Eculizumab salvage therapy for delayed hemolysis transfusion reaction in sickle cell disease patients

Dumas, Guillaume; Habibi, Anoosha; Onimus, Thierry; Merle, Jean‐Claude; Razazi, Keyvan; Dessap, Armand Mekontso; Galactéros, Frédéric; Michel, Marc; Bacchi, Veronique Frémeaux; Pirenne, France; Bartolucci, Pablo

doi:10.1182/blood-2015-09-669770

Cited by 88 publications

(79 citation statements)

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“…One of the main findings of this study is that DHTR had frequently been misdiagnosed: only 7% of DHTRs were diagnosed in the Emergency Room at the time of readmission and, for 18%, the diagnosis was made retrospectively at the next medical visit. 8 The median time to diagnosis was 10 [8][9][10][11][12][13][14] days but the first signs appeared an average of 9 days after the triggering transfusion.…”

Section: Discussionmentioning

confidence: 99%

“…8,10 We and others have also described using rituximab, the chimeric anti-CD20 monoclonal Ab, for patients with prior DHTR(s) with alloimmunization to prevent further alloimmunization, 9,10,17 and eculizumab, a monoclonal Ab targeting complement C5, for some life-threatening episodes. 14 We describe a unique series of 99 DHTR episodes that occurred in 69 adult SCD patients to improve clinicians' and biologists' awareness of this potentially serious syndrome. Our aim was to better characterize DTHR clinical and biological features and outcomes.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…Erythropoietin (Talano et al, 2003;de Montalembert et al, 2011), rituximab (Noizat-Pirenne et al, 2007Bachmeyer et al, 2010) and eculizumab (Dumas et al, 2016) have been used in hyperhaemolysis but further evaluation is required to substantiate their role. A small observational study on alloimmunised sickle cell patients with a history of severe DHTR has suggested that rituximab may potentially minimise the risk of further alloimmunisation and severe DHTR, but does not prevent haemolysis in all patients (Noizat-Pirenne et al, 2015).…”

Section: Guidelinementioning

confidence: 99%

Guidelines on red cell transfusion in sickle cell disease. Part I: principles and laboratory aspects

et al. 2016

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“…More recent data suggest that eculizumab, an anti-C5 monoclonal antibody, may also be effective for salvage therapy for severe DHTRs with hyperhemolysis. 33,34 In addition to antibody sensitization, activation of complement likely contributes to the hemolysis of both autologous and allogeneic RBCs in severe DHTRs with hyperhemolysis. 32 It has been demonstrated that dense sickle-erythrocytes may be more susceptible to complement-mediated lysis.…”

Section: Discussionmentioning

confidence: 99%

Challenges in the treatment and prevention of delayed hemolytic transfusion reactions with hyperhemolysis in sickle cell disease patients

et al. 2019

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BACKGROUND Delayed hemolytic transfusion reactions (DHTRs) are serious complications of RBC transfusion that can occur in previously alloimmunized patients. Patients who require episodic transfusions during heightened inflammatory states, such as patients with sickle cell disease (SCD), are particularly prone to alloimmunization and developing DHTRs with hyperhemolysis. While efforts to mitigate these hemolytic episodes via immunosuppressive drugs can be employed, the relative efficacy of various treatment options remains incompletely understood. CASE REPORTS In this study, we explored five patients with SCD and multiple RBC alloantibodies who received various forms of immunosuppressive therapy in an attempt to prevent or treat severe DHTRs. RESULTS The clinical course for these five patients provides insight into the difficulty of effectively treating and preventing DHTRs in patients with SCD with currently available immunosuppressive therapies. CONCLUSION Based on our experience, and the current literature, it is difficult to predict the potential impact of various immunosuppressive therapies when seeking to prevent or treat DHTRs. Future mechanistic studies are needed to identify the optimal treatment options for DHTRs in the presence or absence of distinct alloantibodies in patients with SCD.

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Eculizumab salvage therapy for delayed hemolysis transfusion reaction in sickle cell disease patients

Cited by 88 publications

References 14 publications

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

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

Guidelines on red cell transfusion in sickle cell disease. Part I: principles and laboratory aspects

Challenges in the treatment and prevention of delayed hemolytic transfusion reactions with hyperhemolysis in sickle cell disease patients

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