Successful Administration of Rituximab To Prevent Recurrence of Delayed Haemolytic Transfusion Reaction Developed in a Sickle Cell Disease Patient.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2904-2904
Author(s):  
France Noizat-Pirenne ◽  
Philippe Chadebech ◽  
Marc Michel ◽  
Dora Bachir ◽  
Frederic Galacteros ◽  
...  
Keyword(s):  
B Cells ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Hip Replacement ◽  
Lymphocyte Subsets ◽  
Good Condition ◽  
Transfusion Reaction ◽  
Cell Disease ◽  
Life Threatening ◽  
Positive Direct

Abstract Background: Delayed hemolytic transfusion reaction (DHTR) is a life-threatening complication frequently reported in sickle cell disease patients (SCD) patients. The hallmarks of DHTR in SCD are a dramatic drop in post-transfusion hemoglobin (Hb) caused by destruction of both donor and recipient red blood cells (RBCs) and hemolysis exacerbation by further transfusion. Destruction of autologous and transfused RBCs can be triggered by auto-antibodies produced as a result of transfusion. As rituximab specifically targets circulating B cells and is successfully used to treat several auto-immune diseases, we thought that it could be beneficial in preventing this immune-mediated transfusion complication. We report the case of a SCD patient who already experienced many DHTR due to auto-antibodies and who needed again transfusion for surgery. Rituximab was administered prior transfusion. Patient and method: The SCD patient was a poly-immunized 33-year-old man who had experienced 2 life-threatening DHTR with auto and allo-antibodies following transfusion for orthopedic surgery. He was scheduled again in 2005 and 2007 for hip replacement. In 2007, he received 1000 mg of rituximab 3 days before surgery and transfusion and 7 days after the procedure. For both episodes, routine serological evaluation, hematologic parameters and lymphocyte subsets were determined. IL-10 transcripts were quantified. IL6 and TNFα were evaluated in sera after rituximab infusion. Results: In 2005, the patient received 7 crossmatched-compatible units at day 0 of surgery and developed a severe auto-immune haemolytic anemia at day 13 as demonstrated by serological evaluation revealing RBC auto-antibodies without new allo-antibodies, a positive direct antiglobulin test (DAT) with anti-C3d/anti-IgG. Hb dropped to 2 g/dL and patient consciousness was impaired. Renal failure ensued. Then, he received 6 more units compatible with the known allo-antibodies, and was given steroids, cyclophosphamide and erythropoietin. The patient clinical status gradually improved. Lymphocyte subsets increased on day 14. Natural killer cells increased ten times. IL10 transcripts were over 900 copies at day 15 and around 50 copies at day 32. In 2007, as transfusion was absolutely necessary for hip replacement, we thought that rituximab could prevent recurrence of DHTR for this patient by inhibiting development of auto-antibodies. Seven crossmatched-compatible units were transfused. Sera remained compatible with transfused RBCs, DAT and eluate remained negative. Hb A rose up to 40% after transfusion and decreased slowly to reach 17% on day 21. Rituximab treatment resulted in marked depletion of B cells. Existing allo-antibodies (anti-C, anti-Fya, anti-S) and levels of total IgG, IgM and IgA remained stable. Dosage of IL6 and TNFα after rituximab infusions did not reveal any cytokine-release syndrome attesting the immediate safety of the procedure. Three months after treatment, the patient was in good condition. Conclusion: This observation shows for the first time that DHTR can be prevented. We believe that the use of rituximab should be considered when a new transfusion seems inevitable in patients with SCD and a prior history of life-threatening DHTR with production of auto-antibodies. In this setting, rituximab prevented DHTR without causing significant side-effects.

A Severe Case of Delayed Haemolytic Transfusion Reaction in a Sickle Cell Disease Patient: Immuno-Haematological Study, Cytokine Transcripts and Lymphocyte Subsets Analysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 954-954
Author(s):  
France Noizat-Pirenne ◽  
Helene Ansart-Pirenne ◽  
Anne Plonquet ◽  
Philippe Chadebech ◽  
Anoosha Habibi ◽  
...  
Keyword(s):  
Case Report ◽  
Natural Killer Cells ◽  
Sickle Cell Disease ◽  
Natural Killer ◽  
Sickle Cell ◽  
Lymphocyte Subsets ◽  
Transfusion Reaction ◽  
Cell Disease ◽  
Killer Cells ◽  
Life Threatening

Abstract Background: Delayed haemolytic transfusion reaction (DHTR) may be a life-threatening complication in sickle cell disease (SCD) patients. DHTR is characterized by a marked drop in hemoglobin (Hb) and is frequently accompanied with intensification of the disease symptoms. Pathogenesis of DHTR is not completely understood as autologous RBCs are probably destroyed and allo-antibodies against transfused RBCs in the course of the accident are not always detected. Here we describe a case of serious DHTR and analyse lymphocyte subsets and cytokine transcripts. Case report: A 33-year-old man with SCD was scheduled for hip replacement. He was poly-immunized (anti-RH2, -RH23, -RH30, -FY1, -FY3,-MNS3, -YT2) and had history of 2 DHTR. He received 7 units of crossmatch-compatible blood at day 0 of surgery. On days 5 and 8, sera were still compatible with samples of units received at day 0. Direct antiglobulin test (DAT) and eluate were negative. Hb remained stable at 6 g.dl−1. On day 14, the patient presented pain, fever and signs of hemolysis including a drop in Hb to 3.5 g.dl−1, LDH at 12460 U per L, bilirubin at 111 μmol/L and renal failure. Serological and eluate evaluation revealed the presence of antibodies against all RBCs tested (including units previously transfused at day 0), DAT positive with anti-C3 and anti-IgG. Hb dropped to 2.5 g.dl−1, the patient presenting neurologic symptoms. Because of the life-threatening anemia, he received 4 units that were compatible only with the known antibodies, associated with corticoids and cyclophosphamide. An anti-MNS5 was finally detected explaining partly the positive reactions against all RBCs tested. Then, additional U-negative units were transfused. The patient gradually improved symptomatically and was discharged from the high dependency unit on day 30. Hb level reached 6 g.dl−1. As compared to day 0, vigorous expansion (ten times) of Natural Killer subset (CD56+, CD16+) was observed on day 14 during hemolysis. This expansion was correlated to an increase of IL-10 transcripts whereas IL-2 and IFNγ transcripts were not detected. After treatment (day 32) lymphocyte subsets returned to the day 0 level and IL10 transcripts disappeared. Conclusion : This case report confirms that DHTR can be induced by transfusion of crossmatch-compatible units. In this poly-immunized SCD patient, transfusion has elicited production of auto-antibodies. The observed expansion of Natural Killer cells during the hemolysis suggests that Natural Killer cells could participate, through an ADCC mechanism, to the destruction of both transfused and autologous RBCs. The involvement of IL-10 on Natural Killer FcγRIIIa receptor expression and Natural Killer cytotoxicity will be discussed.

scholarly journals Two Consecutive Episodes of Severe Delayed Hemolytic Transfusion Reaction in a Sickle Cell Disease Patient

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Clarisse Mpinganzima ◽  
Alf Haaland ◽  
Anne Guro Vreim Holm ◽  
Swee Lay Thein ◽  
Geir Erland Tjønnfjord ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Combined Treatment ◽  
Disease Patient ◽  
Transfusion Reaction ◽  
Cell Disease ◽  
Initial Surgery ◽  
Hemolytic Transfusion Reaction ◽  
Life Threatening ◽  
Delayed Hemolytic Transfusion Reaction

Patients with sickle cell disease (SCD) suffer from anemia and painful vaso-occlusive crisis (VOC) and sometimes need blood transfusions. Delayed hemolytic transfusion reaction (DHTR) is a rare life-threatening complication observed in SCD and mimics VOC. We describe a female SCD patient undergoing three surgical procedures during which DHTR developed following the first two. Prior to a planned tonsillectomy, she received transfusion and three days after surgery developed severe hemolysis as well as pain and respiratory symptoms. On suspicion of VOC, she received additional transfusions and became hemodynamically unstable, and her hemolytic anemia worsened. Gradually, she recovered and could be discharged after two weeks; DHTR was not suspected. Sixteen months later, an arthroplasty was performed due to avascular necrosis, and again she was transfused preoperatively. Similar to the initial surgery, she developed symptoms and signs of VOC after three days, but this time, DHTR was suspected and further transfusions were withheld. Although immunosuppressive medication did not alleviate the condition, she improved on combined treatment with darbepoietin, rituximab, and eculizumab. Six months later, a second arthroplasty was performed uneventfully after prophylaxis with rituximab and without transfusion. DHTR should be considered in the presence of severe, unexplained hemolysis following a recent transfusion, and additional transfusions in this setting should be given only on vital indication.

Life-threatening delayed hyperhemolytic transfusion reaction in a patient with sickle cell disease: effective treatment with eculizumab followed by rituximab

Transfusion ◽  
2015 ◽  
Vol 55 (10) ◽  
pp. 2398-2403 ◽  
Author(s):  
Mark Boonyasampant ◽  
Ilene C. Weitz ◽  
Brian Kay ◽  
Chaiyaporn Boonchalermvichian ◽  
Howard A. Liebman ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Effective Treatment ◽  
Sickle Cell ◽  
Transfusion Reaction ◽  
Cell Disease ◽  
Life Threatening

scholarly journals Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management

Blood ◽  
2012 ◽  
Vol 120 (3) ◽  
pp. 528-537 ◽  
Author(s):  
Karina Yazdanbakhsh ◽  
Russell E. Ware ◽  
France Noizat-Pirenne
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Cell Disease ◽  
Factors Associated ◽  
Life Threatening ◽  
Red Blood Cell Transfusions ◽  
Transfusion Reactions

Abstract Red blood cell transfusions have reduced morbidity and mortality for patients with sickle cell disease. Transfusions can lead to erythrocyte alloimmunization, however, with serious complications for the patient including life-threatening delayed hemolytic transfusion reactions and difficulty in finding compatible units, which can cause transfusion delays. In this review, we discuss the risk factors associated with alloimmunization with emphasis on possible mechanisms that can trigger delayed hemolytic transfusion reactions in sickle cell disease, and we describe the challenges in transfusion management of these patients, including opportunities and emerging approaches for minimizing this life-threatening complication.

scholarly journals Hemolysis Inhibits Humoral B Cell Responses and Modulates Alloimmunization Risk in Patients with Sickle Cell Disease

Blood ◽  
2020 ◽  
Author(s):  
Mouli Pal ◽  
Weili Bao ◽  
Rikang Wang ◽  
Yunfeng Liu ◽  
Xiuli An ◽  
...  
Keyword(s):  
B Cells ◽  
Sickle Cell Disease ◽  
B Cell ◽  
Sickle Cell ◽  
Cell Response ◽  
Cell Activity ◽  
Immunomodulatory Activity ◽  
Heme Oxygenase 1 ◽  
Cell Disease ◽  
B Cell Response

Red blood cell alloimmunization remains a barrier for safe and effective transfusions in sickle cell disease (SCD), but the associated risk factors remain largely unknown. Intravascular hemolysis, a hallmark of SCD, results in the release of heme with potent immunomodulatory activity, although its effect on SCD humoral response, specifically alloimmunization, remains unclear. Here, we found that cell-free heme suppresses human B cell plasmablast/plasma cell differentiation by inhibiting the DOCK8/STAT3 signaling pathway, which is critical for B cell activation, as well as by upregulating heme oxygenase 1 (HO-1) through its enzymatic byproducts, carbon monoxide and biliverdin. Whereas non-alloimmunized SCD B cells were inhibited by exogenous heme, B cells from the alloimmunized group were non-responsive to heme inhibition and readily differentiated into plasma cells. Consistent with a differential B cell response to hemolysis, we found elevated B cell basal levels of DOCK8 and higher HO-1-mediated inhibition of activated B cells in non-alloimmunized compared to alloimmunized SCD patients. To overcome the alloimmunized B cell heme insensitivity, we screened several heme-binding molecules and identified quinine as a potent inhibitor of B cell activity, reversing the resistance to heme suppression in alloimmunized patients. B cell inhibition by quinine only occurred in the presence of heme and through HO-1 induction. Altogether, these data suggest that hemolysis can dampen the humoral B cell response and that B cell heme responsiveness maybe a determinant of alloimmunization risk in SCD. Quinine by restoring B cell heme sensitivity may have therapeutic potential to prevent and inhibit alloimmunization in SCD patients.

scholarly journals Management of chronic respiratory complications in children and adolescents with sickle cell disease

2020 ◽  
Vol 29 (157) ◽  
pp. 200054
Author(s):  
Michele Arigliani ◽  
Atul Gupta
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Current Knowledge ◽  
Sub Saharan Africa ◽  
Cell Disease ◽  
Respiratory Complications ◽  
Progressive Decline ◽  
Blood Disorder ◽  
Life Threatening ◽  
Sub Saharan

Sickle cell disease (SCD) is a life-threatening hereditary blood disorder that affects millions of people worldwide, especially in sub-Saharan Africa. This condition has a multi-organ involvement and highly vascularised organs, such as the lungs, are particularly affected. Chronic respiratory complications of SCD involve pulmonary vascular, parenchymal and airways alterations. A progressive decline of lung function often begins in childhood. Asthma, sleep-disordered breathing and chronic hypoxaemia are common and associated with increased morbidity. Pulmonary hypertension is a serious complication, more common in adults than in children. Although there is a growing attention towards respiratory care of patients with SCD, evidence regarding the prognostic meaning and optimal management of pulmonary issues in children with this condition is limited.This narrative review presents state-of-the-art evidence regarding the epidemiology, pathophysiology and therapeutic options for chronic respiratory complications commonly seen in paediatric patients with SCD. Furthermore, it highlights the gaps in the current knowledge and indicates future directions for studies that aim to improve our understanding of chronic respiratory complications in children with SCD.

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