BLOOD TRANSFUSION Ferdi Menda,M.D. Assistant Prof of Anesthesiology Yeditepe University

Today’s Topics Available Blood Products n Current Estimates of Transfusion Risks n Fatal Transfusion Reactions n Transfusion Reactions n Indications for Adult Blood Transfusions n

Indications for Transfusion (Adults)

Quality Quality Defining Defining Administering the S S Right Right quantity S S Right Right component S S Right Right way S S Right Right time S Right S Right patient S Right reason with informed consent and adequate documentation of process& outcomes

Packed Red Blood Cells Symptomatic Anemia: Angina Claudication Diaphoresis Dyspnea Fatigue TIA Syncope Tachycardia Postural Hypotension Asymptomatic anemia with Hgb <7 g/dl n Pre- or Post-operative Hgb <10 g/dl or Hct <30% n Acute blood loss >15% of estimated blood volume or n estimated blood loss of 750 ml Acute blood loss with evidence of inadequate oxygen n delivery Hgb <9 g/dl in patient ona chronic transfusion regimen n

Canadian Critical Care Trial Group Study compared “restrictive” (Hgb<7) to “liberal” (Hgb<10) transfusion strategies among critically ill patients. The “restrictive” strategy was as effective and superior to the “liberal” transfusion strategy among patients less than 55 and without cardiac disease. Patients had an overall greater decrease in mortality and less complications. They concluded that a transfusion threshold of 7 g/dl is safe in critically ill patients, including those with minimal cardiopulmonary disease.

Platelets Patient… Maintain platelet ct. above… Marrow failure> 10-20,000/mm 3 Invasive procedure> 50,000/mm 3 Neurosurgical or > 100,000/mm 3 ophthalmologic procedure Bleeding patient> 50,000/mm 3 Bleeding with functional 50-100,000/mm above baseline 3 platelet defect Neonates > 100,000/mm 3

Fresh Frozen Plasma PTT >50 sec or INR> 1.5 (PT> 20 sec) Diffuse microvascular bleeding in massive n transfusion (>1 blood volume) with abnormal parameters Emergency reversal of Warfarin (Coumadin) n anticoagulation when evidence of bleeding present or emergency surgery required Deficiency of specific factors of the n coagulation system when virus-inactivated concentrates not available

Cryoprecipitate Fibrinogen <100mg /dl Factor XIII deficiency Diffuse microvascular bleeding and fibrinogen n <120 mg/dl Von Willebrand’s disease or hemophilia n unresponsive to DDAVP and no appropriate factor concentrates available Uremic bleeding (if DDAVP is ineffective) n

Risks of Transfusion

The safest transfusion is the one not given Medicine

Transfusion Risks: Infectious Current Risks of Infection from “Test Negative” Blood Components (USA) Agent Risk HIV-1/21 in 2.1 million HCV1 in 1.9 million HBV1 in 205,000-488,000 WNV1 in 12 million Bacteria (cultured apheresis1 in 75,000 platelets, 2004-2006 ARC)

Transfusion Risks: Non-Infectious, Early Onset Noninfectious Risks of Transfusion, Early Onset (within hrs) Risk Published Rates Febrile, nonhemolytic nonseptic reaction RBC:1 per 100-500 units Platelets: 1-1.5% Circulatory overload (TACO)1 per 100-2,000 units Hemolysis of incompatible RBCs1 per 13,000-200,000 1 per 1.3-1.7 million (fatal) Hemolysis from incompatible plasma1 per 46,000 (21% plasma incompatible) TRALI1 per 1,000-5,000 Allergic reaction, mild1 per 4,000 RBC, 3-5% plts Allergic reaction, severe; anaphylactic1 per 25,000 (RBC), 1 per 2,000 plts

Transfusion Risks, Late Onset Noninfectious Risks of Transfusion, Late Onset (days to months) Risk Published Rates Formation red cell antibody(s)1 per 200 RBC units (9% pts) Delayed hemolytic reaction1 per 5,000-10,000 Iron overload Essentially all chronically transfused patients Immune suppression All show variable suppression Formation of HLA antibodies 7-15% if multiply transfused Formation of anti-platelet Ab 0.85% of patients Graft-versus-host disease<1 per1 million

Transfusion Reactions

Transfusion reactions Timing: acute versus delayed reaction n Severity: fatal versus non-fatal n Cause: immunologic, infectious, n cardiovascular overload All reactions must be reported to the n lab for investigation and documentation

Transfusion Reactions- Common Febrile n Allergic n Cardiovascular Overload n

Transfusion Reactions- Serious TRALI (transfusion-related acute lung injury) n Hemolytic n Bacterial contamination n Anaphylactic n Graft vs. host disease n

Leading Causes of Fatal Reactions: Cases Reported to FDA, FY07-08 TRALI (51%) n Incompatible blood (23%) n Patient mis-identification: 50-75% n Clerical errors: 10-15% n Technical errors: 10-15% n Bacterial contamination (13%) n Anaphylaxis (5%) n

Transfusion Fatality Update Transfusion-Related Fatalities Reported in FY2005 thru FY2008 Source: Fatalities Reported to FDA Following Blood Collection and Transfusion, Annual Summary for Fiscal Year 2008, March 2009

Transfusion Fatality Update Transfusion-Related Fatalities Reported in FY2005 thru FY2008 Source: Fatalities Reported to FDA Following Blood Collection and Transfusion, Annual Summary for Fiscal Year 2008, March 2009

Allergic Reaction Frequency: Hives or rash RBCs:1 per 4,000, Platelets: 3-5% n Hives or rash n Few/localized– slow infusion rate, antihistamines Rx n Generalized or cardiorespiratory S/Sx– D/C infusion n Triggered by donor proteins or medications n Can develop bronchospasm, GI symptoms n Rx: antihistamines; steroids (severe rxns) n

Volume overload Frequency: Too rapid or too largea volume transfused 1 per 100-2,000 units n Too rapid or too largea volume transfused n Usually pre-existing history of heart or lung n disease Rx: slow infusion rate, diuretics n May need to “split”a unit of blood if transfusion n time will exceed4 hours

Hemolytic Reactions, Acute Frequency n RBCs:1 per 13,000-200,000 n 1 per 1.3-1.7 million (fatal) n ABO incompatibility (usually) n Misidentified patient or clerical error n Rx: Supportive (treat shock, DIC) n

Hemolytic Reactions, Delayed Frequency–1 per 5,000-10,000 RBCs n Patient has RBC antibodies n Chronically transfused patients (10- 40%) n Multiparous females n Unexplained drop in Hgb 3-10 days n after transfusion Rx: Antigen negative blood n

Septic Transfusion Reaction Bacterial contamination of blood product n Frequency–1 in 75,000 n Platelet transfusions most common cause n Room temperature storage n Contamination during blood collection, processing or n pooling Strep and Staph; gram negative bacteria n Platelet products cultured before release by SBB n Rx: Supportive, antibiotics n

Anaphylactic Reaction (Severe Allergic) Frequency n RBCs:1 per 25,000, Platelets:1 per 2,000 n IgA deficient patient with anti-IgA n antibodies Symptoms are immediate (1-2 ml) n Hypotension, shock, bronchospasm n Rx: Supportive; washed RBCs/platelets n

TRALI: Transfusion-Related Acute Lung Injury Donor or patient has cytotoxic white cell n antibodies (HLA or HNA) Patient or donor has cognant antigen n Symptoms within6 hours of transfusion n Acute injury to capillary-alveolar membrane of n lungs Protein-rich fluid leaks into alveolar air spaces n Hypoxemia, fever, pulmonary edema n All require O2 therapy, may require mechanical n ventilation Chest x-ray: pulmonary edema fluid without CHF n changes

TRALI: Treatment& Diagnosis Supportive care: n O , mechanical ventilation, inotropic agents n 2 AVOID diuretics, steroids? n Diagnosis: n Demonstrate HLA and/or HNA antibodies and n matching antigen in patient and donor Differential Diagnosis: n congestive heart failure, acute left ventricular failure n acute circulatory (volume) overload n pulmonary embolism n rapidly progressive pneumonia n acute respiratory distress syndrome (ARDS) n

TRALI Prevention Frequency of TRALI related to amount of plasma in blood product Platelets and FFP> RBC n Donors with history of prior pregnancies, transfusion, n tissue transplant at higher risk for HLA/HNA antibodies Blood supplier (SBB) provides male-only FFP n Female AB FFP may be provided if emergency FFP n inventory shortage Blood providers considering screening of platelet and n FFP donors History of prior pregnancies, transfusion, tissue n transplants HLA/HNA antibodies n

TRALI and Blood Products Source: Fatalities Reported to FDA Following Blood Collection and Transfusion, Annual Summary for 2006, March 2009

TRALI Edema Fluid

TRALI Edema Fluid

TRALI Chest X-Ray

Suspected Transfusion Reaction STOP transfusion; Keep IV open with NS n Promptly notify laboratory and attending MD n Verify clerical information; n Patient ID, bag tag and label n Complete transfusion reaction report n Order transfusion reaction workup in CareCast n Send report with bag (tubing attached) to lab n Lab will determine what samples need to be n collected and contact pathologist on-call

Massive Blood Transfusion one unit of whole blood equals 450 ml in US 37

Definition Replacement by transfusion of more than 50 % of a patient's blood volume in 12 - 24 hours Adult patients requiring > 4 units of PRBCs in first hour of resuscitation or. pediatric patient requiring > 20 ml/kg of PRBCs in first hour of resuscitation. 38

Problems in Massive Transfusion: Lethal triad Hypothermia, acidosis, coagulopathy, usually occurs after uncontrolled bleeding often at 16 units. It exemplifies the issues associated with massive bleeding and volume and blood product replacement

Hypothermia Reduces the enzymatic activity of plasma coagulation proteins Has a greater effect by preventing the activation of platelets via traction on the glycoprotein Ib/IX/V complex by von Willebrand factor. In tests of shear-dependent platelet activation, this pathway stops functioning in 50 percent of individuals at 30º C, and is markedly diminished in most of the rest.

Acidosis Interferes with the assembly of coagulation factor complexes involving calcium and negatively-charged phospholipids. The activity of the factor Xa/Va/prothrombinase complex is reduced by 50, 70, and 90 percent at a pH of 7.2, 7.0, and 6.8, respectively.

COMPLICATIONS OF CITRATE INFUSION Large amounts of citrate are given with massive blood transfusion, since blood is anticoagulated with sodium citrate and citric acid. Metabolic alkalosis Decline in the plasma free calcium concentration

Free hypocalcemia Citrate binding of ionized calcium can lead to a clinically significant fall in the plasma free calcium concentration. This change can lead to paresthesias and/or cardiac arrhythmias in some patients

Goal of Massive Blood Transfusion Maintain Hb >8 g/dl Maintain platelet count >75 · 109 /L Maintain PT & APTT < 1.5 · mean control Maintain Fibrinogen > 1.0 g/L

The coagulation system should be frequently monitored with measurements of the PT, aPTT and platelet count, preferably after each 5 units of blood replaced. If the PT and PTT exceed 1.5 times the control value, the patient should be transfused with 2 units of fresh frozen plasma. If the platelet count falls below 50,000/microL, 6 units of platelets should be given.

A blood warmer should be used whenever more than three units are transfused. Hypothermia should be either avoided or minimized. Acid–base balance and the plasma ionized calcium and potassium levels should be periodically monitored, particularly in patients with coexistent liver or renal disease or in those with massive hemorrhage and low cardiac output