Immunomodulatory and Pro-thrombotic roles of Red Cells. Increasing molecular and clinical evidence supports the role of RBCs in physiological hemostasis and pathologic thrombosis. Recent evidence ranging from in vivo clot formation models to large database studies suggest that transfused RBCs may have a role in accelerating thrombus generation. Transfused RBCs have been proposed to modulate the inflammatory cascade. In addition, during the storage period, RBCs develop storage lesions, including metabolic, biochemical, and physical changes responsible for accumulation of bioreactive substances such as microparticles, which can have a prothrombogenic potential. Literature linking RBC transfusions to thrombotic outcomes, proposed mechanistic pathways for the same and ongoing and future research efforts will be presented.
Platelets: Hemostatic and pro-thrombotic roles. In the last 20 years it has become apparent that platelets perform immune functions in addition to their hemostatic properties. Platelets are a rich source of pro- inflammatory and immunomodulatory molecules, including IL-6 and CD40L, and play an important role in host defenses. Platelet transfusions are, therefore, involved in adverse reactions that are due to these inflammatory properties, including the well described TRALI, TACO, fever and rigors. What are less well known are the in vitro, animal model and epidemiologic cohort studies that demonstrate that platelet transfusions contribute to organ failure, thrombosis and mortality. This literature will be reviewed, and possible future studies and mitigating factors such as leukoreduction, plasma reduction and ABO matching will be addressed.
Platelet Microparticles: Tiny but mighty! Platelet activation, whether biochemical or through shear stress, causes the platelet plasma membrane to breach, and subsequently shed surface proteins, bioactive fragments, cytoplasmic contents, and membrane fragments known as microparticles (MP). Platelet microparticles (PMP) are the most prevalent in circulation, representing up to 90% of all MP. Clinical findings have revealed that patients with thrombocytopenic disorders such as heparin-induced thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), sickle cell disease, and certain malignancies are also associated with increased levels of PMP, which may contribute to prevention of bleeding and a higher risk of thrombosis. In addition, studies have shown that stored platelets have increased levels of PMP that are directly correlated to the length of the storage period. Lastly, the PMP membrane has been found to be 50 to 100-fold more procoagulant than the surface of activated intact platelets. Few in vitro experiments will be demonstrated to support these facts along with future study plans.
Analyze the evolving role of red cells in physiological hemostasis as well as pathological thrombosis and understand the current research evidence base exploring this question.
Assess the immunomodulatory functions in addition to hemostatic properties of platelets and understand in vitro, animal model and epidemiologic cohort studies linking platelet transfusions to organ failure, thrombosis and mortality.
Appraise the procoagulant properties of platelet microparticles and evidence supporting their contribution to thrombotic outcomes.