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  1. Approach To Medicine
  2. Hematology
  3. Transfusion

Transfusion

Modified 02:09, 22 Feb 2016 by apavel | Page History
    Table of Contents
    1. 1. Packed RBC Transfusions
      1. 1.1. Introduction / Basic Compatibility
      2. 1.2. Important Points
      3. 1.3. Blood Preparations
      4. 1.4. EPO
    2. 2. Transfusion Indications/Tresholds
      1. 2.1. Important Trial
    3. 3. Transfusion Reactions
    4. 4. Platelets
      1. 4.1. Matching
      2. 4.2. Guidelines for Platelet Transfusions
      3. 4.3. Refractoriness of Platelet Transfusion
    5. 5. Plasma
    6. 6. Cryoprecipitate
    7. 7. Other
    8. 8. Coagulopathy Principles
      1. 8.1. Investigations
      2. 8.2. Treatment:

    .

    Source: MKSAP 16

    Packed RBC Transfusions

    Introduction / Basic Compatibility

    • ABO antigen groups
    • Anti-A/B developed even if never exposed to the major blood antigens
    • Rh system
      • Consists of antigens: C/D/E (D most immunogenic, in fact "Rh+" only refers to "D" antigen).
    • "Type and Screen" (aka forward and back-type)
      • Determine antigens present on recipient's RBCs and what antibodies in recipient's serum.
      • Antibody screen: alloantibodies that patient has (prior blood exposure or pregnancy)
    • "Crossmatch"
      • Find compatible unit, and mix patient's serum with donor RBCs, to see if agglutinates.  
      • (donor's serum against patient's RBC's not tested, thought packed RBCs have very little serum)
    • Bottom Line:
      • "Type and Screen" --> if unsure if will give blood
      • "Crossmatch" --> if sure will give blood (all crossmatching prior to transfusion).

     

     

    Important Points

    • 1 unit of pRBCs = 250-300cc of volume
    • 1 unit of pRBC expected to increase Hb by 10 g/L
    • Only true indication for pRBC transfusion is to improve oxygen carrying capacity of blood.

     

    Blood Preparations

    • Leukoreduction of pRBCs
      • Removal of leukocytes (either at time of collection or leukocyte filter in-line)
      • Recommended extra washings if patient had febrile non-hemolytic reaction
      • RCTs: Decreases HLA alloimmunization, decreases febrile non-hemolytic reactions, reduce CMV transfusion.
    • Washed Red Cells
      • For pts with transfusion-related urticaria or anaphylaxis (antibodies to donor blood plasma proteins)
      • pRBCs are washed with saline
      • Patients with IgA deficiency can have Anti-IgA, can react to donor blood (anaphylactic).  Washing x5 is protective

    EPO

    • Used in renal insufficiency (reduces need for transfusion).
    • Targeting >100-120 g/L should NOT be done (high risk of VTE, CV events, etc..)
    • Use of EPO in cancer is highly controversial (risk of tumor progression, increased mortality)

     

    Transfusion Indications/Tresholds

     

    Erythrocytes

    • Critically ill patients with hemoglobin <7 g/dL (70 g/L)
    • Critically ill patients with cardiopulmonary disease with hemoglobin <7-10 g/dL (70-100 g/L)
      • Controversial (if CV disease, but no ischemia, maybe lower). 

    Platelets (Treatment)

    • Active bleeding with platelet count <50,000-100,000/µL (50-100 × 109/L)
    • Active bleeding with dysfunctional platelets

    Platelets (Prophylaxis)

    • Platelet count <10,000/µL (10 × 109/L) in patients with leukemia with no other bleeding risk factors
    • Platelet count <50,000/µL (50 × 109/L) and planned surgery
    • Platelet count <100,000/µL (100 × 109/L) and planned intracranial surgery

    FFP

    • Multiple clotting deficiencies with active bleeding (e.g., DIC, liver disease)
    • Thrombotic thrombocytopenic purpura
    • Reversal of warfarin in patients with intracranial bleeding
    • Factor replacement when specific factor concentrates not available
    • Massive transfusion of packed red blood cells to avoid dilutional coagulopathy

    Cryoprecipitate

    • Hypofibrinogenemia or dysfibrinogenemia
    • Factor XIII deficiency
    • Hemophilia A or von Willebrand disease if factor concentrate not available

    Source: MKSAP16 - ACP

     

    Important Trial

    • TRIC Trial
    • Pop'n: 838 critically ill pts NOT ACTIVELY BLEEDING with euvolemia after initial treatment after 72hrs post-admission.
      • Restrictive strategy: tfsn threshold 70 g/L  --> transfuse to maintain 70-90 g/L
      • Liberal strategy: tfsn threshold 100 g/L  --> transfuse to maintain 100-120 g/L
      • Outcomes:
        • 30 day mortality: NO difference
        • Hospital Mortality: Restrictive BETTER
        • Less Critically Ill: Restrictive BETTER
        • ≤ 55yo: Restrictive BETTER
        • Cardiac Disease: NO difference
      • Conclusion: Restrictive (70 g/L) strategy is at least as effective or superior to liberal (100 g/L) patients with no active bleeding and no cardiac compromise.

    Transfusion Reactions

    TransfusionRxnsChart.png

     

    Transfusion Complication

    Preventive/Treatment Measures

    Febrile reaction

    Prevention: antipyretics, leukoreduction

    Treatment: stop the transfusion and rule out an acute hemolytic
    transfusion reaction, antipyretics, consider antibiotics

    Allergic reaction

    Prevention: antihistamine, washing of cellular blood products

    Treatment: antihistamine, epinephrine if severe

    Anaphylaxis

    Prevention: washing cellular blood products, IgA-deficient donor

    Treatment: stop the transfusion, IV fluids, epinephrine, supportive care

    Transfusion-related acute lung injury

    Prevention: eliminate multiparous women as blood donors

    Treatment: supportive care, supplemental oxygenation

    Graft-versus-host disease

    (RISK: Bone marrow transplant pts)

    Prevention: γ-irradiation

    Treatment: supportive care

    Cytomegalovirus transmission

    Prevention: leukoreduction, cytomegalovirus-negative donor

    Treatment: antivirals including ganciclovir or foscarnet

    Source: MKSAP16/ACP

     

    Fever

    • Stop transfusion to R/O acute hemolytic transfusion reaction (most dreaded complication)
    • Consider antibiotics

     

    Allergic Reaction

    • Urticaria
      • Does not require interruption of transfusion
    • Anaphylaxis / Anaphylactic Shock
      • Manage accordingly
      • Test for IgA deficiency
      • Washed RBCs with plasma removed advised for future transfusions

     

    Transfusion-Related Acute Lung Injury (TRALI)

    • Indistinguishable from ARDS (1 in 5000 risk)
    • Anti-Leukocyte antibodies in donor blood bind granulocytes in recipient blood --> become trapped in pulmonary circulation --> inflammatory lung injury
    • Leading cause of death from blood transfusions
    • Usually 6h post-transfusion
    • Management:
      • Stop transfusion (first sign of resp compromise)
      • Supportive care (as in ARDS)
      • Repeat Transfusions: unclear recommendations... theoretically can use washed RBCs (no WBCs, no plasma)

     

    Immune Suppression

    • Transfusions known to suppress immune system (think twice in sepsis!)

     

    Bacterial Contamination

    • Septic transfusion Reaction
    • Criteria: (any of the following within 5 hours)
      • Temp > 39.0 (or 2 deg higher than before transfusion)
      • Rigors
      • HR > 120/min (or >40 higher than pre tranfusion)
      • Decrease or Increase in BP > 30mmHg
    • Treatment:
      • Majority Staph, although gram negatives common.
      • Seal transfusion bag + send to micro to culture.
      • Broad spectrum antibiotics (i.e. vancomycin + cefepime)

     

    Under Construction (other transfusion reactions)

    Platelets

    • Obtained by either pooled random-donor platelet concentrates or single-donor apheresis.
    • Stored for max 5 days at room temperature.  (high risk of bacterial growth at room temp).
      • Highest risk blood product for sepsis (S. aureus is most common) + fevers (high leukocytes)
      • If fevers is an issue, can leukoreduce (but removes 25% of platelets too!)
    • Single adult dose of platelets raises count by 20,000-30,000 /uL 1hr post-transfusion (Marino ICU book says 7000-10000?)
    • Transfused platlets survive 7-9 days
    • Check platelet level 1 hour post-transfusion to check if refractory.

     

    Matching

    • ABO/Rh(D) matching generally not required for plts.
    • Alloimmunization to HLA can happen, leads to refractoriness to future transfusions (must match HLA class if happens).

     

     

    Guidelines for Platelet Transfusions

    • Based on "Evidence-based platelet transfusion guidelines" Hematology Am. Soc. Hematol. Euc. Program (2007)
    • Platelet Target Indication
      100,000/uL Neurosurgical / CNS bleeding
      50,000/uL Non-neurosurgical procedures and non-CNS bleed
      10,000/uL

      ** controversial ** Prophylactic platelet transfusion trigger (efficatious and cost-effective)

      Studied in nonbleeding patients with leukemia (no increase in bleeding)
      (see below for discussion)
    • Prophylatic platelet transfusion trigger is controversial:
           Transfuse chronic thrombocytopenic patients <10,000 or only transfuse when bleeding?
      • "only transfusion when bleeding" option shown safe in select groups (autologous peripheral blood stem cell transplantations).  - 50% reduction in need for platelet transfusions. 
      • Trials ongoing. 
    • Milestone Notes
      100,000/uL

      - ACTIVE Intracranial bleed or RISK of intracranial bleed

      - ACTIVE bleeding + hemostasis Impaired (i.e. platelet dysfunction)
      50,000/uL - ACTIVE Non-CNS Bleeding (normal platelet function)
      40,000/uL - PREVENTION: Sufficient for laparotomy, craniotomy, tracheostomy, percutaneous liver biopsy, bronch, endoscopy+bx
      20,000/uL

      - PREVENTION: Lumbar punctures

      - PREVENTION: Risk of bleed from pre-existing lesions (i.e. peptic ulcer disease)
      10,000/uL - Central Venous Catheter
      5000/uL - Studied: very small risk of bleed (if vasculature intact)

    Refractoriness of Platelet Transfusion

    • Inappropriately low increment in plts following transfusion (sometimes defined as <10,000 /uL increment).
      • Non-Immune Causes:
        • Fever, DIC, Drugs (amphotericin B).
      • Immune Causes:
        • Alloimmunization to HLA platelet antigens (1/3 of platelet refractoriness, often in multiple transfusions).
    • If Identified:
      • Freshest single-donor, ABO-matched platelets transfused
      • If unsuccessful and HLA antibodies identified, HLA-matched platlets or cross-matched compatible platlets should be used.
    • Source: MKSAP 16 (ACP)

    Plasma

    • Fresh Frozen Plasma (FFP)
      • Typical 1 unit = 200-300cc's
      • (1-2 doses usually not effective for coagulation, need 10-15 cc/kg)
      • (Hence 70kg man = 700cc's --> 4 units of FFP)
    • Contains all coagulation factors
    • Indications:
      • Warfarin reversal in bleeding patients
      • TTP treatment (exchange)
      • Dilutional coagulopathy (massive transfusions)
      • Bleeding patients with factor deficiencies (DIC)
    • Prophylactic use is not proven. (not recommended)
    • Risks:
      • Infectious risk is similar to pRBCs
      • Volume Overload (large volume, stays intervascularly)
      • TRALI (Lung Injury --> FFP causes agglutination of recipient leukocytes)
      • Febrile/Alleric Rections
      • Anaphylactic (Rare)

    Cryoprecipitate

    • FFP frozen --> thaw to 4°C --> spin down precipitate
    • Unlike FFP does not contain all clotting factors
    • Used: 1-2u per 10kg.
    • Contains:
      • F VIII (not high enough for Hemophilia A)
      • vWF
      • F XIII
      • Fibronectin
      • Fibrinogen.
    • Indications:
      • Bleeding patients with Hypofibrinogenemia (Liver disease, thrombolytic disease, DIC)
      • Factor XIII deficient (RARE)
    •  

     

    Other

    • Other Blood Products
      • IVIG (immunoglobulin)
      • Factor VIII and IX
      • Alpha-1-antitrypsin
      • Protein C
      • Anti-thrombin concentrates
      • Albumin
    • Risks are smaller (samples processed)

     

    Coagulopathy Principles

    • Types:
      • Thrombocytopenia - Primary hemostasis
        • Petechiae, Mucosal Bleeding, 
        • Causes:
          • DIC
          • End-Stage Liver Failure

    Investigations

    • Platelets, aPTT, PT/INR
    • Peripheral blood smear
      • Platelet morphologic abnormalities, red-cell fragmentation, dysplasia?
    • Extra Tests: Fibrinogen Level, D-Dimer, Bleeding Time (clinical)
      • Interpretation:
      •  

    Treatment:

    • DO NOT treat to correct lab abnormalities
    • Treatment only indicated if actively bleeding or surgical procedure is needed.
    • Transfusing Fresh Frozen Plasma principles:
      • In old days widespread to transfuse 1:1 (pRBC:FFP) or 2:1, but survival advantage studies were flawed (survival bias).  Now new study shows in (non-massive transfusion): FFP tsfn worsens ARDS by 12x and multiple organ dysfunction syndrome by 6x.  The best ratio is unknown. 
      • DO NOT TRANSFUSE PLATELETS WITH pRBC IN NON-MASSIVE TRANSFUSIONS (<10u).
      • FFP Transfusions:
        • High incidence of Transfusion Related Lung Injury (TRLI)
        • High incidence of infections: HIV infection, Creutzfeld-Jakob
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