Yale Center for Hemostasis and Thrombosis in Women’s and Children’s Health (Con’t.)

Inherited and acquired thrombophilic conditions are associated with enhanced thrombin generation and fibrin deposition which leads to uteroplacental thrombosis. A constellation of adverse pregnancy outcomes, namely second and third trimester fetal loss, preeclampsia and abruption are the clinical sequellae of this pathologic condition. Recurrence risks for each of these events vary widely, ranging from five to over sixty percent. Since there are agents, namely, aspirin and heparin that may reduce the chance of having an adverse pregnancy outcome, determining which group of patients is at higher risk for such untoward outcome would be beneficial.

Thrombophilia is a multigenic disorder. We have shown a thrombophilia dose dependent increase in coagulation activation marker levels as the number of thrombophilic conditions present increases (Table1). We have further demonstrated that women with thrombophilic conditions have elevated levels of Thrombus precursor Protein TM, soluble fibrin polymers and tumor necrosis factor alpha in the first trimester (Tables 2, 3). Potentially these and other components of the coagulation and inflammatory cascades will be helpful in identifying high risk patients, and provide a tool for monitoring preventive therapies. For example, deficiency of protein Z, a plasma protein which serves as a co-factor for a protease inhibitor for Factor Xa, has been reported recently to be associated with fetal loss.

Recently, we found that mean 1st trimester maternal plasma protein Z levels (ug/ml) are significantly lower among thrombophilic patients compared to pregnant controls with normal outcomes (2.0+/-0.9 vs. 2.2+/-0.8 p‹0.04), and that there is a trend toward thrombophilic patients and adverse pregnancy outcome having the lowest protein Z levels. A large multicenter clinical trial is necessary to determine the best course of treatment and detection of these thrombophilic conditions.

Since at least 10% of the population harbors a thrombophilic mutation, a significant number of women, approximately 400,000 women per year in the United States alone, are potentially at risk for pregnancy complications. Fortunately however, the majority of women will experience an uncomplicated outcome. The Center for Thrombosis and Hemostasis in Women’s Health is devoted to providing expert, coordinated care through a multidisciplinary approach to patients at risk for thrombosis related sequellae and bleeding disorders, including ITP, von Willebrand disease, Factor deficiencies, neonatal alloimmune thrombocytopenia, and other inherited disorders.

Other special circumstances, including postmenopausal women on estrogen replacement and women with malignancy are also appropriate candidates for referral given the increased thrombotic risk under these circumstances. Interested patients can participate in research studies and trials devoted to these topics.

A clinical care coordinator/ research nurse assists in patient education and enrollment. Faculty members of the department of Laboratory Medicine and division of Hematology are an integral component of the Center’s mission. Biweekly case presentation will highlight the most complex cases requiring an integrated approach to management. Educating medical students, residents, fellows, other faculty members and allied health professionals is an important goal of the Center. Teaching occurs in a variety of settings, including, direct patient care, formal rounds, conferences, and symposia, sponsored by the Center, and other organizations, such as the March of Dimes.