiency in Shear-dependent Thrombus and Fibrin Formation [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/paradoxical-platelet-inhibitory-effect-of-protein-c-deficiency-in-shear-dependent-thrombus-and-fibrin-formation/. Accessed January 26, 2022.
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