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Biomedical subjects

Lucy A Norris

Publications and source records attributed to Lucy A Norris.

5 recordsLinked to original sources

Tinzaparin sodium for thrombosis treatment and prevention during pregnancy.

OBJECTIVE: This study was undertaken to assess the pharmacodynamic profile, safety, and efficacy of tinzaparin during pregnancy. STUDY DESIGN: Fifty-four pregnant women, 12 for treatment of thrombosis and 42 for thromboprophylaxis, received tinzaparin by once daily injection. Four-hour postdose anti-Xa results were analyzed by use of repeated measures statistical methods. RESULTS: One woman (3.4%) on the 175 anti-Xa U/kg dose and three women (20%) on the 50 anti-Xa U/kg dose required a dose increase during the initial dose titration phase to achieve target anti-Xa activity. No thrombotic events occurred. CONCLUSION: The 175 anti-Xa U/kg dose is appropriate for treatment and for high-risk thromboprophylaxis throughout pregnancy. In pregnant women at moderate risk of thrombosis, a higher tinzaparin dose is required than in the nonpregnant state and 75 anti-Xa U/kg appears to be appropriate. The majority of women do not need a dose increase with advancing gestation.

Female↗

Low molecular weight heparin (tinzaparin) therapy for moderate risk thromboprophylaxis during pregnancy. A pharmacokinetic study.

Low molecular weight heparin (LMWH) is used increasingly for prophylaxis and treatment of venous thromboembolism during pregnancy. However, the prophylactic dose for patients at moderate risk varies between centers, and the recommended LMWH dose for the non pregnant patient is frequently used in pregnant women. The aim of this study was to investigate the effects of pregnancy on the pharmacokinetics of anti-Xa levels during moderate risk thromboprophylaxis with the LMWH, tinzaparin. In 24 pregnant women, one of three doses of tinzaparin (50, 75 or 100 IU/kg) were given according to the treating physician's assessment of their risk profile. Four-hour peak anti-Xa levels were measured throughout pregnancy and 24-hour profiles were measured at 28 and 36 weeks gestation. Doses were adjusted when peak anti-Xa levels fell below 0.1 IU/ml and, in some cases, when levels at 10 and 18 hours post injection were undetectable (<0.05 IU/ml). Our results showed that women receiving tinzaparin (50 IU/kg) frequently had peak (4 hour) anti-Xa levels below 0.1IU/ml and that 46% of these patients required dose adjustment. Similarly anti-Xa levels were also found to be low over the 24-hour period. A starting dose of 75 IU/kg, once daily, gave greater anti-Xa cover over the 24-hour period and may avoid the need for dose adjustment. The results suggest that the pharmacokinetics of tinzaparin are affected by pregnancy. Larger studies are required to determine whether an increased tinzaparin dose (75 IU/kg) would be more effective in the prevention of thrombosis during pregnancy than 50 IU/kg.

Adult↗

Blood coagulation.

Blood coagulation can be initiated by two pathways: the extrinsic pathway, which is triggered by release of tissue factor from the site of injury, and the intrinsic system, which is stimulated by contact with a negatively charged surface. Following initial triggering, a series of serine proteases are sequentially activated, culminating in the formation of thrombin, the enzyme responsible for the conversion of soluble fibrinogen to the insoluble fibrin clot. Activation of coagulation is tightly regulated. Initiation by tissue factor is inhibited by tissue factor pathway inhibitor. Antithrombin can inactivate many of the serine proteases, including thrombin, by forming stable complexes which are rapidly cleared from the circulation. Protein C and protein S combine to inactivate coagulation factors V and VIII. The deposition of excess fibrin is prevented by the fibrinolytic system which can lyse fibrin into fibrin degradation products. Both genetic and environmental factors can influence the activation of coagulation and may predispose affected individuals to thrombosis.

Blood Coagulation↗