Study of Abnormal Blood Clotting in Children With Stroke

Overview

Effective treatment and prevention strategies for childhood stroke and porencephaly can only be developed once the causes are understood. There is increasing evidence that inherited and acquired coagulation abnormalities alone or in combination with environmental factors, predispose to arterial and venous thrombosis. Inherited abnormalities of factor V Leiden, prothrombin, protein C, protein S, and antithrombin III may account for many of these thromboses. At present there is little information on the existing distribution of these coagulation anomalies in children with thrombosis. Recent reports also suggest that these clotting abnormalities may be responsible for some instances of intracranial hemorrhage, porencephaly, cerebral palsy and fetal death. This study will measure the frequency of several coagulation factor abnormalities (factor V Leiden, prothrombin 20210A, protein C, protein S, antithrombin III, and antiphospholipid antibodies) in children with a history of porencephaly and stroke, and will compare these to the prevalence of these mutations in population controls and family members. We will also describe the exogenous conditions which in concert with these coagulation factors, may have led to the development of thrombosis in these children....

OBJECTIVES: Effective treatment and prevention strategies for childhood stroke and porencephaly can only be developed once the causes are understood. There is increasing evidence that inherited and acquired coagulation abnormalities, alone or in combination with environmental factors, predispose to arterial and venous thrombosis. Inherited abnormalities of factor V leiden, prothrombin, protein C, protein S, and antithrombin III may account for many of these thromboses. At present there is little information on the existing distribution of these coagulation anomalies in children with thrombosis. Recent reports suggest that these clotting abnormalities may be responsible for some instances of intracranial hemorrhage, porencephaly, cerebral palsy and fetal death. The objectives of this protocol are: 1) to determine the frequency of coagulation abnormalities in children with porencephaly or stroke as compared to healthy children, 2) to determine the frequency of coagulation abnormalities in children with porencephaly or stroke as compared to their family members, 3) to determine the frequency of coagulation abnormalities in mothers of children with stroke as compared to mothers of healthy children, and 4) to describe the exogenous conditions, which in concert with coagulation factors, may have led to the development of thrombosis in children with stroke. STUDY POPULATION: This study will examine: 1) children with a history of porencephaly or stroke, 2) their biological mothers, fathers, and siblings, 3) healthy volunteer children, and 4) healthy volunteer mothers. DESIGN: This is a case-control study conducted at the National Institute of Neurological Disorders and Stroke. Children with a history of porencephaly or stroke before 18 years of life, their first-degree relatives, healthy volunteer children, and healthy volunteer mothers will be enrolled. Each subject may complete a blood draw, buccal smear, questionnaire, and/or review of medical records depending on their study group. OUTCOME MEASURES: This study will measure the frequency of several coagulation factors among the study's different population groups as well as examine the exogenous conditions that may have contributed to stroke in these children. Analysis will be descriptive and quantitative.