Age Predicts Recurrence in Pediatric Cerebral Thrombosis

MUNSTER, Germany, June 8 -- Children who have a cerebral venous thrombosis before the age of two are unlikely to have another, found researchers here.

In a multi-national cohort study of 396 consecutively enrolled children with a cerebral thrombosis, 22 had another thrombosis, usually within six months, according to Ulrike Nowak-Gttl, M.D., of the University Hospital of Munster, and colleagues in the European Thromboses Study Group.

But recurrences were only seen in children whose first event occurred after they were two years old, Dr. Nowak-Gttl and colleagues reported online in The Lancet Neurology.

Other factors that independently predicted recurrence were non-use of anti-coagulant medications before the relapse, repeated blockage on venous imaging, and heterozygosity for the G20210A mutation in factor II, the researchers found.

While such events in children are rare, they are clinically important, Dr. Nowak-Gttl and colleagues said, and little has been known about prognostic factors.

To help fill in the gaps, they analyzed the cohort of children with a first episode of cerebral venous thrombosis in Germany, Israel, the United Kingdom, and Belgium.

Of the 396 patients enrolled in the study, 12 died within two weeks of various causes, including infection, brain hernia following edema, and intracranial bleeding.

Analysis of the survivors (followed for a median of 36 months) showed:

• 6% of the children had a recurrence and 3% had a recurrent cerebral thrombosis.
• Children who were not given anticoagulant medications before the relapse were 11 times more likely to have a recurrence. The hazard ratio was 11.2, with a 95% confidence interval from 3.4 to 37.0, which was significant at P<0.0001.
• Those with persistent occlusion were four times as likely to relapse as those whose veins re-canalized. The hazard ratio was 4.1, with a 95% confidence interval from 1.1 to 14.8, which was significant at P<0. 032.
• Those with one copy of the G20210A mutation in the gene for clotting factor II were also four times as likely to relapse. The hazard ratio was 4.3, with a 95% confidence interval from 1.1 to 16.2, which was significant at P<0. 034.
• Among the 22 patients who had a recurrent thrombosis, 70% occurred within the six months after the first event.

One implication of the findings is that prophylactic anticoagulants should be given to patients, albeit on a case-by-case basis taking into account the risk factors, the researchers said.

The cautioned that routine use of such drugs has to balanced against the risk of bleeding in active children.

Such thrombotic events are challenging for physicians and parents, said Meredith Golomb, M.D., of Indiana University School of Medicine in Indianapolis, writing in an accompanying commentary.

The current study "provides some important answers; however, physicians, patients, and the patients' families have many more questions." Dr. Golomb said.

Among those questions:

• Can doctors reassure parents of a child younger than two that the likelihood of a recurrence is slim?
• Which patients must stay on anti-coagulants and which can be weaned off?
• What doses are appropriate?

Both the study authors and Dr. Golomb said more study is needed to tease out answers to those and other questions.