Perinatal stroke – risk factors and management

Abstract

SummaryStroke is an uncommon but increasingly recognised cause of mortality and long-term neurological morbidity in children. A significant number of these events appear to be caused by thromboembolic disease and, as with other childhood thrombotic problems, the incidence of central nervous system events appears highest during the neonatal period. In contrast to peripheral arterial and venous thrombotic problems, it is likely that a proportion of cerebral thromboembolic events occur either in utero or perinatally and reflect different risk factors from those occurring in older infants and children. The pathophysiology of perinatal stroke is complex and in many cases is likely to be multifactorial. It is now recognised that risk factors may relate to both maternal and placental problems as well as fetal and neonatal disorders. Large prospective studies of perinatal stroke are currently lacking and efforts to define the relative contribution from each of these areas are at an early stage. The complex nature of these disorders requires collaboration between a number of different disciplines including obstetrics, fetal medicine, pathology, neonatology and neurology. Of particular interest to haematologists is the possible impact of prothrombotic abnormalities in the pathophysiology of these events and also the potential for the use of antithrombotic agents in both management and prevention.

The evaluation and management of postnatal thromboses

“…Although an extensive laboratory search for a prothrombotic disorder is controversial, 17,18,86,96 it is our opinion that the weight of evidence 1-4,6,9,22 -24,30-37,62,97-101 supports a step-wise thrombophilia investigation in the presence of a clinically significant postnatal thromboembolic event, regardless of the 109 number of other predisposing risk factors (Tables 3 and 4). The protein-based assays (Tables 3 and 4) are affected by the thrombotic event and must be repeated at 3 to 6 months of life before a definitive diagnosis can be made.…”

“…26 The superior and lateral sinuses are the most frequently involved vessels. 86 Up to 30% of cases have reported venous infarction with subsequent hemorrhage. 87 The diagnosis of CSVT is best achieved through diffusion MRI with venography.…”

“…73 Major questions exist regarding how to interpret and manage heterozygous congenital prothrombotic disorders and if a neonate with a significant TE event warrants a complete thrombophilia evaluation. 18,73,86,96 Despite a high prevalence of multiple thrombophilic gene mutations in the Caucasian population, 30 a high percentage of neonates do not develop thromboses, even with multiple acquired risk factors. 17 However, many experts believe that screening for the presence of a heterozygous disorder is warranted in a neonate with a significant TE event, regardless of the presence of other risk factors.…”

“…Surgery is recommended only for those with hydrocephalus or large intracerebral hematomas with mass effect. 73,86 Clinical risk factors for postnatal thrombosis Acquired risk factors The presence of central venous and arterial catheters is the greatest acquired risk for the development of postnatal TE. [2][3][4]18,29 Although these types of catheters have improved care for the smallest and most critically ill neonates, they clearly predispose an infant to significant risks for thrombus formation.…”

“…The explanation is that these antibodies are transported across the placenta and may serve as a nidus for thrombosis in the neonate. 16,86,114 Infants born to mothers with a history of antiphospholipid antibodies are recommended to be observed closely for signs and symptoms of thromboses. 16 Evaluation of clinically symptomatic postnatal thromboses The proper evaluation of a neonate with a clinically significant postnatal thrombosis can be somewhat confusing, mainly because there are limited studies that have focused on the necessary evaluation, treatment and follow-up of a neonate with a postnatal TE event.…”