Hematuria and Hemoglobinuria in Pediatric Patients Diagnosed with Newly Diagnosed Immune Thrombocytopenic Purpura.

Abstract

With the recent popularity of anti-D immune globulin for the treatment of immune thrombocytopenic purpura (ITP) has come an uncommon observation of hemoglobinuria and presumed intravascular hemolysis (IVH) during or after treatment. Rarely, IVH has led or contributed to severe acute renal failure, disseminated intravascular coagulation and death. The mechanism of IVH is unknown but may involve a particular predisposition of the patient to aggravated or exaggerated hemolysis. Analysis of two reports by Gaines (Blood 2000; 95:2525–9; Blood 2005; 106:1415–21), and others suggest that a considerable proportion of patients with IVH have had comorbid conditions, including myelodysplasia, hematologic malignancy, suspected autoimmune disease or acute infections associated with hemolysis. From a recent prospective randomized trial in children with newly diagnosed ITP (Tarantino, et al J Pediatr 2006; 148:489–94), we studied the impact of preexisting hematuria or presumed hemoglobinuria on treatment outcome and adverse events related to hemolysis. In the clinical trial, children with newly diagnosed ITP were randomized to receive either anti-D immune globulin (either 50 μg/kg [anti-D50] or 75μg/kg [anti-D75], once) or IVIg (0.8g/kg once). The mean decline in hemoglobin concentration on day 7 following treatment was 1.6 g/dL, 2.0 g/dL and 0.2 g/dL, respectively. No patients were observed to have frank hematuria or hemoglobinuria following anti-D or IVIg treatment. However, the maximum decline in hemoglobin concentration (measured on day 7 after treatment) was 5.5 g/dL, 5.2 g/dL and 2.6 g/dL in the anti-D 50, anti-D75 and IVIg groups, respectively. Pretreatment analysis of urine revealed that 24 of 91 (9 male, 15 female) patients had a positive dipstick for at least trace blood. The age of patients with a heme-positive and heme-negative urine dipstick was not significantly different. Seventy-seven (85%) had a microscopic analysis performed. Of those that were dipstick positive for blood, 56% (13/24) were positive for the presence of red blood cells (RBCs), defined as greater than three RBC/high power field (HPF), 44% had 3 or less red blood cells present. One patient had moderate blood and 2+ bacteria on the dipstick, 15–19 RBC per high power field. The decline in hemoglobin concentration 7 days after treatment was not significantly influenced by pretreatment hematuria or hemoglobinuria. The mean decline in hemoglobin was 1.49 g/dL in patients with a heme-positive urine dipstick (including one patient with a 5.5g/dL decline in hemoglobin), 1.26 g/dL in patients with heme-negative urine and 1.2 g/dL in patients with hematuria (>3 RBCs/HPF). The decline in hemoglobin at 7 days did not differ significantly between the anti-D treated groups among patients with heme-positive urine before treatment. Patients were less likely to have a positive platelet response (platelet count >20 × 109/L) at 24 hours and at 7 days (>50 × 109/L) if RBCs were present in the pretreatment urine, p = 0.05 and 0.03, respectively. Similarly, patients were less likely to have a positive platelet response at 24 hours and at 7 days if the pretreatment urine dipstick was heme-positive, p = 0.03 and 0.03, respectively. Pretreatment hematuria or presumed hemoglobinuria was not a predictor of hemoglobin decline following anti-D or IVIg treatment in children with newly diagnosed ITP but was associated with a poorer platelet response to treatment.