Vasospasm
Vasospasm, referring to blood vessel constriction, can occur secondary to subarachnoid hemorrhage following a ruptured aneurysm. This is most likely to occur within 21 days and is seen radiologically within 60% of such patients. The vasospasm is thought to be secondary to the apoptosis of inflammatory cells such as macrophages and neutrophils that become trapped in the subarachnoid space. These cells initially invade the subarachnoid space from the circulation in order to phagocytose the hemorrhaged red blood cells. Following apoptosis, it is thought there is a massive degranulation of vasoconstrictors, including endothelins and free radicals, that cause the vasospasm. Risk factors
Intracranial aneurysms may result from diseases acquired during life, or from genetic conditions. Hypertension, smoking, alcoholism, and obesity are associated with the development of brain aneurysms. Cocaine use has also been associated with the development of intracranial aneurysms.Other acquired associations with intracranial aneurysms include head trauma and infections. Genetic associations
Coarctation of the aorta is also a known risk factor, as is arteriovenous malformation. Genetic conditions associated with connective tissue disease may also be associated with the development of aneurysms. This includes:
autosomal dominant polycystic kidney disease,
neurofibromatosis type I,
Marfan syndrome,
multiple endocrine neoplasia type I,
pseudoxanthoma elasticum,
hereditary hemorrhagic telangiectasia and
Ehlers-Danlos syndrome types II and IV.Specific genes have also had reported association with the development of intracranial aneurysms, including perlecan, elastin, collagen type 1 A2, endothelial nitric oxide synthase, endothelin receptor A and cyclin dependent kinase inhibitor. Recently, several genetic loci have been identified as relevant to the development of intracranial aneurysms. These include 1p34–36, 2p14–15, 7q11, 11q25, and 19q13.1–13.3.
Society and culture
Legal status
NovoSeven was approved for use in the United States in March 1999, and indicated for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX. It was approved in October 2006, and indicated for the treatment of bleeding episodes and for the prevention of bleeding in surgical interventions or invasive procedures in patients with acquired hemophilia.NovoSevenRT was approved for use in the United States in May 2008, as a room temperature stable formulation. In January 2010, the label was updated to include a black box warning on serious thrombotic adverse events associated with the use of NovoSeven RT outside labeled indications.In April 2020, coagulation factor VIIa (recombinant)-jncw (Sevenfact) was approved for use in the United States.On 19 May 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Cevenfacta, intended for the treatment of bleeding episodes. The applicant for this medicinal product is Laboratoire français du Fractionnement et des Biotechnologies (LFB). The active substance of Cevenfacta is eptacog beta (activated), a blood coagulation factor (ATC code: B02BD08). Eptacog beta is almost identical to, and functions like, coagulation factor VII. It activates factor X, which starts the clotting process and thereby provides control of the bleeding.