An Evidence Based Approach to Transfusion

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An Evidence Based Approach to Transfusion

• Terry Gernsheimer, MD
• U W School of Medicine
• Puget Sound Blood Center
• June 1, 2008

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Transfusion Indications

• Relieve symptomatic anemia
• improve O2 delivery
• Replacement of rapid blood loss
• Correction of clotting abnormalities
• in a bleeding patient
• prophylaxis for a planned procedure

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Hemoglobin Level and Symptoms
Linman JW, New Engl J Med 1968 279812-8
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Effect of Hematocrit on Hemodynamics
Levine E, et al, Transfusion 1990 3011-14
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Hebert et al. New Engl J Med 1999 340409-417
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Hebert et al. New Engl J Med 1999 340409-417
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Effect of Hematocrit on Mortality in Elderly
Patients with Acute MI
Wu et al. N Engl J Med, 2001345 1230-1236
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Relationship Between Platelet Count and Hemorrhage
All Bleeding Skin Epistaxis Excluded Gross
Hemorrhage
Gaydos LA et al, New Engl J Med 1962 266905-9
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Harker LA Slichter SJ. New Engl J Med
1972287155-9
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The Relationship of the Bleeding Time to
Platelet Count
175 150 100 50 25
Platelets X 103/ ?L
5 10 15 20 25
30 gt30
Bleeding Time (min)
Harker LA Slichter SJ. New Engl J Med
1972287155-9
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Bleeding Complications with Invasive Line
Placement

• HDS Med Svc Surg Svc Trauma
  Svc Total
• 0 0/37 1/320
  (0.3) 0/42
  1/299 (.25)
• 1-7 7/77 (9) 2/194 (1)
  1/84 (1) 10/355 (2.87)
• 8 4/8 (50) 0/4
  1/11 (9) 5/23
  (22)
• Total 11/22 (9) 3/518 (0.6)
  2/137 (1.4) 16/777 (2)

3 points PT 18-24, PTT 48-64, Platelets
20-49,000, Creatinine gt 1.4 4 points PT gt24,
PTT gt64, Platelets lt20,000
DeLoughery T et al. Transfusion199636827-31
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175 150 100 50 25
A S P I R I N
Platelet Inhibitors
Platelets X 103/ ?L
Platelet Dysfunction
5 10 15 20 25
30 gt30
Bleeding Time (min)
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Duration of Aspirin - Platelet Effect

Days after stopping aspirin
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Duration of Aspirin - Platelet Effect
platelet count (x 103/µL
Days after stopping aspirin
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Platelet Inhibitors

• Eptifibatide (Integrelin)
• Tirofiban (Aggrastat)
• Ticlopidine
• Clopidogrel
• NSAIDS

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Mechanisms of the Uremic Hemostatic Defect

• Defects in platelet function and metabolism
• Defects of vascular endothelial/
• smooth muscle cell metabolism
• Abnormal platelet vessel wall interactions
• Anemia of renal failure

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The Importance of Hematocrit for Platelet Function
Correlation of BT and Hct r -0.476 p lt 0.001
Effect of 2-unit RBC apheresis or
plateletpheresis on bleeding time
Valeri et al. Transfusion 200141977-83.
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Concentric Layers of Flowing Blood
Arterial Wall
Plasma layer Platelets
Axial stream RBCs
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Effective Therapeutic Regimens for Uremic Bleeding

• Dialysis
• Red Blood Cell transfusion
• Erythropoietin
• Desmopressin (DDAVP)
• Cryoprecipitate
• Conjugated estrogens
• Transdermal low dose estrogens

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Blood
Centrifuge
PRP
1Unit PRBC
Centrifuge
1 Unit Platelets
1 U
Platelets
1 Unit Plasma
Freeze, Thaw, Centrifuge
Freeze
1 Unit FFP
1 Bag
1 Bag Cryoprecipitate
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Available Platelet Components

• Pooled Whole Blood (2 8 U)
• Apheresis
• Family Donor
• HLA Selected Donor

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Expected Platelet Increment
1 unit 4 units 6 units
1.0 x 10 4.0x 10 6.0 x 10 50 lb/
22,000/ul 88,000/ul 132,000/ul 23 kg 100
lb/ 11,000 44,000 66,000 45 kg 150 lb/
7,400 29,600 44,400 68 kg 200 lb/
5,500 22,000 33,000 91 kg
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Blood Component Modification

• Leukocyte Depletion
• CMV Screening
• Gamma Irradiation
• Volume Depletion
• Cell Washing

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HLA Antigens on Transfused Cells
B
RBC
Platelet
A
B
B
A
DR
WBC
A
B
DR
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TRAP Study Group New Engl J Med, 1996
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Transfusion Transmitted CMV in the
Immunocompromised Patient

• Disseminated disease more common
• Pneumonitis
• Retinitis
• Hepatitis
• Graft loss

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Prevention of CMV Infection
Use of CMV Seronegative Blood Components
Seronegative Donor Seropositive Donor CMV
- CMV unscr CMV - CMV unscr Bowden
1/32 (3) 8/25 (32) 3/12 5/16 Miller
2/45 (4) 14/44 (32) 6/19
7/17 Use of Leukocyte Poor Blood Components
Control Leukocyte Poor Verdonck
-
0/29 Bowden - 1/32 De Witte
- 0/28 Bowden
7/30 0/35
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Leukocyte Reduction Indications

• Direct Evidence
• Febrile transfusion reactions
• Prevention of CMV transmission
• Prevention of alloimmunization to platelets

Implied Evidence Prevention of alloimmunization
for organ transplant
Little or No Evidence Prevention of nvCJD
transmission
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Gamma Irradiation - Indications

• Prevention of TR Graft vs Host Disease
• Immunocompromised patients
• Premature infants
• HSCT patients
• Leukemia
• Lymphoproliferative disease
• Intensive chemotherapy
• Recipients donors who share HLA antigens

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Transfusion Related Graft vs. Host Disease
Dr. G A2 A2 B51 B57 Dr. Gs Bro A2
A2 B57 B57
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Indices Predictive of Microvascular Bleeding
Predictive value
Sensitivity
Specificity Positive Negative PT ratio
1.3 (INR 1.3) 89 50
33 94 1.8 (INR 1.6) 44
96 80 84 PTT
Ratio 1.3 56
56 26
82 1.8 56
96 83
87 Platelet count ? 50,000/cc or
89 93 73
96 Fibrinogen ? 50 mg/dl
Ciavarella et al, Br J Haematol. 198767365-8
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Fresh Frozen Plasma Task Force Recommendations
Pre-procedure / Trauma Known coagulation factor
deficiency PT gt1.5 X Normal (INR gt1.6) Urgent
reversal of warfarin Microvascular bleeding PT
gt1.5 X Normal (INR gt1.6) Massive transfusion
with continued bleeding (ATIII Deficiency,
TTP)
CAP 1994 ASA 2006
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Fresh Frozen Plasma - Dosage
Volume of 1 Unit FFP 200-250 cc 1 cc plasma
contains 1 u coagulation factors Factor
recovery with transfusion 40 70 kg X .05
plasma volume of 35 dl (3.5 L) 80 u 2.3 u/dl
2.3 (of normal 100 u/dl) 35 dl
1 Unit FFP contains 200 u coagulation factors
1 Unit FFP provides 80 u coagulation factors
In a 70 kg Patient 1 Unit FFP increases most
factors 2.5 4 Units FFP increase most factors
10 10-15cc/kg
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CryoprecipitateTask Force Recommendations

• Fibrinogen lt80-100mg/dl
• No available factor concentrates or DDAVP
• Pre-procedure/trauma
• Bleeding patient
• massive transfusion and microvascular bleeding
• peripartum and DIC
• platelet dysfunction

CAP 1994 ASA 2006
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Laboratory Tools
What do you really need to know? Platelets
number function Coagulation
Factor Fibrinolysis
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Intrinsic Pathway (Neg Charged Surface)
Extrinsic Pathway (Vascular Injury)
Tissue Factor (TF)
F. XIa
Factor XI
Factor VII
F. VIIa
Factor IX
F. IXa
TF
VIIIa
F. Xa
Factor X
Factor X
F.Va
Thrombin
Prothrombin (II)
Fibrin
Fibrinogen
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Recombinant VIIa (Novo-Seven)

• Severe Hemophilia A
• Inhibitor patients
• Warfarin overdose
• Cerebral bleeding
• Thrombocytopenia
• Liver disease and transplantation
• Massive trauma
• Vascular surgery

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Adverse Effects of Transfusion

• Transmission of infections
• Transfusion reactions
• Graft vs Host disease
• Immunomodulation
• Post-transfusion purpura

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Infections that can be Transmitted by Transfusion

• HIV 11,900,000 units
• Hepatitis C 11,000,000 units
• Hepatitis B 11,000,000 units
• HTLV I II 1640,000 units
• CMV 50-95 of units
• West Nile Virus

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Other Transfusion Transmitted Infections

• Bacterial contamination
• Chagas Disease
• Yersinia, Syphilis
• Babesiosis
• Transfusion transmitted prions Fact or fantasy?

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Transfusion Reactions

• Febrile non-hemolytic Txn Rxn 1 20 100
• Urticarial 1 50-100
• Bacterial Contamination lt 1 2,000
• Transfusion Related Acute 1 500
  -10,000
• Lung injury (TRALI)
• Anaphylaxis 1 20,000
• Acute Hemolytic Transfusion Rxn 1 30,000
  
• Delayed Hemolytic Transfusion Rxn 1 35,000 (?)

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Transfusion Related Acute Lung Injury (TRALI)

• 10 14 of reported transfusion fatalities
• Non-fatal incidence increasing 1997 - 3, 1998 -
  12, 1999 - 17
• 90 anti HLA anti PMN
• As little as 50cc Plasma

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Intravascular Hemolytic Transfusion
ReactionsSymptoms

• Chest or back pain
• Chills
• Flushing

• Dyspnea
• Nausea
• Sense of doom

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Intravascular Hemolytic Transfusion Reaction -
Signs

• Hemoglobinemia
• Hemoglobinuria
• Anuria Renal Failure
• Bleeding
• DIC

• Fever
• Hypotension
• Tachycardia
• 10 Mortality

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Management of Transfusion Reactions

• Stop transfusion Keep line open
• Clerical check
• Examine plasma for free hemoglobin

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Management of Transfusion Reactions

• Stop transfusion Keep line open
• Clerical check
• Examine plasma for free hemoglobin
• Serologic examination
• Test for hemolysis
• LDH, bilirubin, haptoglobin

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