Antithrombin-α for the prophylaxis of venous thrombosis in congenital antithrombin deficiency

ATryn(?) is a transgenically produced recombinant antithrombin (AT) concentrate licensed in Europe and the USA for the thromboprophylaxis of hereditary AT-deficient patients undergoing surgical procedures who are at a high risk of venous thromboembolism. It is also licensed, in the USA only, for prevention the of venous thromboembolism in association with delivery and the immediate post-partum period. ATryn is administered as a continuous intravenous infusion, with weight-adjusted loading and maintenance dosing regimens. Recombinant AT has an identical amino acid structure with minor glycosylation differences to endogenous AT. ATryn has a shorter half-life but an equivalent efficacy to that of plasma-derived AT concentrates in the prevention of venous thromboembolism in this rare distinct group with a high thrombotic risk. In addition, this recombinant product should be free from the risk of human viral or prion transmission.     

What is the proper place of the ross procedure in our modern armamentarium?

Despite nearly four decades of experience, the role of pulmonary valve autotransplantation (Ross procedure) in the treatment of aortic valve disease in adults and children continues to evolve and remains controversial. As the picture of late results has unfolded, alternating waves of enthusiasm and caution have characterized its use and have led to ongoing refinements in indications and operative technique. At present, it is seen as indispensable in the treatment of aortic valve disease in infants and small children (for whom no satisfactory replacement alternative exists and for whom growth is essential), attractive for adolescents and young adults who wish to avoid anticoagulants because of childbirth and lifestyle considerations, a reasonable option for selected adults who desire biologic solutions with potentially better durability than conventional bioprostheses, and contraindicated for the elderly and those with connective tissue disorders. Young patients with bicuspid aortic valve are the most common potential recipients, but also the most controversial, because of the risk of autograft dilatation. Optimal matching of prosthesis to patient is a clinical challenge for all caretakers involved in the treatment of valvular heart disease; this review provides guidelines to identify those patients who will benefit most from the Ross procedure, and those for whom it is inadvisable.     

What is the place of the new WHO antenatal care model in a teaching hospital setting?

The basic component of the new World Health Organization (WHO) antenatal care model prescribes reduced number of clinic visits and limited investigations for low-risk pregnant women. The objectives of this study were to determine the proportion of pregnant women seeking antenatal care in a Nigerian teaching hospital who qualify for the basic component and to document difficulties that may arise with the classifying form. In December 2004, 234 pregnant women who had initiated antenatal care were enrolled for the study. Using the classifying form, 157 (67%) were eligible for the basic component, 41 (18%) for special care, but 36 (15%) women could not be classified. Those that did not know the birth weight of their last babies accounted for most (89%) of the unclassified group. The WHO antenatal care model was the most appropriate and relevant method for our hospital where a large percentage (67%) of prenatal women were eligible for the basic component. However, we consider that the classifying form should be adapted to accommodate all pregnant women.     

What is the role of the microenvironment in MDS?

Treating myelodysplastic syndromes (MDS) remains challenging. Hematopoiesis occurs within a heterogeneous, complex and dynamic microenvironment, and a multiplicity of mutations in hematopoietic stem and progenitor cells (HSPCs) lead to MDS. But is there a role for the microenvironment? Here we review experimental and conceptual arguments that support a role for the microenvironment, provide evidence for the disruption of the microenvironment in MDS, and explore microenvironmental signals that may provide a targetable and conserved vulnerability in MDS that transcend genetic heterogeneity.     

Does preoperative pharmacologic prophylaxis reduce the rate of venous thromboembolism in pancreatectomy patients?

BackgroundWhether the risk of venous thromboembolism (VTE) may be reduced by preoperative administration of prophylactic heparin is unknown. We hypothesized that timing of heparin administration does not significantly alter the incidence of VTE in pancreatic surgery.MethodsAn analysis was conducted using data from Massachusetts General Hospital's National Surgical Quality Improvement Program from 2012 to 2017. All patients admitted for elective pancreatic resection were included. The primary outcome was development of VTE. Multivariable regression was performed, adjusting for patient demographics and various clinical factors.ResultsIn total, 1448 patients were analyzed, of whom 1062 received preoperative heparin (73.3%). Overall, 36 (2.5%) patients developed VTE. On unadjusted analysis, there was no statistically significant difference between patients who received preoperative heparin compared with those who did not (2.6% vs. 1.3%, respectively; p = 0.079). On adjusted analysis, there was an association with increased VTE rates among patients who received preoperative heparin (OR 2.93, 95% CI 1.10–7.81; p = 0.031).ConclusionThere was an association between preoperative heparin administration and increased incidence of VTE on adjusted analysis, possibly reflecting appropriate surgical judgment in patient selection for prophylaxis. These data question the inclusion of preoperative VTE pharmacologic prophylaxis as a reliable quality indicator.     

Transgenic mouse models of venous thrombosis: fulfilling the expectations?

During the last 15 years, transgenic mice have been generated that carry defective and/or mutant alleles of the natural anticoagulant pathways and display a spontaneous thrombotic phenotype. With the generation of these mouse lines, better opportunities became available for investigating both existing and novel risk factors for venous thrombosis. In addition, these models could serve as a tool for evaluating novel antithrombotic strategies. This review summarizes these mouse models and evaluates whether they have fulfilled the expectations.