Pharmacokinetics of Low Molecular Weight and Unfractionated Heparin in Pregnancy

Study Overview
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Brief Summary
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To determine, through pharmacokinetic parameters, the ideal dosing protocol for dalteparin (a low molecular weight heparin) and unfractionated heparin for women desiring pregnancy who have evidence of an acquired (specifically, antiphospholipid syndrome) or inherited thrombophilia.

Detailed Description
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This study's specific objectives include: Evaluating pharmacokinetic (concentration-time) and pharmacodynamic (concentration- effect) parameters for dalteparin and UFH prior to pregnancy, during the 1st, 2nd and 3rd trimesters and postpartum, using revised dosing protocols based on previous study. Determining therapeutic response to the heparins, i.e. live birth rate and lack of maternal or fetal complications, in relation to drug exposure, based on AUC. Documenting maternal and fetal complications during pregnancy for dalteparin and UFH, using the revised dosing protocols.

Official Title
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Pharmacokinetics of Low Molecular Weight and Unfractionated Heparin in Pregnancy

Conditions
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Recurrent Pregnancy Loss, Fetal Demise, Abortion, Habitual, Antiphospholipid Antibodies, Inherited Thrombophilia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Two or more consecutive, otherwise unexplained miscarriages under 10 weeks of gestation, or, an otherwise unexplained intrauterine fetal demise of at least 10 weeks of gestation, and, Persistently positive antiphospholipid antibodies, or, presence of Factor V Leiden, or, Prothrombin 20210A, or, antithrombin, protein S, or protein C deficiency, or, hyperhomocysteinemia associated with the methylenetetrahydrofolate reductase (MTHFR) polymorphism. Exclusion Criteria: Inability or refusal to give written informed consent. Inability or refusal to self-administer heparin throughout pregnancy. Hemoglobin value below 9.5 g/dL Heparin use is contraindicated. Renal disease. Documented history of thrombosis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 44 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| A<br>Subjects opting for treatment with unfractionated heparin | |
| B<br>Subjects opting for treatment with low molecular weight heparin | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The best dosing strategy for either unfractionated or low molecular weight heparin will be the one exhibiting the best balance between a modified Akaike information criterion value, residual sum of squares, and coefficient of determination. |  | Pre-pregnancy, 1st, 2nd, 3d Trimester and post-partum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent Pregnancy Loss, Habitual abortion, Fetal demise, Antiphospholipid antibodies, Inherited thrombophilia