Recombinant activated factor VII for acute subdural haematoma in an elderly patient taking fondaparinux
Toulon, France
* E-mail: bordes.julien{at}neuf.fr
Editor—Acute subdural haematoma is one of the most common neurosurgical emergencies. Anticoagulants may be a contributing factor. Emergency treatment aims to normalize haemostasis to limit haematoma expansion, as rapidly as possible. We report a case of subdural haematoma in a patient on treatment with fondaparinux which was antagonized by recombinant activated factor VII (rFVIIa).
A 76-yr-old man receiving fondaparinux 7.5 mg once a day for prevention of stroke due to atrial fibrillation was admitted with cranial trauma after a fall. His Glasgow coma scale (GCS) was 15/15, and there were no focal abnormalities on initial clinical examination. One hour later, his level of consciousness had decreased (GCS 11/15). A brain CT scan revealed an acute subdural haematoma. Two hours later, his neurological status seriously worsened (GCS 7/15) with unilateral mydriasis. A repeat brain CT scan revealed further bleeding with massive oedema and transtentorial herniation. It was decided to evacuate the haematoma as an emergency after administration of rFVIIa (90 µg kg–1) to antagonize the fondaparinux. A craniotomy and clot evacuation was performed and haemostasis was successfully and easily achieved. By 12 h, intracranial pressure had increased to >40 mm Hg and a CT scan showed diffuse, massive oedema associated with hemispheric ischaemia. The patient died at 24 h from refractory intracranial hypertension.
Fondaparinux (Arixtra®) is the first synthetic selective factor Xa inhibitor. As with any anticoagulant therapy, there is a risk of bleeding complications. However, there is, as yet, no recommended antidote. rFVIIa has been reported to be effective in reversing anticoagulant effect of fondaparinux. In healthy volunteers, rFVIIa normalized haemostasis for at least 6 h after a single dose of 90 µg kg–1.1 These results have been confirmed in vitro.2 We found only one case report of the use of rFVIIa, in a patient with haemorrhagic shock after fondaparinux 2.5 mg who was successfully treated with rFVIIa (90 µg kg–1), combined with anti-fibrinolytic (tranexamic acid 15 mg kg–1), which reduced bleeding within 1 h.3 In our case, advanced age and reduce renal clearance may have been risk factors for bleeding. We think that rFVIIa administration contributed to limit the bleeding during neurosurgery by antagonizing fondaparinux, and facilitating surgical haemostasis. It is possible that earlier administration may have avoided the subdural haematoma expansion we observed. Safety of rFVIIa is still controversial. One of the potential risks is arterial or venous thrombosis. In volunteers, a single dose of 90 µg kg–1 did not result in an overshoot of coagulation.1 A clinical study comparing rFVIIa with placebo in intracerebral haemorrhage did not report any increased frequency of adverse events in the rFVIIa group,4 but another showed an increased frequency of serious thrombotic events.5 In our case, it is possible that the hemispheric ischaemia demonstrated by the CT scan at 12 h was the result of a prolonged cerebral herniation, or the result of a vessel thrombosis caused by rFVIIa administration.
Anticoagulant therapy may expose patients to serious side-effects. The risk–benefit assessment is particularly important for new anticoagulants such as fondaparinux, for which the management of bleeding complications is poorly documented. The use of rFVIIa as an antidote may be effective in life-threatening bleeding. As with other anticoagulant therapy and related intracranial haemorrhage, the timing of treatment has a major effect on the capability of rFVIIa to limit development of a haematoma. The potential risk of rFVIIa causing thrombosis must be taken into account before administration.
References
1 Bijsterveld NR, Moons AH, Boekholdt SM, et al. Ability of recombinant factor VIIa to reverse the anticoagulant effect of the pentasaccharide fondaparinux in healthy volunteers. Circulation (2002) 106:2550–4.
2 Lisman T, Bijsterveld NR, Adelmeijer J, et al. Recombinant factor VIIa reverses the in vitro and ex vivo anticoagulant and profibrinolytic effects of fondaparinux. J Thromb Haemost (2003) 1:2368–73.[CrossRef][Web of Science][Medline]
3 Huvers F, Slappendel R, Benraad B, van Hellemondt G, van Kraaij M. Treatment of postoperative bleeding after fondaparinux with rFVIIa and tranexamic acid. Neth J Med (2005) 63:84–6.
4 Mayer SA, Brun NC, Broderick J, et al. Safety and feasibility of recombinant factor VIIa for acute intracerebral hemorrhage. Stroke (2005) 36:74–9.
5 Mayer SA, Brun NC, Begtrup K, et al. Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med (2005) 352:777–85.
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