Transfusion Medicine Types, Indications and Complications

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					Transfusion Medicine:
 Types, Indications and
       David Harford
      History of Transfusions
• Blood transfused in humans since mid-
• 1828 – First successful transfusion
• 1900 – Landsteiner described ABO groups
• 1916 – First use of blood storage
• 1939 – Levine described the Rh factor
           Transfusion Overview
• Integral part of medical treatment
• Most often used in Hematology/Oncology, but
  other specialties as well (surgery, ICU, etc)
• Objectives
   –   Blood components
   –   Indications for transfusion
   –   Safe delivery
   –   Complications
              Blood Components
• Prepared from Whole blood collection or apheresis
• Whole blood is separated by differential centrifugation
   – Red Blood Cells (RBC’s)
   – Platelets
   – Plasma
       • Cryoprecipitate
       • Others
• Others include Plasma proteins—IVIg, Coagulation
  Factors, albumin, Anti-D, Growth Factors, Colloid volume
• Apheresis may also used to collect blood components
  Differential Centrifugation
              First Centrifugation
                                                        Closed System

Whole Blood          Satellite Bag      Satellite Bag
 Main Bag                  1                  2

   RBC’s               Plasma
Differential Centrifugation
         Second Centrifugation

RBC’s            Platelet-rich

                   Platelet          Plasma
 RBC’s           Concentrate
                  Whole Blood
• Storage
   – 4° for up to 35 days
• Indications
   – Massive Blood Loss/Trauma/Exchange Transfusion
• Considerations
   – Use filter as platelets and coagulation factors will not
     be active after 3-5 days
   – Donor and recipient must be ABO identical
              RBC Concentrate
• Storage
   – 4° for up to 42 days, can be frozen
• Indications
   – Many indications—ie anemia, hypoxia, etc.
• Considerations
   – Recipient must not have antibodies to donor RBC’s
     (note: patients can develop antibodies over time)
   – Usual dose 10 cc/kg (will increase Hgb by 2.5 gm/dl)
   – Usually transfuse over 2-4 hours (slower for chronic
• Storage
   – Up to 5 days at 20-24°
• Indications
   – Thrombocytopenia, Plt <15,000
   – Bleeding and Plt <50,000
   – Invasive procedure and Plt <50,000
• Considerations
   – Contain Leukocytes and cytokines
   – 1 unit/10 kg of body weight increases Plt count by 50,000
   – Donor and Recipient must be ABO identical
                   Plasma and FFP
• Contents—Coagulation Factors (1 unit/ml)
• Storage
   – FFP--12 months at –18 degrees or colder
• Indications
   – Coagulation Factor deficiency, fibrinogen replacement, DIC, liver
     disease, exchange transfusion, massive transfusion
• Considerations
   –   Plasma should be recipient RBC ABO compatible
   –   In children, should also be Rh compatible
   –   Account for time to thaw
   –   Usual dose is 20 cc/kg to raise coagulation factors approx 20%
• Description
   – Precipitate formed/collected when FFP is thawed at 4°
• Storage
   – After collection, refrozen and stored up to 1 year at -18°
• Indication
   –   Fibrinogen deficiency or dysfibrinogenemia
   –   vonWillebrands Disease
   –   Factor VIII or XIII deficiency
   –   DIC (not used alone)
• Considerations
   – ABO compatible preferred (but not limiting)
   – Usual dose is 1 unit/5-10 kg of recipient body weight
      Granulocyte Transfusions
• Prepared at the time for immediate transfusion (no
  storage available)
• Indications – severe neutropenia assoc with
  infection that has failed antibiotic therapy, and
  recovery of BM is expected
• Donor is given G-CSF and steroids or Hetastarch
• Complications
   – Severe allergic reactions
   – Can irradiate granulocytes for GVHD prevention
      Leukocyte Reduction Filters
• Used for prevention of transfusion reactions
• Filter used with RBC’s, Platelets, FFP,
• Other plasma proteins (albumin, colloid
  expanders, factors, etc.) do not need filters—
  NEVER use filters with stem cell/bone marrow
• May reduce RBC’s by 5-10%
• Does not prevent Graft Verses Host Disease
               RBC Transfusions
• Type
  – Typing of RBC’s for ABO and Rh are determined for
    both donor and recipient
• Screen
  – Screen RBC’s for atypical antibodies
  – Approx 1-2% of patients have antibodies
• Crossmatch
  – Donor cells and recipient serum are mixed and
    evaluated for agglutination
                   RBC Transfusions
• Dose
   – Usual dose of 10 cc/kg infused over 2-4 hours
   – Maximum dose 15-20 cc/kg can be given to hemodynamically
     stable patient
• Procedure
   –   May need Premedication (Tylenol and/or Benadryl)
   –   Filter use—routinely leukodepleted
   –   Monitoring—VS q 15 minutes, clinical status
   –   Do NOT mix with medications
• Complications
   – Rapid infusion may result in Pulmonary edema
   – Transfusion Reaction
               Platelet Transfusions
• ABO antigens are present on platelets
   – ABO compatible platelets are ideal
   – This is not limiting if Platelets indicated and type
     specific not available
• Rh antigens are not present on platelets
   – Note: a few RBC’s in Platelet unit may sensitize the
     Rh- patient
              Platelet Transfusions
• Dose
  – May be given as single units or as apheresis units
  – Usual dose is approx 4 units/m2—in children using 1-2
    apheresis units is ideal
  – 1 apheresis unit contains 6-8 Plt units (packs) from a
    single donor
• Procedure
  – Should be administered over 20-40 minutes
  – Filter use
  – Premedicate if hx of Transfusion Reaction
• Complications—Transfusion Reaction
   Transfusion Complications
• Acute Transfusion Reactions (ATR’s)
• Chronic Transfusion Reactions
• Transfusion related infections
     Acute Transfusion Reactions
•   Hemolytic Reactions (AHTR)
•   Febrile Reactions (FNHTR)
•   Allergic Reactions
•   Coagulopathy with Massive transfusions
•   Bacteremia
Frequency of Transfusion Reactions
  Adverse Effect           Frequency     Comments

  Acute Hemolytic Rxn      1 in 25,000   Red cells only

  Anaphylactic hypotensive 1 in 150,000 Including IgA

  Febrile Nonhemolytic     1 in 200      Common

  Allergic                 1 in 1,000    Common

  Delayed Hemolytic        1 in 2,500    Red cells only

  RBC alloimmunization     1 in 100      Red cells only

  WBC/Plt                  1 in 10       WBC and Plt only
      Acute Hemolytic Transfusion
          Reactions (AHTR)
• Occurs when incompatible RBC’s are transfused into a
  recipient who has pre-formed antibodies (usually ABO or
• Antibodies activate the complement system, causing
  intravascular hemolysis
• Symptoms occur within minutes of starting the transfusion
• This hemolytic reaction can occur with as little as 1-2 cc of
• Labeling error is most common problem
• Can be fatal
          Symptoms of AHTR
•   High fever/chills
•   Hypotension
•   Back/abdominal pain
•   Oliguria
•   Dyspnea
•   Dark urine
•   Pallor
                What to do?
               If an AHTR occurs
• ABC’s
• Maintain IV access and run IVF (NS or LR)
• Monitor and maintain BP/pulse
• Give diuretic
• Obtain blood and urine for transfusion reaction
• Send remaining blood back to Blood Bank
    Blood Bank Work-up of AHTR
•   Check paperwork to assure no errors
•   Check plasma for hemoglobin
•   DAT
•   Repeat crossmatch
•   Repeat Blood group typing
•   Blood culture
       Labs found with AHTR
•   Hemoglobinemia
•   Hemoglobinuria
•   Positive DAT
•   Hyperbilirubinemia
•   Abnormal DIC panel
        Monitoring in AHTR
• Monitor patient clinical status and vital
• Monitor renal status (BUN, creatinine)
• Monitor coagulation status (DIC panel–
  PT/PTT, fibrinogen, D-dimer/FDP, Plt,
• Monitor for signs of hemolysis (LDH, bili,
 Febrile Nonhemolytic Transfusion
        Reactions (FNHTR)
• Definition--Rise in patient temperature >1°C
  (associated with transfusion without other fever
  precipitating factors)
• Occurs with approx 1% of PRBC transfusions and
  approx 20% of Plt transfusions
• FNHTR caused by alloantibodies directed against
  HLA antigens
• Need to evaluate for AHTR and infection
                     What to do?
                   If an FNHTR occurs
•   Use of Antipyretics—responds to Tylenol
•   Use of Corticosteroids for severe reactions
•   Use of Narcotics for shaking chills
•   Future considerations
    –   May prevent reaction with leukocyte filter
    –   Use single donor platelets
    –   Use fresh platelets
    –   Washed RBC’s or platelets
       Washed Blood Products
• PRBC’s or platelets washed with saline
• Removes all but traces of plasma (>98%)
• Indicated to prevent recurrent or severe reactions
• Washed RBC’s must be used within 24 hours
• RBC dose may be decreased by 10-20% by
• Does not prevent GVHD
 Allergic Nonhemolytic Transfusion
• Etiology
   – May be due to plasma proteins or blood
   – Best characterized with IgA given to an IgA deficient
     patients with anti-IgA antibodies
• Presents with urticaria and wheezing
• Treatment
   – Mild reactions—Can be continued after Benadryl
   – Severe reactions—Must STOP transfusion and may
     require steroids or epinephrine
• Prevention—Premedication (Antihistamines)
 Transfusion Related Acute Lung Injury
• Clinical syndrome similar to ARDS
• Occurs 1-6 hours after receiving plasma-
  containing blood products
• Caused by WBC antibodies present in
  donor blood that result in pulmonary
• Treatment is supportive
• High mortality
        Massive Transfusions
• Coagulopathy may occur after transfusion
  of massive amounts of blood
• Coagulopathy is caused by failure to replace
• See electrolyte abnormalities
  – Due to citrate binding of Calcium
  – Also due to breakdown of stored RBC’s
      Bacterial Contamination
• More common and more severe with
  platelet transfusion (platelets are stored at
  room temperature)
• Organisms
  – Platelets—Gram (+) organisms, ie Staph/Strep
  – RBC’s—Yersinia, enterobacter
• Risk increases as blood products age (use
  fresh products for immunocompromised)
   Chronic Transfusion Reactions

• Alloimmunization
• Transfusion Associated Graft Verses Host
  Disease (GVHD)
• Iron Overload
• Transfusion Transmitted Infection
• Can occur with erythrocytes or platelets
• Erythrocytes
   – Antigen disparity of minor antigens (Kell, Duffy, Kidd)
   – Minor antigens D, K, E seen in Sickle patients
• Platelets
   – Usually due to HLA antigens
   – May reduce alloimmunization by leukoreduction (since
     WBC’s present the HLA antigens)
   Transfusion Associated GVHD
• Mainly seen in infants, BMT patients, SCID
• Etiology—Results from engraftment of
  donor lymphocytes of an immunocompetent
  donor into an immunocompromised host
• Symptoms—Diarrhea, skin rash,
• Usually fatal—no treatment
• Prevention—Irradiation of donor cells
        Transfusion Associated
•   Hepatitis C
•   Hepatitis B
•   HIV
•   CMV
    – CMV can be diminished by leukoreduction,
      which is indicated for immunocompromised
                             Leukocyte       Gamma         CMV           Single Donor
                             Depletion       Irradiation   Negative      Platelets
                             Filter                                      (Apheresis)

Febrile Transfusion
Reactions                         X1                                           X
                                  X                                            X
                                  ?2                           X
Transfusion Related
GVHD                                            X
      1 In PRBC transfusion
      2 Leukocyte Reduction by filtration may be an alternative to CMV-negative blood
• Blood Components
  – Indications
  – Considerations
• Preparation and Administration of blood
• Acute and chronic transfusion reactions
    Transfusion Reaction Summary
•   AHTR can be fatal
•   Stop the Transfusion
•   Monitor for symptoms and complete evaluation
•   FNHTR is a diagnosis of exclusion
•   TRALI (ARDS-like reaction)
•   Chronic Transfusion reactions
•   Prevention methods – using filters, irradiation and