Nonsurgical bleeding diathesis in anemic thrombocytopenic patients: role of temperature, red blood cells, platelets, and plasma-clotting proteins.
Research at the Naval Blood Research Laboratory (Boston, MA) for the past four decades has focused on the preservation of red blood cells (RBCs), platelets (PLTs), and plasma-clotting proteins to treat wounded servicemen suffering blood loss. We have studied the survival and function of fresh and preserved RBCs and PLTs and the function of fresh and frozen plasma-clotting proteins. This report summarizes our peer-reviewed publications on the effects of temperature, RBCs, PLTs, and plasma-clotting proteins on the bleeding time (BT) and nonsurgical blood loss. The term nonsurgical blood loss refers to generalized, systemic bleeding that is not corrected by surgical interventions. We observed that the BT correlated with the volume of shed blood collected at the BT site and to the nonsurgical blood loss in anemic thrombocytopenic patients after cardiopulmonary bypass surgery. Many factors influence the BT, including temperature; hematocrit (Hct); PLT count; PLT size; PLT function; and the plasma-clotting proteins factor (F)VIII, von Willebrand factor, and fibrinogen level. Our laboratory has studied temperature, Hct, PLT count, PLT size, and PLT function in studies performed in non-aspirin-treated and aspirin-treated volunteers, in aspirin-treated baboons, and in anemic thrombocytopenic patients. This monograph discusses the role of RBCs and PLTs in the restoration of hemostasis, in the hope that a better understanding of the hemostatic mechanism might improve the treatment of anemic thrombocytopenic patients. Data from our studies have demonstrated that it is important to transfuse anemic thrombocytopenic patients with RBCs that have satisfactory viability and function to achieve a Hct level of 35 vol percent before transfusing viable and functional PLTs. The Biomedical Excellence for Safer Transfusion (BEST) Collaborative recommends that preserved PLTs have an in vivo recovery of 66 percent of that of fresh PLTs and a life span that is at least 50 percent that of fresh PLTs. Their recommendation does not include any indication that preserved PLTs must be able to function to reduce the BT and reduce or prevent nonsurgical blood loss. One of the hemostatic effects of RBC is to scavenge endothelial cell nitric oxide, a vasodilating agent that inhibits PLT function. In addition, endothelin may be released from endothelial cells, a potent vasoconstrictor substance,to reduce blood flow at the BT site. RBCs, like PLTs at the BT site, may provide arachidonic acid and adenosine diphosphate to stimulate the PLTs to make thromboxane, another potent vasoconstrictor substance and a PLT-aggregating substance. At the BT site, the PLTs and RBCs are activated and phosphatidyl serine is exposed on both the PLTs and the RBCs. FVa and FXa, which generate prothrombinase activity to produce thrombin, accumulate on the PLTs and RBCs. A Hct level of 35 vol percent at the BT site minimizes shear stress and reduces nitric oxide produced by endothelial cells. The transfusion trigger for prophylactic PLT transfusion should consider both the Hct and the PLT count. The transfusion of RBCs that are both viable and functional to anemic thrombocytopenic patients may reduce the need for prophylactic leukoreduced PLTs, the alloimmunization of the patients, and the associated adverse events related to transfusion-related acute lung injury. The cost for RBC transfusions will be significantly less than the cost for the prophylactic PLT transfusions.
Valeri
C Robert
CR
NBRL, Inc., and Boston VA Healthcare System, Boston, Massachusetts, USA. navblood@nbrl.org
Khuri
Shukri
S
Ragno
Gina
G
D000740:Anemia / Q000097:blood* / Q000150:complications; D001777:Blood Coagulation; D016063:Blood Loss, Surgical / Q000706:statistics & numerical data; D004198:Disease Susceptibility; D004906:Erythrocyte Count; D006470:Hemorrhage / Q000453:epidemiology*; D006801:Humans; D010976:Platelet Count; D013696:Temperature; D013921:Thrombocytopenia / Q000097:blood / Q000150:complications*