James, Andra H

Background Hereditary and acquired thrombophilia are risk factors for venous thromboembolism (VTE). Whether testing helps guide management decisions is controversial. Objective These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about thrombophilia testing. Methods ASH formed a multidisciplinary guideline panel covering clinical and methodological expertise and minimizing bias from conflicts of interest. The McMaster University GRADE Centre provided logistical support, performed systematic reviews, and created evidence profiles and evidence-to-decision tables. The Grading of Recommendations Assessment, Development, and Evaluation approach (GRADE) was used. Recommendations were subject to public comment. Results The panel agreed on 23 recommendations regarding thrombophilia testing and associated management. Nearly all recommendations are based on very low certainty in the evidence due to modeling assumptions. Conclusions The panel issued a strong recommendation against testing the general population before starting combined oral contraceptives (COCs) and conditional recommendations for thrombophilia testing in the following scenarios: (a) patients with VTE associated with nonsurgical major transient or hormonal risk factors; (b) patients with cerebral or splanchnic venous thrombosis, in settings where anticoagulation would otherwise be discontinued; (c) individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance to avoid COCs/hormone replacement therapy; (d) pregnant women with a family history of high-risk thrombophilia types; and (e) patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE. For all other questions, the panel provided conditional recommendations against testing for thrombophilia.

Because up to 12% of obstetric patients meet criteria for the diagnosis of thrombocytopenia in pregnancy, it is not infrequent that the anesthesiologist must decide whether to proceed with a neuraxial procedure in an affected patient. Given the potential morbidity associated with general anesthesia for cesarean delivery, thoughtful consideration of which patients with thrombocytopenia are likely to have an increased risk of spinal epidural hematoma with neuraxial procedures, and when these risks outweigh the relative benefits is important to consider and to inform shared decision making with patients. Because there are substantial risks associated with withholding a neuraxial analgesic/anesthetic procedure in obstetric patients, every effort should be made to perform a bleeding history assessment and determine the thrombocytopenia etiology before admission for delivery. Whereas multiple other professional societies (obstetric, interventional pain, and hematologic) have published guidelines addressing platelet thresholds for safe neuraxial procedures, the US anesthesia professional societies have been silent on this topic. Despite a paucity of high-quality data, there are now meta-analyses that provide better estimations of risks. An interdisciplinary taskforce was convened to unite the relevant professional societies, synthesize the data, and provide a practical decision algorithm to help inform risk-benefit discussions and shared decision making with patients. Through a systematic review and modified Delphi process, the taskforce concluded that the best available evidence indicates the risk of spinal epidural hematoma associated with a platelet count ≥70,000 × 10 6 /L is likely to be very low in obstetric patients with thrombocytopenia secondary to gestational thrombocytopenia, immune thrombocytopenia (ITP), and hypertensive disorders of pregnancy in the absence of other risk factors. Ultimately, the decision of whether to proceed with a neuraxial procedure in an obstetric patient with thrombocytopenia occurs within a clinical context. Potentially relevant factors include, but are not limited to, patient comorbidities, obstetric risk factors, airway examination, available airway equipment, risk of general anesthesia, and patient preference.

Background and Purpose— Women have poorer outcomes from stroke than men. Women also have risk factors that are unique, including pregnancy and hormone therapy. Hormone therapy for postmenopausal replacement increased the risk of ischemic stroke according to results of the Women’s Health Initiative clinical trials. Based on the current understanding of the mechanisms of action of estrogen, the reasons for this increased risk are uncertain. One method to better understand the reasons for this increased risk is to re-evaluate estrogen’s role in the neurovascular unit, simplistically comprised of the neurons, glia, and endothelial cells, as well as the processes of inflammation, and hemostasis/thrombosis. Besides the role of estrogen there are many gaps of knowledge about issues specific to women and stroke. Summary of Review— A multidisciplinary workshop was held in August 2005 to summarize the current evidence for estrogen and, more generally, stroke in women, and to provide recommendations for future basic, preclinical, and clinical research studies. Conclusions— These studies may ultimately change the approach to stroke prevention and treatment in women.