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Case History

image A 36-year-old pregnant woman is referred at 16 weeks gestation with a raised platelet count. Her haemoglobin level is 11.4 g/dl, white cell count 12 × 109/l and platelets 924 × 109/l. This is her first pregnancy and she has been previously fit and well.

How would you investigate the thrombocytosis?


image The differential diagnosis (Table 25.1) is between primary and secondary causes. Pseudothrombocytosis (leukocytes/red cells misread as platelets by the automated counter) can generally be excluded on a blood film. In unselected patients attending hospital, thrombocytosis is due to reactive/secondary causes in 88%–97%. The most common secondary causes are infection, tissue damage, malignancy and chronic inflammatory disorders.1 Since thrombocytosis can be the presenting feature of malignancy (commonly gastrointestinal, lung and lymphoma), all patients require follow-up if a cause is not identified. Weight loss, fatigue, poor appetite, night sweats, symptoms of bone marrow failure and splenomegaly suggest a primary disorder, while symptoms and signs of secondary thrombocytosis reflect the underlying cause (e.g. splenectomy scar). Those with a primary cause usually have higher platelet and leukocyte counts, haematocrit, lactate dehydrogenase (LDH) and serum potassium (pseudohyperkalaemia occurs due to leakage of intracellular potassium during blood clotting in vitro; a lithium–heparin/plasma sample will be more accurate). Abnormalities on the full blood count and film, in addition to thrombocytosis, suggest a primary cause and vitamin B12 may be raised (but is also elevated in liver disease, carcinoma, leukaemia and leukocytosis). Those with a secondary cause usually have a higher erythrocyte sedimentation rate (ESR) and higher fibrinogen level. Additional investigations for a secondary cause will be directed by history and examination but may include serum ferritin, antinuclear antibody (ANA) and infection screen. If a primary cause is suspected, bone marrow aspirate and trephine with cytogenetic analysis are required.

Table 25.1Differential diagnosis of thrombocytosis

The pathogenesis of secondary thrombocytosis is not fully understood but may be mediated by thrombopoietin and pro-inflammatory cytokines such as interleukin-6. Secondary thrombocytosis does not appear to increase the risk of thrombosis unless additional risk factors are present, such as recent surgery or underlying malignancy. Primary thrombocytosis, caused by clonal stem cell abnormalities, is associated with an increase in arterial or venous thrombotic events, which are reported in 12% of patients. A maternal history of unexplained abortion, stillbirth or pre-eclampsia also suggests a primary cause.

On further questioning, she has had two first-trimester miscarriages. She has no ...

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