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15 An unstable haemoglobin and a myeloproliferative neoplasm

A 26‐year‐old man was well known to the Haematology clinic and had a chronic compensated haemolytic anaemia due to the unstable haemoglobin, haemoglobin Köln. He suffered exacerbations of haemolysis with intercurrent infection but his condition would settle thereafter. A typical full blood count showed Hb 114 g/l, WBC 4.7 × 10⁹/l, neutrophils 2.4 × 10⁹/l and platelets 154 × 10⁹/l. His blood film is illustrated above; bite cells and irregularly contracted cells are evident (left and centre ×100 objective) and Heinz bodies were prominent (right, methyl violet ×100). Somewhat unexpectedly, he developed progressive and ultimately massive splenomegaly though his haemolytic disorder appeared clinically unchanged. CT scanning showed a 25 cm spleen with no focal abnormality; there was no evidence of chronic liver disease or portal hypertension and no lymphadenopathy was apparent. His full blood count now showed Hb 125 g/l, WBC 12.7 × 10⁹/l, neutrophils 8.9 × 10⁹/l and platelets 1830 × 10⁹/l. He underwent a splenectomy in view of progressive splenic symptoms. The spleen weighed 2700 g (normal 200 g). Histological examination showed massive expansion of the red pulp with congested sinuses and extramedullary haemopoiesis. There was no evidence of lymphoma.

The post‐operative blood film is shown above (×100). There is a marked thrombocytosis with profound platelet anisocytosis and hyposplenic features but bite cells are not now obvious. An unrelated myeloproliferative neoplasm was now considered likely and a bone marrow trephine biopsy was taken. The sections showed a hypercellular marrow with expansion of all lineages (below left, H&E) (all images below ×50), increased reticulin staining (grade 2–3/3, below centre) and megakaryocyte clustering (below right, immunoperoxidase for CD42b).

The features here support a diagnosis of a myeloproliferative neoplasm and molecular studies showed a pathogenic intragenic CALR deletion. In the circumstances it is difficult to accurately classify this myeloproliferative neoplasm but the diagnosis is likely to be primary myelofibrosis. This patient has two unrelated disorders which had caused understandable diagnostic difficulty. It is important to link any new development to a known disorder but it is also advisable that the clinician keeps an open mind, and considers all potential options when patients show an unexpected clinical evolution.

MCQ

1 Unstable haemoglobins:Affect only the α or β globin chainCan be associated with the presence of two variant haemoglobins as well as haemoglobin ACan be detected by instability on heating or exposure to isopropanolHave normal oxygen affinityWhen clinically manifest, usually indicate homozygosityFor answers and discussion, see page 206.