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Many problems with transfusions are related to infection' In 1985, the chance for hepatitis was 10%

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Title: Many problems with transfusions are related to infection' In 1985, the chance for hepatitis was 10%


1
  • Many problems with transfusions are related to
    infection. In 1985, the chance for hepatitis was
    10 and HIV 0.5

2
TABLE 47-11Percentage Risk of Transfusion-Transmi
tted InfectionWith 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 lt 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
3
TABLE 47-12Infectious Disease Testing For Blood
Transfusions (1998)
  • Discontinue serum alanine aminotransferase
    testing
  • Hepatitis C antibody testing
  • Antibody to hepatitis B core antigen
  • HIV-1
  • HIV-2
  • HIV Ag (p24 antigen)
  • HTLV I/II
  • Serologic test for syphilis)

From JAMA 19952741374 HIV, human
immunodeficiency virusHTLV, human T-cell
lymphotropic virus
4
IMPROVE TESTING
Molecular testing Viral inactivation
5
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
6
NUCLEIC ACID TECHNOLOGY (NAT) TESTING WILL BE
USED ON
  • HBV
  • Hepatitis A
  • Parvovirus 19
  • West Nile Virus

7
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

8
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
9
MALARIA
  • 2 to 3 cases/year for 40 years
  • Since 1982, all cases were from emigrants or
    residents from endemic areas

10
WEST NILE VIRUS
  • 4,000 cases of which 21 are transmitted by
    transfusion
  • In 2002, 23 cases
  • 43 were immunocompromised
  • 8 were gt 70 years

Science 2003 2991824 N Engl J Med 2003
3491236
11
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

12
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

13
PLATELET INDUCED SEPSIS
  • 57 year old post blood stem cell transplant for
    multiple myeloma
  • Post MI CABG deep vein thrombosis
  • Neutropenic fever
  • Gave platelets
  • 40C, dyspnea, 85 SAT, AF
  • Culture positive for klebsiella pneumonia

14
RULE
If a patient has a fever within 6 hours after
receiving platelets, then it is platelet induced
sepsis until proven otherwise.
15
BACTERIAL CULTURE
  • Prior to culture, risk was
  • RBC 1/300,000
  • Platelets 1/25,000

16
WHAT IS THE DIFFERENTIAL DIAGNOSIS WHEN
HYPOTENSION OCCURS DURING BLOOD ADMINSTRATION?
  • Hemolytic transfusion reaction
  • Sepsis
  • Anaphylaxis
  • TRALI /-
  • Isolated

Body temperature
17
  • Should all blood (packed red cells) have the
    white blood cells removed?

18
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

19
Table 1B Adverse Effects Associated with Donor
Leukocytes (4)
  • Probable
  • Immunomodulatory effects
  • Cancer recurrence
  • Postoperative infections

20
WHATS NEW?
  • Leukoreduction of all red cells and platelet
    products
  • Europe uses it
  • Canada - only platelets for cost
  • Should eliminate CMV

21
INDICATIONS FOR BLOOD
Should not be dictated by single
hemoglobin Should be based on patients risk of
inadequate oxygenation BUT, rarely indicated
Hbg gt 10 gm/dl and always indicated lt 6
gm/dl Abstract not written by committee
Anesthesiology 199684732
22
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 1998279217-221
23
SHOULD POSTOPEATIVE HEMOGLOBIN BE MORE THAN
8.5gms/? (Mayo Clinic)
  • The incidence of post-CPB blindness from optic
    neuropathy is decreased.

24
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 92615-20
25
BLOOD GROUPS- A REVIEW
  • Human erythrocytes gt300 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
26
ABO INCOMPATIBILITY
Alicia Gruber-Kalamas, MD, University of
California San Francisco
27
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
28
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
29
Rh AND THE PREGNANT WOMAN
  • Transplacental passage of D-positive fetal RBCs
    into D-negative mother produces anti-D (IgG)
  • Anti-D IgG traverses the placenta and coats fetal
    RBCS 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
30
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
31
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
32
Succesful Prevention of Post-Transfusion Rh
Alloimmunization by IV WinRho
  • Anderson, et al A. J. Hematology 1999 60245
  • Case Report
  • 10 mo old D-negative female
  • Received 40 ml D-positive PRBCs
  • Administered 1200mcg IV WinRho
  • At 1 year follow-up, no evidence of Anti-D

Alicia Gruber-Kalamas, MD, University of
California San Francisco
33
RBC Exchange with Rh-negative Cells An
Alternative Approach
  • Werch et al Transfusion 1993 33530
  • 22 y/o Rh-negative woman received 10 units
    Rh-positive PRBCs
  • 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
34
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
35
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
36
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 PRBCs, 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
37
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
38
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
Crystalloids re-evaluate
Indication for immediate transfusion
No
Indications for type O blood BP lt 70 mm Hg
PT, PTT get fibrinogen
Yes
Crystalloids blood by lab values
No
Give 2 units PRBC
Indications for transfusion protocol BP lt 90
mmHg after 2 PRBC Blood loss circulating
blood volume
Yes
Review labs Coagulopathy present?
Yes
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
Hct lt 30 percent?
Yes
Give whole blood (preferred) or packed cells to
HCT 30
No
PT gt transfusion threshold
Transfusions thresholds HCT, PT, PTT INR gt
2.0 usually INR gt eye, brain, airway, 1.7
bleeding platelets lt 75,000 usually
fibrinogen lt 100 mg/dl
No
Give platelets, 6 packs to PC 25-50, 000
PC lt transfusion threshold?
Yes
No
Anticipated ongoing blood loss
Transfuse to maintain thresholds Hct lt 30
percent FFP with PC ratio of 11 Platelets
with PC in ratio of 11
No
De-activate massive transfusion protocol
39
TABLE 47-6CORRELATION BETWEEN PLATELET COUNTAND
INCIDENCE OF BLEEDING
  • Platelet Count Total No. No. of Patients
  • gt 100,000 21 0
  • 75,000 - 100,000 14 3
  • 50,000 - 75,000 11 7
  • lt 50,000 5 5

(Cells/mm3)
of Patients
With Bleeding
58
Data from Miller et al
40
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

41
LIMITATIONS OF BLOOD TRANSFUSIONS
  • Transmission of infectious diseases
  • Dependent on volunteer donors (shortage?)
  • Need for typing and cross-matching
  • Short shelf-life

42
RECOMBINANT HEMOGLOBIN (rHb)
  • A genetically engineered recombinant human
    hemoglobin which can be used as red blood cell
    substitute

43
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44
OLD HISTORIC PROBLEMS
Kidney failure Oxygen dissociation curve
45
  • WHAT ABOUT THE
  • OXYGEN AFFINITY?

46
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50
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

51
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.)

52
PREDICTION
In 15 years, human blood will not be used as a
blood transfusion (at least for the purpose of
delivering oxygen.)
53
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