Heparin rescues factor V Leiden-associated placental failure independent of anticoagulation in a murine high-risk pregnancy model.

Low molecular weight heparin (LMWH) is being tested as an experimental drug for improving pregnancy outcome in women with inherited thrombophilia and placenta-mediated pregnancy complications, such as recurrent pregnancy loss. The role of thrombotic processes in these disorders remains unproven, and the issue of antithrombotic prophylaxis is intensely debated. Using a murine model of factor V Leiden-associated placental failure, we show that treatment of the mother with LMWH allows placental development to proceed and affords significant protection from fetal loss. Nonetheless, the therapeutic effect of LMWH is not replicated by anticoagulation; fondaparinux and a direct Xa inhibitor, C921-78, achieve anticoagulation similar to LMWH but produce little or no improvement in pregnancy outcome. Genetic attenuation of maternal platelet aggregation is similarly ineffective. In contrast, even a partial loss of thrombin sensitivity of maternal platelets protects pregnancies. Neonates born from these pregnancies are growth retarded, suggesting that placental function is only partially restored. The placentae are smaller but do not reveal any evidence of thrombosis. Our data demonstrate an anticoagulation-independent role of LMWH in protecting pregnancies and provide evidence against the involvement of thrombotic processes in thrombophilia-associated placental failure. Importantly, thrombin-mediated maternal platelet activation remains central in the mechanism of placental failure.

Physiologic imaging in acute stroke: Patient selection.

Treatment of acute stroke is changing, as endovascular intervention becomes an important adjunct to tissue plasminogen activator. An increasing number of sophisticated physiologic imaging techniques have unique advantages and applications in the evaluation, diagnosis, and treatment-decision making of acute ischemic stroke. In this review, we first highlight the strengths, weaknesses, and possible indications for various stroke imaging techniques. How acute imaging findings in each modality have been used to predict functional outcome is discussed. Furthermore, there is an increasing emphasis on using these state-of-the-art imaging modalities to offer maximal patient benefit through IV therapy, endovascular thrombolytics, and clot retrieval. We review the burgeoning literature in the determination of stroke treatment based on acute, physiologic imaging findings.

Creation and Validation of an EMR-based Algorithm for Identifying Major Adverse Cardiac Events while on Statins.

Statin medications are often prescribed to ameliorate a patient's risk of cardiovascular events due in part to cholesterol reduction. We developed and evaluated an algorithm that can accurately identify subjects with major adverse cardiac events (MACE) while on statins using electronic medical record (EMR) data. The algorithm also identifies subjects experiencing their first MACE while on statins for primary prevention. The algorithm achieved 90% to 97% PPVs in identification of MACE cases as compared against physician review. By applying the algorithm to EMR data in BioVU, cases and controls were identified and used subsequently to replicate known associations with eight genetic variants. We replicated 6/8 previously reported genetic associations with cardiovascular diseases or lipid metabolism disorders. Our results demonstrated that the algorithm can be used to accurately identify subjects with MACE and MACE while on statins. Consequently, future e studies can be conducted to investigate and validate the relationship between statins and MACE using real-world clinical data.