Guidance for the prevention and treatment of cancer-associated venous thromboembolism.

Venous thromboembolism (VTE) is a highly prevalent complication of malignancy with emerging changes in incidence, diagnosis and treatment paradigms. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. We address a) the appropriate workup to search for occult malignancy in patients with idiopathic VTE, b) identification of high-risk cancer patients for primary thromboprophylaxis, c) the appropriate immediate and long-term treatment for people with cancer diagnosed with acute thromboembolism, d) the appropriate duration of anticoagulation and e) the appropriate treatment strategy in patients with recurrent VTE on anticoagulation. Areas of controversy and future directions in this field are highlighted.

Guidance for the use of thrombolytic therapy for the treatment of venous thromboembolism.

Patients with venous thromboembolism (VTE) are prone to the development of both short-term and long-term complications that can substantially affect their functional capacity and quality of life. Patients with deep vein thrombosis (DVT) often develop recurrent VTE or the post-thrombotic syndrome, whereas patients with pulmonary embolism (PE) can develop long-term symptoms and functional limitations along a broad spectrum extending to full-blown chronic thromboembolic pulmonary hypertension. Clinicians who care for patients showing severe clinical manifestations of DVT and PE are often faced with challenging decisions concerning whether and how to escalate to more aggressive treatments such as those involving the use of thrombolytic drugs. The purpose of this chapter is to provide guidance on how best to individualize care to these patients.

Guidance for the prevention and treatment of the post-thrombotic syndrome.

The post-thrombotic syndrome (PTS) is a frequent, potentially disabling complication of deep vein thrombosis (DVT) that reduces quality of life and is costly. Clinical manifestations include symptoms and signs such as leg pain and heaviness, edema, redness, telangiectasia, new varicose veins, hyperpigmentation, skin thickening and in severe cases, leg ulcers. The best way to prevent PTS is to prevent DVT with pharmacologic or mechanical thromboprophylaxis used in high risk patients and settings. In patients whose DVT is treated with a vitamin K antagonist, subtherapeutic INRs should be avoided. We do not suggest routine use of elastic compression stockings (ECS) after DVT to prevent PTS, but in patients with acute DVT-related leg swelling that is bothersome, a trial of ECS is reasonable. We suggest that selecting patients for catheter-directed thrombolytic techniques be done on a case-by-case basis, with a focus on patients with extensive thrombosis, recent symptoms onset, and low bleeding risk, who are seen at experienced hospital centers. For patients with established PTS, we suggest prescribing 20-30 mm Hg knee-length ECS to be worn daily. If ineffective, a stronger pressure stocking can be tried. We suggest that intermittent compression devices or pneumatic compression sleeve units be tried in patients with moderate-to-severe PTS whose symptoms are inadequately controlled with ECS alone. We suggest that a supervised exercise training program for 6 months or more is reasonable for PTS patients who can tolerate it. We suggest that management of post-thrombotic ulcers should involve a multidisciplinary approach. We briefly discuss upper extremity PTS and PTS in children.

Guidance for the management of venous thrombosis in unusual sites.

Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. The treatment of VTE is undergoing tremendous changes with the introduction of the new direct oral anticoagulants and clinicians need to understand new treatment paradigms. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. In this chapter, we address the management of patients presenting with venous thrombosis in unusual sites, such as cerebral vein thrombosis, splanchnic vein thrombosis, and retinal vein occlusion. These events are less common than venous thrombosis of the lower limbs or pulmonary embolism, but are often more challenging, both for the severity of clinical presentations and outcomes and for the substantial lack of adequate evidence from clinical trials. Based on the available data, we suggest anticoagulant treatment for all patients with cerebral vein thrombosis and splanchnic vein thrombosis. However, in both groups a non-negligible proportion of patients may present with concomitant bleeding at the time of diagnosis. This should not contraindicate immediate anticoagulation in patients with cerebral vein thrombosis, whereas for patients with splanchnic vein thrombosis anticoagulant treatment should be considered only after the bleeding source has been successfully treated and after a careful assessment of the risk of recurrence. Finally, there is no sufficient evidence to support the routine use of antithrombotic drugs in patients with retinal vein occlusion. Future studies need to assess the safety and efficacy of the direct oral anticoagulants in these settings.

Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism.

Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a brief focused literature review followed by a multidisciplinary consensus guidance recommendation. Issues addressed included initial anticoagulant dosing recommendations, recommended baseline laboratory monitoring, managing dose adjustments, evidence to support a relationship between laboratory tests and meaningful clinical outcomes, special patient populations including extremes of weight and renal impairment, duration of necessary parenteral therapy during the transition to oral therapy, candidates for outpatient treatment where appropriate and management of over-anticoagulation and adverse effects including bleeding and heparin induced thrombocytopenia. This article concludes with a concise table of clinical management questions and guidance recommendations to provide a quick reference for the practical management of heparin, low molecular weight heparin and fondaparinux.

Bleeding complications in patients on new oral anticoagulants for venous thromboembolism in Kenya.

BACKGROUND: The incidence of bleeding complications in patients with venous thromboembolism (VTE) on new oral anticoagulants (NOACs) has not been widely studied in contemporary clinical practice in Africa. The purpose of this study was to determine the rates of major bleeding, clinically relevant non-major bleeding (CRNM) and minor bleeding associated with NOAC use. METHODS: A retrospective review was carried out of patients diagnosed with venous thromboembolism and treated with NOACs at the Aga Khan University Hospital, Nairobi, from January 2014 to December 2019. Clinical and outcome data were collected from medical records and the hospital mortality database. All patients with VTE aged > 18 years and initiated on NOACS were recruited. Patients with missing information were excluded. They were followed up from the time of commencement of oral anticoagulation to completion of therapy, or to the time of the first major bleed, CRNM or minor bleeding. Data on bleeding were obtained from the hospital database and through telephone interviews. Unadjusted rates of the first major bleeding event or CRNM were calculated as the number of bleeding events per 100 person-years. RESULTS: Two hundred and forty-three patients with VTE were recruited and 222 (91.4%) were initiated on rivaroxaban, 12 (4.9%) on dabigatran and nine (3.7%) on apixaban, with a median follow up of 213 [interquartile range (IQR): 119-477] days. The median age of the patients was 57 (IQR: 45-71) years. A total of 64 bleeding events were identified in 50 (20.6%) patients. Overall, the incidence rate for bleeding events was 17.24 per 100 patient-years. The incidence rate of major bleeding was 3.79 per 100 person-years. Gastrointestinal bleeding was the most common major bleeding site. There were more females with bleeding events (70.7%) compared to males. Anaemia and the use of aspirin and other antiplatelets were associated with a higher incidence of major and CRNM bleeding [relative risk (RR) = 3.77, confidence interval (CI) = 1.37-10.39, p = 0.005 and RR = 8.89, CI = 2.06-38.33, p = 0.0003, respectively]. CONCLUSIONS: Most of these bleeds were minor, with the gastrointestinal tract being the most common source of major bleeding and menorrhagia being the commonest cause of bleeding. Anaemia and the use of aspirin were associated with a higher incidence of major bleeding.

Do direct oral anticoagulants (DOACs) cause delayed surgery, longer length of hospital stay, and poorer outcome for hip fracture patients?

PURPOSE: The perioperative consequences of direct oral anticoagulants (DOACs) in hip fracture patients are not sufficiently investigated. The primary aim of this study was to determine whether DOAC-users have delayed surgery compared to non-users. Secondarily, we studied whether length of hospital stay, mortality, reoperations and bleeding complications were influenced by the use of DOAC. METHODS: The medical records of 314 patients operated for a hip fracture between 2016 and 2017 in a single trauma center were assessed. Patients aged < 60 and patients using other forms of anticoagulation than DOACs were excluded. Patients were followed from admission to 6 months postoperatively. Surgical delay was defined as time from admission to surgery. Secondary outcomes included length of hospital stay, transfusion rates, perioperative bleeding loss, postoperative wound ooze, mortality and risk of reoperation. The use of general versus neuraxial anaesthesia was registered. Continuous outcomes were analysed using Students t test, while categorical outcomes were expressed by Odds ratios. RESULTS: 47 hip fracture patients (15%) were using DOACs. No difference in surgical delay (29 vs 26 h, p = 0.26) or length of hospital stay (6.6 vs 6.1 days, p = 0.34) were found between DOAC-users and non-users. DOAC-users operated with neuraxial anaesthesia had longer surgical delay compared to DOAC-users operated with general anaesthesia (35 h vs 22 h, p < 0.001). Perioperative blood loss, transfusion rate, risk of bleeding complications and mortality were similar between groups. CONCLUSION: Hip fracture patients using DOAC did not have increased surgical delay, length of stay or risk of reported bleeding complications than patients without anticoagulation prior to surgery. The increased surgical delay found for DOAC-users operated with neuraxial anaesthesia should be interpreted with caution.

Effectiveness and safety of dabigatran in Latin American patients with atrial fibrillation: Two years follow up results from GLORIA-AF registry.

BACKGROUND: Real-world data from different regions are needed to support the external validity of controlled trials and assess the impact of new oral anticoagulants (NOAC) in clinical practice. METHODS: "GLORIA-AF" is a large, ongoing, multicenter, global, prospective registry program in patients with newly diagnosed non-valvular atrial fibrillation (NVAF) at risk of stroke. Newly diagnosed patients with NVAF (within 4.5 months) and a CHA2DS2-VASc score ≥ 1 were consecutively enrolled. The study objective was to estimate the incidence rate of stroke and major bleeding after a two year follow up of patients on dabigatran that participated in the "GLORIA-AF" study (Phase II) in Latin America. RESULTS: Latin America included 378 eligible patients that received dabigatran in eight countries (Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Perú, and Venezuela): 56.3% were male; mean age was 70.3 ± 10.8 years; 43.4% had paroxysmal AF; 36.0% persistent AF and 20.6% permanent AF. Mean CHA2DS2-VASc score was 3.2 ± 1.4; mean HAS-BLED score was 1.2 ± 0.8. Incidence rates for clinical events after 2-years of follow-up per 100 patient-years were as follows: stroke 0.33 (95% CI: 0.04-1.17), major bleeding 0.49 (95% CI: 0.10-1.42) and all-cause death 4.06 (95% CI: 2.63-6.00). Persistence with dabigatran at 6, 12 and 24 months was 91%, 86%, and 80%, respectively. CONCLUSION: These regional data shows the sustained safety and effectiveness of dabigatran over two years of follow-up, consistent with already available evidence. An increase in accessibility and incorporation of NOAC to anticoagulant treatment strategies could potentially have a positive impact on AF stroke prevention in Latin America.