Case history

An 86 year old man was referred from a community hospital for further investigation of his anaemia. On examination he was alert, oriented, and haemodynamically stable. He was pale with extensive ecchymoses over his trunk and upper limbs. He had a tender swollen left arm (see figure). There were no other relevant findings.

Investigations showed a haemoglobin concentration of 59g/l with a mean corpuscular volume of 101fl, platelets 319x109/l, and white cell count of 9.1x109/l. Blood film showed no evidence of haemolysis; there were no target cells or hypersegmented neutrophils, but the film confirmed a macrocytic anaemia. Concentrations of vitamin B-12 and folate were normal, as were results of thyroid and liver function tests. Coagulation screen showed a normal prothrombin time but a markedly prolonged activated partial thromboplastin time of 108.7s (35-45s).

Questions

(1) What are the common causes of an isolated prolonged activated partial thromboplastin time?
(2) What other investigations would you do?
(3) What is the diagnosis?

Answers

(1) A prolonged activated partial thromboplastin time ocurs in individuals with haemophilia or as a consequence of heparin administration. Heparin is the commoner of the two.
(2) Further investigations showed a factor VIII level of less than 1% with normal levels of factor IX. Antifactor VIII antibodies were shown with activity against human factor VIII but not porcine.
(3) Acquired haemophilia.

Discussion

Acquired haemophilia is a rare disorder, but an important and often unrecognised cause of bleeding in elderly people. It usually presents as bleeding into skin or muscle, although it can occur at any site. The resulting anaemia can provoke angina or heart failure in affected individuals. Our patient was short of breath, with a raised jugular vein pulse and peripheral oedema. Acquired haemophilia can be associated with an underlying autoimmune disease, malignancy, pregnancy, or drugs. Although our patient had a raised erythrocyte sedimentation rate, autoimmune screen was negative, calcium and phosphate were normal, and prostate specific antigen less than 0.1nmols/mL. A venogram carried out to investigate the cause of his swollen arm suggested compression of the left brachiocephalic vein within the mediastinum. Computed tomography of the chest showed this was due to an ectatic aortic arch; there were no other abnormalities. Further investigations have not revealed any malignancy and spontaneous acquisition of factor VIII antibodies is known to occur in isolation.

Management of acquired haemophilia aims to eliminate the antifactor VIII antibody while controlling any active bleeding.

Various forms of immunosuppression have been tried. These most frequently include corticosteroids and cyclophosphamide, although plasmapheresis and intravenous immunoglobulin have been used.

Control of active bleeding relies on increasing factor VIII levels. This can be achieved by provision of exogenous human or porcine factor VIII or stimulating endogenous production with desmopressin. Alternatively, prothrombin complex concentrate or recombinant factor VII can be given.

This patient had a good response to initial treatment with prednisolone 1mg/kg and cyclophosphamide 2mg/kg, activated partial thromboplastin time falling to 75secs after five days of treatment. However, two weeks later, the patient developed a painful right hip, indicating a likely haemarthrosis. This acute bleed was treated with prothrombin complex concentrates and intravenous immunoglobulin was given to suppress the antibody. This produced a rise in factor VIII levels from less than 1% to 30% of normal.

Acquired haemophilia has an overall mortality of 20%, but early recognition and prompt treatment of the condition can result in a favourable clinical outcome.