Acenocoumarol therapy in pediatric patients.

To determine guidelines for administering and monitoring acenocoumarol therapy in children, 93 patients (median 5.1 years, range: 0.2-18 years) were prospectively evaluated over a 33-month period. The loading doses used were: <1 year, 0.20 mg x kg-1; >1-5 years, 0.09 mg x kg-1; 6-10 years, 0.07 mg x kg-1; 11-18 years, 0.06 mg x kg-1. In this study, the loading dose and the dose to achieve and maintain target therapeutic range (TTR) for acenocoumarol are age-dependent, with infants having the highest and teenagers having the lowest requirements. The use of a different loading dose according to age has allowed most of the children (80%) in all the age groups to achieve TTR in less than 1 week. No patients had serious bleeding or thrombotic complications. We conclude that there is an age-dependent response to acenocoumarol in pediatric patients. The implementation of an age-adjusted loading dose regimen reduces the length of hospitalization required to achieve effective anticoagulant therapy.

Prothrombotic abnormalities in children with venous thromboembolism.

PURPOSE: The aim of this study was to determine the frequency of acquired or inherited prothrombotic disorders in a pediatric population with venous thromboembolism (VTE). PATIENTS AND METHODS: From May 1992 to April 1998, 56 consecutive children with VTE were prospectively studied at a single center. RESULTS: The median age was 8.4 years (range, 0.1-18 years). There was a male predominance. Fifty (89%) children had thrombosis in the lower venous system. Risk factors were detected in 54 (96%) children. Twenty-one (38%) thrombotic episodes were related to central venous lines. Family history of thrombosis was positive in 13 (23%) patients. In 26 (46%) patients, a prothrombotic disorder was detected. Nine of them had inherited disorders (protein C deficiency, 5 patients; protein S deficiency, 3 patients; Factor V Leiden mutation, 1 patient), and 13 children had acquired disorders (antiphospholipid antibodies, 5 patients; antithrombin deficiency, 8 patients). The remaining four showed combined abnormalities (Factor V Leiden mutation associated with inherited protein S deficiency, 1 patient; acquired antithrombin deficiency, 2 patients and inherited antithrombin deficiency, 1 patient). CONCLUSIONS: In the series, a high percentage of prothrombotic disorders was detected; thus, a complete hemostatic evaluation should be performed in all of the children with VTE whether the patients have one or more risk factors.

Prethrombotic disorders in children with arterial ischemic stroke and sinovenous thrombosis.

BACKGROUND: Arterial ischemic stroke (AIS) and sinovenous thrombosis (SVT) are relatively rare events in children. The contribution of prethrombotic disorders to the etiology of these entities has not been completely elucidated. OBJECTIVES: To determine the frequency of inherited and acquired prethrombotic disorders in a pediatric population with AIS and SVT and to report clinical and radiological features. METHODS: From May 1992 to April 1997, 30 consecutive children with AIS and 10 children with SVT were assisted at a single institution. Hemostatic evaluation was performed for all the children. Evaluation included the following assays: protein C, protein S, antithrombin, plasminogen, activated protein C resistance, factor V Leiden mutation, and the detection of antiphospholipid antibodies. Data concerning baseline demographics, risk factors, presenting features, family history of thrombosis, and radiological findings were also recorded. RESULTS: One or more prethrombotic disorders were present in 9 children (30%) with AIS (inherited protein S deficiency, 2 patients; inherited protein C deficiency, 1 patient; acquired antithrombin deficiency, 2 patients; antiphospholipid antibodies, 3 patients; and antiphospholipid antibodies and plaminogen deficiency, 1 patient) and in 5 children (50%) with SVT (inherited protein S deficiency, 1 patient; acquired antithrombin deficiency, 3 patients; and antiphospholipid antibodies, 1 patient). CONCLUSIONS: Most children studied presented both a variety of risk factors for thrombosis and concomitant prethrombotic disorders. Therefore, a complete hemostatic evaluation for all children with AIS and SVT should be performed, despite the presence of obvious clinical risk factors or lack of family history of thrombosis.

Behavior of diluted activated partial thromboplastin time in pregnant women with a lupus anticoagulant.

The present study was developed to verify whether a reduction in phospholipid concentration could increase the activated partial thromboplastin time (APTT) sensitivity to detect lupus anticoagulant (LA) during pregnancy. The authors studied 38 pregnant women (10 normal subjects and 28 patients with associated clinical complications) and 40 nonpregnant control subjects. Tests to detect LA, including APTT, platelet neutralization procedure (standard APTT), the kaolin clotting time, the diluted Russell viper venom test neutralized by lysed platelets, and factor assays, were performed. Positive results were found in 5 of 28 pregnant women with associated clinical complications. The APTT, using three different phospholipid concentrations (standard and more diluted cephalin), was performed on plasma samples and on its 1:1 mixture with normal plasma. The behavior of standard and diluted APTT was similar in negative LA pregnant women and nonpregnant control subjects. The mean values showed nonsignificant differences. Four of five pregnant women with positive LA findings had a prolonged APTT, which was not corrected by the addition of normal plasma using standard conditions. When diluted phospholipids were used, only one of them had a prolonged APTT that was corrected by the addition of normal plasma. Therefore, the highest sensitivity (80%) and specificity (100%) of the APTT to detect LA in pregnant women were obtained using the standard conditions.

Uso del DDAVP en pacientes con enfermedad de von willebrand y trombocitopatias / DDAVP use in patients with Von Willebrands disease and thrombocitopathy

Se evaluó la eficacia de la desmopresina (DDAVP) por vía intranasal o endovenosa en 5 pacientes con enfermedad de von Willebrand y en uno con una trombocitopatía tipo déficit del pool de depósito. En 2 casos con 250 microng de DDAVP intransales sde observó aumento en el FVIII, vWFAg y vWFRCo, y la adhesividad plaquetaria. Esto desapreció a las 6 horas y no llegó a duplicar los valores basales. En 3 casos con 500 microng de DDAVP intranasales. La adhesividad plaquetaria se incrementó con una duración breve en 2 casos y sin alcanzar niveles normales en el tercero. El aumento en el FVIII, vWFAg y vWFRCo se observó en 2 de los 32 casos ue partieron de niveles basales normales. El tiempo de sangría se acortó en 2 pacientes. Globalmente se consideró que en los 3 casos con 500 microng, la respuesta fue inadecuada y debería optarse por la vía endovenosa. En el pacietne con trombocitopatía se administraron 4 microng endovenosos de DDAVP (una sexta parte de la dosis teórica). La adhesividad plaquetaria se normalizó y el tiempo de sangría se acortó pero el efecto se agotó a las 2 horas. Estos ensayos sugieren que la vía intranasal puede lograr correción delos parámetros alterados en la enfermedad de von Willebrand de breve duración; pero que como los resultados pueden no ser satisfactorios, siempre debe ser probada previamente a su indicación terapéutica (AU)

Uso del DDAVP en pacientes con enfermedad de von willebrand y trombocitopatias / DDAVP use in patients with Von Willebrand's disease and thrombocitopathy

Se evaluó la eficacia de la desmopresina (DDAVP) por vía intranasal o endovenosa en 5 pacientes con enfermedad de von Willebrand y en uno con una trombocitopatía tipo déficit del pool de depósito. En 2 casos con 250 microng de DDAVP intransales sde observó aumento en el FVIII, vWFAg y vWFRCo, y la adhesividad plaquetaria. Esto desapreció a las 6 horas y no llegó a duplicar los valores basales. En 3 casos con 500 microng de DDAVP intranasales. La adhesividad plaquetaria se incrementó con una duración breve en 2 casos y sin alcanzar niveles normales en el tercero. El aumento en el FVIII, vWFAg y vWFRCo se observó en 2 de los 32 casos ue partieron de niveles basales normales. El tiempo de sangría se acortó en 2 pacientes. Globalmente se consideró que en los 3 casos con 500 microng, la respuesta fue inadecuada y debería optarse por la vía endovenosa. En el pacietne con trombocitopatía se administraron 4 microng endovenosos de DDAVP (una sexta parte de la dosis teórica). La adhesividad plaquetaria se normalizó y el tiempo de sangría se acortó pero el efecto se agotó a las 2 horas. Estos ensayos sugieren que la vía intranasal puede lograr correción delos parámetros alterados en la enfermedad de von Willebrand de breve duración; pero que como los resultados pueden no ser satisfactorios, siempre debe ser probada previamente a su indicación terapéutica