J Neurol Neurosurg 1998;65:617 617 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.5.617 on 1 November 1998. Downloaded from

EDITORIAL COMMENTARY

Is inherited a risk factor for arterial stroke?

The term thrombophilia describes an increased tendency there is a striking association between both V Leiden and to clinical associated with laboratory evidence prothrombin G20210A and cerebral venous of abnormal haemostasis. Causes include inherited defi- thrombosis.45 ciencies of natural (antithrombin, protein What is the relevance of these findings for clinical prac- C, and ), polymorphisms causing resistance to tice? It seems reasonable to continue to screen patients activated ( ) or disturb- younger than 50 presenting with ischaemic stroke for ing the normal proclot or anticlot balance (prothrombin thrombophilia, recognising that positive results have to be G20210A mutation), and disorders which are polygenic or interpreted with caution. Firstly, inherited abnormalities of interact with dietary and environmental factors (high this type are found in a significant proportion of the normal factor VIII and hyperhomocysteinaemia). Inherited throm- population, often without any history of thrombosis. bophilias, most commonly factor V Leiden and high VIII, Secondly, concentrations of protein C, protein S, and anti- are risk factors in most cases of venous thromboembolism are depressed after stroke. The blood tests 1 under the age of 40. It is therefore tempting to assume that should be repeated at least 3 months after the acute event

a similar relation will be found in arterial thrombosis, espe- before concluding that inherited deficiency is present. copyright. cially as stroke in young people often remains unexplained Coumarins lower protein C and S, so if the patient is on even after extensive investigation of other possible causes. warfarin interpretation is unreliable; interrupting antico- In the previous issue of this Journal, pp 508−511 Ganesan agulation to confirm thrombophilia may be appropriate. et al described a prospective case-control study of 60 chil- The finding of inherited thrombophilia in a patient with dren with arterial ischaemic stroke which failed to show stroke should always raise the possibility that an infarct that any significant association between inherited throm- may seem arterial has in fact resulted from cerebral venous bophilia and stroke. Haemostatic abnormalities were thrombosis or paradoxical embolism, because of the initially found in 24% of the patients, but only 12% (eight stronger association of thrombophilia with venous throm- children) were confirmed when the tests were repeated 3 bosis. We do not know if finding inherited thrombophilia in months later, after the acute phase. Two children had a patient with stroke indicates an increased risk of thrombophilia in association with moyamoya disease (pro- recurrent stroke. In general, it seems reasonable to ignore tein S deficiency, V Leiden) which is consistent with previ- http://jnnp.bmj.com/ 2 the association if other strong risk factors for stroke are ous findings in this entity. One child had activated protein found, but in patients in whom no other cause is C resistance without factor V Leiden, a combination established, lifelong anticoagulation should be considered. sometimes seen with high VIII status. Ganesan et al did not The decision should be made in consultation with an report VIII concentrations or the prothrombin G20210A experienced specialist. In some patients, mutation. The remaining six children (12%) were found to particularly those with the factor V Leiden mutation, it have the factor V Leiden mutation. This was not may be more appropriate to anticoagulate only patients significantly diVerent from the control group of Ganesan et

with recurrent thrombosis. on September 29, 2021 by guest. Protected al, in whom the prevalence of V Leiden was 5%, but because ethnic origin strongly determines the frequency of MARTIN M BROWN this predominantly white polymorphism, the ethnic Division of Clinical Neuroscience composition of study and control groups (not given by DAVID BEVAN Department of Haematology, St George’s Hospital , Ganesan et al) should have been carefully matched. London SW17 0RE, UK It can be concluded that inherited thrombophilia does not seem to be a major cause of stroke in children, except perhaps in the category of moyamoya disease. It remains 1 Rosendaal FR. Thrombosis in the young: epidemiology and risk factors. A focus on . Thromb Haemost 1997;78:1–6. possible that there would have been a significant 2 Tsuda H, Hattori S, Tanabe S, et al. Thrombophilia found in patients with association between thrombophilia and stroke if a larger Moyamoya disease. Clin Neurol Neurosurg 1997;99:S229–33. 3 Ridker PM, Hennekens CH, Lindpainter K, et al. Mutation in the gene cod- series of ethnically matched children had been available for ing for coagulation factor V and the risk of myocardial infarction, stroke study, especially as the odds ratio for the incidence of and venous thrombosis in apparently healthy man. N Engl J Med 1995;332: 912–7. stroke associated with V Leiden was more than doubled. 4 Martinelli I, Landl G, Merati G, et al. Factor V gene mutation is a risk fac- Although there have been anecdotal reports of arterial tor for cerebral venous thrombosis. Thromb Haemost 1996;75:393–4. 5 Martinelli I, Sacchi E, Landi G, et al. High risk of cerebral-vein thrombosis stroke associated with thrombophilia, a large study failed to in carriers of a prothrombin gene mutation and in users of oral contracep- 3 confirm any significant association in adults. By contrast, tives. N Engl J Med 1998;338:1793–7.