A 12-year-old girl was referred to the endocrinology clinic for investigation of short stature. She had signs of early puberty yet had precocious menstruation associated with menorrhagia. She gave a recent history of recurrent epistaxis. There was no family history of a bleeding disorder. She reported cold intolerance, dry skin and a tendency for hair to fall.
On examination she was pale with no evidence of purpura or significant bruising. There was no enlargement of lymph nodes, liver or spleen. She had a small smooth goitre. Full blood count confirmed anaemia with a Hb 90 g/l; platelets and WCC were normal. Coagulation profile revealed prothrombin time 13.7 seconds (normal 9.7-12.1), APTT 35.3 seconds at the ULN and fibrinogen normal. Factor VIII Coagulant was 39 %, Von Willebrand factor 33% and Factor VIII (RAG) was 27% (normal range for these factors being 50-200%). TSH was >150 mU/l with undetectable free thyroid hormones. Thyroglobulin and microsomal antibodies were positive.
These tests confirmed Von Willebrand's disease (Type-1) in association with autoimmune hypothyroidism. She commenced thyroxine replacement and the menstrual disturbance and coagulation factors returned to normal.
Discussion: Von Willebrand factor plays an important role in primary haemostasis by binding to both platelets and endothelium, and is the most common inherited bleeding disorder. However Acquired Von Willebrand's disease is a rare entity that is primarily associated with lympho- and myeloproliferative disorders. It has been described in hypothyroidism and complete correction of the clotting abnormality with thyroxine is proof of the causal relationship. Deficient protein synthesis seen in hypothyroidism with reduction in clotting factor levels is the suggested pathophysiological mechanism. Excessive bleeding or easy bruising in patients presenting with hypothyroidism should prompt detailed investigation of the haemostatic system.
22 - 24 Mar 2004
British Endocrine Societies