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The hemostasis system is composed of procoagulant, anticoagulant, and fibrinolytic proteins that interact with endothelial and blood cells and with each other in a complex system of checks and balances to maintain blood flow while preventing both hemorrhage and thrombosis. Pregnancy is a unique physiological state in which biological alterations predispose both mother and fetus to both bleeding and clotting. The placenta is a vascular interface for maternal and fetal blood exchange which predisposes the mother to hemorrhage. Maternal hemostasis presents a compensatory hypercoagulability including elevated factor VIII, von Willebrand factor, fibrinogen and thrombin generation, decreased thrombin regulation with resistance to activated protein C and decreased free protein S, and decreased fibrinolysis with increased plasminogen activator inhibitors. The placental vascular surface is of fetal trophoblastic origin that derives many characteristics of endothelium but differs in that tissue factor is constitutively expressed. Ontogeny of fetal hemostasis is characteristic. Platelets, von Willebrand factor, factor VIII, and fibrinogen are expressed and mature early in gestation, while vitamin K-dependent and contact factors exhibit delayed development. The fetal hemostatic system has a decreased capacity to generate or regulate thrombin, resulting in a fragile balance with little capacity to compensate under stress conditions, particularly in the infant born prematurely. Dysfunction of the maternal/placental/fetal unit gives rise to gestational disorders including preeclampsia, fetal growth restriction, placental abruption, and premature delivery. Knowledge of normal hemostasis levels and function are critical to evaluate bleeding or clotting syndromes in the pregnant woman and her fetus or newborn infant.

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Background: Acquired hemophilia A (AHA) is a disease caused by antibody formation inhibiting the function of factor VIII, causing bleeding. Recombinant porcine factor VIII (rpFVIII) escapes human FVIII antibody recognition and can provide life-saving hemostasis. However, the development of antibodies against pFVIII can limit its use. We report two cases in which loss of response to rpFVIII occurred, likely because of inhibiting antibodies. In case 1, the patient achieved hemostasis but lost response to rpFVIII within a few days. In the second case, rpFVIII controlled bleeding but the patient experienced diminishing half-life of rpFVIII infusions over time, necessitating a switch to emicizumab which provided lasting hemostasis. Key Clinical Question: Based on our experience with these cases, we reviewed the available literature regarding the use of rpFVIII in AHA. The Key Clinical Question was to determine how often inhibitors were associated with rpFVIII treatment failure. Clinical approach and conclusions: We identified 43 AHA patients across five studies who were treated with rpFVIII. Twenty-two patients (51%) developed pFVIII inhibitors and seven cases (16%) reported loss of efficacy associated with an inhibitor. In conclusion, rpFVIII can be a life-saving therapy in AHA. However, clinicians should be aware that pFVIII antibody development can reduce the efficacy and duration of response. Recombinant pFVIII's limitations support the utility of further investigation of alternative therapies such as emicizumab in early AHA management.

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BACKGROUND: Emicizumab, a bispecific antibody factor VIII mimetic, is approved for prophylaxis in hemophilia, and has different risks and side effects compared to factor VIII products. OBJECTIVE: To better understand the early impact of emicizumab on our patients at the University of Colorado Hemophilia and Thrombosis Center (UCHTC), we evaluated adverse reactions, factor prophylaxis overlap, and bleeding rates after starting emicizumab through a quality improvement project. PATIENTS/METHODS: A retrospective chart review and structured phone interview were conducted from June to September 2019 for all patients who had started emicizumab at the UCHTC. Data about emicizumab dosing, reactions, bleeding events, and bleeding treatment were collected in 68 children and adults (aged 0.55-79.8 years, on emicizumab a median 213 days; range, 51-1229 days) with hemophilia A (35.3% with past or current inhibitor). RESULTS: Adverse reactions were primarily skin reactions, with no anaphylactic reactions or thrombosis. Bleeding events, defined as pain or swelling treated with factor or supportive measures, demonstrated wide variability, with 25 of 68 experiencing zero bleeds and 5 of 68 experiencing >8 bleeds per year. The most prevalent bleed type was traumatic musculoskeletal bleeding. Bleeding events occurred more often in the first 10 weeks after starting emicizumab, but no time period was without bleeding events. The majority of patients were prescribed every-week or every-2-week dosing, but some had alternative dosing frequency. CONCLUSIONS: Real-world emicizumab use in our center was characterized by variations in prescribing practices and bleeding outcomes and lack of severe adverse reactions.

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INTRODUCTION: In response to the increasing complexity of care for patients with bleeding disorders, we established new clinical teams for our hemophilia treatment center (HTC). AIMS: We undertook a quality improvement project to improve the coordination and communication with our patients by establishing primary assignments of clinical staff to individual patients (primary teams). METHODS: A quality improvement project group was formed that established the goals and assignment of primary teams. Patients were surveyed for their knowledge of their primary teams as well as their ability to schedule and contact their primary providers. As a measure of the effects on clinical staff, a balancing survey was also conducted among providers impacted by the clinical assignment of teams. RESULTS: Our results demonstrate improvements across both coordination and communication as reported by patients. Additionally, the assignment of primary teams was met with high satisfaction and improvement in coordination and communication as reported by the clinical staff members of the HTC. CONCLUSIONS: Initiation of a quality improvement project and the creation of a primary team system were feasible at a large HTC and resulted in improvements in both patient-reported and staff-reported outcomes of coordination and communication of care.

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Venous thromboembolism (VTE) is a highly morbid condition with several available oral anticoagulant treatment options. Numerous studies have been published comparing warfarin to direct oral anticoagulants; however, several populations remain underrepresented in these reports. We surveyed members of The Venous ThromboEmbolism Network U.S. working group regarding their oral anticoagulant preferences for the treatment of VTE in different and challenging populations. In individuals with VTE and no other medical comorbidities, respondents preferred either rivaroxaban (48.7%) or apixaban (48.7%). Apixaban (53.3%) was preferred in elderly individuals with an increased risk of bleeding. Warfarin was preferred in individuals with liver or kidney dysfunction (42% and 47%), altered metabolism (>55%), and antiphospholipid antibody syndrome (84.2%). Low-molecular-weight heparin was preferred in individuals with malignancy (56.6%), followed by edoxaban (23.7%). These findings may help guide clinicians when choosing an anticoagulant in these challenging situations and demonstrate the urgent need for additional study in these groups.

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It is estimated that >10,000 patients who undergo cystectomy for bladder cancer in the US each year receive a conventional ileal conduit and that >2,000 receive a continent urinary diversion. Case reports of primary intestinal adenocarcinomas in urinary conduits have been published recently, mainly in the urology literature. An epidemic of such cancers in this small, high-risk population seems to be emerging, particularly in conduits that utilize the colon. A case report and literature review was carried out. We describe a patient with a new primary adenocarcinoma arising in a colonic neobladder. We summarize prior literature describing intestinal adenocarcinomas that developed in an intestinal segment used for urinary diversion. Patients with urinary conduits of all types (particularly those utilizing colon rather than ileum) are at high risk of developing a second primary intestinal adenocarcinoma in the conduit. This population is likely to benefit from surveillance measures aimed at detecting such cancers. The primary form of therapy remains adequate surgical resection. General surgeons should be aware of such patients as they may be involved in the diagnosis of, and surgery for, the cancer in the conduit.

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