99 Episodes of Delayed Hemolysis Post transfusion Reaction among Adult Patients with Sickle Cell Disease; Clinical Presentation, Prognosis, and Treatment

Introduction: Transfusion is a major therapeutic of sickle cell disease (SCD) patients. However one of the serious complications of transfusions is represented by the delayed hemolytic transfusion reaction (DHTR) with a significant mortality. It occurs a few days after transfusion and is accompanied by a vaso-occlusive crisis often at the forefront. The biological diagnosis of DHTR is made by the rapid decline and disappearance of Hb A in sickle cell patients who were transfused a few days to a few weeks ago. This event is associated with a significant in lactico-dehydrogenase (LDH) increase and worsening of anemia.

Material and method: We retrospectively analyzed 99 episodes of DHTR that have occurred in 69 patients with SCD (65 hemoglobin S/S, 3 S/C and 1 S/ ß+thalassemia) followed in our national referral center over 12 years period ( 2000-2013). Their clinico-biological prsentation, their management and evolution is described in this study.

Results: The transfusion was indicated to treat or prevent acute complications. 48.4% of cases were to treat acute complications ( chest syndrome or vaso-occlusive crisis etc…). In 51.5% of cases the indication was to avoid the occurrence of complication (surgery, pregnancy ...). 27% of episodes in this study occurred in pregnant women.

The median delay between transfusion and the first clinical sign of DHTR was 9,4 days [3-22]. The clinical presentation in emergency was a painful vaso-occlusive crisis in 89 % of cases; an acute chest syndrome was associated in 22% of cases. The most frequent clinical manifestation was the presence of reddish urine (hemoglobinuria) in 94% des cases. The mean lower hemoglobin level was 5.4 +/- 1,6 g/dl observed on average at 11,6 +/- 6 days after the transfusion. The mean highest level of LDH level was 1707 +/- 1306 UI/l at day 10,9 +/-4,7 and reticulopenia 190+/- 97/mm3 was frequently present . HbA was the lowest at 14 days +/- 5. A management in intensive care unit was required in 45% cases and six patients died.

In 35 cases another transfusion was decided, including 24 cases for whom the diagnosis of DHTR was not initially made. Seven transfusions were decided because of multiple organ failure. The analysis of the hemoglobin A level revealed that 82% of the transfusions were ineffective at day 15.

53% of patients had not received any specific treatment except the treatment of the crisis. In term of management, recombining erythropoietin (Epo) was used in 46 cases (46%), combined with intravenous immunoglobulin (IgG) in 4, corticosteroids and Epo in 3 cases and rituximab + Epo in two, Eculizumab and Epo in 2 cases, and only IgG was used in 2 cases. 6 patients died during this period due to the hemolysis. These deaths occurred very rapidly in the context of multiorgan failure including acute pulmonary heart.

Conclusion: The post transfusion hemolysis is under diagnosed. Their morbidity and mortality is high (6 deaths of 99 episodes). Transfusion indications should be restricted in patients with previous history of hemolysis. Early diagnosis DHTR could help introduce treatments to erythropoiesis-stimulating bearing the reticulopenia that accompanies this complication. Immunomodulators may reduce the response in case of need for further transfusion.