Delayed hemolytic transfusion reaction in adult sickle‐cell disease: presentations, outcomes, and treatments of 99 referral center episodes

Abstract

Delayed hemolytic transfusion reaction (DHTR) is one of the most feared complications of sickle-cell disease (SCD). We retrospectively analyzed the clinical and biological features, treatments and outcomes of 99 DHTRs occurring in 69 referral center patients over 12 years. The first clinical signs appeared a median of 9.4 [IQR, 3-22] days after the triggering transfusion (TT). The most frequent DHTR-related clinical manifestation was dark urine/hemoglobinuria (94%). Most patients (89%) had a painful vaso-occlusive crisis and 50% developed a secondary acute chest syndrome (ACS). The median [IQR] hemoglobin-concentration nadir was 5.5 [4.5-6.3] g/dL and LDH peak was 1335 [798-2086] IU/L. Overall mortality was 6%. None of the patients had been receiving chronic transfusions. Among these DHTRs, 61% were developed in previously immunized patients, 28% in patients with prior DHTR. Among Abs detected after the TT in 62% of the episodes, half are classically considered potentially harmful. No association could be established between clinical severity and immunohematological profile and/or the type and specificity of Abs detected after the TT. Management consisted of supportive care alone (53%) or with adjunctive measures (47%), including recombinant erythropoietin and sometimes rituximab and/or immunosuppressants. Additional transfusions were either ineffective or worsened hemolysis. In some cases, severe intravascular hemolysis can be likely responsible for the vascular reaction and high rates of ACS, pulmonary hypertension and (multi)organ failure. In conclusion, clinicians and patients must recognize early DHTR signs to avoid additional transfusions. For patients with a history of RBC immunization or DHTR, transfusion indications should be restricted. Am. J. Hematol. 91:989-994, 2016. © 2016 Wiley Periodicals, Inc.

Fatal Delayed Hemolytic Transfusion Reaction and Hyperhemolysiswithout Detectable Alloantibodies or Autoantibodies in a Patient withSickle Cell Disease: A Case Report and Literature Review

“…This complication has a reported incidence of 3% to 7% in transfused SCD patients, and 4% to 12% of DHTRs may be fatal [14]. Other DHTR cases with no detectable anti-RBC antibodies were reported in the literature in approximately 30% of cases, but the pathophysiological mechanism mediating red cell destruction is still unclear [3,15]. Because cross-match and antibody screening involve inherent complications, specific antibodies cannot be systematically excluded in similar cases involving non-detectable antibodies.…”

“…DHTR in sickle cell patients is a well-known complication of transfusion, entailing a significant drop in Hb (>25%) 5 to 15 days after transfusion. It is often caused by a secondary immune response to an antigen on the donor's erythrocytes and leads to the destruction of transfused erythrocytes [3,9,13]. This complication has a reported incidence of 3% to 7% in transfused SCD patients, and 4% to 12% of DHTRs may be fatal [14].…”

“…Clinicians should take these recommendations into consideration in order to optimize transfusion practice and avoid the risk of DHTR in less well-known and less-well monitored patients and in patients who do not undergo transfusions on a regular basis. Habibi et al [3] reported that DHTR occurs in patients who receive relatively few transfusions (10 RBC units on average), and that, for more than half of these patients, the transfusion that triggered the episode was prescribed as a one-off preventive measure; these patients had rarely, if ever, been transfused. Whenever patients with SCD are admitted into the hospital, an investigation should be carefully carried out to learn about the individual's transfusion history and any episode involving prior antibodies.…”

“…In such cases, intravenous immunoglobulin (IVIG) and Erythropoietin (EPO) should be administered concurrently [7]. For severe cases, EPO-Eculizumab should be considered [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. In cases where additional transfusions are necessary, EPO-Rituximab may prove successful [3].…”

“…Nevertheless, transfusion is potentially hazardous in patients with SCD and some complications, including delayed hemolytic transfusion reaction (DHTR), are not easily prevented. DHTR typically occurs in patients 5-15 days after transfusion and is often associated with a vaso-occlusive crisis characterized by the following symptoms: anemia, dark (cola-colored) urine, elevated indirect bilirubin, and increased levels of lactate dehydrogenase (LDH) [2,3]. It remains unknown why some cases of DHTR directly involve or lead to hyperhemolysis syndrome (HS), causing the destruction of both donor and recipient red blood cells, brisk intravascular hemolysis, and very low levels of total hemoglobin (Hb) (below pretransfusion levels) [4][5][6].…”