D-Dimer and Fibrin Degradation Products Impair Platelet Signaling: Plasma D-Dimer Is a Predictor and Mediator of Platelet Dysfunction During Trauma
| Autor: | Christopher C. Verni, Carrie A. Sims, Scott L. Diamond, Antonio Davila |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Blood Platelets
medicine.medical_specialty medicine.medical_treatment 030204 cardiovascular system & hematology Fibrin Fibrin Fibrinogen Degradation Products 03 medical and health sciences 0302 clinical medicine Thrombin Internal medicine Fibrinolysis medicine Humans Platelet biology Chemistry Impaired platelet aggregation 030208 emergency & critical care medicine Convulxin Articles General Medicine GPRP Endocrinology Tissue Plasminogen Activator biology.protein GPVI medicine.drug |
| Zdroj: | J Appl Lab Med |
| ISSN: | 2475-7241 2576-9456 |
| DOI: | 10.1093/jalm/jfaa047 |
| Popis: | Background Platelet dysfunction often accompanies trauma-induced coagulopathy. Because soluble fibrin impairs platelet glycoprotein VI (GPVI) signaling and platelets of trauma patients can display impaired calcium mobilization, we explored the role of fibrinolysis on platelet dysfunction during trauma. Methods Convulxin-induced GPVI calcium mobilization was investigated in healthy platelet-rich plasma (PRP) pretreated with thrombin and tissue plasminogen activator (tPA). Blood samples from healthy participants (n = 7) and trauma patients (n = 22) were tested for platelet calcium mobilization, plasma D-dimer, platelet D-dimer binding (via flow cytometry), and platelet lumi-aggregometry. Results For healthy platelets, maximal platelet dysfunction was observed when cross-linked soluble fibrin (no tPA) or cross-linked fibrin degradation products (FDPs) were generated in suspension before convulxin stimulation. Lack of fibrin polymerization (inhibited by Gly-Pro-Arg-Pro [GPRP]) or lack of factor XIIIa cross-linking (T101-inhibited) restored GPVI signaling, whereas non–cross-linked FDPs only partially blocked signaling induced by convulxin. In addition, D-dimer added to healthy PRP impaired platelet aggregation and dense granule release induced by various agonists. Plasma D-dimer level was strongly correlated (R = 0.8236) with platelet dysfunction as measured by platelet calcium mobilization induced with various agonists. By 48 to 120 h after trauma, plasma D-dimer levels declined, and platelet function increased significantly but not to healthy levels. Trauma platelets displayed elevated D-dimer binding that was only partially reduced by αIIbβ3-inhibitor GR144053. After 60-minute incubation, washed healthy platelets resuspended in plasma from trauma patients captured approximately 10 000 D-dimer equivalents per platelet. Conclusions During trauma, D-dimer and FDPs inhibit platelets, potentially via GPVI and integrin αIIbβ3 engagement, contributing to a fibrinolysis-dependent platelet loss-of-function phenotype. |
| Databáze: | OpenAIRE |
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