Clinical, laboratory features and available treatment options among patients with aplastic anaemia attending Muhimbili national hospital, Tanzania

Abstract

Background: Aplastic anaemia (AA) is a rare, potentially life-threatening disease presenting with hypocellular fatty marrow and reduction in the blood count of all blood cell lines; the red cells, white cells and platelets. A cell- mediated autoimmune mechanism has been implicated in the pathogeneis of AA. Gold standard treatment is with either allogeneic haemopietic stem cell transplant or intensive immunosuppressive therapy with ATG followed by cyclosporine. AA is associated with high morbidity and mortality if left untreated. There is a paucity of studies on AA in Tanzania and East Africa. A fraction of AA patients evolve to paroxysmal nocturnal haemoglobinuria (PNH): this is associated with the appearance of a population of blood cells deficient in GPI-anchored proteins (GPI-negative: sometimes referred to belonging to a PNH clone). Aim: To describe the clinical presentation, laboratory features, treatment modalities, and presence of GPI negative red cells population among patients with AA attending Muhimbili National Hospital. Participants: All patients with AA who attended MNH from September 2016 to March 2017. Study design: Descriptive cross-sectional study Methods: Consenting patients were sequentially recruited from inpatient and outpatient haematology unit. A structured questionnaire was used to obtain information on the socio-demographic characteristics, clinical history, physical signs and treatment modalities. Blood and urine samples were collected for investigations. Analysis was done using spss statistics version 20. Comparison between patients with AA alone and those with GPI negative red cell population with various characteristics was analyzed by using Fischer’s exact test and statistical differences were considered to be significant if p value was less than 0.05 Results: A total of 40 patients with AA were recruited. Seventeen (43%) were males. The median (IQR) age at diagnosis was 24 (15-33) years. The male to female ratio was 1:1.4. Forty eighty percent of patients had severe AA, 20% had very severe AA and 32% had non severe AA. Anaemia was the dominant clinical presentation (78%) followed by bleeding tendencies (70%) and fever (48%). The median (IQR) haemoglobin level was 6.6(5.4-8.8)g/dl, median (IQR) absolute reticulocyte count was 10 (6.25-16) X10⁹/L, median (IQR) absolute neutrophil count was 0.49(0.01-1.04) X10⁹/L, and the median (IQR) platelet count was 17.50(9.63-41.00) X10⁹/L. None of the patients had haemoglobinuria or positive Ham’s test. Twenty six samples were analyzed for presence of GPI deficient red cells, and in 42%, GPI deficient red cells were significantly higher than seen in normal controls (>0.2%). In three patients the PNH clone comprised more than 1% of red cells. Of the patients with significant GPI negative red cells population, 91% had been diagnosed with AA for more than one year before recruitment, and 82% were found to have less transfusion requirement within six months. Seventy eight percent of all patients were treated with a combination of supportive therapy and cyclosporine alone. Four patients (10%) were referred abroad and received intensive immune suppression therapy with ATG and cyclosporine. One patient (3%) received allogeneic haemopoietic stem cell transplant. Ten percent of patients had received only supportive treatment with blood transfusion and antibiotics. Conclusion: AA mostly affects people below the age of 40 years. The majority of patients with AA attending MNH have either severe or very severe AA. Almost half of patients with AA have PNH clones, although they do not have as yet any clinical or laboratory evidence of haemolysis (PNH-sc). Treatment offered at MNH includes supportive treatment and immune suppression with cyclosporine alone. Recommendation: There is a need of providing definitive therapy for AA in Tanzania.