Physiology of Transfusion Therapy

Indications for Transfusion Enhance oxygen carrying capacity of blood by expanding red call mass. Replace clotting factors, either lost, consumed, or not produced.

Enhancement of Oxygen Carrying Capacity Majority of arterial blood oxygen binds with hemoglobin reversibly. Release of O2 to tissues depend on many factors, the oxygen saturation being the most important. The saturation of hemoglobin molecules with O2 determines the binding affinity.

Enhancement of Oxygen Carrying Capacity As saturation increases, affinity decreases, release of O2 to tissues is then enhanced. The partial pressure of O2 required to saturate 50% of the Hb molecules is called P-50. P-50 value is increased with fever, acidosis, increased 2,3 DPG, thus O2 is released to tissues with greater ease under these circumstances. However with hypothermia, alkalosis, and decreased 2,3 DPG affinity is increased, release decreased.

O2 Carrying Capacity Tissue oxygenation also depends on tissue oxygen demands. Under normal circumstances, there is a physiologic reserve between O2 delivery (1000cc/min) and consumption (250cc/min). Despite this large reserve, clinical circumstances, such as massive MOSF, can have consumption outstripping delivery.

O2 Carrying Capacity Hb normally ranges between 12-18g/dL depending on race, age, sex, medical condition. Old tradition of keeping Hb at 10 is not valid. A Hb of 7-8 has been demonstrated to be adequate except in patients with CAD, COPD. It is clear that the rate and magnitude of blood loss, state of tissue perfusion, pre-existing cardiopulmonary disease all affect the ability of the patient to tolerate lower concentrations of Hb.

O2 Carrying Capacity Decreased levels of 2,3 DPG increase O2- Hb binding affinity. 2,3 DPG levels may decrease by 30% in blood stored for greater than 2 weeks, by 60-70% in 3 weeks. When transfused, this old blood has a significantly diminished ability to release O2 to tissues.

Enhancement of Hemostasis The second most common indication for transfusion is repletion of hemostatic agents. It is not safe to simply correct abnormal lab values, or to blindly adhere to old unproven surgical dictums.

Enhancement of Hemostasis Replacement products should be used only in preparation for elective surgery, or with clinically significant abnormalities in hemostasis. These include disorders of consumption or production of fibrinogen, intrinsic or extrinsic factor defects, platelet dysfunction.

Packed Red Blood Cells Prepared by removing 200 cc of plasma from fresh whole blood, to achieve a final HCT of 70-80%. They are kept anticoagulated with CPD (citrate, phosphate, dextrose), stored in liquid state at 4 degrees or frozen at –80C. The longer the storage, the lower the rate of survival. Immediate (90%), 6 weeks (65%).

Cryopreserved RBC This technique utilizes rapid cooling of PRBC to –80C in 40% glycerol, post transfusion survival is 80-90%, 2,3 DPG levels are normal, antigenic reactions minimized. Large quantities of red cells can be stored for many years. Kind of expensive!

Autotransfusion Involves collection and immediate reinfusion of patient’s own blood for volume replacement an d to increase red cell mass. Massive exsanguination from either blunt or penetrating trauma without gross enteric contamination best candidates. Eliminates risk of histocompatability reactions, infectious disease.

Autotransfusion Not without risk, most common complication is thrombocytopenia. When patients receive more than 4L of blood, platelet count may drop to less than 50,000, risk of ATN increased from debris of plasma-free Hb. Also risk of air embolism, particulate microemboli, DIC.

Pre-Donation Increased with public awareness of transmission of infection with blood transfusion. Blood storage in pre-donation is similar to PRBC (42 day maximum). Contraindications include significant CAD, COPD, existence of a hematologic disorder.

Products That Enhance Hemostasis Fresh Frozen Plasma-Single donor, same risk of HIV, Hepatitis as PRBC. Frozen at 8C, this temperature protects Factor V and VII in particular. FFP contains components of the coagulation, fibrinolytic, and complement systems.

Products That Enhance Hemostasis Useful in treating deficiencies in 2,5,7,8,9,10,11. Also in Coumadin reversal, ATIII deficiency. Type and Rh specific plasma should be used. Urticaria, fatal pulmonary edema.

Cryoprecipitate Used to replenish Factor VIII or fibrinogen. Formed as a plasma concentrate that consists primary as Factor VIII and fibrinogen. In addition it contains Factor XIII, vWF, fibronectin. Stored at 37C. Above this Factor VIII destroyed. Disadvantage is multiple donors, increased risk of hemolytic reactions due to small amts of anti-A, anti-B, and Rh antibodies left over in preparation.

Platelets Collected by repeated centrifugation of fresh whole blood, and suspension in cc of plasma at 22C. Remain viable up to 5 days, most efficacious if used within 24-48h of pooling. After that lose ability to produce thromboxane A-2, a potent vasoconstrictor and platelet aggregator. Risk of infectious complications equal to number of donors, must be ABO and Rh compatible, since donor plasma is present.

Complications of Transfusion  Immunologic reactions  Metabolic reactions  Infectious complications

Immediate Hemolytic Reactions ABO incompatibility most commonly caused by sample labeling, misidentification. Reaction soon after transfusion started.

Immediate Hemolytic Reactions Change in mental status, SOB, hypotension, back pain, chest pain, facial flushing, cyanosis, tachycardia, profound shock. Can end in DIC, acute renal failure, death. Normally haptoglobin is capable of binding free Hb in plasma. The complex is then cleared by reticuloendothelial system. If this clearance mech is exceeded….

Immediate Hemolytic Reactions Renal failure produced by free hemoglobin bound to albumin to form methalbumin. Hemoglobinuria occurs, hypotension and vasoconstriction cause a reduction in GFR, thrombi form in renal tubules. Circulating antibody complexes released in to circulation make renal failure worse. In OR may present as diffuse bleeding.

Delayed Hemolysis Infrequent, related to red cell antigens other than A or B. Can occur 3-21 days after blood is infused. Symptoms include malaise and fever. Labs show low Hb, elevated indirect bilirubin. Usually observe if stable.

Allergic Reactions Transfusion of antibodies or antigens to which the recipient is sensitive. Urticaria, chills, itching, fever. Occurs frequently, 2% of transfusions. In rare occasions, can cause anaphylactic shock.

Febrile Reactions Most common transfusion reaction (7% of transfusions.). Due to antileukocyte antibodies that develop as a result of prior transfusions. Fever, chills, flushing, tachycardia. May progress to hypertension, cyanosis, collapse. Rule out bacterial contamination and ABO incompatibility when it occurs.

Anaphylactoid Reactions When recipient is sensitized to IgA, a common immunoglobulin. Fever, chills, bronchospasm, diarrhea, abdominal pain, vascular collapse. Transfusion related acute lung injury- Rare, caused by antibodies to recipients WBC, clot in pulmonary circulation.

Bacterial Contamination All blood products except albumin and serum globulins carry HIV and Hepatitis risk. That’s because they are heat treated. 19% of all fatal reactions involve blood products with contamination. 1-2% of all blood products may be contaminated with bacteria.

Bacterial Contamination Most common cold growing, endotoxin- producing, gram negative organisms are klebsiella, pseudomonas, identified in 68% of the reported reactions. Gram positive organisms responsible usually staph. Contamination arises from donor. Hypotension, fever, abd pain, extremity pain,sepsis.

Bacterial Contamination Onset shortly after transfusion begins, temp spikes at 12 h intervals. Absence of hemoglobin in urine and presence of bacteria in the blood product confirms diagnosis. Mortality 50-80%. Most common blood product cause of contamination is platelets…not refrigerated.

Viral Contamination Hepatitis most common % risk per unit. Most common is Hepatitis C (85-98%), incubation 8 weeks, chronic in 50% of patients. HIV risk 1: 1,000,000- 2,000,000 per unit blood. CMV, EBV especially in premature infants, transplant patients.

Other Problems Citrate- causes hypocalcemia, also direct cardiac depressant. From massive rapid transfusions of PRBC. Replace calcium 1 gram for each 6 units transfused, since in a trauma scenario, checking ionized Ca not practical…

Other Problems Hypothermia, coagulopathy, leftward shift in O2 dissociation curve, less release. Dilutional thrombocytopenia, after transfusion of more than 10 units blood. Hyperkalemia- as a result of ADP pump inactivation in stored blood, potassium levels can reach 70 meq/L. Watch out in renal patients…Not really a problem though….