Transcript Chicago - Sept. 1999

Many problems with transfusions
are related to infection. In 1985,
the chance for hepatitis was 10%
and HIV 0.5%
TABLE 47-11
Percentage 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
HBV
1/200,000
59
8-10
HIV human immunodeficiency virus type 1: HTLV human T-cell lymphotropic
virus: HCV hepatitis C virus: HBV hepatitis B virus
TABLE 47-12
Infectious 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 47-13
Tests 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 47-14
INFECTIOUS 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 BANNED
FROM 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 47-8
TRANSFUSION 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?
• 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
* Weiskopf et al. JAMA 1998;279;217-221
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
Donor blood antigen
+
Recipient antibodies (IgM)
Activates Complement
Intravascular Hemolysis
Hemoglobinemia
Hemoglobinuria
DIC
Profuse Bleeding
Acute Circulatory Collapse
Anuria
DEATH
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 Rhpositive PRBC’s
•
RBC exchange with Rh-negative cells 12 hours postexposure 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
Blood to lab
4 units PRBC (0+)
in ED (0-) women
Indication for immediate
transfusion
Yes
An Algorithm for Massive Transfusion*
No
No
Give 2 units PRBC
Crystalloids + re-evaluate
Crystalloids +
blood by lab values
Yes
Give 4 units of FFP and
6 packs of platelets
No
Hct < 30 percent?
Yes
Give whole blood (preferred)
or packed cells to HCT 30
No
PT > transfusion
threshold
No
PC < transfusion
threshold?
No
Anticipated ongoing
blood loss
No
De-activate massive
transfusion protocol
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
Yes
Review labs
Coagulopathy present?
From blood sample:
• CBC including platelets
• PT, PTT
• Fibrinogen
Yes
Give platelets, 6 packs to
PC 25-50, 000
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
Transfuse to maintain thresholds:
• Hct < 30 percent
• FFP with PC ratio of 1:1
• Platelets with PC in ratio of 1:1
TABLE 47-6
CORRELATION BETWEEN PLATELET COUNT
AND INCIDENCE OF BLEEDING
Platelet Count
Total No.
of Patients
No. of Patients
With Bleeding
> 100,000
21
0
75,000 - 100,000
14
3
50,000 - 75,000
11
7
< 50,000
5
5
(Cells/mm3)
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 halflife 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.)