Acute renal failure from hemolytic transfusion reactions

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Acute renal failure from hemolytic transfusion
reactions

• Brad Weaver, MD
• 9/25/07

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Acute hemolytic transfusion reaction

• ABO incompatability is the major cause of death
  from transfusion
• 125 deaths reported to FDA due to ABO
  incompatable transfusion from 1976 to 1985.
  Sazama et al. Transfusion 1990 Sep30(7)583-90.
• IgM anti-A and anti-B fix complement ? rapid
  intravascular hemolysis
• Acute renal failure from ATN
• DIC
• Shock
• Hyperkalemia
• Renal failure can be caused by direct toxicity of
  hemoglobin and by renal ischemia from shock

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Hemoglobinuria

• Alpha-Beta dimers MW 34,000 -- small enough to
  be filtered by glomerulus

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Proposed mechanisms of renal injury

• 1. Obstruction of tubules with heme pigment
  casts
• 2. Oxidative damage to proximal tubule by
  released free iron
• ?Low FENa characteristic

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Prevention of ARF

• Volume repletion
• Alkalinization of urine
• Mannitol diuresis

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Alkalinization of urine and mannitol

• Hemoglobin less likely to precipitate with
  Tamm-Horsfall protein in alkaline urine
• Alkalinization stabilizes reactive iron species
• Mannitol acts as an osmotic diuretic, dilates
  renal vasculature, and is an antioxidant

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A retrospective seriesBrown et al. J Trauma
56(6) 2004

• Series of 382 patients with serum CK
  concentration gt5000 U/L, 154 (40 percent) were
  treated with bicarbonate and mannitol
• No statistically significant difference in the
  incidence of
• renal failure as defined by Cr gt2.0 (22 versus 18
  percent)
• dialysis (7 versus 6 percent)
• death (15 versus 18 percent)

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A case reportAmyot et al. Intensive Care Med.
25. 1999

• A 30yo man with myoglobin-induced renal failure
  was treated with CVVH for 33h
• Blood flow 150 mL/min, ultrafiltration rate 2 to
  3L/h
• Serum myoglobin (MW 17,000) concentration
  decreased from 92,000 ug/L to 28,600 ug/L after
  18h
• Required HD for 25 days and eventually recovered
  normal renal function

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Preventing hemolysis recombinant complement
receptor 1 Yazdanbakhsh et al. Blood 101 (12)
2003

• Complement receptor 1 (CR1) transmembrane
  protein that inhibits C3 and C5 convertases and
  cofactor for serum protease 1
• Mouse study recombinant soluble form of CR1
  inhibited complement activation in mice with
  pre-existing anti-A transfused with human group A
  RBCs
• RBC survival increased by 50