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840 Part VI: The Erythrocyte Chapter 54: Hemolytic Anemia Resulting from Immune Injury 841

In patients taking α-methyldopa in the absence of hemolysis, a than in adults, ranging from 4 to 30 percent, 313,364–369 with higher mortal-
positive DAT has not necessarily been an indication for stopping the ity rates in those with chronic AHA 313,368,369 and associated autoimmune
drug. However, given all the choices available, it is prudent to con- thrombocytopenia (Evans syndrome). 369,370 Evans syndrome was noted
sider alternative antihypertensive therapy. Because less information on in 37 percent of children with AHA in one large study, a much higher
the natural history of autoantibodies induced by drugs other than α- frequency than observed in adults. 369
methyldopa is available, discontinuation of the offending drug is advis- Patients with idiopathic cold agglutinin disease often have a rela-
able unless no suitable alternative exists. tively benign course and survive for many years. 9–11 Occasionally, death
Glucocorticoids are generally unnecessary, and their efficacy is results from infection or severe anemia or, not uncommonly, from an
questionable. However, prednisone is effective in patients with CLL and underlying lymphoproliferative process.
autoimmune hemolysis caused by purine analogues, 88,89 as are cyclospo- The postinfectious forms of cold agglutinin disease typically are
230
rine, rituximab, and intravenous immunoglobulin. For treatment of self-limited. Recovery generally occurs in a few weeks. A few cases with
CLL, combination of cyclophosphamide with fludarabine, with or with- massive hemoglobinuria have been complicated by acute renal failure,
out rituximab, seems to reduce the frequency of fludarabine-induced requiring temporary hemodialysis.
AHA. 229,230 Transfusions should be given in the unusual circumstance of Postinfectious forms of paroxysmal cold hemoglobinuria termi-
severe, life-threatening anemia. Problems with crossmatching, similar nate spontaneously within a few days to weeks after onset, 12–15 although
to those encountered in warm-antibody AHA, may occur in patients the Donath-Landsteiner antibody may persist in low titer for several
10
with a strongly positive IAT, for example, in α-methyldopa–related years. Most patients with chronic idiopathic paroxysmal cold hemo-
cases. Patients with hemolytic anemia resulting from the hapten/drug globinuria survive for many years despite occasional paroxysms of
adsorption mechanism should have a compatible crossmatch because hemolysis.
the serum antibody reacts only with drug-coated cells. However, if ther- Immune hemolysis in response to drugs usually is mild, and the
apy with the offending drug is still in progress, transfused cells may be prognosis is good. Occasional episodes of exceptionally severe hemo-
destroyed at an increased rate as they become coated with drug in vivo. lysis with renal failure or death have been reported, usually because of
Patients with ternary complex–mediated hemolysis will also hemolyze drugs operating through the ternary complex mechanism or purine
transfused RBCs until the offending drug clears from the plasma. analogues in patients with CLL. 39,56,58,62–65,67,86,108,109 In hemolysis resulting
Several cases of transfusion-associated graft-versus-host disease as from ternary complex or hapten/drug adsorption mechanisms, the DAT
a result of purine analogues have been reported in CLL patients trans- becomes negative shortly after the drug is discontinued, that is, soon
fused for hemolysis. 90,358,359 Such patients, who have an immunodefi- after the drug clears from the circulation. In addition, the hemolysis
ciency state secondary to CLL, impairing their ability to eliminate the associated with α-methyldopa–induced autoantibodies ceases promptly
transfused lymphocytes, should receive irradiated blood products. after drug cessation. However, a positive DAT of gradually diminishing
intensity may remain for weeks or months.
COURSE AND PROGNOSIS

Patients with idiopathic warm-antibody AHA have unpredictable clini- REFERENCES
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