Alloimmunization Does Not Modify the Clinical Profile of Sickle Cell Disease Patients from Salvador-Brazil

Abstract

Introduction: The hemoglobinopathies are the most common monogenic disorders known. A mutation in the gene for β globin gave origin to hemoglobin S, an abnormal hemoglobin originated in Africa. Sickle cell disease (SCD) is characterized by the presence of hemoglobin S, which results in vasoocclusion episodes and hemolytic anemia throughout patients life. Vascular occlusion leads to acute events and progressive disabling organ damage. Sickle cell anemia is the homozygous state SS, while hemoglobinopathy SC is a doubly heterozygous state, where hemoglobin S occurs in combination with hemoglobin C. Brazil has a prominent African ancestry and SCD is highly prevalent in some regions of the country. In Bahia State, for example, neonatal screening data have shown that, from every 650 children born alive, one has SCD, mostly homozygous SS. Among other therapeutic measures, packed red blood cells (RBC) play a prominent role in SCD management. In situations such as acute chest syndrome (ACS), primary and secondary prevention of stroke, splenic or hepatic sequestration crisis, severe anemia, complicated pregnancy, isquemic organ damages and others, the transfusions may save lives. Although RBC may contribute to reduce morbidity and improve quality of life in SCD patients, there still are risks. Among other risk categories, alloimmunization may result from transfusions and occurs in 5 % to 50 % of SCD patients. It is still not known whether allosensibilization significantly affects the clinical outcomes in SCD. Objecive: The purpose of this study was to compare the clinical profile of multitransfused adult SCD patients who developed alloantibodies (ALO) to patients with the same disease, coming from the same population who did not become alloimmunized (non-ALO). Methods: This is a cross sectional study where medical records of SCD patients, referred to a reference center of Salvador, the capital of Bahia State, Brazil, were reviewed. Only SCD patients 18 years of age or older were included. They had received at least 3 RBC transfusions from 2004 to 2007, or had any alloantibody identified during this period. Patient characteristics, clinical findings, number of transfusions, frequency and specificity of alloantibodies, laboratory data, and the main clinical outcomes were reviewed. Results: a hundred and eight patients were included: 105 SS and 3 SC. The pre-transfusional RBC matching was done to ABH, D,C,c,E,e and Kell antigens. 56 patients developed alloantibodies (53 SS and 3 SC). Anti-E, anti-K, and anti-C were the most prevalent alloantibodies identified (39,3 %, 21,4 % and 16,1 %, respectively). Among the variables addressed in this study, age (higher in non-ALO, .041) and antiglobulin test positivity, more prevalente in ALO (.0001), depicted statistically significant difference. A few patients developed immune hemolysis, controlled successfully with corticosteroids. Alloimmunization was more prevalent among women, although no statistically significant difference was reached between ALO and non-ALO Other variables such as number of transfusions, hematological profile, biochemical data and complications such as stroke, leg ulcers, osteonecrosis, renal disease, abnormal cardiac features, and pulmonary hypertension did not show significant difference between both groups. Conclusion: his study shows that, although alloimmunization is a potential dangerous consequence of RBC transfusions, it did not modify the clinical profile of SCD alloimmunized patients. The concomitance of allosensibilization and autoantibodies in SCD leads to additional difficulties in the RBC matching for transfusion and may exacerbate hemolysis. In order to address autoimmunity in SCD, prospective studies with larger samples are needed.

The erythrocyte alloimmunisation in patients with sickle cell anaemia: a systematic review

“…After the articles were read, 21 were selected (Fig. ) (Al‐Saeed, ; Padmanabhan & Chandrasekaran, ; Olujohungbe et al ., ; Bashawri, ; Meunier et al ., ; Natukunda et al ., ; Zanette et al ., ; Helman et al ., ; Aly et al ., ; Wahl et al ., ; Diarra et al ., ; O'Suoji et al ., ; Fasano et al ., ; Desai et al ., ; Karafin et al ., ; Michot et al ., ; Nickel et al ., ; Sins et al ., ; Tatari‐Calderone et al ., ; Allali et al ., ; Sippert et al ., ).…”

Challenges of alloimmunization in patients with haemoglobinopathies

“…In patients with SCD, alloantibodies to the Rh system (most commonly, C and E) and to the Kell (K) antigen comprise over two‐thirds of the RBC antibodies encountered in all populations studied (Davies et al , ; Rosse et al , ; Castro et al , ; Ameen et al , ; Dias Zanette et al , ; Natukunda et al , ). This includes antibodies in these systems with uncommon specificity (V, hr b , C w , Js b ) that are more common in patients with SCD.…”

Red blood cell alloimmunization in patients with sickle cell disease: correlation with HLA and cytokine gene polymorphisms

“…Even some alloimmunized patients who are not chronically transfused are 20 times more likely to form additional antibodies after one or more transfusion events . Alloimmunization is a major obstacle to the management of this patient population because it alters the longevity of transfused RBCs, leading to decreased transfusion benefits, increased transfusion requirements, extensive laboratory workups, and investment of significant time and resources …”