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Topic 8: Transfusion Reactions, Topic 9: Autoimmune Hemolytic Anemia,…

- - - - TAGVHD
        Transfusion-Associated Graft-Versus-Host Disease
        
        immunologic attack by donor's lymphocytes
        
        infiltration of systemic tissues with donor immune cells
        
        Cause: :!?: HLA Ag difference between donor and Px, immunocompetent cells of donor, Px can't reject immunocompetent cells
        
        People at risk (Infants, Cancer Px, immunocompromised Px)
        Symptoms:
        
        Rash
        
        Fever
        
        Diarrhea
        
        Treatment: gamma irradiation of blood component
        Illustration of RBCs against each other
        check me out!
        
        → More about TA-GVHD
        
        Rule in: (2-6 weeks after transfusion)
        (a) skin rash
        (b) enlarged liver → increased liver enzymes
        (c) marrow aplasia
        (d) pancytopenia
        After definite dx: liver/ skin biopsy
        chronic inflammation, necrosis, lymphocyte satellitosis
      - PTP
        Post-Transfusion Purpura
        
        1-24 days after transfusion = there is thrombocytopenia w/ bleedin, delayed immune complication of tranfusion
        
        Cause: :!?:sensitized HPA (human platelet Antigen) by pregnancy or transfusion is reexposed by transfusion
        most common 👉 HPA a1
        Symptoms:
        Bleeding (E.g. mucous: gums & nose; GI), Purpura,
        Prevention!!!
        
        limit transfusion
        
        Treatment:
        IVIG🥇
        FFP 🥈
      - Serological Hemolytic
        
        Detection of new Abs in 24hrs transfusion
        -secondry to amnestic response
        
        can occur during primary immune respone
        
        may or may not associate to shortened rbc survival
        
        Cause: :!?: Transfusion of incompatible blood during emergency or massive transfusion
        Symptoms:
        
        Pallor
        
        Jaundice
        
        ⬆️Bilirubin
        
        ⬇️ Hgb
        
        Prevention!!!
        
        limit transfusion
        
        obtain tranfusion history
        
        Accurate record keeping
        
        Treatment: AHG crossmatch compatible, transfuse Ag negative
      - Iron Overload
        non immune complication, multiple organ damage because of excessive iron accumulation
        People at risk (Px with Congenital hemolytic anemia, thalassemia, aplastic anemia)
        Symptoms: multiple organ failure
        Prevention!!!
        
        prevent iron accumulation by chelation
        
        transfusion of neocytes
        
        red cell exchange
        
        Treatment: Iron-chelating agents
        (parenteral deferoxamine, oral deferiprone, oral defarasirox)
  - - - Mild
        Allergic Mild (Urticarial Transfusion Reaction)
        
        Px Ab reacts to allergen present sa donor blood
        
        Cause: :!?: Activation of Px mast cells due to donor plasma w/ allergens
        Symptoms: Weals, hives, erythema, or pruritus
        Prevention!!!
        
        premedication = antihistamines
        
        transfuse washed components
      - Severe
        Allergic Severe (anaphylactoid or anaphylactic)
        
        IgA-deficiency-related anaphylactic reaction.
        
        cause: :!?: Caused by transfusion of IgA postive blood to an IgA- deficient recipient who have developed anti-IgA.
        *Symptoms:* Bronchoconstriction, angioedema, diarrhea and cardiovascular instability (cardiac arrest, hypotension, shock, arrythmia)
        Prevention!!!
        
        For IgA absolute deficient patients provide IgA
        deficient blood components
        
        Treatment: subcutaneous epinephrine
    - - TRALI
        Transfusion-related acute lung injury
        
        associated fatalities
        
        within 6 hours - may respiratory distress and hypoxemia
        
        cause: :!?: antibody of donor against human neutrophil antigens of Px
        Symptoms: sever hypoxemia
        Prevention!!!
        
        use leukocyte reduced components
        
        Treatment: supplemental oxygen, mechanical ventilation
      - TACO
        Transfusion-associated circulatory
        overload
        
        latrogenic, transfusion infuced hypervolemia
        
        Cause: :!?: the heart can''t take it💔
        (workload exceeded ability of heart) = CHF
        Symptoms:
        
        severe hypoxemia
        
        ⬆️ BP
        
        ⬆️ central venous pressure
        
        Jugular vein distension
        
        Prevention!!!
        
        slow transfusion rate
        
        transfuse in small volumes
        
        Treatment: supplemental oxygen, Diuretics
        Severe cases 👉 therapeutic phlebotomy💉
    - - TAS (Transfusion Associated Sepsis)
        
        Acute nonimmune transfusion reaction;
        2ºC higher than normal body temp; rigors & hypotension
        
        cause: :!?: Bacteria to px by contaminated blood product (Yersinia Enterocolitica)
        Symptoms: Fever/chills, hypotension, shock (septic)
        Prevention!!!
        
        Check for the presence of clots
        
        brown or purple discoloration or hemolysis
      - FNHTR (Febrile Nonhemolytic Transfusion Reaction)
        
        immune mediated, increase 1ºC body temp, most common transfusion reaction
        
        cause: :!?: release of endogenous
        pyrogens due to preformed Abs, Due to platelet storage changes, production and
        release of biologically active cytokines.
        Symptoms: Fever, chills, nausea or vomiting, tachycardia,
        increase in blood pressure, and tachypnea.
        Prevention!!!
        
        Prestorage leukocyte reduction
      - AHTR
        
        Acute hemolysis due to incompatibility w/ in 24hrs
        
        cause: :!?: Improper px identification
        symptoms: fever, chills, tachycardia, hemoglobinuria, hemoglobinemia, hypotension
- - - - I. Corticosteroid Administration
        & Use of IV Immunoglobulin 💉
        
        Prednisone (100-200mg)
        
        IVIG: used in conjuction with corticosteroid therapy
      - III. Immunosuppressive Drugs 💊
        
        Azathioprine (Imuran) and cyclophosphamide: destroys dividing cells ≠ antibody synthesis
        
        Cyclosporin
        
        Rituximab: targets B lymphocytes
      - II. Splenectomy 🩺
        
        → to ↓ Ab prod.
        → to remove site of
        RBC destruction
      - Note: transfusion should be avoided because it may accelerate hemolysis;
        → if anemia is LIFE-THREATENING,
        0.5-1unit of PRBCs to relieve symptoms
  - - - Discontinuation/ substitution of drugs
        → px should be observed for resolution of the anemia to confirm drug-induced hemolytic process
    - - Drug-dependent/ Immune complex/ Innocent Bystander Mechanism:
        drugs combine with plasma proteins to form immunogens
        
        drug-antibody complex → complement cascade
      - Drug adsorption (Hapten) mechanism:
        drugs bind to proteins, act as immunogen/ induce production of Ab (IgG)
        
        a. Penicillin: px who receive 10millions/day = low incidence
        b. Cephalosporins
      - Membrane modification:
        drugs (cephalosporins) modify RBCs so plasma proteins (e.g. IgG, ImG, and IgA, and complement) can bind to the membrane
      - Autoantibody formation:
        drugs alter RBC membrane components = induces the production of an autoantibody that recognizes RBC antigens
        Ex: Methyldopa alters the function of T-suppressor cells and suggest that this upset in the immune system would allow production of the antibody against self
  - - - Anemia (fatugue, dizziness, dyspnea)
        
        Fever, Jaundice
        
        Blood film: poikilocytosis, retics,
        
        Lab findings: DAT: positive (+)
- - - - Rh Typing: when px cells are coated with Ig OR
        high protein in Rh typing rgts = false positive (+)
        
        🧑‍🔧
        
        Perform D antigen typing to control test (negative control of px cells & anti-D antisera)
        
        Use of antisera with similar protein conc. (e.g. 6% albumin, commercial matched diluent)
        → if 6% albumin is POSITIVE: pretreat cells with EDTA/ glycine acid (EGA)/ chloroquine diphosphate (CDP) to remove Ig from RBCs
        
        Rosette test 🏵️ for Weak D (e.g fetal-maternal hemorrhage)
        → demonstrates small number of D pos in D neg cell suspension
      - DAT: Positive DAT due to RBC alloantibodies (from transfusion/ drug-induced)
        
        🧑‍🔧
        
        Examine the DAT microscopically (observe presence of mixed-field)
        
        Px drug history 💊
        
        Prepare an eluate (dapat has strongest e (+) reaction)
      - ABO Typing: not affected = do not cause agglutination after addition of anti-A and anti-B at RT
  - - - ABO Typing: directly agglutinate = false positive (+)
        
        🧑‍🔧
        
        Wash 🧼 px cells 1-2x with normal saline to 37ºC
        (Warm-washed, saline-suspended RBCs)
        
        Incubate 🛁 to 37ºC 15-30 mins prior to washing
        
        Use thiol rgnts to disperse autoagglutination
      - Rh Typing: Cold-reactive IgM auto agglutinins can activate complement in vitro = false positive (+) in Weak D antiglobulin test
        
        🧑‍🔧
        
        Wash 🧼 px cells 1-2x with warm saline
        
        Use thiol rgnts to disperse autoagglutination
      - DAT: clotted samples due to complement activation = false positive (+)
        
        🧑‍🔧
- - - - Procedure (Harmening):
        
        3 sets of 3 test tubes, labeled A1–A2–A3, B1–B2–B3, and C1–C2–C3, containing the patient’s serum are incubated at various temperatures with group O RBCs that express the P antigen
        
        Tubes 1 and 2 of each set contain 10 drops of patient’s serum, and tubes 2 and 3 of each set contain 10 drops of fresh normal serum as a complement source.
        
        One volume of 50% suspenion of washed P+ RBCs is added to each tube, and all tubes are mixed.
        
        After mixing, the three A tubes are then placed in a melting ice bath for 30 minutes and subsequently for 1 hour at 37°C (biphasic incubation).
        
        The three B tubes are placed in a melting ice bath for 90 minutes.
        
        The three C tubes are kept at 37°C for 90 minutes.
        
        After the appropriate time has passed, the tubes are centrifuged, and supernatant fluids are examined for hemolysis.
- - - - MILD
        
        Urticarial Transfusion Reaction
        
        Px Ab reacts to allergen present sa donor blood
        
        Cause: :!?: Activation of Px mast cells (release of histamines = vasoconstriction) due to donor plasma w/ allergens
        
        Symptoms🪧: Mucocutaneous: urticaria, weals, hives, erythema, or pruritus (i.e. itching)
        
        Prevention!!!
        
        Premedication 💊 = antihistamines (vasodilation)
        
        Transfuse washed components (since there is excess plasma proteins in unwashed compo.)
      - SEVERE
        
        Anaphylactoid or anaphylactic
        
        IgA/ haptoglobin deficiency-related anaphylactic reaction.
        
        Cause: :!?: Caused by transfusion of IgA postive blood to an IgA-deficient recipient who have developed anti-IgA.
        
        Symptoms🪧: Bronchoconstriction, angioedema, diarrhea and cardiovascular instability (cardiac arrest, hypotension, shock, arrythmia)
        
        Prevention!!!
        
        Provide IgA deficient blood components to IgA absolute deficient px
        (Therefore those IgA DEFICIENT PX WITHOUT anti-IgA DO NOT NEED IgA-deficient donor products)
        
        Treatment 📝: subcutaneous epinephrine
      - Diagnosis 🩺: appearance of signs and symptoms during/ within 2 hrs after end of transfusion and exclusion of possible drugs, environmental, and dietary causes (thus we ask px allergies, intake of antihistamines etc)
    - - TAS
        
        Transfusion Associated Sepsis
        
        Acute nonimmune transfusion reaction;
        2ºC higher than normal body temp; rigors & hypotension
        
        Cause: :!?:
        Bacteria to px by contaminated blood product
        Yersinia enterocolitica: in RBC units (purple)
        Pseudomonas spp.: in RBC units
        Propionibacterium acnes: in RBC units from skin
        Staph epidermidis & Bacillus cerus: in platelets
        
        Symptoms 🪧: Fever/chills, hypotension, shock (septic)
        
        Prevention!!!
        
        Check for the presence of clots
        
        brown or purple discoloration or hemolysis
        
        Treatment 📝:
        
        Administer antibiotics
      - FNHTR
        
        Febrile Nonhemolytic Transfusion Reaction
        
        immune mediated
        increase 1ºC body temp, most common transfusion reaction
        
        Cause: :!?:
        
        Release of endogenous
        pyrogens due to preformed Abs
        
        Due to platelet storage changes, production and
        release of biologically active cytokines
        
        Symptoms🪧: Fever, chills, nausea or vomiting, tachycardia,
        increase in blood pressure, and tachypnea.
        
        Prevention!!!
        
        Prestorage leukocyte reduction
        
        Treatment📝:
        
        Administer antipyretics
      - AHTR
        
        Acute Hemolytic Transfusion Reaction
        
        Acute hemolysis due to incompatibility w/ in 24hrs
        
        Cause: :!?: Improper px identification
        
        symptoms 🪧: Rapid onset: fever, chills, tachycardia, hemoglobinuria, hemoglobinemia, hypotension
        
        treatment 📝:
        
        discontinue transfusion
        
        treat DIC (microclots = renal dysfunction) if present
    - - TRALI
        
        Transfusion-Related Acute Lung Injury
        
        Leading cause of transfusion-associated fatalities
        
        Within 6 hours–may respiratory distress (dyspnea, tachypnea, and hypoxemia)
        
        cause: :!?: Plasma transfusion (antibody) of donor against leukocytes in plasma (antibody against human neutrophil antigens (HNA) of Px)
        
        Symptoms🪧: Severe hypoxemia
        
        Prevention!!!
        
        Use leukocyte reduced components
        
        Test for anti-human neutrophil antigen (HNA) and anti-HLA antibodies ang donors
        
        Treatment 📝: supplemental oxygen, mechanical ventilation
        
        Common Cause of Acute Lung Injury (ALI)
        
        I. 1º Pulmonary Causes
        
        Pneumonia
        
        Severe asthma
        
        Infarction
        
        II. 2º Pulmonary Causes
        
        Shock
        
        Drug overdose
        
        Sepsis
        
        Trauma
        
        → DIAGNOSE TRALI IF:
        (a) Absence of TRALI PRIOR to transfusion
        (b) ALI DURING or WITHIN 6 hrs after transfusion
        (c) Hypoxemia by blood gas or O2 testing
        (d) Radiographic evidence of pulmonary edema
        (e) Exclusion of circulatory overload of pulmonary edema
      - TACO
        
        Transfusion-Associated Circulatory Overload
        
        Rapid transfusion/ over transfusion of blood
        
        latrogenic, transfusion infuced hypervolemia
        
        2nd common cause of TR death
        
        Cause: :!?: the heart can''t take it💔 (workload exceeded ability of heart) = CHF
        
        Symptoms🪧:
        
        severe hypoxemia
        
        ⬆️ BP
        
        ⬆️ central venous pressure
        
        Jugular vein distension
        
        Prevention!!!
        
        Slow transfusion rate
        
        Transfuse in small volumes
        
        Treatment📝: supplemental oxygen, Diuretics
        Severe cases 👉 therapeutic phlebotomy💉
      - 🌮