Massive Transfusion and Transfusion Reactions

Massive Transfusion

Massive transfusion is defined as the administration of greater than 1 total blood volume (10 – 20 units of blood) in 24 hours or replacing 1/2 of the blood volume in < 1 hour *(*about 5 – 10 units)

Common products used in Massive Transfusion include 6 pRBCs, 4 FFP, and 1 unit of platelets.

• Indications for Massive Transfusion
  • Cardiac surgery
  • Trauma
  • Ruptured AAA
  • Liver transplant
  • Obstetric catastrophes
• Complications of Massive Transfusion
  • Hypothermia: blood products are stored cold. This worsens coagulopathy if they are not run through a warming device
  • Coagulopathy: dilutional thrombocytopenia (platelets likely < 100,000 after 10 units of pRBC) and dilutional coagulopathy (labile factors V and VIII are decreased in stored blood)
  • Acid-base abnormalities: stored blood has a pH of < 7.0 due to the production of CO2 (this is rapidly eliminated by breathing). Acidosis more commonly occurs due to reduced tissue perfusion
  • Citrate toxicity: Citrate in CPDA chelates Ca2+ causing acute hypocalcemia (>65ml/min in a healthy adult). Can also bind magnesium to cause hypomagnesemia
  • Hyperkalemia: K+ shifts out of pRBCs during storage. Stop transfusion and treat hyperkalemia if EKG changes occur
  • Impaired O2-Deliver capacity: stored blood has less 2,3-DPG which shifts the O2-Hb dissociation curve to the left causing Hb to hold on to oxygen and not release it at the target sites.

Transfusion Reactions

Acute Hemolytic Transfusion Reaction (AHTR)

• Pathophysiology
  • ABO incompatibility: IgM intravascular hemolysis of donor RBC by recipient anti-A and or anti-B antibodies (Type II hypersensitivity reaction) and Immune-mediated destruction of recipient RBCs by donor anti-A or anti-B antibodies (Receiving large volumes of platelet-rich plasma or FFP)
  • Non-ABO related: Destruction of donor RBCs by alloantibodies to non-ABO RB antigens
  • RBC destruction from mechanical, thermal, or osmolar injuries
• Signs and symptoms
  • Fever, chills
  • Flank pain and burning pain at the IV site (can be masked by General Anaesthesia)
  • Tachycardia, Hypotension
  • Diffuse oozing and brown urine
• Treatment
  • Stop blood products
  • Maintain alkaline urine output (bicarbonate, mannitol, furosemide, or crystalloid fluid)
  • Supportive care
• Complications of Acute Hemolytic Transfusion Reaction.
  • DIC
  • Shock
  • Renal Failure (Hemoglobinuria → Acute Tubular Necrosis)

Febrile Non-Hemolytic Transfusion Reaction

Benign; occurs in 0.5 – 1% of transfusions

• Pathophysiology
  • Blood products stored for long → Cytokines (TNF, IL-1) leak from WBCS → Fever and mild immunologic reaction
  • Preformed recipient antibodies against leukocytes → Lysis of remaining leucocytes in blood products → inflammatory reaction
  • Features: Fever, Chills, Malaise, Pediatric patients
• Treatment
  • Paracetamol
  • Diphenhydramine (Benadryl)
  • Slow transfusion
  • Can prevent by giving leukoreduced blood

Transfusion-related allergic reaction (Anaphylactic reaction)

Occurs within minutes and can be life-threatening. Associated with IgA deficiency (has IgA antibodies). For patients with known IgA deficiency, washed blood can be given (reduced amount of plasma proteins and immunoglobulins)

• Pathophysiology
  • Preformed IgE antibodies on the surface of recipient mast cells → binds to donor plasma proteins (Donor IgA in IgA deficiency recipients) → Mast cell degranulation and histamine release
  • Features: Shock, Hypotension, Pruritus, Urticaria, Respiratory distress
• Treatment
  • Stop blood
  • IV fluids
  • Epinephrine
  • Antihistamine
  • ACLS

Transfusion-related acute lung injury (TRALI)

Occurs 4-6 hours after transfusion. Due to plasma-containing products (platelets and FFP > pRBCs). Usually, donor antibodies react to recipient leukocytes. Mortality of 5-10% (the leading cause of transfusion-related mortality. Diagnosis of exclusion (after ruling out sepsis, volume overload, and cardiogenic pulmonary edema)

• Pathophysiology of TRALI
  • Sequestration and priming of neutrophils in the pulmonary endothelium secondary to recipient comorbidities
  • Transfusion with FFP or platelets
  • Antibodies and Certain lipids (Soluble factors) activate recipient granulocytes
  • Release of inflammatory mediators (TNF, IL-1, Lysozyme, Leukotrienes, Prostaglandins)
  • Increased vascular permeability
  • Plasma transudation into interstitium
  • NON-CARDIOGENIC PULMONARY EDEMA
• Pathophysiology of TACO
  • Increased susceptibility to volume overload: Heart failure, Renal dysfunction, Hypoalbuminemia, Positive fluid balance
  • Product transfusion (250-250 mL/unit is bound to expand intravascular compartment)
  • Expands Intravascular volume
  • Increased pulmonary venous hydrostatic pressure
  • CARDIOGENIC PULMONARY EDEMA
• Signs and symptoms
  • Dyspnoea
  • Hypoxemia
  • Hypotension
  • Fever
  • Pulmonary edema
• Treatment
  • Supportive care
  • Similar to ARDS (Oxygen, mechanical ventilation, tidal volume 6-8 cc/kg)
  • Diuretics not indicated (since the cause is microvascular leak and not fluid overload)

TACO vs TRALI

Delayed Hemolytic Transfusion Reaction

• Previous sensitization tor Rhesus or minor blood group (Kell, Duffy, Kidd) antigens – transfusion, pregnancy, transplantation
• Re-exposure
• Anamnestic response
• Increased anti-RBC alloantibodies 4H to 28 days post-transfusion
• Binding of alloantibody IgG mocs to donor RBCs
• Extravascular hemolysis
• Self-limited

Post-transfusion purpura

• Previous sensitization to platelet antigens – pregnancy, transfusions
• Re-exposure to platelet antigens
• Anamnestic response resulting in increased anti-platelet alloantibodies
• Binding of alloantibody IgG mocs on both donor and platelets
• Destruction of platelets in the RES (Liver, spleen)
• Bleeding diathesis
• Petechiae, Purpura,
• Treatment: IVIG, High-dose steroids