Acute renal failure from
hemolytic transfusion
reactions
Brad Weaver, MD
9/25/07
Acute hemolytic transfusion reaction
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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
Sep;30(7):583-90.
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IgM anti-A and anti-B fix complement  rapid
intravascular hemolysis
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Acute renal failure from ATN
DIC
Shock
Hyperkalemia
Renal failure can be caused by direct toxicity of
hemoglobin and by renal ischemia from shock
Hemoglobinuria
Alpha-Beta dimers MW 34,000 -- small enough
to be filtered by glomerulus
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
Red Urine
Red sediment = hematuria
Red supernatant
Heme negative = beeturia, porphyria, rifampin
Heme positive
Clear plasma = myoglobinuria Red plasma = hemoglobinuria
Prevention of ARF
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Volume repletion
Alkalinization of urine
Mannitol diuresis
Alkalinization of urine and mannitol
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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
A retrospective series
Brown et al. J Trauma 56(6) 2004
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Series of 382 patients with serum CK
concentration >5000 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 >2.0 (22 versus 18
percent)
 dialysis (7 versus 6 percent)
 death (15 versus 18 percent)
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A case report
Amyot et al. Intensive Care Med. 25. 1999
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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
Preventing hemolysis – recombinant
complement receptor 1
Yazdanbakhsh et al. Blood 101 (12) 2003
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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%