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Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, exerts far-reaching effects on public health and socio-economic welfare. The majority of infected individuals have mild to moderate symptoms, but a significant proportion develops respiratory failure due to pneumonia. Thrombosis is another frequent manifestation of Covid-19 that contributes to poor outcomes. Vitamin K plays a crucial role in the activation of both pro- and anticlotting factors in the liver and the activation of extrahepatically synthesised protein S which seems to be important in local thrombosis prevention. However, the role of vitamin K extends beyond coagulation. Matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of soft tissue calcification and elastic fibre degradation. Severe extrahepatic vitamin K insufficiency was recently demonstrated in Covid-19 patients, with high inactive MGP levels correlating with elastic fibre degradation rates. This suggests that insufficient vitamin K-dependent MGP activation leaves elastic fibres unprotected against SARS-CoV-2-induced proteolysis. In contrast to MGP, Covid-19 patients have normal levels of activated factor II, in line with previous observations that vitamin K is preferentially transported to the liver for activation of procoagulant factors. We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be compatible with enhanced thrombogenicity. Taking these data together, we propose a mechanism of pneumonia-induced vitamin K depletion, leading to a decrease in activated MGP and protein S, aggravating pulmonary damage and coagulopathy, respectively. Intervention trials should be conducted to assess whether vitamin K administration plays a role in the prevention and treatment of severe Covid-19. ispartof: BRITISH JOURNAL OF NUTRITION vol:126 issue:2 pages:191-198 ispartof: location:England status: published

Anticoagulant treatment of pediatric cerebral venous thrombosis has not been evaluated in randomized trials. We evaluated the safety and efficacy of rivaroxaban and standard anticoagulants in the predefined subgroup of children with cerebral venous thrombosis (CVT) who participated in the EINSTEIN-Jr trial. Children with CVT were randomized (2:1), after initial heparinization, to treatment with rivaroxaban or standard anticoagulants (continued on heparin or switched to vitamin K antagonist). The main treatment period was 3 months. The primary efficacy outcome, symptomatic recurrent venous thromboembolism (VTE), and principal safety outcome, major or clinically relevant nonmajor bleeding,were centrally evaluated by blinded investigators. Sinus recanalization on repeat brain imaging was a secondary outcome. Statistical analyses were exploratory. In total, 114 children with confirmed CVT were randomized. All children completed the follow-up. None of the 73 rivaroxaban recipients and 1 (2.4%; CVT) of the 41 standard anticoagulant recipients had symptomatic, recurrent VTE after 3 months (absolute difference, 2.4%; 95% confidence interval [CI], 22.6% to 13.5%). Clinically relevant bleeding occurred in 5 (6.8%; all nonmajor and noncerebral) rivaroxaban recipients and in 1 (2.5%; major [subdural] bleeding) standard anticoagulant recipient (absolute difference, 4.4%; 95% CI, 26.7% to 13.4%). Complete or partial sinus recanalization occurred in 18 (25%) and 39 (53%) rivaroxaban recipients and in 6 (15%) and 24 (59%) standard anticoagulant recipients, respectively. In summary, in this substudy of a randomized trial with a limited sample size, children with CVT treated with rivaroxaban or standard anticoagulation had a low risk of recurrent VTE and clinically relevant bleeding. This trial was registered at clinicaltrials.gov as #NCT02234843. © 2020 by The American Society of Hematology This study was supported by Bayer AG and Janssen Research and Development.

Introduction: Cancer-associated venous thromboembolism remains an important but challenging aspect in the treatment of patients with cancer. Recently, alternatives to injection of low-molecular-weight heparin (LMWH) have been introduced, the non-vitamin K antagonist oral anticoagulants (NOACs), which could potentially alleviate patients from burdensome daily injections. Areas covered: This review discusses the available evidence exploring the role of NOACs in the treatment and secondary prevention of cancer-associated venous thromboembolism, from randomized trials, observational data, contemporary guideline recommendations, and patient perspectives. Expert opinion: Edoxaban, rivaroxaban, and apixaban have proven attractive alternatives to LMWH for the treatment of cancer-associated venous thromboembolism. Contemporary guidelines have promptly endorsed the use of NOACs in patients with most cancer types. Nonetheless, issues remain regarding bleeding risk, interactions with medical cancer treatment, and the effectiveness and safety for extended treatment periods. There are head-to-head comparisons of the NOACs, and therefore no data favoring the use of one NOAC over the others. Patient’s preferences are highly diverse and should be part of routine considerations when weighing risks and benefits associated with various available anticoagulant drugs.

Introduction The treatment options for advanced heart failure patients drastically changed with the introduction of left ventricular assist devices (LVADs), either as bridge to transplant or as destination therapy for patients ineligible for transplant. Despite major benefits in terms of survival, functional status and quality of life, managing patients with LVADs comes with several challenges. The most significant challenge is balancing between the risks of thrombotic and bleeding complications. Areas covered The present review describes the pathophysiological mechanisms explaining the alterations in the hemostatic profile of LVAD patients, and summarizes current evidence to guide clinical decision making with regard to anticoagulant treatment and management of bleeding complications. Expert opinion LVAD patients require life-long anticoagulant therapy to reduce the risk of pump thrombosis. However, exposing LVAD patients to anticoagulant therapy, in combination with common acquired coagulopathies after LVAD implantation such as acquired von Willebrand syndrome, comes with high risks of bleeding. There is a need for randomized controlled trials in LVAD patients to determine the optimal antithrombotic regimen and find the most effective balance between thrombotic and bleeding complications. In addition, strategies to specifically target the acquired von Willebrand syndrome and its associated angiodysplasias need to be evaluated in the LVAD population.

It is well-known that atrial fibrillation carries an increased risk of stroke and dementia. The connecting pathogenic common mechanism is the thromboembolic state provided by atrial fibrillation, which is responsible for the acute cerebral events, as well as more saddle anatomic lesions, which accumulating over time, could lead to a progressive cognitive decline. It is plausible, instinctively, that oral anticoagulation could decrease this risk, although the possibility of micro-haemorrhages, which cannot be ignored, could make anticoagulation in this contest even dangerous. In this regard, whether there are firm, well established, evidences documenting a significant reduction in stroke occurrence with anticoagulant treatment in atrial fibrillation, the same level of evidences are not supporting the treatment in preventing dementia. Bringing some more clarity to this issue could have some considerable advantages, also in term of healthcare cost containment, considering the high prevalence of atrial fibrillation and dementia in the elderly.

Aims Edoxaban treatment for stroke prevention in atrial fibrillation (AF) has mainly been investigated in randomized controlled trials, and data reflecting clinical practice are limited. We ascertained the clinical effectiveness and safety of edoxaban 30 and 60 mg once daily among Danish patients with AF. Methods and results This was an observational study based on Danish nationwide registries collecting information for administrative purposes. From June 2016 through November 2018, we identified 3405 patients initiating edoxaban. After exclusions, 2285 AF patients were followed for the effectiveness outcome of thromboembolism (ischaemic stroke and/or systemic embolism) and bleeding outcomes (composite of major bleeding, gastrointestinal bleeding, and intracranial haemorrhage), as well as bleeding requiring hospitalization. Population mean age was 75 years and 43% were female; 643 patients received the 30 mg edoxaban dosage regimen and 1642 initiated 60 mg edoxaban. During follow-up, we observed 41 thromboembolic events and 89 bleeding events of which 40 events required hospitalization. Among patients with 30 mg edoxaban, the rate (per 100 person-years) of thromboembolism was 2.07 vs. 1.62 for 60 mg edoxaban. Rates of bleeding were similar for the two dosages at ∼3.85. Bleeding requiring hospitalization occurred at a rate of 1.74 for 30 mg edoxaban and 1.69 with 60 mg edoxaban. Conclusion In this nationwide cohort of Caucasian AF patients treated with edoxaban for stroke prevention, the clinical effectiveness and safety were in line with data from the ENGAGE AF-TIMI 48 trial. Studies investigating comparative effectiveness and safety for edoxaban in comparison with other choices of antithrombotic treatment options are needed.

Hemorrhagic strokes (ICH) affects mainly young active people, with increasing incidence in developing countries. Mortality is high in acute phase, and patients are prone to complications related to stroke itself and to coexisting medical conditions. Patients with ICH are at high risk in developing deep venous thrombosis (DVT) with secondary pulmonary embolism (PE). Prevention of venous thrombotic events in hemorrhagic stroke patients requires intermittent pneumatic compression and preventive doses of low molecular weight heparins (LMWH) in high-risk patients. If DVT and /or PE occurs, the therapeutic management should balance the risk of recurrent cerebral bleeding and the life-threatening risk of PE, making the decision to start anticoagulation challenging. We present a case of a young patient with a large hypertensive capsulo-lenticular hemorrhage, who was diagnosed with pulmonary embolism 21 days after stroke onset. The decision was for anticoagulant treatment initial with LWMH, and switch to direct oral anticoagulants (DOAC) after 10 days; strict control of vascular risk factors of the patients (hypertension, diabetes and obesity) was achieved. Rehabilitation treatment, delayed until day 21, was recommended with progressive intensity. Evolution of the patient was favorable, with complete hematoma resorbtion under DOAC treatment at 10 weeks follow-up and important motor recovery. Rehabilitation program was intensive during this interval, and strongly contributive to neurologic improvement.

Objective: To evaluate the risk factors for developing rectus sheath hematoma (RSH). Study Design: An observational study. Place and Duration of Study: Department of General Surgery, Hitit University School of Medicine, Erol Olcok Training and Research Hospital, Turkey; from January 2018 to April 2020. Methodology: Patients with RSH were studied. Those with other pathologies in rectus sheath, and repeat studies, were excluded. Demographic data, presenting symptoms, comorbidities, medications administered containing anticoagulant drugs, imaging results, laboratory findings, coagulation parameters, length of hospital stay, treatments administered, type of RSH, morbidity, mortality and risk factors of increased bleeding diathesis, were recorded. Results: Of the 61 studied patients, 56 (91.8%) had at least one chronic disease, and 77% were receiving anticoagulation therapy. RSH size was significantly larger for patients taking acetylsalicylic acid than for patients taking other anticoagulants, and an RSH area less than 1,924 mm2 was associated with increased length of hospital stay. Binary logistic regression analysis showed that a unit increase in gender was associated with a 1.5-fold increase in the risk of greater RSH size, and that female gender was associated with a 45.3-fold risk of increase in the risk of RSH. Notably, if up to 4 units of erythrocyte suspension replacement is not applied for conservative treatment of RSH, RSH size may increase by 23.5 times. Conclusion: Risk factors of RSH include chronic obstructive pulmonary disease, congestive heart failure, coronary artery disease, atrial fibrillation, asthma, hypertension, diabetes mellitus, chronic renal failure, prior abdominal surgery, female sex, older age, anticoagulant drug use and cancer-related immunosuppression. © 2021 College of Physicians and Surgeons Pakistan. All rights reserved. 2-s2.0-85107951971 PubMed: 34102772

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan, China, in late December 2019 and has since spread rapidly around the world. Severe coronavirus disease 2019 (COVID-19) pneumonia patients have abnormal blood coagulation function, but their thromboembolism prevalence is still unknown. We reported a case of a 49-year-old man infected with COVID-19, presenting with fever, chest pain, limb weakness, myalgia, and dyspnea. The patient was diagnosed with severe COVID-19 pneumonia, pulmonary thromboembolism (PTE), deep vein thrombosis (DVT), and cerebral infarction. He received supportive and empirical treatment including anticoagulant treatment, anti-inflammatory treatment, oxygen supply, and inhalation therapy. The patient's symptoms, CT images, and laboratory results improved after treatment, and a throat swab was reported to be negative for SARS-CoV-2 virus by polymerase chain reaction (PCR) test. However, on day 51 of illness onset, CT reexamination demonstrated hemorrhagic infarction. Anticoagulant therapy was discontinued temporarily. After the patient tested negative for SARS-CoV-2 virus by PCR test six more times, he was discharged and remained in home quarantine. This case highlights the importance of clinician attentiveness to the appearance of multiple thromboembolism, especially in patients with severe pulmonary damage. It also emphasizes the diagnostic value of early CT imaging and the need for effective treatment once thrombotic events occur.

BACKGROUND: Improved imaging techniques have increased the incidence of subsegmental pulmonary embolism (ssPE). Indirect evidence is suggesting that ssPE may represent a more benign presentation of venous thromboembolism not necessarily requiring anticoagulant treatment. However, correctly diagnosing ssPE is challenging with reported low interobserver agreement, partly due to the lack of widely accepted diagnostic criteria. OBJECTIVES: We sought to derive uniform diagnostic criteria for ssPE, guided by expert consensus. METHODS: Based on an extensive literature review and expert opinion of a Delphi steering committee, two surveys including statements regarding diagnostic criteria and management options for ssPE were established. These surveys were conducted electronically among two panels, respectively: expert thoracic radiologists and clinical venous thromboembolism specialists. The Delphi method was used to achieve consensus after multiple survey rounds. Consensus was defined as a level of agreement >70%. RESULTS: Twenty-nine of 40 invited radiologists (73%) and 40 of 51 clinicians (78%) participated. Following two survey rounds by the expert radiologists, consensus was achieved on 15 of 16 statements, including on the established diagnostic criteria for ssPE (96% agreement): a contrast defect in a subsegmental artery, that is, the first arterial branch division of any segmental artery independent of artery diameter, visible in at least two subsequent axial slices, using a computed tomography scanner with a desired maximum collimator width of ≤1 mm. These criteria were approved by 83% of the clinical venous thromboembolism (VTE) specialists. The clinical expert panel favored anticoagulant treatment in case of prior VTE, antiphospholipid syndrome, pregnancy, cancer, and proximal deep vein thrombosis. CONCLUSION: The results of this analysis provide standard radiological criteria for ssPE that may be applicable in both clinical trials and practice. ispartof: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS vol:4 issue:8 pages:1251-1261 ispartof: location:United States status: published

Background The role of venous obstructions as a risk factor for recurrent venous thromboembolism has never been evaluated. This study aimed to determine whether there is a difference in prevalence of venous obstructions between patients with and without recurrent venous thromboembolism. Furthermore, its influence on the development of post-thrombotic syndrome and patient-reported quality of life was assessed. Methods This matched nested case-control study included 32 patients with recurrent venous thromboembolism (26 recurrent deep-vein thrombosis and 6 pulmonary embolism) from an existing prospective cohort of deep-vein thrombosis patients and compared them to 24 age and sex matched deep-vein thrombosis patients without recurrent venous thromboembolism. All participants received standard post-thrombotic management and underwent an additional extensive duplex ultrasonography. Post-thrombotic syndrome was assessed by the Villalta-scale and quality of life was measured using the SF36v2 and VEINES-QOL/Sym-questionnaires. Results Venous obstruction was found in 6 patients (18.8%) with recurrent venous thromboembolism compared to 5 patients (20.8%) without recurrent venous thromboembolism (Odds ratio 0.88, 95%CI 0.23–3.30, p = 1.000). After a median follow-up of 60.0 months (IQR 41.3–103.5) the mean Villalta-score was 5.55 ± 3.02 versus 5.26 ± 2.63 (p = 0.909) and post-thrombotic syndrome developed in 20 (62.5%) versus 14 (58.3%) patients, respectively (Odds ratio 1.19, 95%CI 0.40–3.51, p = 0.752). If venous obstruction was present, it was mainly located in the common iliac vein (n = 7, 63.6%). In patients with an objectified venous obstruction the mean Villalta-score was 5.11 ± 2.80 versus 5.49 ± 2.87 in patients without venous obstruction (p = 0.639). Post-thrombotic syndrome developed in 6 (54.5%) versus 28 (62.2%) patients, respectively (Odds ratio 1.37, 95%CI 0.36–5.20, p = 0.736). No significant differences were seen regarding patient-reported quality of life between either groups. Conclusions In this exploratory case-control study patients with recurrent venous thromboembolism did not have a higher prevalence of venous obstruction compared to patients without recurrent venous thromboembolism. The presence of recurrent venous thromboembolism or venous obstruction had no impact on the development of post-thrombotic syndrome or the patient-reported quality of life.

Background Splanchnic vein thrombosis (SVT) is an uncommon but potentially life-threatening disease usually related to different underlying clinical conditions. The risk of SVT recurrences is high over time in patients with an underlying permanent prothrombotic condition. Vitamin K antagonists (VKA) represent the mainstay of treatment for SVT. Data about the efficacy and safety of direct oral anticoagulants (DOACs) are reported in the literature for the treatment of acute SVT, but less is known about their application for the secondary prophylaxis of venous thromboembolism (VTE). The aim of this study was to assess the efficacy and safety of long-term DOACs therapy in patients at high-risk of thrombosis, compared to VKA. Methods This is a retrospective single-centre study including 70 patients with SVT on long-term anticoagulant treatment with VKA followed-up at our Units between January 2017 and December 2019. All the patients were at high thrombotic risk defined as the presence of a permanent prothrombotic condition requiring long-term anticoagulation. During follow-up, 28 patients were shifted to DOACs and their clinical outcomes were compared to those of the patients who continued VKA therapy. All the arterial and venous thrombotic events of the splanchnic and extra-splanchnic districts as well as the haemorrhagic adverse events occurring during follow-up were recorded. Results Of the seventy patients enrolled in the study, 36 patients (51.4%) had a single-segment involvement thrombosis (28.5% of portal vein, 7.1% of superior mesenteric vein, 4.3% of splenic vein, 11.5% of hepatic veins) and 34 patients (48.6%) had multi-segment involvement at the time of diagnosis. 42 patients (60%) continued VKA therapy and 28 (40%) were switched to DOACs. Median follow-up was 6 years (range 2-8) during VKA and 1.9 years (range 1-5.2) during DOACs. The incidence of thrombotic events was similar between patients on VKA and those on DOACs. Patients on VKA developed deep vein thrombosis (DVT), and of the patients on DOACs 1 developed NSTEMI and 1 DVT. No major haemorrhagic events occurred. Minor bleedings occurred in 26% of patients on VKA and in none of the DOACs patients (P: 0.09). Conclusions Our results highlight that DOACs could represent an effective and safe alternative to the VKA for secondary prophylaxis in SVT patients at high risk of thrombosis.

Since December 2019, the seriousness of coronavirus disease 2019 (COVID‐19) pandemic has been on escalation (Lu, et al 2020). Coagulopathy is common in critically ill patients with COVID‐19 (Tang, et al 2020b). Systemic microvascular thrombosismay occur in most deaths, which was further identified by a recent autopsy (Luo 2020). However, less has been known about the coagulation parameter D‐dimer in the progression of COVID‐19. In this study, we describe 279 COVID‐19 patients recruited from three hospitals in Hubei Province, China, and then investigate the dynamic relationship between D‐dimer level and the progression of COVID‐19.

In the Hokusai VTE Cancer study, edoxaban was non-inferior to dalteparin for the composite outcome of recurrent venous thromboembolism (VTE) and major bleeding in 1,050 patients with cancer-associated VTE. The absolute rate of recurrent VTE was 3.4% lower with edoxaban, whereas the absolute rate of major bleeding was 2.9% higher. The present analysis focuses on the sites, clinical presentation, course and outcome of bleeding events, and the associated tumour types. Major bleeds and their severity (categories 1–4) were blindly adjudicated by a committee using a priori defined criteria, and data were analysed in the safety population. Major bleeding occurred in 32 of 522 patients given edoxaban (median treatment duration, 211 days) and in 16 of 524 patients treated with dalteparin (median treatment duration, 184 days); no patients had more than one major bleed. There were no fatal bleeds with edoxaban, and two with dalteparin. Severe bleeding at presentation (category 3 or 4) occurred in 10 (1.9%) and 11 (2.1%) patients in the edoxaban and dalteparin groups, respectively. The excess of major bleeding with edoxaban was confined to patients with gastrointestinal cancer. However, severe major bleeding at presentation (category 3 or 4) in this sub-group occurred in 5 of 165 (3.0%) and in 3 of 140 (2.1%) patients given edoxaban or dalteparin, respectively.In conclusion, this analysis suggests that while oral edoxaban is an appropriate alternative to subcutaneous dalteparin for treatment of cancer-associated VTE, the use of edoxaban in patients with gastrointestinal cancer requires careful benefit–risk weighting.

Objective This article assesses the impact of renal impairment (RI) on the efficacy and safety of anticoagulation in patients with cancer-associated thrombosis from the Comparison of Acute Treatments in Cancer Hemostasis (CATCH) study (NCT01130025). Materials and Methods Renal function was assessed using the Modification of Diet in Renal Disease equation in patients with cancer-associated thrombosis who received either tinzaparin (175 IU/kg) once daily or warfarin for 6 months, in an open-label, randomized, multi-centre trial with blinded adjudication of outcomes. Associations between baseline RI (glomerular filtration rate [GFR] Results Baseline-centralized GFR data were available for 864 patients (96% of study population). RI was found in 131 patients (15%; n = 69 tinzaparin). Recurrent VTE occurred in 14% of patients with and 8% of patients without RI (relative risk [RR] 1.74; 95% confidence interval [CI] 1.06, 2.85), CRB in 19% and 14%, respectively (RR 1.33; 95% CI 0.90, 1.98), major bleeding in 6.1% and 2.0%, respectively (RR 2.98; 95% CI 1.29, 6.90) and mortality rate was 40% and 34%, respectively (RR 1.20; 95% CI 0.94, 1.53). Patients with RI on tinzaparin showed no difference in recurrent VTE, CRB, major bleeding or mortality rates versus those on warfarin. Conclusion RI in patients with cancer-associated thrombosis on anticoagulation was associated with a statistically significant increase in recurrent VTE and major bleeding, but no significant increase in CRB or mortality. No differences were observed between long-term tinzaparin therapy and warfarin.

The article presents a clinical analysis of the patient with a newly developed unprovoked episode of venous thromboembolic events. It discusses the challenges in the diagnosis of pulmonary embolism, the need for thrombolytic therapy in patients with pulmonary arterial thromboembolism of medium risk. The guidelines for diagnosis of antiphospholipid syndrome in accordance with modern principles are provided. It also considers the issues of anticoagulant treatment.

The article presents a clinical discussion of the patient with recurrent venous thromboembolic complications. It also provides recommendations on modern principles of diagnostics, choice of medical tactics in patients with this pathology. Much attention is paid to the issues of anticoagulant treatment, which inadequacy or failure results in the development of severe, difficultly treatable complications.

Introduction Cerebral microbleeds (CMB) are associated with intracerebral haemorrhage. Therefore they may represent a concern if anticoagulant and/or antiplatelet therapy is needed. The aim of this study was to determine the prevalence of CMB in patients with acute myocardial infarction (AMI), and to follow their progression at 3 months under dual antiplatelet therapy (DAPT). Methods This prospective study included patients aged over 60 hospitalized in intensive cardiac care unit in our city for AMI. These patients underwent a first brain Magnetic resonance imaging (MRI) within 72 h of admission, that was repeated 3 months. Results 108 patients were included between November 2016 and December 2018. The prevalence of CMB was 21.3%, with a female predominance of 65.2% vs 32.1% (p = 0.004). Diabetes is significantly associated with the presence of CMB, 45.5% vs 21.2% (p = 0.021). Patients with at least one acute CMB had higher haemorrhagic risk as evaluated with CRUSADE score (40.5 ± 13.6 vs 31.2 ± 14.8 (p = 0.004). Multivariate analysis showed that only female sex was associated with the presence of a CMB on the initial MRI. On repeated MRI, an increase in CMB was observed in 6% of patients. Our results suggest that discharge treatment with anticoagulant in combination with antiplatelet therapy may be an independent predictor of early progression of CMB. Conclusion Our study confirms the high prevalence of CMB in patients over 60 years with AMI. The association of anticoagulant with DAPT, 3 months after stenting, may be an independent factor of CMB progression.

Introduction Indications for left atrial appendage occlusion (LAAO) are varied and patients require individual management strategies. However, currently no guidelines exist for postprocedure oral anticoagulation (OAC) after an LAAO procedure. Aim To evaluate the effect of OAC on thromboembolism, bleeding and mortality following the LAAO procedure for patients with AF. Material and methods One hundred and thirty-nine consecutive patients with nonvalvular atrial fibrillation (NVAF) who underwent LAAO with the LARIAT device were followed for at least 40 months. Decisions about OAC and its modifications were individualized based on clinical presentation, patient and physician preferences. Results Following LAAO, 52 (41%) patients did not receive OAC (No-OAC group) and 75 (59%) patients received OAC (OAC group), without any intergroup differences in CHADS2, CHA2DS2-VASc score or other thromboembolic risk factors. The median HAS-BLED score was higher in the OAC-group (median 3 (3-4) vs. 3 (2-4), p = 0.014). During a median follow-up time of 51 (43-57) vs. 55 (48-59) months in the No-OAC group and in the OAC group (p = 0.19) there were no significant differences between groups in ischemic stroke/TIA, 0 (0%) vs. 2 (2.7%), other thromboembolic events, 0 (0%) vs. 1 (1.3%), life-threatening, disabling or major events, 2 (3.7%) vs. 2 (2.7%), or annual mortality rate, 1.9% vs. 0.9%, respectively. Conclusions There is no need for OAC after the LAAO procedure. Omitting OAC after an LAAO procedure in AF patients: (1) has similar stroke prevention rates as patients on OAC, (2) has similar bleeding prevention rates as patients on OAC, (3) has similar safety endpoints and long-term efficacy as patients on OAC.

The review tells about challenges of antithrombotic therapy in patients after acute coronary syndrome. The efficacy and safety of long-term administration of anticoagulants (warfarin as well as novel anticoagulants), in addition to standard antiplatelet therapy, is discussed. The focus is on rivaroxaban, low doses of which are officially indicated for the prevention of cardiovascular death and myocardial infarction in patients after acute coronary syndrome occurring with increased values of myocardial injury markers. Clinical characteristics of patients feasible for this treatment approach are considered .

Cancer is one the most prevalent risk factors in patients diagnosed with deep vein thrombosis or pulmonary embolism. Patients with cancer and venous thromboembolism have a higher risk of mortality when compared to patients with cancer without venous thromboembolism and a higher risk of recurrent thrombosis when compared with patients with venous thromboembolism without cancer. This increased risk of recurrence is not only observed after anticoagulant treatment is stopped, but also during anticoagulant treatment. Clinical trials have shown that the use of low molecular weight heparin during the first three to six months after venous thrombosis in patients with cancer is associated with a significantly lower risk of recurrence than the use of vitamin K antagonists and, thus, low molecular weight heparin is currently recommended as the treatment of choice by international guidelines. Unfortunately, the optimal management of recurrent venous thromboembolism during anticoagulant treatment remains poorly defined. In general, patients should firstly be assessed for treatment compliance, for the occurrence of heparin-induced thrombocytopenia, and for the presence of mechanical compression from tumour masses. Possible strategies include switching to a different anticoagulant drug, in particular from vitamin K antagonists to low molecular weight heparin; increasing the dose of the anticoagulant drug; or inserting an inferior vena cava filter. The results of recent registries show that the current approach to cancer patients with recurrent venous thromboembolism in routine clinical practice is highly heterogeneous.

Essentials Cancer patients receiving anticoagulants for venous thromboembolism have an elevated bleeding risk. This secondary analysis of CATCH assessed characteristics of clinically relevant bleeding (CRB). CRB occurs in 15% of cancer patients with thrombosis using therapeutic doses of anticoagulation. After multivariate analysis, risk factors for CRB were age >75 years and intracranial malignancy. Summary Background Cancer patients with acute venous thromboembolism (VTE) receiving anticoagulant treatment have an increased bleeding risk. Objectives We performed a prespecified secondary analysis of the randomized, open-label, Phase III CATCH trial (NCT01130025) to assess the rate and sites of and the risk factors for clinically relevant bleeding (CRB). Patients/Methods Patients with active cancer and acute, symptomatic VTE received either tinzaparin 175 IU kg-1 once daily or warfarin (target International Normalized Ratio [INR] of 2.0-3.0) for 6 months. Fisher's exact test was used to screen prespecified clinical risk factors; those identified as being significantly associated with an increased risk of CRB then underwent competing risk regression analysis of time to first CRB. Results Among 900 randomized patients, 138 (15.3%) had 180 CRB events. CRB occurred in 60 patients (81 events) in the tinzaparin group and in 78 patients (99 events) in the warfarin group (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.45-0.89). Common bleeding sites were gastrointestinal (36.7%; n = 66), genitourinary (22.8%; n = 41), and nasal (10.0%; n = 18). In multivariate analysis, the risk of CRB increased with age > 75 years (HR 1.83, 95% CI 1.14-2.94) and intracranial malignancy (HR 1.97, 95% CI 1.07-3.62). In the warfarin group, 40.4% of CRB events occurred in patients with with an INR of 75 years and intracranial malignancy.

Introduction: Patients with cancer are at increased risk of (recurrent) venous thronnboembolism. They are also at increased risk of bleeding. This makes treatment of venous thromboembolisms (VTE) in cancer patients challenging. Areas covered: In this review, we will focus on the safety of anticoagulant treatment of VTE in cancer patients. We will discuss the absolute and relative bleeding risks associated with the various types of anticoagulants, specifically focusing on low-molecular-weight heparins (LMWH), vitamin K antagonist (VKA) and the new oral anticoagulants (NOACs). Expert opinion: Monotherapy with LMWH is recommended for treatment of acute VTE in cancer patients. The bleeding risk associated with LMWH is comparable to VKAs, but LMWH are more effective in preventing recurrent VTE. More evidence on the efficacy and safety of NOACs in cancer patients is needed.

Antithrombin deficiency is a strong risk factor for venous thromboembolism (VTE), but the absolute risk of the first and recurrent VTE is unclear. The objective of this paper is to establish the absolute risks of the first and recurrent VTE and mortality in individuals with antithrombin deficiency. The databases Embase, Medline Ovid, Web of Science, the Cochrane Library, and Google Scholar were systematically searched for case–control and cohort studies. Bayesian random-effects meta-analysis was used to calculate odds ratios (ORs), absolute risks, and probabilities of ORs being above thresholds. Thirty-five publications were included in the systematic review and meta-analysis. Based on 19 studies, OR estimates for the first VTE showed a strongly increased risk for antithrombin deficient individuals, OR 14.0; 95% credible interval (CrI), 5.5 to 29.0. Based on 10 studies, meta-analysis showed that the annual VTE risk was significantly higher in antithrombin-deficient than in non-antithrombin-deficient individuals: 1.2% (95% CrI, 0.8–1.7) versus 0.07% (95% CrI, 0.01–0.14). In prospective studies, the annual VTE risk in antithrombin deficient individuals was as high as 2.3%; 95% CrI, 0.2–6.5%. Data on antithrombin deficiency subtypes are very limited for reliable risk-differentiation. The OR for recurrent VTE based on 10 studies was 2.1; 95% CrI, 0.2 to 4.0. The annual recurrence risk without long-term anticoagulant therapy based on 4 studies was 8.8% (95% CrI, 4.6–14.1) for antithrombin-deficient and 4.3% (95% CrI, 1.5–7.9) for non-antithrombin-deficient VTE patients. The probability of the recurrence risk being higher in antithrombin-deficient patients was 95%. The authors conclude that antithrombin deficient individuals have a high annual VTE risk, and a high annual recurrence risk. Antithrombin deficient patients with VTE require long-term anticoagulant therapy.

The article takes into consideration practical issues of novel oral anticoagulants (factor Xa inhibitors) usage with the aim of prevention of thromboembolic complications in nonvalvular atrial fibrillation. A clinical case presented the patient with this pathology under high risk of thromboembolic complications with several years follow-up.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are currently defined as venous thromboembolism (VTE) since they share pathophysiological features and the treatment is similar in many respects. It has been determined that more than 90% of PE cases originate from DVT in the legs. PE, which is difficult to diagnose, has a mortality rate of 12% when untreated. The worldwide increase in obesity, cancer diseases, and average survival time also contribute to the increase in the incidence of VTE. Traditional treatment of VTE includes heparin, low-molecular-weight heparin, and warfarin. Despite availability for oral use, warfarin has a narrow therapeutic range and a wide range of food interactions. After many years of research, new oral anticoagulant agents (NOACs) are expected to overcome these handicaps in treatment. In this review, the use of NOACs in the treatment of VTE is investigated in the light of current guidelines.

SummaryLow-molecular-weight heparin (LWMH) is recommended as the preferred anticoagulant treatment over vitamin K antagonists (VKA) for venous thromboembolism (VTE) in patients with cancer. However, there is uncertainty about the duration and dose of LMWH treatment. Therefore, we designed this multinational survey to assess the current approach to the treatment of patients with cancer and VTE. An electronic survey tool was used to disseminate a survey containing 49 questions on different aspects of the treatment of patients with cancer and VTE, among both thrombosis and non-thrombosis specialists. A total of 229 invitations were sent, and 141 completed the survey (60% of the total). Fifty-eight percent of the respondents were from Europe, 35% from the US and the remaining 7% from other countries. Respondent’s specialties included haematology (23%), oncology (18%), pulmonology (15%) and general internal medicine (15%). LMWH was indicated as the first choice for the long-term treatment by 82% of the respondents, of whom 60% used full therapeutic doses and 40% chose a dose reduction. When continuing anticoagulants after the long-term treatment period, 44% of respondents preferred LMWH, 10% VKA, while the remaining 45% chose per individual patient for either LMWH or VKA. In conclusion, we observed a relatively high observance rate of the guidelines with respect to the use of LMWH for the long-term treatment of VTE in cancer. In contrast, the dose of LMWH and the type of anticoagulant chosen after the initial 3–12 months varied substantially, probably reflecting the limited available evidence.

Splanchnic vein thrombosis (SVT) and cerebral vein thrombosis (CVT) are two manifestations of unusual site venous thromboembolism (VTE). SVT includes thrombosis in the portal, mesenteric or splenic veins, and the Budd–Chiari syndrome. CVT encompasses thrombosis of the dural venous sinuses and thrombosis of the cerebral veins. Unusual site VTE often represents a diagnostic and therapeutic challenge because of the heterogeneity in clinical presentation, the limited evidence available in the literature on the acute and long-term prognosis of these diseases, and the lack of large randomized controlled trials evaluating different treatment options. This narrative review describes the approach to patients with SVT or CVT by examining the diagnostic process, the assessment of potential risk factors and the appropriate anticoagulant treatment.

Introduction: Spontaneous spinal epidural hematomas are rare. However, in patients on anticoagulant treatment the risk may increase. Symptomatically patients may present with radiculopathy and even progressive neurological deficits. Case description: We present a case of a warfarin treated patient with left L5 radiculopathy. MRI was evaluated as showing a lumbar disc prolapse or synovial cyst at L4-L5 level. The patient was operated and an organized material was removed and analysed as a hematoma. No prolapsed disc or synovial cyst was found. The patient was neurologically restored following the operation. Discussion and Evaluation: This case illustrates how spontaneous epidural spinal hematomas can present with symptoms of radiculopathy and radiologically be misinterpreted as a protruding disc or cyst. Conclusion: Warfarin treated patients may have an increased risk of spontaneous spinal epidural hematomas.

Objective: To investigate the effect of anticoagulant treat­ment and perinatal outcomes in patients with primary or secondary recurrent pregnancy loss without cause other than inherited trombophilia. Methods: A total of 143 pregnant patients with recurrent pregnancy loss (≥2 abortus) and had no detected cause other than thrombophilia, were included in the study. Pa­tients with no livebirth history were accepted as primary and patients with at least one livebirth were as second­ary recurrent spontaneous aborters (PrimRSAs and Se­cRSAs). Inherited thrombophilia genetic results of the patients in both groups were compared. The effects of low-molecular weight heparin (LMWH) and low-dose as­pirin (LDA) treatments alone or together, livebirth rates and pregnancy outcomes were investigated. Results: Sixty-eight patients were in PrimRSAs and 75 were in SecRSAs. Ages, numbers of total, early and late pregnancy loss of both groups were similar. In PrimRSAs 49 (72.1%) and in SecRSAs 50 (66.6%) patients had three or more inherited thrombophilia genetic mutations. Of 113 patients who used LMWH+LDA during pregnancy 88 (77.6%) had livebirth; however, of 19 patients who used LMWH 6 (31.6%) and of 11 women who used LDA 8 (72.7%) had livebirth. Livebirth rate was significantly high­er in patients who used LMWH+LDA together (p=0.001). Livebirth rates were higher in SecRSAs than PrimRSAs irrespective to the anticoagulant treatment (p=0.002). Conclusion: LMWH and LDA treatment together may in­crease livebirth rates in patients with recurrent pregnancy loss and inherited thrombophilia. Having at least one live­birth of the patients is a good prognostic factor. J Clin Exp Invest 2016; 7 (1): 29-34

Introduction. The microangiopathic antiphospholipid syndrome (MAPS) is a subset of APS comprising those patients presenting with thrombotic microangiopathy and demonstrable antiphospholipid antibodies. Renal involvement occurs frequently in the course of MAPS with clinical symptoms of acute renal failure, hypertension, proteinuria and erythrocyturia. Case report. The report presents the patient with MAPS confirmed by kidney biopsy in the course of undifferentiated connective tissue disease.Conclusion. The authors emphasize the importance of effective anticoagulant treatment in order to inhibit thrombosis and renal damage in the course of MAPS.

Introduction: Atrial fibrillation (AF) is associated with an increased risk of thromboembolic events. Many patients with AF receive chronic anticoagulation, either with vitamin K antagonists (VKAs) or with non-VKA oral anticoagulants (NOACs). We sought to analyze variables associated with prescription of NOAC. Methods: Patients with AF under anticoagulation treatment were prospectively recruited in this observational registry. The sample comprised 1290 patients under chronic anticoagulation for AF, 994 received VKA (77.1%) and 296 NOAC (22.9%). Univariate and multivariate analyses were performed to identify variables associated with use of NOAC. Results: Mean age was 73.8 ± 9.4 years, and 42.5% of the patients were women. The CHA2DS2-VASc score was 0 in 4.9% of the population, 1 in 24.1%, and ≥2 in 71% (median = 4, interquartile range = 2). Variables associated with NOAC treatment were major bleeding (odds ratio [OR] = 3.36; confidence interval [CI] 95%: 1.73-6.51; P < .001), hemorrhagic stroke (OR = 3.19; CI 95% 1.00-10.15, P = .049), university education (OR = 2.44; CI 95%: 1.55-3.84; P < .001), high diastolic blood pressure (OR = 1.02; CI 95%: 1.00-1.03; P = .006), and higher glomerular filtration rate (OR 1.01, CI 95% 1.00-1.01; P = .01). And variables associated with VKA use were history of cancer (OR = 0.46; CI 95%: 0.25-0.85; P = .013) and bradyarrhythmia (OR = 0.40; CI 95% 0.19-0.85; P = .020). Conclusion: Medical and social variables were associated with prescription of NOAC. Major bleeding, hemorrhagic stroke, university education, and higher glomerular filtration rate were more frequent among patients under NOAC. On the contrary, patients with history of cancer or bradyarrhythmias more frequently received VKA.

cagliyan, caglar/0000-0002-2529-4995; Kaya, Hasan/0000-0003-3923-4026 WOS: 000350492000007 PubMed: 23742948 The aim of the study was to assess the factors associated with the anticoagulation treatment in patients with atrial fibrillation (AF). A total of 2242 consecutive patients who had been admitted with AF on their electrocardiogram were included in the study. After excluding valvular AF, 1745 patients with nonvalvular AF were analyzed. Mean CHA2DS2-VASc score [cardiac failure, hypertension, age >= 75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 -74 and sex category (female)], frequency of persistent/permanent AF, hypertension, diabetes mellitus (DM), stroke history, body mass index, and left atrial diameter were significantly higher in patients receiving anticoagulant therapy. Stroke history, persistent/permanent AF, hypertension, DM, age, heart failure, and left atrial diameter were independent predictors of warfarin prescription. Labile international normalized ratio was the only independent negative predictor of effective treatment with warfarin. In this study, we demonstrated that stroke history, persistent/permanent AF, hypertension, DM, and left atrial diameter were positive predictors, whereas advanced age and heart failure were negative predictors of oral anticoagulant use in patients with nonvalvular AF.

Objectives Antithrombotic treatment for retinal vein occlusion (RVO) is controversial, although RVO has been surmised as a predictor of a subsequent vascular event. We aimed to evaluate risk factors, the effects of antithrombotic therapy and the occurrence of subsequent vascular events in patients with a first episode of RVO, according to age of RVO onset. Methods In this prospective cohort study, patients with central (CRVO) and branch RVO (BRVO) confirmed by fluorescein angiography were studied; they were divided according to age. Cardiovascular risk factors and thrombophilia were evaluated. Anticoagulants or aspirin were given for at least 3 months. Patients were followed every 6–12 months and vascular events were recorded. Results One hundred CRVO and 32 BRVO patients were enrolled. Five of 60 (8.3%) patients 50 yr, are likely at risk of a subsequent vascular event.

Summary. Background: Little information is available on the long-term clinical outcome of cerebral vein thrombosis (CVT). Objectives and methods: In an international, retrospective cohort study, we assessed the long-term rates of mortality, residual disability and recurrent venous thromboembolism (VTE) in a cohort of patients with a first CVT episode. Results: Seven hundred and six patients (73.7% females) with CVT were included. Patients were followed for a total of 3171 patient-years. Median follow-up was 40 months (range 6, 297 months). At the end of follow-up, 20 patients had died (2.8%). The outcome was generally good: 89.1% of patients had a complete recovery (modified Rankin Score [mRS] 0–1) and 3.8% had a partial recovery and were independent (mRS 2). Eighty-four per cent of patients were treated with oral anticoagulants and the mean treatment duration was 12 months. CVT recurred in 31 patients (4.4%), and 46 patients (6.5%) had a VTE in a different site, for an overall incidence of recurrence of 23.6 events per 1000 patient-years (95% confidence Interval [CI] 17.8, 28.7) and of 35.1 events/1000 patient-years (95% CI, 27.7, 44.4) after anticoagulant therapy withdrawal. A previous VTE was the only significant predictor of recurrence at multivariate analysis (hazard ratio [HR] 2.70; 95% CI 1.25, 5.83). Conclusions: The long-term risk of mortality and recurrent VTE appears to be low in patients who survived the acute phase of CVT. A previous VTE history independently predicts recurrent events.

Background Chronic atrial fibrillation is a prevalent cardiac disorder. The literature indicates varying proportions of those treated with anticoagulants, and varying intensity of anticoagulation. Electronic patient records are providing us with clinical data concerning management of anticoagulant treatment in real-life practice that is useful for audits. We aimed to assess warfarin treatment for chronic atrial fibrillation in primary health care with regard to prevalence, incidence, the proportion treated and the quality of anticoagulation control. Methods Five primary health care centres in Stockholm with a registered population of 75146 participated in a one-year retrospective study of electronic patient records up until May 2000. All patients over 18 years of age with an encounter labelled 'Atrial fibrillation' were identified, and all records of patients on warfarin treatment were manually reviewed. Main outcome measures were number of patients with chronic atrial fibrillation, number of patients on wafarin treatment, and time within the therapeutic prothrombin range. Results In total, 419 patients had chronic atrial fibrillation, giving a prevalence of 0.60% (age-adjusted 0.62%), the age group 65 years or older accounted for 91.6%, and 50.1% were women. Out of these, 50.4% (211 patients) were established on warfarin treatment for chronic atrial fibrillation (0.28% of the population), and there was a predominance of men (p = 0.02). Fifty-four patients started treatment with warfarin for chronic atrial fibrillation (0.07% of the population). Among 25 randomly selected patients on established treatment, the proportion of time within the therapeutic range was 70.2%. Among 24 randomly selected patients starting treatment, the proportion of time with therapeutic values was 54.2% and 66.9% the first and second months of treatment, respectively. Conclusions Chronic atrial fibrillation is common among the elderly in primary health care, and about half of these patients are treated with warfarin. It appears to be under-diagnosed, and may also be under-treated. About two thirds of treatment time is spent within the therapeutic range, and further improvement of the quality of anticoagulation control with warfarin may therefore be hard to achieve.