Hemoglobinuria and Mechanical Hemolysis Associated with Red Blood Cell Transfusion in Pediatric Patients

Mechanical hemolysis is a non-immune mediated destruction of red blood cells that can be associated with blood transfusion. Various etiologies include the use of blood warmers, small bore needles or high infusion rates. We report the investigation of hemoglobinuria cases observed post-packed red blood cell (PRBC) transfusion with subsequent changes in management.

Over a time period of 2 months, 6 events of hemoglobinuria and hemolysis were reported in 5 patients in the pediatric hematology/oncology treatment center. Each child presented with abnormally tea-colored urine following PRBC transfusion. Transfusion reaction workup included a direct antiglobulin test (DAT), urinalysis (UA), serum haptoglobin (H), lactate dehydrogenase (LDH), and total bilirubin (T-B). All patients had a negative or unchanged DAT, negative RBC antibody screen, decreased H, increased T-B, and increased LDH (4 out of 6), suggestive of intravascular hemolysis (Table). In spite of hemolysis, hemoglobin (Hgb)/hematocrit(Hct) increased normally. Multiple factors were investigated to determine a cause: collection and processing of blood units; handling of blood at the transfusion service; and blood administration by nursing staff. The only significant change identified was the implementation of a new infusion pump (pump A) replacing a model that was phased out. A hospital-wide retrospective review of urinalysis (UA) was performed over a one month time period, along with prospective UA surveillance in the outpatient unit.

In the 6 cases, a total of 10 irradiated PRBC units (7 with citrate phosphate dextrose buffer (CPDA1, HCT 65–80%) and 3 with additive solution (AS-5, HCT 55–65%)) were transfused. Although Pump A had been validated by the manufacturer with non-irradiated additive solution units, an in vitro study with irradiated CPDA1 RBC units was performed to compare pump A with an alternative pump B. Samples were taken after infusion using the pumps only (no needle or catheter) and dripped directly into the test tube for measurement of free hemoglobin (FHb). Irradiated CPDA1 units infused at a low rate (50ml/hr) showed an increase in FHb level at 1998mg/dL with pump A versus 496 mg/dL with pump B. Non-irradiated AS-5 units tested as controls resulted in a FHb level at 246mg/dL with pump A versus 117mg/dL with pump B. CPDA1 units were subsequently replaced with AS-5 units for transfusion. Finally, pump A was replaced by pump B in the outpatient hematology oncology unit. In vitro studies are still ongoing to determine if irradiation of the PRBC may also play a role in the mechanical hemolysis observed with pump A.

One month retrospective UA review found no association between patients with hemoglobinuria and RBC transfusion. The UA prospective surveillance performed in the outpatient unit revealed that 7 of 26 patients had trace hemoglobinuria. Each one had a confounding factor (chronic hemolysis) for hemoglobinuria.

Preliminary investigation determined that the infusion of highly concentrated irradiated RBC (CDPA1) using a specific commercial pump was associated with mechanical hemolysis. The change to less concentrated RBC units through an alternative pump has been to date, an effective corrective action.

No relevant conflicts of interest to declare.