A review of aplastic/hypoplastic anaemia diagnosed on bone marrow samples at the haematology laboratory at National Health Laboratory Service (NHLS), Inkosi Albert Luthuli Central Hospital, Durban, KwaZulu-Natal.

Abstract

Aplastic Anaemia (AA) is a bone marrow failure syndrome (BMFS) characterized by bone marrow aplasia and peripheral blood pancytopenia. The presenting symptoms in patients with AA are often those of anaemia, haemorrhage or purpura and, less frequently, infection. These symptoms usually lead to medical evaluation (1, 2). Presentation can range from non-severe or moderate, to sometimes life-threatening cytopenias. In the Western World, the annual incidence of Acquired Aplastic Anaemia (AAA) is 2 cases per million persons (3). A biphasic age distribution has been reported. AA primarily affects children, young adults, and those over 60 years of age. Males and females display no significant difference in incidence. The majority (70-80%) of AA cases are classified as idiopathic, as their primary aetiology is unknown (4). Drugs or infections that precipitate bone marrow failure, can be identified in a subset of AA cases. AA is constitutional in approximately 15-20% of patients, with the commonest inherited bone marrow failure syndrome (IBMFS) being Fanconi Anaemia (FA). Five percent of idiopathic AA have undiagnosed IBMFS because the full disease phenotype has not manifest itself (5, 6). An autoimmune pathogenesis is favored to cause stem cell depletion. Severe AA is invariably fatal without treatment. The currently available treatment options including allogeneic bone marrow transplantation (BMT), are improving patient survival in developed countries (2, 7, 8). Paroxysmal nocturnal haemoglobinuria (PNH) is a rare clonal haemopoietic stem cell (HSC) disorder which may arise de novo or evolve from AA. This bone marrow failure disorder manifests with haemolytic anaemia, marrow failure (peripheral blood cytopenias) and thrombophilia. AA and PNH are closely related, and small PNH clones are detectable in more than half of AA patients. PNH is also the most common clonal disorder that occurs in AA patients after treatment with immunosuppressive therapy (IST) (7, 9-18). This project was conducted in order to delineate the demographic and clinico-haematological profile of the adult patient cohort diagnosed with AA within the Kwa-Zulu Natal (KZN) public health care sector. Inkosi Albert Luthuli Central Hospital (IALCH) in Cato Manor, Durban is the only public sector hospital in Kwa-Zulu Natal (KZN) equipped with the facilities and resources to diagnose this rare condition, as well as to treat AA. Due to the rare occurrence of this haematological disorder, there is a paucity of information regarding AA in South Africa (SA), as well as in African countries in general. To date, there have been no published studies on Adult AA from our centre or other centres within SA. Aims and objectives: The aim of this retrospective observational study was to collect data regarding the demographics, clinical presentation, aetiology/associations, laboratory parameters and outcome of adult patients with a bone marrow diagnosis of Aplastic Anaemia at the National Health Laboratory Service (NHLS), IALCH, Durban, KZN, over a 10-year period. The specific objectives of the study were to illustrate patient demographics, to correlate the full blood count (FBC), bone marrow aspirate and trephine (BMAT) findings and to document disease severity. Other aims included documenting aetiological associations, in particular viruses such as Human Immunodeficiency Virus (HIV), and connective tissue disorders such as systemic lupus erythematosus (SLE). Another objective in HIV infected patients, was to establish if a relationship with the CD4 count/viral load and disease presentation, exists. The presence, or subsequent emergence, of a PNH clone and cytogenetic abnormalities, if any, were also documented. Patient outcomes, including response to treatment and overall survival, was also assessed. Methods: BMAT biopsies with a confirmed diagnosis of Aplastic/Hypoplastic anaemia at the NHLS Haematology Laboratory at IALCH, were reviewed over a 10-year period (2005-2015). Demographic data, clinical information and laboratory parameters were recorded on a standardized data collection sheet, and then transcribed onto a Microsoft Excel spreadsheet for analysis. The demographic and clinical data was obtained from the referral forms and clinical notes. Laboratory results were extracted from the TrakCare Lab Information System (LIS). Results: A total of 92 BMATs were reviewed. There were 42 males (M) and 50 females (F), with a M:F ratio of 0.8:1. The median age at presentation was 24 years, with an absence of a second peak of presentation in older patients. Twenty nine patients had very severe AA (VSAA), 36 had severe AA (SAA) and 27 had non severe AA (NSAA). Symptoms of thrombocytopenia (TCP) prevailed in the majority (61%) of patients at presentation, followed by symptoms of anaemia (53%). Symptoms of neutropenia, occurring in 6 patients (7.5%), were the least frequent. Ninety three percent of patients presented with pancytopenia. Thirty percent of patients had a severe anaemia (Hb <6g/dl). Sixty percent of patients had a severe thrombocytopenia (platelets < 20x109/l). A severe neutropenia (ANC < 0.5 x 109/l) was observed in 62% of patients. Reversal of the lymphocyte: neutrophil ratio was observed in 92% of patients. All bone marrow trephines were markedly hypocellular for age. Twenty two patients had an initial failed BMAT biopsy. Cytogenetic abnormalities were noted in 2 patients at presentation. The majority of patients had idiopathic AA, with no identifiable aetiology. Two patients had FA, and a PNH clone was demonstrable in 4 patients at presentation. Thirteen patients (16.3%) were HIV positive. Four patients were pregnant at the time of presentation and their outcomes varied. Different modalities of treatment were used, including observation, androgens, immunosuppressive therapy [ciclosporin (CSA) with/without anti-thymocyte globulin (ATG)] and allogeneic bone marrow transplantation (BMT). Thirteen patients did not reach the clinical haematology unit, 35 patients are alive, 22 patients demised and 22 have been lost to follow up (LTFU). Two patients had clonal evolution to PNH and one to MDS. Conclusion: The clinico-epidemiological profile of patients in this study is similar to that reported in the literature. A significant number of patients did not reach the clinical haematology unit at IALCH. An unusually high number of failed initial BMATs were performed at peripheral hospitals. HIV associated AA was not increased in this patient cohort.