The use of an appropriate anticoagulation regiment for the treatment of venous thromboembolism (VTE) in patients with concomitant thrombocytopenia is based on anecdotal evidence and the opinions of managing physicians. The current guidelines suggest that therapeutic levels of anticoagulants may be safely administered to patients who have a minimum platelet count of 50 x 109/L. However, it has recently been suggested that the minimal platelet threshold for safe anticoagulation treatment can be provided at a reduced platelet count of 30 x 109/L. Thus, in order evaluate these platelet threshold we used a thromboelastography (TEG) model to evaluate the clotting parameters of whole blood at predefined platelet counts in the presence of unfractionated heparin (UFH) and low-molecular weight heparin (LMWH). Due to the importance of red blood cells on hemostasis a whole blood TEG model was designed in order to mimic in vivo hemostasis. Clotting was initiated using different concentrations of tissue factor for each anticoagulant at therapeutic and prophylactic levels of UFH and LMWH at predefined platelet counts. In the presence of therapeutic concentrations of either UFH or LMWH, there were no significant differences in TEG parameters of whole blood clots between platelet counts of 30 x 109/L and 50 x 109/L when clotting was driven by the extrinsic pathway. At prophylactic levels of LMWH clot formation was less compromised. Furthermore, no significant difference was noted between platelet-depleted blood (PDB; <10 x 109/L) and 30 x 109/L with respect to r-time. This suggests LMWH at prophylactic levels has no significant bearing on clot formation at a lower platelet threshold versus therapeutic levels of LMWH. Overall, it shows that clot formation is similar for UFH and LMWH when platelet counts are reduced from 50 x 109/L to 30 x 109/L. This work provides insight on the potential for anticoagulation at a reduced platelet threshold in thrombocytopenic conditions. / Thesis / Master of Science (MSc)

No description available.

Statement of the problem The primary objective of this thesis was to determine the best study design to evaluate the safety and effectiveness of an intermediate dose of low molecular weight heparin for secondary prevention of pregnancy associated VTE (PAVTE). An RCT was deemed unfeasible,so the use of a single arm study with prior evaluation of feasibility with a pilot study is proposed. // Methods - A systematic review was conducted to evaluate the efficacy of current strategies used for secondary prevention of PAVTE.A survey was used to elicit the non-inferiority margin. // Results - The pooled proportion of recurrent VTE in patients treated with full dose LMWH was 0.012(95% CI 0.006 to 0.02) and the rate of major bleeding was 0.025(95% CI=0.01 to 0.041). The non-inferiority margin was elicited at 2.5%. // Conclusions - Although a randomized controlled trial should be conducted whenever possible, in certain scenarios they are unfeasible. Therefore, an alternative study design should perhaps be used to evaluate the safety and efficacy of therapeutic strategies.

Statement of the problem The primary objective of this thesis was to determine the best study design to evaluate the safety and effectiveness of an intermediate dose of low molecular weight heparin for secondary prevention of pregnancy associated VTE (PAVTE). An RCT was deemed unfeasible,so the use of a single arm study with prior evaluation of feasibility with a pilot study is proposed. // Methods - A systematic review was conducted to evaluate the efficacy of current strategies used for secondary prevention of PAVTE.A survey was used to elicit the non-inferiority margin. // Results - The pooled proportion of recurrent VTE in patients treated with full dose LMWH was 0.012(95% CI 0.006 to 0.02) and the rate of major bleeding was 0.025(95% CI=0.01 to 0.041). The non-inferiority margin was elicited at 2.5%. // Conclusions - Although a randomized controlled trial should be conducted whenever possible, in certain scenarios they are unfeasible. Therefore, an alternative study design should perhaps be used to evaluate the safety and efficacy of therapeutic strategies.

Thesis (doctoral)--Lund University, 1994. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1994. / Added t.p. with thesis statement inserted.

Statement of the problem The primary objective of this thesis was to determine the best study design to evaluate the safety and effectiveness of an intermediate dose of low molecular weight heparin for secondary prevention of pregnancy associated VTE (PAVTE). An RCT was deemed unfeasible,so the use of a single arm study with prior evaluation of feasibility with a pilot study is proposed. // Methods - A systematic review was conducted to evaluate the efficacy of current strategies used for secondary prevention of PAVTE.A survey was used to elicit the non-inferiority margin. // Results - The pooled proportion of recurrent VTE in patients treated with full dose LMWH was 0.012(95% CI 0.006 to 0.02) and the rate of major bleeding was 0.025(95% CI=0.01 to 0.041). The non-inferiority margin was elicited at 2.5%. // Conclusions - Although a randomized controlled trial should be conducted whenever possible, in certain scenarios they are unfeasible. Therefore, an alternative study design should perhaps be used to evaluate the safety and efficacy of therapeutic strategies.

published_or_final_version / Pharmacology / Doctoral / Doctor of Philosophy

published_or_final_version / Biochemistry / Master / Master of Philosophy

Thesis (Ph.D.)--Virginia Commonwealth University, 2009. / Prepared for: Dept. of Medicinal Chemistry. Title from resource description page. Includes bibliographical references.