BLOOD GROUPS- A REVIEW Human erythrocytes >300 antigenic determinants Only ABO and Rh important in the majority of blood transfusions Most severe transfusion reactions due to ABO incompatibility Alicia Gruber-Kalamas, MD, University of California San Francisco

ABO INCOMPATIBILITY Alicia Gruber-Kalamas, MD, University of California San Francisco

THE Rh SYSTEM - Rh gene 3 chromosomal loci with 6 alleles -D antigen is the most common and most immunogenic -Approximately 80-85% Caucasians have D antigen - Individuals lacking this allele are called “Rh-negative” -Only develop antibodies against the D antigen after exposure (transfusion/pregnancy) Alicia Gruber-Kalamas, MD, University of California San Francisco

Rh ANTIBODIES IgG class of immunoglobulins Lack capacity to bind complement Elimination of red cells primarily in the spleen Clinical symptoms mild, generally limited to fever/chills Alicia Gruber-Kalamas, MD, University of California San Francisco

Rh AND THE PREGNANT WOMAN Transplacental passage of D-positive fetal RBC’s into D-negative mother produces anti-D (IgG) Anti-D IgG traverses the placenta and coats fetal RBC’S leading to extravascular hemolysis Clinically manifest as hemolytic disease of the fetus and newborn- anemia, hepatosplenomegaly, hydrops fetalis, and death Alicia Gruber-Kalamas, MD, University of California San Francisco

Rh PROPHYLAXIS- Rhlg 1968 RhIg first licensed for prophylactic administration via IM route (RhoGam) IgG anti-D derived from human plasma Exact mechanism unknown 20 mcg purified RhIG provides protection against 1 ml Rh-positive blood WinRho IV preparation Alicia Gruber-Kalamas, MD, University of California San Francisco

PREVENTION OF POST-TRANSFUSION Rh-ALLOIMMUNIZATION The protective effect of RhIg is dose dependent RhIg can prevent Rh immunization if: 1) Sufficient dose is administered 2) RhIg is given within 72 hours of exposure Alicia Gruber-Kalamas, MD, University of California San Francisco

Succesful Prevention of Post-Transfusion Rh Alloimmunization by IV WinRho Anderson, et al A. J. Hematology 1999; 60:245 Case Report 10 mo old D-negative female Received 40 ml D-positive PRBC’s Administered 1200mcg IV WinRho At 1 year follow-up, no evidence of Anti-D Alicia Gruber-Kalamas, MD, University of California San Francisco

RBC Exchange with Rh-negative Cells: An Alternative Approach Werch et al Transfusion 1993; 33:530 22 y/o Rh-negative woman received 10 units Rh-positive PRBC’s RBC exchange with Rh-negative cells 12 hours post-exposure in addition to RhIG 11 months later delivered healthy, Rh-negative child; no evidence of Anti-D Alicia Gruber-Kalamas, MD, University of California San Francisco

FOLLOW-UP Blood Bank informed of the error Calculated dose was 27,000 IU WinRho 3000 IU IV Q8hrs x 9 doses ($$$$$$) Pt will require follow-up at 6 months to check for presence of anti-D antibodies Alicia Gruber-Kalamas, MD, University of California San Francisco

PROCEDURE AT SFGH Blood bank alerted to activation of “911” If pt male, 2U O-positive sent to ED; if pt female, 2U O-negative sent to ED 6U O-positive is kept in OR at all times O-negative must be sent from Blood Bank Alicia Gruber-Kalamas, MD, University of California San Francisco

IN SUMMARY Rh D Antigen is of huge clinical significance for young females and women of child-bearing age If a Rh-negative women inadvertently receives Rh-positive PRBC’s, whole blood, or platelets, the appropriate calculated dose of WinRho must be administered within 72 hours of exposure Alicia Gruber-Kalamas, MD, University of California San Francisco

WHAT IS CORRECT BLOOD TYPE? FFP Type O Type A Type B Type AB Type O OK No No No Type A OK OK No No Type B OK No OK No Type AB OK OK OK OK

TABLE 47.5. An Algorithm for Massive Transfusion* From blood sample: • CBC including platelets • PT, PTT • Fibrinogen Blood to lab 4 units PRBC (0+) in ED (0-) women Indication for immediate transfusion No Crystalloids + re-evaluate Indications for type O blood: • BP < 70 mm Hg • PT, PTT • get fibrinogen Yes Crystalloids + blood by lab values No Give 2 units PRBC Indications for transfusion protocol: • BP < 90 mmHg after 2 PRBC • Blood loss = circulating blood volume Yes Yes Review labs Coagulopathy present? Give 4 units of FFP and 6 packs of platelets Monitoring protocol: • Hct, PT, PTT, fibrinogen and platelets • Create flow sheet • EBV70-90 ml/kg No Yes Hct < 30 percent? Give whole blood (preferred) or packed cells to HCT 30 No PT > transfusion threshold Transfusions thresholds • HCT, PT, PTT • INR > 2.0 usually • INR > eye, brain, airway, 1.7 bleeding • platelets < 75,000 usually • fibrinogen < 100 mg/dl No Give platelets, 6 packs to PC 25-50, 000 Yes PC < transfusion threshold? No Anticipated ongoing blood loss Transfuse to maintain thresholds: • Hct < 30 percent • FFP with PC ratio of 1:1 • Platelets with PC in ratio of 1:1 No De-activate massive transfusion protocol

Platelet Count Total No. No. of Patients > 100,000 21 0 TABLE 47-6. CORRELATION BETWEEN PLATELET COUNT AND INCIDENCE OF BLEEDING Platelet Count Total No. No. of Patients > 100,000 21 0 75,000 - 100,000 14 3 50,000 - 75,000 11 7 < 50,000 5 5 of Patients (Cells/mm3) With Bleeding 58 Data from Miller et al

A New Treatment For Transfusion Induced Coagulopathy Recombinant activated coagulation Factor VII (r FVIIa) (NovoNordisk) Rx coagulopathic intraoperatively Expensive Should be viewed as “rescue” therapy until FDA is more evident

LIMITATIONS OF BLOOD TRANSFUSIONS Transmission of infectious diseases Dependent on volunteer donors (shortage?) Need for typing and cross-matching Short shelf-life

RECOMBINANT HEMOGLOBIN (rHb) A genetically engineered recombinant human hemoglobin which can be used as red blood cell substitute

OLD HISTORIC PROBLEMS • Kidney failure • Oxygen dissociation curve

WHAT ABOUT THE OXYGEN AFFINITY?

ADVANTAGES OF rHb No risk of blood-borne infection No need to type and cross-match Optimized oxygen delivery No need for chemical modifications Improved shelf-life Economic scale-up, production, and supply

UPDATE SYNTHETIC BLOOD Biopure produces a product named Hemopure. It is approved in South Africa and will be in the USA and Europe in a year. Stealth Red Cell. Polyglycol covering preventing antibodies from getting to it, but still needs ABO testing. Will lengthen half-life by many days. (or 30 days.)

PREDICTION: In 15 years, human blood will not be used as a blood transfusion (at least for the purpose of delivering oxygen.)