Page 186 - 2019_08-Haematologica-web

G. deVeber et al.
bin deficiency, five children who were lost to follow up and 35 children in whom thrombophilia screening was not performed (Figure 1). We therefore studied 894 con- secutively recruited children aged 1 month to ≤18 years who survived a first episode of AIS (Figure 1, Table 1) and were followed for a median (minimum-maximum) dura- tion of 35 (1-256) months. These patients’ clinical charac- teristics are summarized in Table 1. In total, 160 children (17.9%) experienced a recurrent AIS at a median time from the initial stroke of 3.1 months (minimum-maxi- mum: 0.1-136). Of the 160 children who had a second AIS, 15 (9.4%) died at the time of the second stroke. The overall recurrence rate, with the 95% confidence interval (95% CI), calculated per 100 person-years was 5 (95% CI: 4-6) with a yearly incidence of 0.05%.
Data on antithrombotic prophylaxis prior to a second AIS, i.e. anticoagulation with low molecular weight heparin or a vitamin K antagonist or antiplatelet therapy (with acetylsalicylic acid or clopidogrel), were available for a subgroup of 122 out of the 160 cases on an exploratory basis: antithrombotic prophylaxis was administered inde- pendently of the presence or absence of thrombophilia (P=0.89) or different stroke subtypes (P=0.2). In children with vasculopathy prior to the second AIS, 34 of 72 index patients were on antiplatelet agents (acetylsalicylic acid alone), 19 were being treated with low molecular weight heparin, and one child developed a second stroke while taking a vitamin K antagonist. In patients without vascu- lopathy 15 out of 50 children were on acetylsalicylic acid, in two cases combined with clopidogrel, seven were being treated with low molecular weight heparin and three were on oral anticoagulation with a vitamin K antagonist. Forty- four of the 122 patients did not receive anticoagulation or antiplatelet therapy prior to a second AIS (vasculopathy group n=19; non-vasculopathy group n=25; P=0.05).
Vascular territory of the second arterial ischemic stroke
In the majority of cases (75%) the same vascular territo- ry was involved as in the first AIS. The anterior circulation was involved in 62.5% of cases and the posterior circula- tion in the other 37.5%.
Stroke subtypes
Stroke subtypes are presented in Figure 1 and Table 1. Of the 894 incident pediatric stroke cases, 288 (32.2%) had vasculopathy. The sub-classification of the types of vascular stroke is shown in the Online Supplement. Imaging-confirmed recurrent stroke occurred in 160/880 enrolled children, for (i) cardiac disease 23/109 (21.1%), (ii) vasculopathy 82/284 (28.9%), for (iii) cryptogenic 41/401 (10.2%) and for (iv) other stroke types 14/78 (17.9%). Recurrent AIS was significantly more frequent in patients with vasculopathy (HR 2.5, 95% CI: 1.92-3.5; P<0.001) than in patients with cryptogenic stroke. Calculated per 100 person-years in those with vasculopathy, the recur- rence rate was 8 (95% CI: 6-10) with a yearly incidence rate of 7.7%. The time to recurrence, calculated as the probability of AIS-free survival, comparing pediatric AIS patients with and without vasculopathy, is depicted in Figure 2 (log rank P-value <0.001). No statistically signifi-
Figure 2. Arterial ischemic stroke-free survival in children with vasculopathy compared with that in the remaining children with a normal arterial examina- tion (P<0.001). Two additional patients suffering from cardiac disease, autoim- mune disorder along with short vessel stenosis are included.
Table 1. Clinical characteristics of the 894 children with a first arterial ischemic stroke studied for stroke recurrence.
Characteristics at first stroke onset
Ethnicity
Caucasian
Black
Asian
First nations/Aboriginal Central/South American Mixed ethnicity Unknown
Median age, years [min-max]
Male
Children with a first
cryptogenic AIS
Children with a first vascular stroke
Children with a first cardiac stroke
Children with a recurrent AIS
Patients on treatment prior to second AIS
Canada number (%)
294 (100.0)
166 (56.5) 17 (05.8) 44 (15.0) 2 (0.70) 5 (01.7) 9 (03.1) 51 (17.3)
4.8 [0.1-17.7) 183 (59.4)
43 (14.6) 89 (30.3) 92 (31.3) 76 (25.9) 54 (71.1)
Germany number (%)
379 (100.0)
377 (99.5) -
-
-
-
2 (0.95)
7.1 [0.2 -18] 203 (54.7)
264 (69.5) 86 (22.7) 8 (2.1) 27 (7.1) 17 (63.0)#
UK number (%)
221 (100.0)
190 (86.0) 4 (2.0) 27 (12.2) -
-
-
4.5 [0.1-16.7] 125 (56.5)
96 (43.4) 113 (51.1) 9 (4.1) 57 (25.8) 30 (52.6)
Total number (%)
894 (100.0)
733 (81.2)
6 (0.1-21] 511 (56.8)
403 (45.1) 288 (32.2) 109 (12.2) 160 (17.9) 101 (63.1)
#Cohort data previously published in part.25
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