Maureen Andrew

BACKGROUND: Cerebral sinovenous thrombosis in children is a serious disorder, and information is needed about its prevention and treatment. METHODS: The Canadian Pediatric Ischemic Stroke Registry was initiated in 1992 at the 16 pediatric tertiary care centers in Canada. Children (newborn to 18 years of age) with symptoms and radiographic confirmation of sinovenous thrombosis were included. RESULTS: During the first six years of the registry, 160 consecutive children with sinovenous thrombosis were enrolled, and the incidence of the disorder was 0.67 cases per 100,000 children per year. Neonates were most commonly affected. Fifty-eight percent of the children had seizures, 76 percent had diffuse neurologic signs, and 42 percent had focal neurologic signs. Risk factors included head and neck disorders (in 29 percent), acute systemic illnesses (in 54 percent), chronic systemic diseases (in 36 percent), and prothrombotic states (in 41 percent). Venous infarcts occurred in 41 percent of the children. Fifty-three percent of the children received antithrombotic agents. Neurologic deficits were present in 38 percent of the children, and 8 percent died; half the deaths were due to sinovenous thrombosis. Predictors of adverse neurologic outcomes were seizures at presentation and venous infarcts. CONCLUSIONS: Sinovenous thrombosis in children affects primarily neonates and results in neurologic impairment or death in approximately half the cases. The occurrence of venous infarcts or seizures portends a poor outcome.

OBJECTIVE: We sought to obtain representative data on the risk factors, diagnosis, current management, and short-term outcome of neonatal thrombosis. RESEARCH DESIGN: A case registry was established at McMaster University. Standardized questionnaires were mailed to collaborators at participating centers every 4 to 6 months. SETTING: Eighty-five level III and modified level II neonatal units in North America, Europe, and Australia were invited to join the registry. PATIENTS: Eligible infants were born between January 1990 and June 1993. Large-vessel thrombosis was diagnosed during the first month of life or up to 44 weeks post-conception after premature birth. The clinical impression of thrombotic vessel obstruction was confirmed using at least one imaging technique. RESULTS: Physicians in 64 centers expressed their willingness to participate. A total of 97 cases (excluding stroke) were registered from 29 centers. Spontaneous renal venous thrombosis (n = 21) was diagnosed at a median age of 2 days. The other venous (n = 39), arterial (n = 33), and mixed (n = 4) thromboses presented later; 89% of them were associated with an intravascular catheter and 29% with systemic infection. Doppler ultrasonography was the definitive diagnostic test in 68% of cases; contrast angiography was performed infrequently (14%). A third of all patients (but 62% of infants with renal venous thrombosis) received supportive therapy only. Thrombolytic agents were prescribed for 28% of catheter-associated venous thromboses and 30% of all arterial thromboses. The remainder of the patients were given heparin. Most patients (82%) survived to hospital discharge. Mortality rates were highest among infants with aortic thrombosis or central venous line-associated thrombosis affecting the right atrium or the superior vena cava (33%). CONCLUSIONS: Neonatal thrombosis is diagnosed fairly rarely. With the exception of spontaneous renal venous thrombosis, almost all cases are associated with indwelling catheters. Doppler ultrasound techniques are the most popular means of confirming the diagnosis in virtually all centers. Treatment varies greatly among different centers, probably because of the lack of scientific evidence about the optimum management of affected infants.

Our understanding of the coagulation and fibrinolytic systems (the hemostatic system) in the adult has progressed rapidly in recent years. However, a more complete understanding of the physiology of the hemostatic system in the neonate has lagged behind that of the adult for many reasons. First, the hemostatic system in the newborn exists in a dynamic state and is rapidly evolving toward the adult system. This situation necessitates the generation of not one, but several, reference ranges (or ranges of normal values) in the postnatal period for the various tests and components of the hemostatic system. Also, microtechniques must be used to perform the required assays, both because of the small size of blood samples available and because of the difficulty of obtaining blood from infants. Recently, many of these problems have been resolved, which resulted in a better appreciation of the development of the hemostatic system in the infant. This article reviews our current understanding of the protein components of the coagulation and fibrinolytic systems in the neonate. Reference ranges for normal values of the various tests and components of the hemostatic system have been provided for the premature and full-term infant at birth and during the first 6 months of life.

There is experimental evidence that low-molecular-weight fractions of heparin are as effective as the standard form but cause less bleeding. We therefore performed a double-blind, randomized trial comparing PK10169 low-molecular-weight heparin with placebo for the prevention of venous thrombosis in patients undergoing elective hip surgery. Prophylactic treatment with a fixed dose was begun postoperatively and continued for 14 days. Fifty patients in each treatment group underwent surveillance with [125I]fibrinogen leg scanning and impedance plethysmography. In the first 24 patients, venography was performed only if either surveillance test was positive. Because the rate of venous thrombosis detected in those patients was unexpectedly low, venography was requested in the remaining 76 patients, even if the screening tests were negative. In this latter group, venous thrombosis occurred in 4 patients (10.8 percent) given PK10169 heparin and 20 patients (51.3 percent) given placebo (P = 0.0002); the corresponding rates for proximal-vein thrombosis were 5.4 percent and 23.1 percent, respectively (P = 0.029). In the entire group of 100 patients, venous thrombosis occurred in 12 percent of those given PK10169 heparin and 42 percent of those given placebo (P = 0.0007), and the corresponding rates for proximalvein thrombi were 4 percent and 20 percent, respectively (P = 0.014). The observed hemorrhagic rate was 4 percent in each treatment group. We conclude that prophylaxis with fixed-dose PK10169 heparin is effective and safe for patients undergoing elective hip replacement.