A. Habibi

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

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.

The use of rituximab to prevent severe delayed haemolytic transfusion reaction in immunized patients with sickle cell disease

Delayed haemolytic transfusion reaction (DHTR) is mainly caused by an immune response to transfused red blood cells (RBCs). Immunized patients have a high risk of producing antibodies in response to further transfusion. Controlling the immune response to RBCs is therefore a major goal in sickle cell disease (SCD).

Étude d’une cohorte de 206 patients drépanocytaires adultes transfusés : immunisation, risque transfusionnel et ressources en concentrés globulaires

BACKGROUND Prevention of hemolytic transfusion reactions depends upon our capacity to prevent allo-immunization and conflicts between antigens of transfused red blood cells and antibodies produced by the recipient. In this study, we show that to secure transfusion of sickle cell disease patients, it is necessary to take into account their immunohematologic characteristics in the organization of transfusion. METHODS AND RESULTS Immunohematological data of 206 chronically transfused patients have been collected as well as phenotypes of transfused units. In order to prevent allo-immunization against C and E antigens for patients typed D+C-E-c+e+ (56%), 26% of the transfused units were D-C-E-c+e+. We found that 47% of the patients had a history of allo-immunization, whereas only 15% produced an antibody the day of inclusion in the study. The non-detectable antibodies were frequently known as dangerous for transfusion. Finally, this study shows the frequency of anti-D in D+ patients and anti-C in C+ patients, pointing out the question of partial antigens. CONCLUSION To insure optimal transfusion safety for sickle cell disease patients, three points have to be improved: blood donation within the Afro-Caribbean community living in France, access to history of immuno-hematological data, detection of variant antigens, especially within the RH blood system.

Phenotypic differences of CD4+ T cells in response to red blood cell immunization in transfused sickle cell disease patients

Alloimmunization against red blood cells (RBCs) is the main immunological risk associated with transfusion in patients with sickle cell disease (SCD). However, about 50–70% of SCD patients never get immunized despite frequent transfusion. In murine models, CD4+ T cells play a key role in RBC alloimmunization. We therefore explored and compared the CD4+ T‐cell phenotypes and functions between a group of SCD patients (n = 11) who never became immunized despite a high transfusion regimen and a group of SCD patients (n = 10) who had become immunized (at least against Kidd antigen b) after a low transfusion regimen. We studied markers of CD4+ T‐cell function, including TLR, that directly control lymphocyte function, and their spontaneous cytokine production. We also tested responders for the cytokine profile in response to Kidd antigen b peptides. Low TLR2/TLR3 expression and, unexpectedly, strong expression of CD40 on CD4+ T cells were associated with the nonresponder status, whereas spontaneous expression of IL‐10 by CD4+ T cells and weak Tbet expression were associated with the responder status. A Th17 profile was predominant in responders when stimulated by Jbk. These findings implicate CD4+ T cells in alloimmunization in humans and suggest that they may be exploited to differentiate responders from nonresponders.

La drépanocytose chez l'adulte : quelles urgences pour l'interniste ?

INTRODUCTION Sickle cell disease is an inherited disease characterized by the presence of an abnormal haemoglobin. It is the most prevalent genetic disease at birth in the Ile-de-France area. Internists are involved in the management of acute complications, particularly acute vaso-occlusive crisis. CURRENT KNOWLEDGE AND KEY POINTS Sickle cell disease can be complicated by acute vaso-occlusive crisis, chronic visceral involvement related to the ischaemic process, and infectious complications. In adults, acute vaso-occlusive crisis is the major clinical problem prompting admission to the hospital and the main cause of death. It mainly manifests by osteoarticular pain but other clinical complications can be observed such as acute chest syndrome, priapism, ischaemic or haemorrhagic stroke, abdominal pain and acute multivisceral failure. The treatment of acute vaso-occlusive crisis is symptomatic. Simple transfusion or partial exchange transfusion is required in the more severe form of vaso-occlusive crisis. FUTURE PROSPECTS AND PROJECTS The management of adult patients with sickle cell disease must be based on a multidisciplinary approach. At the present time, more than 50% of patients survive beyond the fifth decade. This better and longer life in developed countries has resulted from basic investigations and symptomatic treatments.

A diagnostic nomogram for delayed hemolytic transfusion reaction in sickle cell disease.

Diagnosis of delayed hemolytic transfusion reactions (DHTR), one of the most dreaded complications of transfusion in patients with sickle cell disease (SCD), is challenging and not straightforward. Current diagnostic approaches are complex and not consensual; they are based on assessment of hemoglobin (Hb) drop and enhanced hemolysis, features also seen during classical vaso‐occlusive events. In this observational study, we tested the hypothesis that the rate of decline in HbA after an index transfusion is a surrogate marker for the destruction of transfused RBC, which could be used diagnostically. We examined 421 transfusion episodes (in 128 patients of a French referral center for SCD) for which an Hb electrophoresis was obtained within 1 week following an index transfusion and repeated within 2 months (before a subsequent scheduled transfusion or during an acute complication). Chart review found DHTR to be present in 26 cases (6.2%), absent in 389 cases (92.4%), and possible in six cases (1.4%). As expected, DHTR was associated with accelerated hemolysis (increased serum bilirubin and lactic dehydrogenase concentrations) and a decline in total Hb as compared to the early post‐transfusion value. However, the decline in HbA concentration appeared more effective in segregating between patients without DHTR and others. We propose a diagnostic nomogram for DHTR based on Hb A as a biologic marker of the survival of transfused RBCs. Am. J. Hematol. 91:1181–1184, 2016.

Management of delayed hemolytic transfusion reaction in sickle cell disease: Prevention, diagnosis, treatment

Transfusion remains a key treatment of sickle cell disease complications. However, delayed hemolytic transfusion reaction, the most serious complication of transfusion, may be life-threatening if hyperhemolysis develops. This syndrome is generally underdiagnosed because its biological and clinical features resemble those of vaso-occlusive crisis, and red blood cell antibodies are frequently absent. Further transfusions may aggravate the symptoms, leading to severe multiple organ failure and death. It is therefore essential to prevent, diagnose and treat this syndrome efficiently. Prevention is based principally on the attenuation of allo-immunization through the provision of extended-matched RBCs or the use of rituximab. However, such treatment may be insufficient. Early diagnosis might make it possible to implement specific treatments in some cases, thereby avoiding the need for secondary transfusion. Diagnosis is dependent on the knowledge of the medical staff. Finally, many treatments, including steroids, immunoglobulins, erythropoietin and eculizumab, have been used to improve outcome. Improvements in our knowledge of the specific features of DHTR in SCD should facilitate management of this syndrome.

Anti-HI can cause a severe delayed hemolytic transfusion reaction with hyperhemolysis in sickle cell disease patients.

Delayed hemolytic transfusion reaction (DHTR) is a life‐threatening condition in sickle cell disease (SCD) patients that is frequently complicated by hyperhemolysis. Antibodies resulting from antigen disparity between donors of European ancestry and patients of African ancestry are common, but situations involving antibodies not classically of clinical significance are also encountered. Anti‐HI is generally considered to be an innocuous naturally occurring antibody.

High immunogenicity of red blood cell antigens restricted to the population of African descent in a cohort of sickle cell disease patients: ALLOANTIBODIES AGAINST LOW-FREQUENCY ANTIGENS IN SCD PATIENTS

Sickle cell disease (SCD) patients undergo multiple red blood cell (RBC) transfusions and are regularly exposed to low‐prevalence (LP) antigens specific to individuals of African descent. This study evaluated the prevalence of antibodies against LP antigens in SCD patients and the need to identify these antibodies in everyday practice.

A clinical risk score for pulmonary artery thrombosis during acute chest syndrome in adult patients with sickle cell disease.

Pulmonary artery thrombosis (PAT) is involved in lung vascular dysfunction during acute chest syndrome (ACS) complicating sickle cell disease (SCD). No clinical score is available to identify patients eligible for multi‐detector computed tomography (MDCT) angiography during ACS. This retrospective study aimed to develop a risk score for PAT during ACS (PAT‐ACS risk score). Patients with SCD were investigated by MDCT during ACS. A logistic regression was performed to determine independent risks factors for PAT and to build the PAT‐ACS risk score. A total of 43 episodes (11·9%) of PAT were diagnosed in 361 episodes of ACS. Multivariate analysis identified four risk factors, which were included in the PAT‐ACS risk score: a baseline haemoglobin >82 g/l, the lack of a triggering factor for ACS, a platelet count >440 × 109/l and a PaCO2 <38 mmHg at ACS diagnosis. The area under the receiver operating characteristic curve for the PAT‐ACS risk score was 0·74 (95% confidence interval [CI] 0·69–0·79) and differed from that of the revised Geneva score (0·63 (95% CI 0·58–0·69); P = 0·04). The negative predictive value of a PAT‐ACS risk score ≥2 was 94%. In conclusion, we propose a simple clinical risk score to identify SCD patients at high risk of PAT during ACS.