LITMIR.BIZ

      A 5‐year‐old girl was admitted as an emergency after a collapse following a fever at home. On assessment she was acutely unwell and hypotensive and had generalised petechiae. The clinical picture was of severe sepsis and after blood cultures had been taken she was commenced on broad‐spectrum antibiotics. The full blood count showed Hb 120 g/l, WBC 20 × 10⁹/l, neutrophils 17 × 10⁹/l and platelets 32 × 10⁹/l. The coagulation profile was indicative of disseminated intravascular coagulation (DIC). The blood film (left images ×100 objective) showed neutrophilia with left shift; in particular there was prominent neutrophil vacuolation and there were cytoplasmic inclusions consistent with the appearance of diplococci. Note also the prominent Döhle bodies in the neutrophils (bottom left). Meningococcal septicaemia now seemed likely and was confirmed on blood cultures and PCR studies.

      A second patient, a 62‐year‐old man, was admitted following a collapse after a 2‐day prodrome of feeling non‐specifically unwell. He had been bitten on the hand by a dog some days previously. He was febrile and hypotensive and had widespread petechiae. His condition deteriorated and he required intubation, ventilation and inotropic support. His full blood count showed Hb 137 g/l, WBC 24.2 × 10⁹/l, neutrophils 22.7 × 10⁹/l and platelets 9 × 10⁹/l. The coagulation screen was again indicative of DIC (PT 25 s, APTT 92 s, TT 17 s, fibrinogen 1.5 g/l and D dimer 88 726 ng/ml). The blood film showed neutrophilia with left shift and some neutrophils had rod‐shaped bacterial inclusions (centre images). Blood cultures grew the Gram‐negative bacillus, Capnocytophaga canimorsus, which is a serious human pathogen that often forms part of normal canine and feline flora.

A third patient, a 66‐year‐old woman was in hospital with obstructive jaundice due to liver metastases from ovarian carcinoma and had external biliary stents in situ. She was receiving weekly paclitaxel chemotherapy. She became acutely unwell, developing hypotension and jaundice. The full blood count showed Hb 57 g/l, WBC 7.3 × 10⁹/l and platelets 177 × 10⁹/l. As in the previous cases, the blood film was informative; it showed profound red cell spherocytosis (right images) with red cell ghosts (top right image) and toxic granulation of neutrophils (bottom right image) but no bacterial inclusions were seen. Despite resuscitation efforts the patient died shortly afterwards. Blood cultures subsequently grew Clostridium perfringens. This bacterium can be a commensal of the normal hepatobiliary and gastrointestinal tracts but becomes a serious and life‐threatening pathogen when it gains access to the blood, most likely in this case in relation to the stent. It produces an alpha lecithinase enzyme which directly lyses the red cell membrane, inducing an acute haemolytic anaemia that further compounds the septicaemia. The blood film features are typical of this condition; the spherocytes are due to membrane perforation, as are the ghost cells where all red cell haemoglobin has been leaked. By the time the blood film has been assessed, most affected patients have succumbed to this form of septicaemia but in some cases the morphological features may indicate the need for rapid active management and save a life.

MCQ

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.

16 Sickle cell anaemia in crisis

      A 33‐year‐old woman with known sickle cell anaemia, newly arrived in the United Kingdom, presented to Accident and Emergency with a painful crisis. She was breathless, febrile and faintly jaundiced. Her FBC showed Hb 51 g/l, RBC 1.72 × 10¹²/l, Hct 0.165, MCV 95.8 fl, MCH 29.8 pg, MCHC 311 g/l, WBC 13.8 × 10⁹/l and platelet count 445 × 10⁹/l. Bilirubin was increased to 141 μmol/l and ALT was mildly increased to 55 u/l. CRP was markedly increased to 137 mg/l. Examination of the blood film (all images ×100 objective) showed boat‐shaped cells (top) but surprisingly infrequent sickle cells. There were some nucleated red blood cells and polychromasia was

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