1. 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

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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

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

16. 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

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

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

20. OLD HISTORIC PROBLEMS
• Kidney failure
• Oxygen dissociation curve

21. WHAT ABOUT THE
OXYGEN AFFINITY?

26. 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

27. 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.)

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