Intracranial Haemorrhage in Patients with An Inherited Bleeding Disorder: A Review of 10 Years Experience in a UK Haemophilia Comprehensive Centre.

Inherited bleeding disorders comprise a heterogeneous group of diseases that reflect abnormalities of coagulation proteins, platelets and blood vessels. Intracranial haemorrhage (ICH) is an unusual but life-threatening complication of such disorders. A 10-year retrospective study was conducted to investigate the episodes of ICH in patients with an inherited bleeding disorder who where followed by a regional haemophilia comprehensive care center in the UK.

All cases of ICH occurring in patients with an inherited bleeding disorder which presented between 1999 and 2009 were retrospectively identified using the haemophilia centre database. Case notes were reviewed and aetiology, clinical features, radiological findings, management and outcome of ICH in this population were studied.

Of 640 patients registered with an inherited bleeding disorder in haemophilia centre database, a total of 10 ICHs in 9 patients were identified. Age of patients ranged from 5 months to 72 years with a higher number of males (M:F = 7:2). Diagnosis included: Severe haemophilia A (3 patients); Mild haemophilia A (1 patient); Severe haemophilia B (1 patient); Type 2A von Willebrand disease (VWD) (1 patient); Type 3 VWD (1 patient); Congenital afibrinogenemia (1 patient); Severe factor V deficiency (1 patient). Two of the patients with severe haemophilia A had inhibitors, one of whom was receiving immune tolerance therapy at the time of the ICH. 7 of ICHs were spontaneous and 3 were trauma-related. ICH was the first significant bleeding event in 2 patients- one with severe haemophilia A, aged 5 months, and one with severe haemophilia B, aged 6 months. Type of ICHs were 7 subdural, 1 subarachnoid and 2 subdural with intracerebral. All patients were symptomatic. Common presenting features were headache (6 patients), vomiting (5 patients), limb paralysis (3 patients), cranial nerve palsy (3 patients) and seizures (2 patients). None had systemic bleeding concurrent to the ICH. Initial diagnostic modality was CT scan without contrast for all patients. The two patients with severe haemophilia A and inhibitors were initially treated with recombinant factor VIIa. The remaining patients with haemophilia were treated with factor VIII/IX concentrate. The patient with severe haemophilia B required surgical evacuation. The patients with severe haemophilia A/B without inhibitors were commenced on long-term prophylaxis with factor replacement therapy following their ICH. The patient with congenital afibrinogenemia was initially treated with fibrinogen concentrate, repeated CT scan on day ten showed significant expansion of hematoma, surgical evacuation was done and he was commenced on long-term prophylaxis. The patient with factor V deficiency received prothrombin complex concentrate (octaplex). The two patients with VWD were treated with haemate P, the patient with type 2A VWD received prophylaxis for 4 weeks. The patient with type 3 VWD died within an hour of admission despite haemate P treatment. Six patients had long-term morbidity including limb weakness, seizure, ventriculoperitoneal shunt and developmental delay. These results are summarized in Table 1.

ICH can occur in patients with a severe inherited bleeding disorder and can result in substantial morbidity and mortality. ICH can also occur in patients with a mild inherited bleeding disorder following trauma. There is no reliable predictor for intracranial bleeding which could aid decision-making in terms of prophylactic therapy to prevent ICH. CT scan is an appropriate initial diagnostic modality. It is important to educate patients and parents about symptoms to allow early diagnosis. Treatment should be administered rapidly to control bleeding in order to limit adverse outcomes.

No relevant conflicts of interest to declare.