Blood transfusion and stem cell transplantation

Blood transfusion

Blood obtained from healthy adult donors is collected and separated into several components for transfusion, including red blood cells (RBCs), platelets, plasma, and rarely, leukocytes (granulocytes). Laboratory tests performed on donor blood include blood typing (ABO and Rh), RBC antibody detection, hepatitis screening, and screening for the infectious agents hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T-cell lymphotropic virus, and syphilis. Cell fractions are usually stored in citrate phosphate dextrose adenine (CPDA) preservative, a solution containing citrate (anticoagulant), phosphate (buffer), dextrose (energy supply), and adenine (to maintain intracellular adenosine triphosphate). Citrate acts as an anticoagulant by binding to calcium, an essential cofactor in the coagulation cascade.

Preserved RBC concentrates maintain viability for up to 35 days, whereas stored platelet concentrates maintain viability for only about 5 days. Cold storage of plasma leads to depletion of coagulation factors V, VIII, and IX within 48 hours, and granulocyte function begins to decline 24 hours after granulocyte concentrate collection. Frozen storage of packed RBCs , platelet concentrates, and plasma significantly extends the shelf life of these blood products. Frozen storage of RBCs and platelets requires the addition of cryoprotective agents to prevent freeze-thaw–mediated cytolysis (glycerol for RBCs and dimethyl sulfoxide for platelets). Frozen storage of granulocytes is not routinely performed because post-thaw recovery of granulocytes rarely exceeds 25%.

The primary indications for transfusion of packed RBCs include severe anemia (hemoglobin >7 g/dL) and significant blood loss. In special circumstances, RBCs can be washed to remove plasma or filtered to remove leukocytes. Washed RBCs are used to minimize exposure of patients with hypersensitivity to plasma proteins to plasma protein and to minimize exposure of neonates to the effects of transfused anticoagulant, potassium, or both. Leukocyte-poor RBCs are provided to multitransfused patients to prevent febrile reactions in those who may have developed anti– human leukocyte antigen (HLA) antibodies to leukocytes and platelets and to immunocompromised patients to reduce the risk of transmission of bloodborne viruses.

Indications for platelet transfusion include severe thrombocytopenia (platelet count <5,000–10,000/μL) caused by marrow failure (aplastic anemia or after myelosuppressive therapy), and bleeding caused by idiopathic thrombocytopenic purpura, massive RBC transfusion, cardiopulmonary bypass, and inherited platelet function disorders.

Granulocyte transfusions are generally limited to patients with all of the following: (1) an absolute granulocyte count below 500/μL, (2) fever, (3) an identified responsible infectious agent, and (4) no fever reduction after 48 hours of appropriate antibiotic therapy. Leukocyte antigen matching is useful in minimizing febrile transfusion reactions and maximizing leukocyte half-life. To prevent serious cytomegalovirus (CMV) infection in immunosuppressed patients, granulocyte transfusions from CMV-negative donors are provided. Graft-versus-host disease induced by donor lymphocytes can be prevented by irradiation of granulocyte concentrates before administration to immunocompromised patients.

Citrated donor plasma is often frozen immediately after collection ( fresh-frozen plasma ) to preserve labile coagulation factors V and VIII, significantly extending the shelf life of this blood product. Indications for plasma transfusion include coagulation factor deficiencies (excluding factors VIII and IX), rapid reversal of warfarin-induced anticoagulation, plasma exchange for thrombotic thrombocytopenic purpura, bleeding with massive blood transfusion, bleeding caused by liver disease-related coagulopathy, and bleeding caused by disseminated intravascular coagulation (DIC).

Frozen plasma that is slowly thawed at 4°C forms a small amount of precipitated material termed cryoprecipitate . Cryoprecipitate is enriched in several procoagulant substances, including factor VIII, von Willebrand factor (VWF), fibrinogen, and factor XIII. Although cryoprecipitate can be used to treat deficiencies of any of these factors, its most common use is in treatment of hypofibrinogenemia. First-line therapies for hemophilia A and VWD are recombinant factor VIII and desmopressin (DDAVP), respectively. DDAVP, an analog of vasopressin, acts by enhancing the release of VWF from endothelial cells.