Transfusion of Patients Undergoing Solid Organ Transplants

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Transfusion of Patients Undergoing Solid Organ
Transplants

• Jeffrey McCullough, M.D.
• American Red Cross Chair, Transfusion Medicine
• Professor, Laboratory Medicine and Pathology
• University of Minnesota
• Minneapolis, Minnesota

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Topics to Be Presented

• Organs Kidney, Heart, Liver, Lungs, Pancreas
• Transfusion
• - Before transplant
• - During transplant
• After transplant
• Special Considerations

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US Organ Transplants, Waiting Lists, and Adult
3-year Grant and Patient Survival Rates

• 
  2000 Graft Patient
• 1999 Waiting
  Survival Survival
• Organ Transplants List
  Rate () Rate ()
• Kidney 12,483 47,770 79 91
• Kidney/ 946 2,466 83
  kidney 90
• pancreas 76 pancreas
• Liver 4,698 16,839 69 76
• Heart 2,185 4,147 77 77
• Lung 885 3,688 55 56
• Heart-lung 49 207 55 55
• Pancreas 363 1,025 51 88
• Intestine 70 151 45 49
• Ramsey, Transfusion Medicine (3rd ed), Simon et
  al (eds), 2002, 622

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Mean Number of Blood Components Transfused During
Transplant Surgery

• Platelet
• n Organ Red Cells
  Concentrates FFP Cryo
• 13 Kidney lt1 (0-2) 0
  (0-0.1) 0 0
• 13 Heart 3.0 (1-6) 2.7
  (0-10.5) 3.0 (0-8) 1.4 (0-5)
• 12 Liver (adult) 17.3 (6-37.1) 21.8
  (3-58) 23.1 (11-42.5) 15.3 (0-40)
• 11 Liver (peds) 7.1 (1-13.7) 7.1
  (1.1-23) 6.8 (0-17.2) 5.6 (0.27)
• 6 Lung 3.4 (1-7) 1.9 (0-6.4)
  1.2 (0-2.7) 1.8 (0-5)
• n Number of institutions providing data.
• Includes plt, pheresis each plt, pheresis
  considered equivalent to 6 plt conc.

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Estimated Total RBC Use for Organ Transplant
Patients in the US 2002

• Organ RBCs Total
• Kidney 12,483 1 12,483
• Kid/Panc 1,309 1 1,309
• Liver 4,698 17.3 81,275
• Heart 2,185 3 6,555
• Lung 885 3.4 3,009
• Heart/Lung 49 3.4 1,666
• Total 106,297
• US Blood Supply 12,500,000
• of US Supply for Organ Transplant lt1.0

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Transfusion of Patients Undergoing Transplant
Surgery Kidney

• Pretransplant
• Patients in renal failure
• Major problem is anemia
• Maintain Hemoglobin with Erythropoietin
• Usually no RBCs needed
• Decreased RBC use 500,000 each year
• During Transplant surgery
• Usually no transfusions needed
• Use leukodepleted RBCs if necessary
• No coagulopathy no platelets or plasma needed
• After transplant surgery
• Usually no transfusions needed

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Example Patient with Renal Failure Receiving
Erythropoietin
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Transfusion of Patients Undergoing Transplant
Surgery Heart

• Before transplant
• Problem is heart failure and anemia
• Maintain Hemoglobin with leukodepleted RBCs
• During transplant surgery
• If no previous cardiac surgery treat as usual
  first time CV surgery
• If previous CV surgery treat as for repeat CV
  surgery patient
• If maintained on cardiac assist device
• Will be anticoagulated
• Large amounts of blood probably needed RBCs,
  plasma, platelets
• After transplant
• - Use leukodepleted RBCs and platelets
• - Treat coagulopathy with plasma and or platelets
  as needed

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Transfusion of Patients Undergoing Transplant
Surgery Lung or Pancreas

• Pancreas
• Patients have diabetes
• Usually no anemia or coagulopathy
• No RBCs, platelets or plasma needed
• Blood use during surgery is small
• Replace as for kidney transplant
• Lung
• - Patients have chronic pulmonary disease or
  emphysema
• - Usually no anemia or coagulopathy
• No RBCs, platelets or plasma needed
• Blood loss during surgery 3 units
• Use leukodepleted RBC products
• Double lung transplant requires more RBCs

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Transfusion of Patients Undergoing Transplant
Surgery Liver

• Before Transplant Surgery
• Patients have hepatic failure and or cirrhosis
  with anemia
• maintain hemoglobin - use RBCs leukodepleted
• - Coagulopathy use frozen plasma
• - May need to improve hemostasis before surgery
• - If large doses plasma needed, consider partial
  exchange transfusion
• Patients may also be thrombocytopenic
• Platelets may also be needed

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Transfusion of Patients Undergoing Liver
Transplant Surgery

• Before Transplant Surgery
• Patients have hepatic failure and or cirrhosis
  with anemia
• Patients may also be thrombocytopenic
• Decreased thrombopoietin production from liver
• Splenomegaly
• May also have poor platelet function
• Thus, platelet transfusions may also be needed

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Transfusion of Patients During Liver Transplant
Surgery

• Liver Removal 4 8 hours
• Large vessels clamped and ligated
• Liver separated from diaphram peritoneum
• Raw surfaces exposed
• May be considerable bleeding
• Anhepatic Stage 1 1.5 hours
• New liver vessels sutured connected
• Liver flushed to remove organ preservative
• Fibrinolysis may occur
• Frozen plasma may be needed
• Use intraoperative blood salvage technique

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Transfusion of Patients During Liver Transplant
Surgery

• Return of new liver 2 4 hours
• Large vessels unclamped
• Blood flow restored
• Hepatic artery and bile duct connected
• Some heparin may remain from donor liver
• Coagulopathy may occur
• Postoperative phase
• Treat anemia and coagulopathy as needed

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Transfusion After Transplant Surgery All Organ
Transplant Recipients

• Standard blood components
• Leukodepleted RBCs and Platelets
• Platelets either apheresis or whole blood-derived
• Indications same as for other patients
• - Maintain hemoglobin
• - Correct coagulopathy if present
• - Maintain adequate platelet count (gt 50,000/uL)

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Special Transfusion Considerations

• Prevention of CMV infection in CMV negative
  patients
• ABO mismatched organs
• RBC antibodies in liver transplant patients
• Passenger lymphocyte syndrome
• Irradiation of blood products

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Cytomegalovirus in Organ Transplant Patients

• Most patients already are carriers from previous
  infection
• No need for CMV negative blood
• A few patients are CMV negative
• Provide CMV safe products before transplant
• If organ is from CMV negative donor
• - Use CMV safe blood products
• CMV safe blood products
• Leukodepletion is satisfactory CMV safe product
• CMV antibody negative donors also CMV safe but,
• No need to test blood donors for CMV antibodies
  if leukodepleted blood is available

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Transfusion of Liver Transplant Patients with
Multiple RBC Antibodies

• Some patients have multiple RBC antibodies
• Difficult to find large number of compatible
  units of RBCs needed for surgery
• If enough compatible units not available
• - Use compatible units for first blood volume
  lost during transplant
• - During surgery, use incompatible units
• - Use remaining compatible units for last part
  of surgery and post operative stage
• Hope that most blood remaining after surgery will
  be compatible that was transfused in last part of
  operation
• Watch for decrease in hemoglobin due to
  destruction of remaining incompatible RBCs

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ABO Incompatible Organ Transplantation

• Organs almost always ABO compatible with patient
• Kidney - rarely ABO incompatible
• Plasma exchange to reduce ABO antibodies in
  patient
• Use A-2 kidney for O or B patients
• Lung and Heart rarely may be ABO incompatible
• Liver almost never ABO incompatible
• Pancreas ABO compatible

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ABO Incompatible Organ Transplantation -
Transfusion Strategy

• Example patient type O donor type A
• RBCs use patient type
• Patient antibody (anti A) would hemolyze donor
• type A RBCs
• But patient type O RBCs have anti A that might
  damage the type A transplanted organ
• Use packed RBCs with very small amount of anti A
• Plasma and Platelets - use organ donor type
• If use large amount of patient type O plasma,
  large amount of anti A may damage transplanted
  type A organ

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ABO Incompatible Organ Transplantation
Transfusion Strategy
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Passenger Lymphocyte Syndrome (PLS)

• Occurs when minor incompatibility between patient
  and organ ( A patient, O organ)
• Immunocompetent donor memory B-lymphocytes and/or
  plasma cells
• Previously sensitized to the recipients
  erythrocyte antigens
• After organ transplanted, cells are exposed to
  corresponding antigen
• Secondary immune response results in antibody
  production

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Passenger Lymphocyte Syndrome (PLS) (cont.)

• Delayed severe rapid hemolysis of patients cells
  occurs
• 5-20 days after transplant and lasts 5-10 days
  but as long as 3 months
• May also cause bystander hemolysis lysis of
  patient own compatible red cells
• Most likely to occur with O donor organ and A
  recipient
• Lymphocytes carried along with organ make anti-A

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Passenger Lymphocyte Syndrome
5-10 days
Mature lymphocytes in graft produce antibodies
before engraftment.
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Example of 2 Patients with Passenger Lymphocyte
Syndrome due to Anti A and Anti B
Sharma et al. Am. J Hematology 2005 80310-311
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Passenger Lymphocyte Syndrome

• Usually involves ABO incompatibility
• Has been demonstrated with non-ABO antibodies
  including D, E, s, Jka, and Jkb
• Has not been observed with cord blood transplants
• Presence of antibodies not always associated with
  hemolysis
• Clinical spectrum of PLS ranges from
  sero-conversion with only positive DAT to renal
  failure of fatal hemolytic reaction
• Factors affecting hemolytic severity include
• - Amount of transplanted lymphoid tissue
• - Number of B-lymphocytes/plasma cells in the
  graft
• - Pre-transplant titer of donors antibody
• - Rapidity of antibody titer rise in the
  recipient
• - Immunosuppressive induction regimen

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Passenger Lymphocyte Syndrome from ABO
Incompatible Heart Transplants

• Decrease in hemoglobin 0.5 g/L/day for
• an average of 13 days
• Maximum decrease was 5 g/Lin 48
• hours and 4g/l in 24 hours
• Transfusion in 4 of 6 patients
• - 3 got 16-19 units of donor type RBCs

Hunt, Transplantation 1998 46246-249
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Passenger Lymphocyte Syndrome from ABO
Incompatible Lung Transplants
Passenger Lymphocyte

• 4/6 lung developed DAT with anti-A eluted
• 2 did not receive organ donor type cells
• Developed evidence of hemolysis
• 1/1 heart lung developed DAT, anti-A eluted,
  severe
• hemolysis require plasma and whole blood
  exchange
• 2/3 bilateral lung transplant developed DAT
  (day 8 and 10)
• Given organ donor type cells,
• No evidence of hemolysis

Salerno, Transplantation 1998 27261-264
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Occurrence of Antibodies and Hemolysis in
Passenger Lymphocyte Syndrome following Organ
Transplant
Ramsey, Transfusion 1991 3176-85
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Passenger Lymphocyte Syndrome (PLS)

• Monitoring for signs of hemolysis
• - DAT daily starting 3 days after transplant
• - CBC daily
• Treatment
• - Transfuse compatible RBCs
• This will be the ABO type of the organ donor not
  the patient
• For instance, patient A, transplanted type O
  organ produces anti A, so use type O RBCs
• Continue donor type until antibody not detected
• - If hemolysis severe
• Carry out red cell exchange with compatible red
  blood cells
• Or plasma exchange to reduce antibody titer

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THE END