Changes in the functional state of platelets in patients with polytrauma

Background. Polytrauma remains the leading cause of global morbidity and mortality and is the cause of more than 10 % of deaths. The purpose of this research was to study the lite­rature data about changes in vascular platelet hemostasis, to investigate the dynamics of the morphofunctional state of platelets, to analyze changes in intravascular platelet activation in patients with polytrauma. Results. Normal blood clotting requires at least 4 components — blood vessels, platelets, the ability of blood to coagulate and fibrinolysis. Determination of components such as indicators of intravascular platelet activation can be an important step in assessing disorders of platelet hemostasis in patients with polytrauma. Vascular platelet hemostasis begins with primary reflex spasm of arterioles, followed by secondary spasm of arterioles, then primary platelet plug is formed (adhesion and aggregation), and, accor­dingly, the consolidation of the thrombus, resulting in the formation of the final platelet thrombus. Even before the contact of platelets with naked collagen, the primary activation of platelets occurs. Initially, the shape of intact platelets changes from discoid form to activated cells of discoechinocytes, spherocytes and, or, spheroechinocytes. We found that on day 3 after injury, with a normal number of platelets in the venous blood, the number of intact platelets, discocytes, decreases, the number of active forms of thrombocytes, discoechinocytes and spheroechinocytes, increases, and, accor­dingly, the total amount of active forms of thrombocytes increases. Normal platelet counts in patients with polytrauma may mask the severity of coagulopathy, and studies of intravascular platelet activation may be a diagnostic component of the vascular platelet hemostasis in patients with polytrauma. Conclusions. In patients with coagulopathy due to polytrauma, there are changes in intravascular platelet activation and platelet aggregation, induced by adrenaline and adenosine diphosphate, on day 3.

The effect of desmopressin on platelet function: a selective enhancement of procoagulant COAT platelets in patients with primary platelet function defects

Key PointsDDAVP is the drug of choice for mild hemophilia A and von Willebrand disease and (by unclear mechanisms) for platelet function disorders. In vivo DDAVP selectively and markedly enhances the ability to form procoagulant platelets by enhancing intracellular Na+ and Ca2+ fluxes.

Red cell-derived microparticles (RMP) as haemostatic agent

SummaryAmong circulating cell-derived microparticles, those derived from red cells (RMP) have been least well investigated. To exploit potential haemostatic benefit of RMP, we developed a method of producing them in quantity, and here report on their haemostatic properties. High-pressure extrusion of washed RBC was employed to generate RMP. RMP were identified and enumerated by flow cytometry. Their size distribution was assessed by Doppler electrophoretic light scattering analysis (DELSA). Interaction with platelets was studied by platelet aggregometry, and shear-dependent adhesion by Diamed IMPACT-R. Thrombin generation and tissue factor (TF) expression was also measured. The effect of RMP on blood samples of patients with bleeding disorders was investigated ex vivo by thromboelastography (TEG). Haemostatic efficacy in vivo was assessed by measuring reduction of blood loss and bleeding time in rats and rabbits. RMP have mean diameter of 0.45 μm and 50% of them exhibit annexin V binding, a proxy for procoagulant phospholipids (PL). No TF could be detected by flow cytometry. At saturating concentrations of MPs, RMP generated thrombin robustly but after longer delay compared to PMP and EMP. RMP enhanced platelet adhesion and aggregation induced by low-dose ADP or AA. In TEG study, RMP corrected or improved haemostatic defects in blood of patients with platelet and coagulation disorders. RMP reduced bleeding time and blood loss in thrombocytopenic rabbits (busulfan-treated) and in Plavix-treated rats. In conclusion, RMP has broad haemostatic activity, enhancing both primary (platelet) and secondary (coagulation) haemostasis, suggesting potential use as haemostatic agent for treatment of bleeding.

Glycoprotein Ibα and von Willebrand factor in primary platelet adhesion and thrombus formation: Lessons from mutant mice

SummaryThe von Willebrand factor (VWF) receptor complex, glycoprotein (GP)Ib-V-IX, and its main ligand VWF play a key role in the adhesion process of platelets to sites of vascular injury. Recent studies in mutant mice have shed new light on the importance of either molecule for the development of arterial and venous thrombosis. In this review, we summarize the most important aspects from these studies.

Determinants of platelet conjugate formation with polymorphonuclear leukocytes or monocytes in whole blood

SummaryFollowing preliminary in-vitro experiments, platelet-leukocyte conjugates and their determinants were evaluated in citrated whole blood from 349 subjects (209 women, age 16–92 years) randomly recruited from the general population. Platelet activation by ADP/collagen but not leukocyte stimulation by fMLP or LTB4 resulted in formation of platelet conjugates with PMN or monocytes. In the population study, mixed cell conjugates, platelet P-selectin and leukocyte CD11b were measured by flow cytometry both at baseline and after in-vitro stimulation with ADP/collagen. The latter significantly increased platelet conjugates with either PMN or monocytes, platelet P-selectin and leukocyte CD11b expression. Platelet count significantly correlated with platelet-PMN, platelet-monocyte conjugates and P-selectin both at baseline and upon stimulation. In all conditions, both conjugate levels correlated with each other, when adjusted for gender, age and platelet count. Age correlated with platelet-PMN conjugate numbers in basal and stimulated conditions and with basal P-selectin. ADP/collagen stimulation resulted in higher P-selectin and conjugates values in women. Among risk factors, a significant correlation was found between conjugate and glucose levels. In conclusion, the presence and formation in whole blood from a large population of plateletleukocyte conjugates reflects primary platelet – but not leukocyte – activation and varies with gender, age, platelet count and blood glucose.