Semin Thromb Hemost
DOI: 10.1055/s-0037-1604109
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Intracranial Hemorrhage: A Devastating Outcome of Congenital Bleeding Disorders—Prevalence, Diagnosis, and Management, with a Special Focus on Congenital Factor XIII Deficiency

Seyed Ezatolla Rafiee Alavi1, Masumeh Jalalvand2, Vahideh Assadollahi3, Shadi Tabibian4, Akbar Dorgalaleh4
  • 1Department of Pathology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
  • 2Department of Biotechnology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
  • 3Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran
  • 4Department of Hematology and Blood Transfusion, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
Further Information

Publication History

Publication Date:
12 September 2017 (eFirst)


Intracranial hemorrhage (ICH) is a medical emergency. In congenital bleeding disorders, ICH is a devastating presentation accompanied with a high rate of morbidity and mortality. The prevalence of ICH is highly variable among congenital bleeding disorders, with the highest incidence observed in factor (F) XIII deficiency (FXIIID) (∼30%). This life-threatening presentation is less common in afibrinogenemia, FVIII, FIX, FVII, and FX deficiencies, and is rare in severe FV and FII deficiencies, type 3 von Willebrand disease and inherited platelet function disorders (IPFDs). In FXIIID, this diathesis most often occurs after trauma in children, whereas spontaneous ICH is more frequent in adults. About 15% of patients with FXIIID and ICH die; the bleeding causes 80% of deaths in this coagulopathy. Although in FXIIID, the bleed most commonly is intraparenchymal (> 90%), epidural, subdural, and subarachnoid hemorrhages also have been reported, albeit rarely. As this life-threatening bleeding causes neurological complications, early diagnosis can prevent further expansion of the hematoma and secondary damage. Neuroimaging plays a crucial role in the diagnosis of ICH, but signs and symptoms in patients with severe FXIIID should trigger replacement therapy even before establishment of the diagnosis. Although a high dose of FXIII concentrate can reduce the rate of morbidity and mortality of ICH in FXIIID, it may occasionally trigger inhibitor development, thus complicating ICH management and future prophylaxis. Nevertheless, replacement therapy is the mainstay of treatment for ICH in FXIIID. Neurosurgery is performed in patients with FXIIID and epidural hematoma and a hemorrhage diameter exceeding 2 cm or a volume of ICH is more than 30 cm3. Contact sports are not recommended in people with FXIIID as they can elicit ICH. However, a considerable number of safe sports and activities have been suggested to have more benefits than dangers for patients with congenital bleeding disorders, and are hence suitable for these patients.