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

Intravascular HemolysisHemoglobinemiaHemoglobinuria

DEATH

DICProfuse Bleeding

Acute Circulatory CollapseAnuria

Donor blood antigen+

Recipient antibodies (IgM)Activates Complement

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)

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

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

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

PREVENTION OF POST-TRANSFUSION Rh-ALLOIMMUNIZATION

The protective effect of RhIg is dose dependent

RhIg can prevent Rh immunization if:1) Sufficient dose is administered2) RhIg is given within 72 hours of exposure

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

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

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

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

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

WHAT IS CORRECT BLOOD TYPE?

Type O OK No No No

Type A OK OK No No

Type B OK No OK No

Type AB OK OK OK OK

FFP Type O Type A Type B Type AB

Blood to lab4 units PRBC (0+)in ED (0-) women

From blood sample:• CBC including platelets• PT, PTT• Fibrinogen

Crystalloids + re-evaluateIndication forimmediate transfusion

Give 2 units PRBC

Review labsCoagulopathy present?

Hct < 30 percent?

PT > transfusion threshold

Anticipated ongoing blood loss

De-activate massivetransfusion protocol

Crystalloids +blood by lab values

Give 4 units of FFP and6 packs of platelets

Give whole blood (preferred)or packed cells to HCT 30

Transfuse to maintain thresholds:• Hct < 30 percent• FFP with PC ratio of 1:1• Platelets with PC in ratio of 1:1

Indications for type O blood:• BP < 70 mm Hg• PT, PTT• get fibrinogen

Indications for transfusion protocol:• BP < 90 mmHg after 2 PRBC• Blood loss = circulating blood volume

Monitoring protocol:• Hct, PT, PTT, fibrinogen and platelets• Create flow sheet• EBV70-90 ml/kg

Transfusions thresholds• HCT, PT, PTT• INR > 2.0 usually• INR > eye, brain, airway, 1.7 bleeding• platelets < 75,000 usually• fibrinogen < 100 mg/dl

PC < transfusion threshold?

No

YesNo

YesYes

NoYes

No

No Give platelets, 6 packs toPC 25-50, 000

Yes

No

No

TABLE 47.5. An Algorithm for Massive Transfusion*

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

(Cells/mm3) of Patients With Bleeding

Data from Miller et al58

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.)