Autologous donated units for elective surgery, large volume hemorrhage, neonatal exchange transfusion
Increase oxygen carrying capacity to tissues, exchange transfusion, red cell exchange
Iron overload, volume overload, chronic asymptomatic anemia
Active bleeding due to deficiency of multiple coagulation factors, risk of bleeding due to deficiency of coagulation factors, urgent reversal of warfarin, massive transfusion
Normalizing abnormal coagulation screen tests in absence of bleeding
Bleeding due to insufficient circulating platelet count or abnormally functioning platelets; prophylactic to prevent bleeding in patients undergoing invasive procedures
40 u filter, hypothermia, risk of thrombosis, bypass circuit, autoimmune thrombocytopenia, thrombotic thrombocytopenic purpura
Bleeding associated with fibrinogen deficiency or factor XIII deficiency, hemophilia A, or von Willebrand’s disease if specific concentrates unavailable
1 unit/10 kg
PRBC – 1 unit of PRBC will increase hemoglobin in the average adult who is not bleeding or hemolyzing by about 1 g/dl or hematocrit by about 3 % . For pediatric patients, the dose is generally 10–20 ml/kg .
FFP – A dose of 10–20 ml/kg is usually sufficient to achieve a plasma factor concentration of 30 % of normal [4, 5].
Platelet – One plateletpheresis unit (≥3 × 1011 platelets) or 4–10 pooled platelet units (≥5.5 × 1010 platelets) for adults or 10–15 ml/kg for pediatric patients should raise platelet count by 50,000–100,000/mm3 [4, 5].
Cryoprecipitate – 1 unit per 10 kg will raise fibrinogen by about 50 mg/dl in the absence of continued consumption or massive bleeding .
There are no known drug interactions with blood products; however, citrate toxicity may result from rapid infusion, especially in the setting of liver disease . Citrate, an anticoagulant used in blood products, is normally metabolized quickly by the liver and binds calcium and magnesium. As such, calcium-containing carrier fluids (e.g., lactated Ringer’s solution) should not be used due to a theoretical risk of clot formation.
Side Effects/Black Box Warnings
Immune reactions – These reactions may be hemolytic or nonhemolytic. Signs of hemolytic immune reaction include urticaria, hypotension, tachycardia, increased airway pressure, hyperthermia, decreased urine output, hemoglobinuria, and microvascular bleeding . Risk of death from severe hemolytic reaction is about one in one million .
Infection risk from handling – Bacterial contamination of blood products is most frequently associated with platelets and is the leading cause of death related to transfusions . This risk is related to storage temperatures of platelets above 20–24 °C. Contaminated platelets may be suspected if a patient develops a fever within 6 h after receiving platelets.
TRALI – Transfusion-related acute lung injury is a non-cardiogenic pulmonary edema resulting from leukocyte antibodies from transfused blood products. The risk is about 1 in 10,000 . It usually manifests 1–2 h after transfusion with peak effect within 6 h. Recovery is usual in 96 h; however, TRALI is one of the three most common causes of transfusion-related deaths , and case fatality rate has been reported between 5 and 10 % .
Infectious disease transmission from donors – Hepatitis C and HIV transmission rates from blood transfusion are now rare (one in one million) , because these diseases can be detected by nucleic acid technology. Risk of hepatitis B transmission is about 1 in 300,000 . Currently, malaria, Chagas disease, and variant Creutzfeldt-Jakob disease cannot be detected .
Transfusion of blood products is vital for when lifesaving resuscitation measures are needed. However, packed red blood cells have limitations and additional risks as discussed above. The development of blood substitutes have been studied for over 50 years in hopes to create an infusible product that serves as an alternative to pRBC . Patients who would most benefit are those with an immediate need for resuscitation products, who are immunoreactive to all blood types, and who reside in areas where pRBCs are difficult to obtain and store or which lack blood banks and in areas where there is increased prevalence of donor blood-borne disease transmittance .
Hemoglobin-based oxygen carriers (HBOCs) are blood substitutes that are constructed from human or bovine blood cells. HBOCs use the natural O2 delivery system of hemoglobin, which is removed from the red cell, purified, and re-polymerized . Hemoglobin consists of two alpha and two beta subunit chains, each of which contains an iron atom that binds oxygen. Some preparations of HBOCs are presented as bags of red colored liquid, and others come in powder form and are to be mixed with an IV fluid for use as an intravenous infusion. Early generations of HBOCs that had high amounts of hemoglobin dimmers and tetramers (no longer in testing) were filtered through renal glomerulus and excreted through the kidneys, while newer versions are too large to be filtered and are metabolized the same way free hemoglobin is, via breakdown in the liver to usable iron, proteins, and bilirubin. Currently, there are three HBOC versions in active testing: polymerized, conjugated, and cross-linked . Preliminary studies suggest that patients treated with certain HBOCs have safely avoided the need for blood transfusion [8, 10]. However, there have been considerable setbacks in the development of these products including renal failure, increased mortality, systemic and pulmonary hypertension, myocardial infarction, hemolysis, and chemical pancreatitis . Although there are no currently approved blood substitutes in the USA for human use, further investigations and clinical trials are underway in hopes of providing efficacious HBOCs with minimal complications (see Table 26.2). One product is approved for veterinary use in the USA and European Union since 1997 and 1998, respectively (Oxyglobin®, hemoglobin glutamer 301 (bovine), OPK Biotech, Cambridge, MA), and one product is approved for human use in South Africa and Russia since 2001 and 2010, respectively (Hemopure®, hemoglobin glutamer 201 (bovine), OPK Biotech, Cambridge, MA).
Clinical studies on HBOCs
α-α intra-tetramer cross-linked human Hba
Suspended – USA 2008
Biopure (now OPK Biotech)
α-α intra- and inter-tetramer cross-linked bovine Hba
Surgery, sickle cell crisis, trauma
Phase III – US FDA denied further clinical trials, 2008
Northfield Laboratories (closed activities)
Inter-tetramer cross-linked human Hba
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