Transfusion

    .

    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 LevelD-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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