Diagnostic Approach to Non-spherocytic Haemolytic Anaemia (NSHA)

Non-spherocytic haemolytic anaemias (NSHA) are constellations of inherited and acquired haemolytic anaemias with haemolysis as the primary presentation. The diagnosis is based on the absence of spherocytes on the PS examination (PS). The hereditary group is mainly constituted by enzymopathies and some surface membrane disorders with subtle RBC changes; while the acquired group comprises mainly of fragmentation syndromes, Paroxysmal nocturnal haemoglobinuria (PNH), and heavy metal toxicity due to Lead or Arsenic. The hereditary NSHA often presents either as chronic or acute haemolytic anaemias of unknown aetiology. The biochemical and haematological investigations favour haemolytic anaemia; however, the underlying aetiology is not clearly obvious and requires an exhaustive workup to reach the final diagnosis. Similarly, disorders like PNH, drugs, and toxins may have an obscure clinical presentation and may require an extensive workup for arriving at a diagnosis. Most of the other causes, like non-immune haemolytic anaemias, secondary to infections, burns, or thrombotic microangiopathies, do not have haemolysis as the primary clinical presentation. Only a very few of them will present as haemolysis primarily, the rest present with very characteristic clinical features, making diagnosis straightforward. The diagnostic algorithm for NSHA begins with a careful examination of PS to rule out the presence of spherocytes and demonstrate a negative Coombs test. Identifying any other specific red cell morphology like elliptocytes, stomatocytes, acanthocytes, echinocytes, sickle cells, fragmented cells, bite cells or basophilic stippling, enable a specific diagnosis on PS itself. The presence of a microcytic hypochromic blood picture and typical clinical presentation enables further workup of Thalassemia and other haemoglobinopathies. Similarly, the presence of bite or blister cells in G6PD deficiency, basophilic stippling in pyrimidine deficiency aids in giving direction to further workup. On the contrary, in the absence of a specific morphology, a careful review of all the clinical and laboratory findings and following a diagnostic algorithm helps in arriving at a diagnosis.