A tight interplay between platelet activation and mitochondrial DNA release promotes platelet storage lesion in platelet concentrates.

BACKGROUND AND OBJECTIVES: Platelet storage lesion (PSL) adversely affects the quality of platelet concentrates (PCs). Platelets are prone to activation during storage. Moreover, elevated free mitochondrial DNA (mtDNA) levels in PCs are associated with a higher risk of adverse transfusion reactions. Therefore, we aimed to evaluate the correlation between platelet activation markers and mtDNA release during PC storage. MATERIALS AND METHODS: Six PCs prepared by the platelet-rich plasma method were assessed for free mtDNA copy number using quantitative real-time PCR and CD62P (P-selectin) expression by flow cytometry on days 0 (PC collection day), 3, 5 and 7 of storage. Lactate dehydrogenase (LDH) activity, pH, platelet count, mean platelet volume (MPV) and platelet distribution width (PDW) were measured as well. The correlation between free mtDNA and other PSL parameters, and the correlation between all parameters, was determined. RESULTS: Significant increases in free mtDNA, MPV and PDW, and a significant decrease in platelet count and pH were observed. CD62P expression and LDH activity elevated significantly, particularly on storage days 5-7 and 0-3, respectively. Moreover, a moderate positive correlation (r = 0.61) was observed between free mtDNA and CD62P expression. The r values between free mtDNA and LDH, pH, platelet count, MPV and PDW were 0.81, -0.72, -0.49, 0.81 and 0.77, respectively. CONCLUSION: The interplay between platelet activation and mtDNA release in promoting PSL in PCs may serve as a promising target for future research on applying additive solutions and evaluating the quality of PCs to improve transfusion and clinical outcomes.

Resveratrol reduces platelet storage lesion by preventing free mitochondrial DNA (mtDNA) accumulation in platelet concentrates during storage.

Platelet activation and mitochondrial damage are among the crucial events leading to the quality reduction of platelet concentrates (PCs) during preparation and storage, called platelet storage lesion. Platelet activation results in the clearance of transfused platelets. Oxidative stress and platelet activation trigger mitochondrial DNA (mtDNA) release into the extracellular milieu which is associated with adverse transfusion reactions. Therefore, we aimed to investigate the effects of resveratrol, an antioxidant polyphenol, on platelet activation markers and mtDNA release. Ten PCs were divided equally into two bags each, one of them was allocated to the control group (n = 10) and another to the case group (resveratrol-treated, n = 10). Free mtDNA level and CD62P (P-selectin) expression level were measured by absolute quantification Real-Time PCR, and flow cytometry on days 0 (the receiving day), 3, 5, and 7 of storage respectively. Moreover, Lactate dehydrogenase (LDH) enzyme activity, pH, platelet count, mean platelet volume (MPV), and platelet distribution width (PDW) were assessed as well. Treatment of PCs with resveratrol can significantly decrease mtDNA release during storage compared to the control. In addition, platelet activation was significantly mitigated. We also observed significantly lower MPV, PDW, and LDH activity in resveratrol-treated PCs compared to the control group on days 3, 5, and 7. Furthermore, resveratrol maintained the pH of PCs on day 7. Resveratrol diminished free mtDNA and maintained biochemical parameters in PCs, possibly by reducing platelet activation. Therefore, resveratrol might be a possible additive solution for improving the quality of stored PCs.

Risk and Management of Intracerebral Hemorrhage in Patients with Bleeding Disorders.

Intracerebral hemorrhage (ICH) is the most dreaded complication, and the main cause of death, in patients with congenital bleeding disorders. ICH can occur in all congenital bleeding disorders, ranging from mild, like some platelet function disorders, to severe disorders such as hemophilia A, which can cause catastrophic hemorrhage. While extremely rare in mild bleeding disorders, ICH is common in severe coagulation factor (F) XIII deficiency. ICH can be spontaneous or trauma-related. Spontaneous ICH occurs more often in adults, while trauma-related ICH is more prevalent in children. Risk factors that can affect the occurrence of ICH include the type of bleeding disorder and its severity, genotype and genetic polymorphisms, type of delivery, and sports and other activities. Patients with hemophilia A; afibrinogenemia; FXIII, FX, and FVII deficiencies; and type 3 von Willebrand disease are more susceptible than those with mild platelet function disorders, FV, FXI, combined FV-FVIII deficiencies, and type 1 von Willebrand disease. Generally, the more severe the disorder, the more likely the occurrence of ICH. Contact sports and activities can provoke ICH, while safe and noncontact sports present more benefit than danger. An important risk factor is stressful delivery, whether it is prolonged or by vacuum extraction. These should be avoided in patients with congenital bleeding disorders. Familiarity with all risk factors of ICH can help prevent occurrence of this diathesis and reduce related morbidity and mortality.