Many problems with transfusions are related to infection. In 1985, the chance for hepatitis was 10% and HIV 0.5%

TABLE 47-11Percentage Risk of Transfusion-Transmitted Infection

With a Unit of Screened Blood in the United States

RISK WINDOW PERIOD (DAYS)

HIV 1/800,000 22 11

HTLV I & II 1/641,000 51

Cytomegalovirus < 1.0% rapidly

HCV 1/600,000 82 8-10

HBV 1/200,000 59

HIV human immunodeficiency virus type 1: HTLV human T-cell lymphotropic virus: HCV hepatitis C virus: HBV hepatitis B virus

TABLE 47-12Infectious Disease Testing For Blood Transfusions (1998)

1. Discontinue serum alanine aminotransferase testing

2. Hepatitis C antibody testing

3. Antibody to hepatitis B core antigen

4. HIV-1

5. HIV-2

6. HIV Ag (p24 antigen)

7. HTLV I/II

8. Serologic test for syphilis)

From JAMA 1995;274:1374

HIV, human immunodeficiency virus:HTLV, human T-cell lymphotropic virus

IMPROVE TESTING

• Molecular testing

• Viral inactivation

TABLE 47-13Tests Used For Detecting Infectious Agents In All Units Of Blood

(2004)

VIRUS RNA MINPOOL ANTIBODY TO

HIV NAT HIV, I, II & O

HCV NAT HCV

HBV HBC

HTLV HTLV I & II

WNV NAT

NAT = nucleic acid technology

WNV = West Nile Virus

HIV human immunodeficiency virus type 1: HTLV human T-cell lymphotropic virus: HCV hepatitis C virus: HBV hepatitis B virus

NUCLEIC ACID TECHNOLOGY (NAT) TESTING WILL BE USED ON:

• HBV

• Hepatitis A

• Parvovirus 19

• West Nile Virus

TABLE 47-14INFECTIOUS DISEASES (2004) - NO TEST

DISEASE RISK

Malaria 2-3 cases per year in USA

Chagas 0.1 -0.2% of units

SARS ?

VCJD ?

V CJD = Variant Creutzfeldt-Jakob Disease

SARS = Severe Acute Respiratory Syndrome

*DONATED BLOOD WILL BE BANNEDFROM DONORS WHO:

• Lived in UK 3 months or longer since 1980

• Lived in Europe 6 months since 1980

• Anyone who has received blood in UK

• Will decrease donors by 8-9%

* American Red Cross

MALARIA

• 2 to 3 cases/year for 40 years

• Since 1982, all cases were from emigrants or residents from endemic areas

WEST NILE VIRUS

• 4,000 cases of which 21 are transmitted by transfusion*

• In 2002, 23 cases**

• 43% were immunocompromised

• 8% were > 70 years

Science 2003; 299:1824

** N Engl J Med 2003; 349:1236

TABLE 47-8TRANSFUSION FATALITIES (2001-2002) IN THE UNITED STATES*

• Bacterial contamination - 17

• TRALI - 16

• Mistransfusion - ABO mismatch - 14

*From the Federal Drug Administration (Oct. 1, 2001 to September, 30, 2002)

TRALI = transfusion related acute lung injury

PLATELET INDUCED SEPSIS

• 33 year old male with chronic pancytopenia from failed allogeneic bone marrow Tx

• Platelets caused hypotension refractory to pressor respiratory failure, acidosis, etc.

• Klebsiella pneumonia

PLATELET INDUCED SEPSIS

• 57 year old post blood stem cell transplant for multiple myeloma

• Post MI & CABG; deep vein thrombosis

• Neutropenic fever

• Gave platelets

• 40°C, dyspnea, 85% SAT, AF

• Culture positive for klebsiella pneumonia

RULE

If a patient has a fever within 6 hours after receiving platelets, then it is platelet induced sepsis until proven otherwise.

BACTERIAL CULTURE

Prior to culture, risk was:

RBC 1/300,000

Platelets 1/25,000

WHAT IS THE DIFFERENTIAL DIAGNOSIS WHEN HYPOTENSION OCCURS DURING BLOOD ADMINSTRATION?

Hemolytic transfusion reaction ++

Sepsis ++

Anaphylaxis

TRALI +/-

Isolated

++ = Body temperature

Should all blood (packed red cells) have the white blood cells removed?

Table 1A: Adverse Effects Associated with Donor Leukocytes (4)

Definitive:

• Nonhemolytic febrile transfusion reactions

• Transmission of leukocyte-associated viruses

• Cytomegalovirus (CMV), Epstein-Barr virus (EBV), HTLV-1

• Alloimmunization

Table 1B: Adverse Effects Associated with Donor Leukocytes (4)

Probable:

• Immunomodulatory effects

• Cancer recurrence

• Postoperative infections

WHAT’S NEW?

• Leukoreduction of all red cells and platelet products

• Europe uses it

• Canada - only platelets for cost

• Should eliminate CMV

INDICATIONS FOR BLOOD *

• Should not be dictated by single hemoglobin

• Should be based on patient’s risk of inadequate oxygenation

• BUT, rarely indicated Hbg > 10 gm/dl and always indicated < 6 gm/dl

• Abstract not written by committee

* Anesthesiology 1996;84:732

TRANSFUSION TRIGGER 1998 *

What are these patient risks that should increase transfusion trigger?

* Weiskopf et al. JAMA 1998;279;217-221

• patients who have a rapid HR (cannot compensate)

• patients who do not increase CO appropriately (cannot compensate)

• presence of vital organ dysfunction

• more blood loss

SHOULD POSTOPEATIVE HEMOGLOBIN BE MORE THAN 8.5gms/%? (Mayo Clinic)

The incidence of post-CPB blindness from optic neuropathy is decreased.

Can The Oxygen Dissociation Curve Be Shifted To The Right In Patients? *

• Allosteric modification of oxygen - Hbg

• 10 mm Hg shift by RSP 13

* Wahr et al: Anesth Analg 2001; 92:615-20

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)

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 administered2) 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?

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 for immediatetransfusion

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

Yes

Yes

No

Yes

No

NoGive platelets, 6 packs toPC 25-50, 000Yes

No

No

TABLE 47.5

An Algorithm for Massive Transfusion*

TABLE 47-6CORRELATION 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 al 58

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.)