Anticoagulation For Deep Vein Thrombosis Research Articles

Direct Oral Anticoagulants Versus Conventional Anticoagulants for Deep Vein Thrombosis.

Academic Emergency MedicineAccepted Articles THE BRASS TACKS: CONCISE REVIEWS OF PUBLISHED EVIDENCE Direct Oral Anticoagulants Versus Conventional Anticoagulants for Deep Vein Thrombosis Brit Long MD, Corresponding Author Brit Long MD [email protected] orcid.org/0000-0003-4770-8869 Brooke Army Medical Center, Department of Emergency Medicine, 3551 Roger Brooke Dr, Fort Sam Houston, TX, United States Correspondence Brit Long, MD, Present Address: 3551 Roger Brooke Dr, Fort Sam Houston, TX 78234, Email: [email protected]Search for more papers by this authorMichael Gottlieb MD, Michael Gottlieb MD orcid.org/0000-0003-3276-8375 Department of Emergency Medicine, Rush University Medical CenterSearch for more papers by this author Brit Long MD, Corresponding Author Brit Long MD [email protected] orcid.org/0000-0003-4770-8869 Brooke Army Medical Center, Department of Emergency Medicine, 3551 Roger Brooke Dr, Fort Sam Houston, TX, United States Correspondence Brit Long, MD, Present Address: 3551 Roger Brooke Dr, Fort Sam Houston, TX 78234, Email: [email protected]Search for more papers by this authorMichael Gottlieb MD, Michael Gottlieb MD orcid.org/0000-0003-3276-8375 Department of Emergency Medicine, Rush University Medical CenterSearch for more papers by this author First published: 14 June 2023 https://doi.org/10.1111/acem.14763 Supervising Editor: Shahriar Zehtabchi This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1111/acem.14763. AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Accepted ArticlesAccepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future. RelatedInformation

Thirty-day outcomes in patients with proximal deep vein thrombosis who discontinued anticoagulant therapy prematurely

IntroductionIn patients receiving anticoagulation for deep vein thrombosis (DVT), a variety of reasons (including active bleeding or high-risk for bleeding) may lead into premature discontinuation of therapy (prior to completing 90 days). The relative frequency and clinical consequences of premature discontinuation in contemporary patients remain unknown. MethodsWe used the data from RIETE, an international registry of patients with venous thromboembolism (VTE), to identify patients with proximal (above knee) lower limb DVT who prematurely discontinued anticoagulation. We assessed the incidence of the composite outcome: pulmonary embolism (PE)-related death, sudden death, or recurrent VTE within the subsequent 30 days after discontinuation and compared the risk of these events vs. the risk in patients without premature discontinuation, once adjusted for demographics and clinical factors. ResultsOf 26,335 patients with proximal DVT recruited from 2001 to 2018, 1322 (5.02%) prematurely discontinued anticoagulation. Thirty days after discontinuation, 12 (0.91%) patients suffered fatal PE (n = 8) or sudden death (n = 4) and 33 (2.50%) had non-fatal recurrent VTE (PE = 15; recurrent DVT = 18). In patients with premature discontinuation, the 30-day incidence of the composite outcome was 1.62 per 1000 patient-days (95%CI: 0.00–3.80). During the first week after discontinuation, the incidence rate was 4.09 per 1000 patient-days (95%CI: 0.65–7.52). The adjusted odds of the composite outcome was 7.88 times (95%CI: 6.39–9.72) higher in patients who discontinued prematurely than in those without premature discontinuation. ConclusionPremature discontinuation of anticoagulation occurred in 5% of patients with proximal DVT, and was associated an 8-fold increased odds for the composite outcome.

Non-medical prescribing: a reflective case study on prescribing anticoagulation for deep vein thrombosis.

Prescribing is a high-risk, complex skill. There are more than 50,000 nurse prescribers in the UK, and it is important that they undertake regular reflection on their clinical practice to enhance their skills. This article reflects on the clinical factors that influenced the author's decision-making when prescribing anticoagulation medication for a patient with deep vein thrombosis. It also explores the evidence base for commonly prescribed anticoagulants.

Healthcare resource use in XALIA: A subgroup analysis of a non-interventional study of rivaroxaban versus standard anticoagulation for deep vein thrombosis

IntroductionThe non-interventional XALIA study compared the safety and effectiveness of rivaroxaban with standard anticoagulation for the treatment of venous thromboembolism in routine clinical practice. This substudy assessed the effect of treatment with rivaroxaban on healthcare resource use, hospital length of stay (LOS) and frequency of hospitalisation. MethodsIn XALIA, patients aged ≥18 years scheduled to receive ≥3 months of rivaroxaban or standard anticoagulation treatment for deep vein thrombosis (DVT) were eligible. Treatment decisions were at the physician's discretion. Healthcare resource use, including hospital admission for the index DVT and initial LOS, was documented. The main analyses in this substudy were conducted in a 1:1 propensity score-matched set (PMS) of patients, with adjustment for cancer at baseline. ResultsIn the PMS analysis, 1124 rivaroxaban-treated patients and 1124 standard anticoagulation-treated patients were included. Baseline characteristics were similar between groups (mean age 60.8 years vs. 61.2 years, DVT only rates of 89.7% vs. 90.2% and cancer rates of 8.4% vs. 8.5%, respectively). Of these, 433/1124 (38.5%) rivaroxaban-treated patients and 438/1124 (39.0%) standard anticoagulation-treated patients were hospitalised. Index event LOS in the PMS analysis was a least-squares mean of 2.6 days shorter with rivaroxaban vs. standard anticoagulation (5.4 vs. 8.0 days; geometric means ratio = 0.67 [95% confidence interval 0.61–0.74, P < 0.001]). ConclusionsIn XALIA, hospital LOS was shorter with rivaroxaban than with standard anticoagulation, consistent with the phase III study results. DVT treatment with rivaroxaban in routine clinical practice may reduce the cost per patient vs. standard anticoagulation.

Drug interaction resulting in massive chest wall hematoma in a patient on therapeutic anticoagulation.

Sir, The incidence of spontaneous large hematomas is rare compared to several case reports of major intracranial bleed in patients on therapeutic anticoagulation. The most commonly involved anticoagulant is warfarin, used in the prevention of thrombo-embolism in deep vein thrombosis, prosthetic valves, atrial fibrillation, etc.[1] The incidence of hematomas requiring invasive intervention is rarely encountered. There is a case of pectoral hematoma reported by Cinar, et al., in a case series, which was managed conservatively.[2] We report a case of an elderly woman, on therapeutic anticoagulation for deep-vein thrombosis, who presented with a large left chest wall hematoma requiring embolization of the bleeding vessel. An 82-year-old female patient was admitted to Intensive Care Unit (ICU) with a history of disorientation for 2 days. She was on therapeutic anticoagulation with warfarin 2 mg OD since 1-year after presenting with chronic deep vein thrombosis due to hyperhomocysteinemia and protein S deficiency and required inferior vena cava filter insertion earlier. Her platelet count and serum creatinine levels were within normal range. At present, she was found to have urinary tract infection for which ertapenem was started. International normalized ratio (INR) at time of admission was 1.8 and was monitored daily and antibiotic was de-escalated to levofloxacin 500 mg intravenous (IV) OD as per the urine culture report and she was shifted to wards. She was back in ICU 3 days later, with a painful swelling in left breast. Ultrasonogram [Figure 1a], chest X-ray [Figure 1b], and CT chest [Figure 1c-​-e]e] showed a large left anterior chest wall hematoma, inseparable from pectoralis major, measuring 15 cm × 8.2 cm axially and 16 cm craniocaudally. Figure 1 (a) Gross appearance. (b) Chest X-ray. (c) Computed tomography (CT) image coronal section. (d) CT image transverse section. (e) CT image, sagittal section Her hemoglobin had dropped to 4.5, and INR had shot up to 6.22 over 3 days. She was resuscitated with IV fluids and packed red blood cells. Fresh frozen plasma and injection Vitamin K 10 mg were given to prevent further bleed. But the hematoma continued to increase in size requiring an emergency angio-embolization of a large branch of left internal mammary artery. INR came down to 0.8 next day. Hemoglobin remained stable, and she went home in 3 days. A significant resorption of the hematoma was observed on review, and anti-coagulant therapy was re-started after 10 days. Hematoma in pectoral muscle has been rarely reported in the literature. Kocer et al. described cases of spontaneous intra-pectoral bleeding.[3] It was considered that in our patient, interaction between levofloxacin and warfarin could have possibly potentiated the action of warfarin, and even mild physiotherapy could have triggered a bleed.[4,5] This case is rare as it occurred over a very short duration and involved an arterial bleed requiring interventional management. The drop in hemoglobin was a very significant 8%. The interaction of warfarin with various medications and food substances is well-known. Its life-threatening complication is something that should be kept in mind considering the fact that levofloxacin is a very common antibiotic prescribed by community physicians for common cold, urinary tract, and upper respiratory tract infections. As noted here, the trigger for a torrential bleed could be very trivial as mild physiotherapy.[4,5] To conclude, a careful screening for interactions is required before prescribing medicines for patients on anticoagulation therapy.

XALIA: rationale and design of a non-interventional study of rivaroxaban compared with standard therapy for initial and long-term anticoagulation in deep vein thrombosis.

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism, poses a substantial clinical risk, and the incidence of these thrombotic-related diseases remains high. Anticoagulation aims to prevent thrombus extension and reduce the risk of recurrent events, particularly fatal pulmonary embolism. In EINSTEIN DVT, rivaroxaban was non-inferior to enoxaparin/vitamin K antagonists for the reduction of recurrent VTE, with a similar safety profile and a net clinical benefit. EINSTEIN EXT investigated patients receiving long-term treatment in whom there was no clear decision about continuing or stopping anticoagulation; rivaroxaban was superior to placebo in the reduction of recurrent VTE, showing an acceptable benefit–risk balance. Rivaroxaban has the potential to replace standard therapy, usually parenteral low molecular weight heparin overlapping with and followed by a vitamin K antagonist, for the treatment of acute symptomatic DVT and the secondary prevention of VTE. As the use of rivaroxaban for DVT treatment increases in clinical practice, a fundamental understanding of its clinical benefits in everyday patient care is essential. XALIA (XArelto for Long-term and Initial Anticoagulation in venous thromboembolism) is a multicentre, prospective, non-interventional, observational study investigating the effectiveness and safety of a single-drug approach with rivaroxaban compared with standard therapy in patients with DVT. The study cohort will include approximately 4800 patients (≥18 years old) with objectively confirmed acute DVT who will be treated for a period of ≥3 months. The primary outcomes will be the incidence of treatment-emergent adverse events (primarily major bleeding), symptomatic recurrent venous thromboembolic events and all-cause mortality. Secondary outcomes include: major cardiovascular events; patient-reported treatment satisfaction and adherence; healthcare resource utilization; reasons for drug switching or interruption of treatment; and adverse events. XALIA will follow an international cohort of patients in more than 20 European countries, and others including Israel and Canada. The first patient was enrolled in June 2012, with results expected in 2015. It is anticipated that XALIA will provide important information on the treatment of DVT in a heterogeneous, unselected patient population in a real-world setting and provide important supplementary information to that obtained from the EINSTEIN DVT phase III study.

Neue orale Antikoagulanzien in der perioperativen Medizin

New oral anticoagulants (NOAC) inhibit factor Xa (Stuart-Prower factor) or factor IIa (thrombin) and are alternatives to vitamin K antagonists. Perioperative indications are deep vein thrombosis prophylaxis for prosthetic hip and knee replacement, therapeutic anticoagulation for deep vein thrombosis as well as the prophylaxis of stroke for patients with atrial fibrillation. Patients on NOACs pose multiple perioperative challenges for all medical disciplines involved. For non-emergency surgery, patients should be evaluated by an anesthesiolgist as early as possible to assess an optimal appointment for surgery and bridging strategy. Management of emergency procedures for patients on NOACs requires an interdisciplinary approach. The individual risk for uncontrolled bleeding versus the urgency for surgery needs to be evaluated on an individual basis. The determination of drug serum levels enables a rough estimation of anticoagulant activity. Emergency procedures in coagulopathy due to active bleeding are treated with the unspecific administration of blood products and coagulation factor concentrates.

Anticoagulant therapy for deep vein thrombosis (DVT) in pregnancy

Thromboembolic complications are much higher in pregnancy due to procoagulant changes. Heparin does not cross the placenta and the use of unfractionated heparin (UFH) is the current established practice in prophylaxis and treatment for thromboembolism in pregnancy. To compare the effectiveness of anticoagulant therapies for the treatment of deep vein thrombosis in pregnancy. The anticoagulant drugs included are UFH, low molecular weight heparin (LMWH) and warfarin. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (March 2010) and reference lists of retrieved studies. Randomised controlled trials comparing any combination of warfarin, UFH, LMWH and placebo in pregnant women. We used methods described in the Cochrane Handbooks for Systemic Reviews of Interventions for assessing the eligibility of studies identified by the search strategy. A minimum of two review authors independently assessed each study. We did not identify any eligible studies for inclusion in the review.We identified three potential studies; after assessing eligibility, we excluded all three as they did not meet the prespecified inclusion criteria. One study compared LMWH and UFH in pregnant women with previous thromboembolic events and, for most of these women, anticoagulants were used as thromboprophylaxis. There were only three women who had a thromboembolic event during the current pregnancy and it was unclear whether the anticoagulant was used as therapy or prophylaxis. We excluded one study because it included only women undergoing caesarean birth. The third study was not a randomised trial. There is no evidence from randomised controlled trials on the effectiveness of anticoagulation for deep vein thrombosis in pregnancy. Further studies are required.

Minimizing costs for treating deep vein thrombosis: the role for fondaparinux

Deep vein thrombosis (DVT) remains a major burden and fondaparinux represents a new option for DVT therapy. We sought to determine if fondaparinux offered financial advantages over low-molecular weight heparin since it is given as a fixed dose over a wide range of patient weights rather then dosed directly on weight and because fondaparinux is not associated with heparin-induced thrombocytopenia (HIT). We conducted a cost-minimization analysis comparing fondaparinux to enoxaparin for acute anticoagulation in DVT. We modeled a cohort of 1,000 hypothetical subjects and drew estimates for model inputs from the published literature. We completed multiple sensitivity analyses to asses the significance of our assumptions and used Monte Carlo simulation to estimate the 95% confidence intervals (CIs) around our estimation of the cost differential for the two agents. In the base case, total disease management costs per patient with fondaparinux are US 472 dollars compared to 769 dollars with enoxaparin. The 95% CI around this difference ranges from US 48 dollars to US 401 dollars. The model was mildly sensitive to the pharmacy acquisition costs of fondaparinux and enoxaparin which was the major driver of overall costs. Neither the rates of nor costs associated with DVT recurrence, major bleeding, nor HIT substantially affected our observations. Breakeven analysis indicated our findings to be robust over a wide range of likely clinical scenarios. From the perspective of a healthcare system, fondaparinux use offers an attractive economic alternative to other agents for initial DVT therapy. Expanded reliance on fondaparinux could potentially result in savings.

PR_179: Warfarin-Related Compartment Syndrome in a Patient Receiving Anticoagulation for Deep Vein Thrombosis: A Case Report

Setting: Veterans hospital inpatient unit. Patient: A 40-year-old man with traumatic brain injury (TBI) and history of recurrent deep vein thrombosis (DVT), with compartment syndrome. Case Description: The patient presented to the rehabilitation clinic complaining of new onset left thigh pain and swelling, with foot paresthesias. Left lower-extremity (LE) examination showed increased warmth, swelling, and tenderness with intact pulses. Spasticity was increased in the left leg. International ratio (INR) was elevated at 4.03 and Doppler ultrasound (US) of the leg was performed to rule out DVT.

MINIMIZING COSTS FOR TREATING DEEP VEIN THROMBOSIS: THE ROLE FOR FONDAPARINUX

Deep vein thrombosis (DVT) remains a major burden and fondaparinux represents a new option for DVT therapy. We sought to determine if fondaparinux offered financial advantages over low-molecular weight heparin since it is given as a fixed dose over a wide range of patient weights rather then dosed directly on weight and because fondaparinux is not associated with heparin-induced thrombocytopenia (HIT). We conducted a cost-minimization analysis comparing fondaparinux to enoxaparin for acute anticoagulation in DVT. We modeled a cohort of 1,000 hypothetical subjects and drew estimates for model inputs from the published literature. We completed multiple sensitivity analyses to asses the significance of our assumptions and used Monte Carlo simulation to estimate the 95% confidence intervals (CIs) around our estimation of the cost differential for the two agents. In the base case, total disease management costs per patient with fondaparinux are $US 472 compared to $769 with enoxaparin. The 95% CI around this difference ranges from $US 48 to $US 401. The model was mildly sensitive to the pharmacy acquisition costs of fondaparinux and enoxaparin which was the major driver of overall costs. Neither the rates of nor costs associated with DVT recurrence, major bleeding, nor HIT substantially affected our observations. Breakeven analysis indicated our findings to be robust over a wide range of likely clinical scenarios. From the perspective of a healthcare system, fondaparinux use offers an attractive economic alternative to other agents for initial DVT therapy. Expanded reliance on fondaparinux could potentially result in savings.

Pharmacodynamic optimization of warfarin therapy II.

A pharmacodynamic (E(max)) model for optimizing warfarin initiation had previously been reported. This study assessed the validity of this model, adjusted further for age in both the initial cohort and another cohort distinct from that used for the formulation of the model. Thirty-one patients undergoing oral anticoagulation for mainly cardiac indications were recruited from Kuala Lumpur. Thirty-four patients undergoing oral anticoagulation for deep vein thrombosis were recruited from Cambridge. They were studied for their anticoagulant response to the initiation of warfarin. The former were intuitively dosed after a 2-day loading of 10 mg warfarin/d. The latter all were commenced on warfarin via a standard 4-day induction protocol of Fennerty et al that allows early estimation of the required maintenance dose. The actual maintenance doses in both cohorts were compared with their predicted doses on the initiation of therapy that was calculated both from this model and from the induction protocol of Fennerty et al. The third day's international normalized ratio and age combination was additive in terms of their influence on the maintenance dose. The predictive model in both cohorts returned similar results and explained at least two thirds of the interindividual variability in warfarin maintenance dose requirements, whereas the induction protocol of Fennerty et al explained only one third of this interindividual variability. Use of this model in the form of the included nomogram should be able to decrease both the occurrence of either under- or overanticoagulation as well as the time taken to initiate treatment and decide the correct maintenance dose during the initiation of oral anticoagulation with warfarin in hospitals. A prospective evaluation of the nomogram is recommended.

3 months of anticoagulation was more effective than 4 weeks for reducing recurrence of thromboembolism

Source Citation Research Committee of the British Thoracic Society. Optimum duration of anticoagulation for deep-vein thrombosis and pulmonary embolism. Lancet. 1992 Oct 10; 340:873-6.

Deep vein thrombosis and pulmonary embolism: clinical presentation and pathophysiologic consequences.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are both characterized by unreliable clinical diagnosis and significant long-term sequelae. In patients with DVT, popliteal valvular insufficiency is associated with increased risk for postphlebitic syndrome. Current data show thrombolytic therapy to be more effective than anticoagulation for DVT, accomplishing significant or complete clearing of the deep venous system in nearly half of all patients treated. Results of investigation show lytic therapy to also be more effective than heparin in treatment of PE, both in terms of acute resolution and long-term function.