Anticoagulation Changes Following Major and Clinically Relevant Nonmajor Bleeding Events in Non-valvular Atrial Fibrillation Patients

Background Bleeding events are common complications of oral anticoagulant drugs, including both warfarin and the direct oral anticoagulants (DOACs). Some patients have their anticoagulant changed or discontinued after experiencing a bleeding event, while others continue the same treatment. Differences in anticoagulation management between warfarin- and DOAC-treated patients following a bleeding event are unknown. Methods Patients with non-valvular atrial fibrillation from six anticoagulation clinics taking warfarin or DOAC therapy who experienced an International Society of Thrombosis and Haemostasis (ISTH)-defined major or clinically relevant non-major (CRNM) bleeding event were identified between 2016 and 2020. The primary outcome was management of the anticoagulant following bleeding (discontinuation, change in drug class, and restarting of same drug class). DOAC- and warfarin-treated patients were propensity matched based on the individual elements of the CHA2DS2-VASc and HAS-BLED scores as well as the severity of the bleeding event. Results Of the 509 patients on warfarin therapy and 246 on DOAC therapy who experienced a major or CRNM bleeding event, the majority of patients continued anticoagulation therapy. The majority of warfarin (231, 62.6%) and DOAC patients (201, 81.7%) restarted their previous anticoagulation. Conclusion Following a bleeding event, most patients restarted anticoagulation therapy, most often with the same type of anticoagulant that they previously had been taking.

Prevention and management of venous thromboembolism in pregnancy: cutting through the practice variation

There is clinical practice variation in the area of prevention and management of venous thromboembolism (VTE) in pregnancy. There are limited data and differing recommendations across major clinical practice guidelines, especially relating to the role of postpartum low-molecular-weight heparin (LMWH) for patients with mild inherited thrombophilia and those with pregnancy-related VTE risk factors. This chapter explores the issues of practice variation and related data for postpartum VTE prevention. Controversial topics of VTE management in pregnancy are also reviewed and include LMWH dosing and the role of anti-Xa level monitoring, as well as peripartum anticoagulation management around labor and delivery.

Results of the International Survey on Adherence with Anticoagulation in Children, Adolescents and Young Adults

Introduction Children, adolescents, and young adults are prescribed chronic anticoagulation with oral and parenteral medications for treatment and prevention of thrombosis. Non-adherence to the recommended dosing, schedule, and monitoring of anticoagulants may lead to poor treatment outcomes. Considering that little is known about adherence to anticoagulation in children, this survey aimed to evaluate provider practices and experiences related to pediatric, adolescent, and young adult patient adherence with anticoagulation. Methods A REDCap ® survey was developed by members of the International Haemostasis and Thrombosis Pediatric and Neonatal Scientific Subcommittee Medication Adherence Working Group. Questions regarding current clinical practices related to medication adherence (i.e., assessment, barriers to addressing adherence) were developed by the multi-disciplinary working group with expertise in anticoagulation, medication adherence, and hematology research. The survey was distributed in electronic form to more than 500 clinicians through the International Society of Haemostasis and Thrombosis plus related professional organizations in the United States, Switzerland, New Zealand, and Australia. Clinicians are eligible for the study if they are involved in anticoagulation management in children and/or adolescents and young adults. Results A total of 112 clinicians completed surveys. The majority (n = 104 , 93%) were pediatric hematology/oncology physicians. Demographic and clinical practice characteristics are shown in Table 1. Ninety-nine (88%) respondents reported that medication adherence is typically assessed for patients in their practice prescribed anticoagulation. Details regarding medication adherence clinical practices are shown in Table 2. Forty-eight (43%) reported that they often or always worry about medication adherence in patients prescribed anticoagulation. While most clinicians (n = 83, 74%) reported they are often or always confident in addressing non-adherence, only 30% (n = 34) reported that they are often or always confident about identifying patients who are non-adherent and only 50 (45%) reported that they often or always have the resources to effectively address non-adherence. Fifty-five (49%) respondents indicated that they had cases where non-adherence resulted in new or recurrent thrombosis and 20 (18%) indicated that they had cases where non-adherence resulted in bleeding. In response to the free text question: "What types of resources would make it easier to measure adherence in your clinic?," themes emerged regarding tools (i.e., validated instruments and electronic apps to measure adherence), communication with pharmacy, and more time and staffing in clinic. When asked: "When you identify a patient/family who is struggling to take their anticoagulation as prescribed or follow-up with labs or appointments for anticoagulation, what do you do?," clinicians discussed identification of barriers; education; involving additional staff including nursing, social work, and pharmacy; consider switching anticoagulation; increase frequency of calls, clinic visits and/or labs; and use of reminders. Some providers reported utilizing shared decision-making or motivational interviewing to improve adherence. Conclusions Clinicians who prescribe anticoagulation for children, teens, and young adults identify medication non-adherence as a clinically significant issue that may result in recurrent thrombosis or bleeding. Clinicians perceive that non-adherence most often occurs when patients skip doses and/or do not follow monitoring recommendations. Current gaps in clinical practice include resources to identify patients who are non-adherent and strategies to improve adherence. A multi-disciplinary team including nurses, physicians, pharmacists, social workers, and psychologists who have dedicated time for anticoagulation management could potentially improve outcomes for children prescribed anticoagulation. As direct oral anticoagulants are approved for children and adolescents, the impact on medication adherence with these treatment options should be evaluated. Figure 1 Figure 1. Disclosures Thornburg: HemaBiologics: Honoraria; CSL Behring: Honoraria; Octapharma: Honoraria; Biomarin: Honoraria, Research Funding; Genentech: Honoraria; Bluebird Bio: Other: data safety monitoring board; Ironwood Pharmaceuticals: Other: data safety monitoring board.

Resolution of possible acquired protein S deficiency after viral suppression in HIV infection

Current literature suggests an increased risk of venous thromboembolism (VTE) in people living with HIV (PLWH) with poorly controlled viraemia and immunodeficiency. VTE treatment guidelines do not specifically address anticoagulation management in PLWH. We report a case of a 33-year-old woman diagnosed with an unprovoked pulmonary embolism (PE) and deemed protein S deficient. Three years later, she was diagnosed with AIDS. Antiretroviral therapy (ART) was promptly initiated with viral suppression and immune reconstitution within 12 months. Eight years after her initial PE, the patient self-discontinued warfarin. Multiple repeat protein S values were normal. ART without anticoagulation has continued for 3 years with no thrombotic events. This case describes a patient with VTE presumably secondary to undiagnosed HIV with possible consequent acquired protein S deficiency. Additional research is needed to understand the characteristics of PLWH with VTE who may warrant long-term anticoagulation as opposed to shorter courses.

Non-bacterial thrombotic endocarditis in pancreatic cancer and other high-risk malignancies: the case for prophylactic treatment

ABSTRACT Non-bacterial thrombotic endocarditis (NBTE) typically affects patients with underlying adenocarcinoma, often of pancreatic origin. If untreated, it can lead to serious morbidity and mortality, including recurrent ischaemic stroke. NBTE is frequently missed or confused with infective endocarditis, leading to inappropriate management. We present the case of a 54-year-old male with newly diagnosed pancreatic malignancy (CA19–9 >120 000) who suffered recurrent deep-vein-thromboses and multiple ischaemic strokes despite full anticoagulation therapy. Transoesophageal echocardiography was correctly performed, but only after a second stroke was NBTE considered. We recommend early clinical suspicion and investigation for NBTE in patients with known or suspected malignancy presenting with neurological symptoms consistent with stroke. Initial calculations indicate this could also be cost-effective. Further, the patient’s significantly elevated tumour-markers and NBTE-severity raise the possibility of a link; if further research established a reliable relationship, routine surveillance of high-risk malignancies could identify patients who might benefit from earlier echocardiography and anticoagulation management.

PICO Questions and DELPHI Methodology for the Management of Venous Thromboembolism Associated with COVID-19

Patients with coronavirus disease 2019 (COVID-19) have a higher risk of venous thromboembolic disease (VTE) than patients with other infectious or inflammatory diseases, both as macrothrombosis (pulmonar embolism and deep vein thrombosis) or microthrombosis. However, the use of anticoagulation in this scenario remains controversial. This is a project that used DELPHI methodology to answer PICO questions related to anticoagulation in patients with COVID-19. The objective was to reach a consensus among multidisciplinary VTE experts providing answers to those PICO questions. Seven PICO questions regarding patients with COVID-19 responded with a broad consensus: 1. It is recommended to avoid pharmacological thromboprophylaxis in most COVID-19 patients not requiring hospital admission; 2. In most hospitalized patients for COVID-19 who are receiving oral anticoagulants before admission, it is recommended to replace them by low molecular weight heparin (LMWH) at therapeutic doses; 3. Thromboprophylaxis with LMWH at standard doses is suggested for COVID-19 patients admitted to a conventional hospital ward; 4. Standard-doses thromboprophylaxis with LMWH is recommended for COVID-19 patients requiring admission to Intensive Care Unit; 5. It is recommended not to determine D-Dimer levels routinely in COVID-19 hospitalized patients to select those in whom VTE should be suspected, or as a part of the diagnostic algorithm to rule out or confirm a VTE event; 6. It is recommended to discontinue pharmacological thromboprophylaxis at discharge in most patients hospitalized for COVID-19; 7. It is recommended to withdraw anticoagulant treatment after 3 months in most patients with a VTE event associated with COVID-19. The combination of PICO questions and DELPHI methodology provides a consensus on different recommendations for anticoagulation management in patients with COVID-19.