Renal failure after anti-D globulin treatment of idiopathic thrombocytopenic purpura

Abstract

Idiopathic thrombocytopenic purpura (ITP) is a disorder of rapid destruction of antibody-coated platelets. Anti-D immune globulin has been used for treatment of ITP in the United States since 1995. Initial studies identified no significant side effects of treatment. However, a recent report highlighted occasional episodes of intravascular hemolysis after anti-D immune globulin. We describe two children with ITP who developed acute renal failure (ARF) after treatment with anti-D immune globulin and also analyze ten additional cases of ARF reported to the manufacturer, Cangene Corporation, through postmarketing surveillance. All episodes of ARF were associated with intravascular hemolysis. Four patients required dialysis. Patient age ranged from 1 to 82 years, but those requiring dialysis were all under age 15 years. Several patients with ARF had preexisting creatinine elevation. Three of the patients with ARF had serologic evidence of acute Epstein-Barr virus (EBV) infection. Renal biopsy in one patient showed acute tubular necrosis, with findings consistent with pigment nephropathy. Anti-D immune globulin, used to treat ITP, may be associated with intravascular hemolysis and resultant ARF. Renal function should be monitored in patients with evidence of intravascular hemolysis. Children and adolescents may have increased risk of ARF requiring dialysis.

Disseminated intravascular coagulation associated with acute hemoglobinemia or hemoglobinuria following Rho(D) immune globulin intravenous administration for immune thrombocytopenic purpura

“…However, the etiology of the hemoglobinemia or hemoglobinuria in these patients has not yet been established as "intravascular hemolysis" in terms of immune-mediated or other mechanisms of hemolysis. 3,6,7,10,20,21 Additionally, the laboratory test results generally available for these patients were routine urinalysis results that were consistent with hemoglobinuria and were presumed to represent hemoglobinuria, given the context of acute hemolysis. However, myoglobinuria, which is also consistent with these results, was not ruled out in all patients.…”

“…That review suggested that patients receiving anti-D IGIV for ITP or secondary thrombocytopenia be closely monitored for signs and symptoms of those or other potential complications of hemoglobinemia, notably disseminated intravascular coagulation (DIC). Although additional case reports of "acute hemolysis" (or similar terms) following anti-D IGIV administration were subsequently published, [4][5][6][7][8][9][10] no hemolysis-associated complications beyond those described in the 15-patient case series were reported.…”

ITP in the 21st Century

“…If treatment was recommended for the hypothetical patients in the US surveys, there was a striking preference for anti-D in 2001 (from 10% to 33%), reflecting the rapid acceptance of anti-D in the late 1990s. There have been recent case reports of severe, even fatal, hemolysis 32 and renal failure 33 as a complication of anti-D. However, at present the actual frequency of these rare side effects is not known, and the medication has been well tolerated by the great majority of ITP patients.…”

A closer look at intravascular hemolysis (IVH) following intravenous anti-D for immune thrombocytopenic purpura (ITP)

“…6 It should also be noted that the diagnostic criteria for IVH in the setting of anti-D treatment are imprecise. Patients not uncommonly experience fever and chills after infusion of IV anti-D, 3 and most cases of marked hemolysis in the authors' experience are due to robust extravascular hemolysis. Moreover, incidental hemoglobinuria may occur in an unexpectedly large proportion of children with ITP, 7 and likely adults, at presentation.…”

“…Also, IVH may be more prevalent in patients with preexisting hemolysis (eg, Evans syndrome or infection with Epstein-Barr virus) and unusually high levels of residual red cell antibodies from prior treatment. [3][4][5] None of the patients treated in our centers were known to have underlying hemolytic conditions, and we would choose alternative modalities in patients with such findings.…”