Evaluation of enoxaparin dosing requirements in infants and children. Better dosing to achieve therapeutic levels.

Increasing the starting dose of enoxaparin results in the early achievement of therapeutic anti-factor Xa levels in children receiving enoxaparin which is critical for effective therapy and the reduction of venipunctures. The aim of this study was: i) to determine the enoxaparin dose required to achieve therapeutic anti-factor Xa levels in infants and children, and ii) to establish whether increasing the starting dose of enoxaparin influenced the time required to reach the therapeutic range and the number of venipunctures required for dose-adjustment, and iii) the radiographic outcome of the thrombosis, where applicable. A retrospective chart review of children who received enoxaparin was carried out at the Stollery Children's Hospital, Edmonton, Alberta, Canada.

Accuracy of the CoaguChek XS for point-of-care international normalized ratio (INR) measurement in children requiring warfarin.

Point-of-care INR (POC INR) meters can provide a safe and effective method for monitoring oral vitamin K antagonists (VKAs) in children. Stollery Children's Hospital has a large POC INR meter loan program for children requiring oral VKAs. Our protocol requires that POC INR results be compared to the standard laboratory INR for each child on several consecutive tests to ensure accuracy of CoaguChek XS (Roche Diagnostics, Basel Switzerland) meter.

Thrombin-thrombomodulin connects coagulation and fibrinolysis: more than an in vitro phenomenon.

Thrombin activatable fibrinolysis inhibitor (TAFI), when activated, forms a basic carboxypeptidase that can inhibit fibrinolysis. Potential physiologic activators include both thrombin and plasmin. In vitro, thrombomodulin and glycosaminoglycans increase the catalytic efficiency of TAFI activation by thrombin and plasmin, respectively.

Comparison of the anticoagulant effect of a direct thrombin inhibitor and a low molecular weight heparin in an acquired antithrombin deficiency in children with acute lymphoblastic leukaemia treated with L-asparaginase: an in vitro study.

Thrombosis occurs in 37% of children with acute lymphoblastic leukaemia (ALL) and is related to an L-asparaginase-induced acquired antithrombin (AT) deficiency. The incidence dictates the need for anticoagulant prophylaxis. Direct thrombin inhibitors (DTI) are independent of AT for effect and may thus have advantages in this population.

Thrombosis in children with malignancy.

Purpose Of Review: The association between thrombosis and malignancy in adults is well known. Children are now surviving malignancies that previously resulted in mortality. Complications, however, occur including thrombosis that result in mortality and morbidity.

The intrinsic threshold of the fibrinolytic system is modulated by basic carboxypeptidases, but the magnitude of the antifibrinolytic effect of activated thrombin-activable fibrinolysis inhibitor is masked by its instability.

Activated thrombin-activable fibrinolysis inhibitor (TAFIa) is intrinsically unstable, a property that complicates the study of its role in regulating fibrinolysis. To investigate the effect of basic carboxypeptidases on fibrinolysis under conditions of constant carboxypeptidase activity, we employed pancreatic carboxypeptidase B (CPB), a homologous, stable basic carboxypeptidase, as a surrogate for TAFIa. Clots formed from TAFI-depleted plasma or from purified components were supplemented with tissue-type plasminogen activator and either CPB or TAFIa.

Thrombin activatable fibrinolysis inhibitor: not just an inhibitor of fibrinolysis.

Objective: To review the activation of thrombin activatable fibrinolysis inhibitor (TAFI) and activity of activated TAFI (TAFIa) as it relates to the regulation of both fibrinolytic and proinflammatory substances.

Data Source: Published articles and reviews (from PubMed, published between 1962 and 2003) on experimental studies of coagulation, fibrinolysis, and inflammation.

Data Synthesis And Conclusions: The principal physiologic role of TAFI is still a matter of debate.

Fibrinogen catabolism within the procoagulant VX-2 tumor of rabbit lung in vivo: Effluxing fibrin(ogen) fragments contain antiangiogenic activity.

Many types of solid tumors are known to be procoagulant environments. This is partly because a hyperpermeable vascular system within the tumor allows plasma hemostatic factors to accumulate in relatively high concentrations in the stroma, and many solid-tumor cells express tissue factor or a procoagulant factor. These circumstances appear to exist in the VX-2 lung tumor of the New Zealand White (NZW) rabbit, and they sustain a measurable turnover of stromal deposits of fibrin(ogen).

Stabilization versus inhibition of TAFIa by competitive inhibitors in vitro.

Two competitive inhibitors of TAFIa (activated thrombin-activable fibrinolysis inhibitor), 2-guanidinoethylmercaptosuccinic acid and potato tuber carboxypeptidase inhibitor, variably affect fibrinolysis of clotted human plasma. Depending on their concentration, the inhibitors shortened, prolonged, or had no effect on lysis in vitro. The inhibitor-induced effects were both tissue-type plasminogen activator (tPA) and TAFIa concentration-dependent.

Overexpression of the 78-kDa glucose-regulated protein/immunoglobulin-binding protein (GRP78/BiP) inhibits tissue factor procoagulant activity.

Previous studies have demonstrated that overexpression of GRP78/BiP, an endoplasmic reticulum (ER)-resident molecular chaperone, in mammalian cells inhibits the secretion of specific coagulation factors. However, the effects of GRP78/BiP on activation of the coagulation cascade leading to thrombin generation are not known. In this study, we examined whether GRP78/BiP overexpression mediates cell surface thrombin generation in a human bladder cancer cell line T24/83 having prothrombotic characteristics.