Management of patients on antithrombotic therapy with severe infections: a joint clinical consensus statement of the ESC Working Group on Thrombosis, the ESC Working Group on Atherosclerosis and Vascular Biology, and the International Society on Thrombosis and Haemostasis.

Patients with severe infections and a pre-existing indication for antithrombotic therapy, i.e. antiplatelet agents, anticoagulant drugs, or their combinations, require integrated clinical counselling among coagulation, infectious disease, and cardiology specialists, due to sepsis-induced coagulopathy that frequently occurs. Bacterial and viral pathogens constitute an increasing threat to global public health, especially for patients with ongoing antithrombotic treatment who have a high risk of thrombotic recurrences and high susceptibility to severe infections with increased morbidity and mortality. Similarly, sepsis survivors are at increased risk for major vascular events. Coagulopathy, which often complicates severe infections, is associated with a high mortality and obligates clinicians to adjust antithrombotic drug type and dosing to avoid bleeding while preventing thrombotic complications. This clinical consensus statement reviews the best available evidence to provide expert opinion and statements on the management of patients hospitalized for severe bacterial or viral infections with a pre-existing indication for antithrombotic therapy (single or combined), in whom sepsis-induced coagulopathy is often observed. Balancing the risk of thrombosis and bleeding in these patients and preventing infections with vaccines, if available, are crucial to prevent events or improve outcomes and prognosis.

Pulmonary embolism: incidence and outcomes in a twelve-year historical series, in Tuscany - Italy (2010-2021).

Background: Pulmonary embolism poses a global health concern. Administrative databases serve as valuable sources for broad epidemiological studies on the prevalence and incidence of major diagnoses or diseases. The primary scope is to provide up-to-date insights into Pulmonary Embolism incidence trends, examining shifts in management and outcomes. Design: This retrospective observational study examines a 12-year dataset from hospitals in the Tuscany Region, covering the first two years of the Covid-19 pandemic. Methods: Administrative data from residents aged 18 and older discharged from hospital between 2010 and 2021 were used for the analysis. Results: Hospitalized pulmonary embolism incidence slightly declined from 2010 to 2019 (64.7 to 60.9 x 100,000; p=0.152). Males under 75 showed a higher incidence rate, while females had higher incidence rates in older age groups. In-hospital and 30-day mortality decreased from 2010 to 2019 (p=0.001 and 0.020 respectively). In 2020, 30-day mortality increased (12.4% vs 10.1%, p=0.029), while in-hospital mortality remained stable. One-year mortality was stable from 2010-2019 but increased in 2020 (32.6% vs 29.4%, p=0.037). Considering the multivariable model, one-year mortality is significantly associated with sex, age, and comorbidities. Conclusions: Our study shows that Pulmonary Embolism persists as a relevant burden in Tuscany region, but with improvements in management over the past decade and a decisive change in pharmacological treatment. Gender-related differences emerge, highlighting the need for a gender-specific healthcare approach.

Use of Oral Anticoagulant Drugs in Patients with Pulmonary Hypertension.

Pulmonary hypertension (PH), in particular pulmonary arterial hypertension and chronic thromboembolic PH, burdens patients with relevant morbidity and mortality. The use of oral anticoagulants (OACs) seems able to mitigate the risk of adverse outcomes and death in these patients. Despite scarce evidence, the use of OAC is recommended to treat PH patients, mainly based on observational data. So far, data are still unclear about the impact of direct oral anticoagulant (DOACs), whereas vitamin K antagonists are the main drugs recommended. More data are needed to fully clarify the role of OAC and DOACs in PH patients.

Myocardial infarction due to thrombotic occlusion despite anticoagulation in Kawasaki disease - a case report.

BACKGROUND: Kawasaki disease (KD) is a pediatric vasculitis. Mainly the coronary arteries become affected due to acute inflammation and formation of coronary artery aneurysms (CAAs) can occur. The larger the CAA, the higher the risk for clinical complications and major adverse cardiac events, as the blood flow changes to vortex or turbulent flow facilitating thrombosis. Such patients may develop life threatening thrombotic coronary artery occlusion and myocardial ischemiaunless anti-platelet and anti-coagulation therapy is timely initiated. CASE PRESENTATION: We present a unique case of a 5-year-old girl with KD associated giant CAAs suffering from myocardial ischemia due to acute progressive thrombus growth despite intensive anticoagulation treatment (acetylsalicylic acid, acenocoumarol and clopidogrel) after 21 months of onset of disease. Thrombus growth continued even after percutaneous coronary intervention (PCI) with thrombolytic treatment and subsequent systemic thrombolysis, finally causing lasting myocardial damage. Acute coronary artery bypass grafting (CABG) was performed, although technically challenging at this very young age. Whereas myocardial infarction was not prevented, follow-up fortunately showed favorable recovery of heart failure. CONCLUSIONS: Anticoagulation and thrombolysis may be insufficient for treatment of acute coronary syndrome in case of impending thrombotic occlusion of giant coronary aneurysms in KD. Our case demonstrates that a thrombus can still continue to grow despite triple anticoagulation therapy and well-tailored cardiovascular follow-up, which can be most likely attributed to the state of low blood flow inside the aneurysm.

Variability of three activated clotting time point-of-care systems in cardiac surgery: reinforcing available evidence.

BACKGROUND: Cardiac surgery with extracorporeal circulation (ECC) requires the administration of anticoagulant drugs to maintain ACT ranges 400-600 seconds, which requires exhaustive coagulation monitoring for which various point-of-care devices are available. However, there is variability between them, so we aimed to compare the values in ACT measurement. METHODS: Simultaneous ACT measurements were performed with the Hemochron Response®, Hemostasis Management System Plus® (HMS Plus®) and Hemochron Signature® systems. RESULTS: A total of 255 simultaneous measurements were taken, the mean and standard deviation (SD) of each device were: Hemochron Signature® 361.1 seconds (SD: 156.9), HMS Plus® 412.8 seconds (SD: 180.9) and Hemochron Response® 422.8 seconds (SD: 187.9), being these differences statistically significant (Fridman's test p < 0.01). For comparisons the Bland-Altman method was used, resulting the Hemochron Response® has 61.7 seconds higher mean values than the Hemochron Signature®, the Hemochron Response® 10 seconds higher than the HMS Plus® and the HMS Plus® 51.7 seconds higher than the Hemochron Signature®. CONCLUSION: The differences found in comparisons are considered to be clinically relevant, which is why it is considered important to make the variability of the different monitoring systems known and to take them into account for optimal control of this parameter and its clinical repercussions.

Patients With Atrial Fibrillation Taking Nonsteroidal Anti-Inflammatory Drugs and Oral Anticoagulants in the ARISTOTLE Trial.

BACKGROUND: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) with oral anticoagulants has been associated with an increased risk of bleeding. We investigated the risk of bleeding and major cardiovascular outcomes in patients with atrial fibrillation taking NSAIDs and apixaban or warfarin. METHODS: The ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n=18 201) compared apixaban with warfarin in patients with atrial fibrillation at an increased risk of stroke. Patients in ARISTOTLE without severe renal (creatine clearance ≤30 mL/min) or liver disease were included in this analysis (n=17 423). NSAID use at baseline, NSAID use during the trial (incident NSAID use), and never users were described. The primary outcome was major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding, gastrointestinal bleeding, heart failure hospitalization, stroke or systemic embolism, and all-cause mortality. NSAID use during the trial, and the interaction between randomized treatment, was analyzed using time-dependent Cox proportional hazards models. RESULTS: Those with baseline NSAID use (n=832 [4.8%]), incident NSAID use (n=2185 [13.2%]), and never users were similar in median age (age [25th, 75th]; 70 [64, 77] versus 70 [63, 75] versus 70 [62, 76]). Those with NSAID use at baseline and incident NSAID use were more likely to have a history of bleeding than never users (24.5% versus 21.0% versus 15.6%, respectively). During a median follow-up (25th, 75th) of 1.8 (1.4, 2.3) years and when excluding those taking NSAID at baseline, we found that incident NSAID use was associated with an increased risk of major bleeding (hazard ratio [HR], 1.61 [95% CI, 1.11-2.33]) and clinically relevant nonmajor bleeding (HR, 1.70 [95% CI, 1.16-2.48]), but not gastrointestinal bleeding. No significant interaction was observed between NSAID use and randomized treatment for any outcome. CONCLUSIONS: A substantial number of patients in the ARISTOTLE trial took NSAIDs. Incident NSAID use was associated with major and clinically relevant nonmajor bleeding, but not with gastrointestinal bleeding. The safety and efficacy of apixaban versus warfarin appeared not significantly to be altered by NSAID use. This study warrants more investigation of the effect of NSAIDs on the outcomes of patients treated with apixaban. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Safety of direct oral anticoagulants in patients with mild to moderate cirrhosis: a systematic review and meta-analysis.

To evaluate major bleeding in cirrhosis with use of traditional anticoagulation or direct oral anticoagulants (DOACs), using a standardized definition. Anticoagulation in patients with cirrhosis is often a clinical conundrum for providers as the necessary balance between thrombotic and bleeding risk is complicated by end organ damage. Recent meta-analyses have sought to evaluate the safety and efficacy of direct oral anticoagulants in patients with liver disease. These recent analyses are limited by various bleeding definitions, broad inclusion criteria, and few indications for anticoagulation. We sought to conduct a meta-analysis using a validated definition for major bleeding and compare rates between traditional anticoagulation and DOACs in patients with cirrhosis. Articles were eligible for inclusion if the international society on thrombosis and hemostasis (ISTH) definition of a major bleed was the primary safety outcome. Additionally, only articles including patients with cirrhosis and receiving treatment with anticoagulation for an indication for stroke prevention or venous thromboembolism were eligible. Eligible articles needed a DOAC comparator group against traditional anticoagulant medication. Seven studies met inclusion criteria and compiled data for 683 patients in the meta-analysis. Pooled trial analysis demonstrated no statistically significant difference in the primary outcome of ISTH major bleeding (OR 0.55, 95%CI 0.28-1.07, I2 0%). Individual secondary outcomes of all bleeding, intracerebral hemorrhage, or gastrointestinal bleeding also demonstrated no significant difference between DOACs and traditional anticoagulation. Use of DOACs in patients with mild to moderate cirrhosis carries similar risk to use of traditional anticoagulation.

Treatment preferences as basis for decision making in patients using direct oral anticoagulants in Spain.

Treatment preferences are considered a relevant decision-making driver by the main atrial fibrillation (AF) guidelines. Direct Oral Anticoagulants (DOACs), considered as similar clinically, have administration differences useful for treatment individualization. Preferences, priorities and satisfaction of DOAC users were assessed through an observational, multicentric (25 hospitals), cross-sectional study including adult AF-patients (and/or caregivers) in Spain. Three study groups were considered according to DOAC posology preferences: (A) once-daily, with water; (B) once-daily, with food; (C) twice-daily. Overall, 332 patients and 55 caregivers were included. Mean (SD) age was 73.7 (10.7) years [58.7 (13.9) for caregivers]; 51.5% women [69.1% for caregivers]; 80.7% showed comorbidities and poly-pharmacy [6.6 (3.3) drugs/day]. No statistically significant differences were shown among study groups. Once-daily administration was preferred by 274 patients (82.5%) [60.8% (Group A); 21.7% (Group B); 17.5% (Group C)], and 47 caregivers (85.5%) [58.2% (Group A); 27.3% (Group B); 14.5% (Group C)]. Once-daily DOACs were prescribed in 42.8% of the patients. Bleeding risk was the main concern for both, patients and caregivers, followed by DOAC posology and interactions. Although treatment satisfaction (patients and caregivers) was high (9.0 and 9.1 points, respectively), match between individual treatment preferences and real prescriptions was only shown in 41.0% of AF-patients, evidencing a need for patient involvement on treatment decision-making. There is not a patient profile linked to treatment preferences, and clinical criteria must be the main driver for decision-making. However, for most AF-patients (elderly patients), aged, with comorbidity, poly-pharmacy and high cardiovascular risk, once-daily DOACs would be the preferred option.

Determinants of anticoagulant therapy in atrial fibrillation at discharge from a geriatric ward: cross sectional study.

Oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), but they are often underused in this particularly high-risk population. The aim of the study was to identify health and functional determinants of oral anticoagulant therapy (OA) in AF at discharge from a geriatric sub-acute ward. A cross-sectional study was conducted and patients who presented with atrial fibrillation were analyzed. They were interviewed, examined, assessed with comprehensive geriatric assessment protocol, and had their hospital records analyzed. Relative risks for OA were counted and multivariable logistic regression model was built. 95 patients took part in the study (22.8% of 416 consecutively admitted to the department, 31.9% men, 73.7% 80 + year-old). 25.8% of them were on antiplatelet drugs and 58.9% on OACs. The percentage on OACs increased significantly to 73.7% at discharge (p = 0.004), mainly due to the new OACs prescription (from 11.8 to 33.3%; p < 0.001). Severe frailty (7 point Clinical Frailty Scale ≥ 6) and anemia presence, but not the risk of bleeding according to the HAS-BLED score, significantly decreased the probability of OACs prescription at discharge. There was also a trend for an association of OACs prescription with the higher total score of CHA2DS2-VASc scale. We conclude that in the real-life population of patients with AF comprehensive geriatric assessment might allow to increase significantly the number of patients on OACs, but it is limited by patient's frailty status and anemia diagnosis.

Prevention of stroke in patients with chronic coronary syndromes or peripheral arterial disease.

Stroke is a common and devastating condition caused by atherothrombosis, thromboembolism, or haemorrhage. Patients with chronic coronary syndromes (CCS) or peripheral artery disease (PAD) are at increased risk of stroke because of shared pathophysiological mechanisms and risk-factor profiles. A range of pharmacological and non-pharmacological strategies can help to reduce stroke risk in these groups. Antithrombotic therapy reduces the risk of major adverse cardiovascular events, including ischaemic stroke, but increases the incidence of haemorrhagic stroke. Nevertheless, the net clinical benefits mean antithrombotic therapy is recommended in those with CCS or symptomatic PAD. Whilst single antiplatelet therapy is recommended as chronic treatment, dual antiplatelet therapy should be considered for those with CCS with prior myocardial infarction at high ischaemic but low bleeding risk. Similarly, dual antithrombotic therapy with aspirin and very-low-dose rivaroxaban is an alternative in CCS, as well as in symptomatic PAD. Full-dose anticoagulation should always be considered in those with CCS/PAD and atrial fibrillation. Unless ischaemic risk is particularly high, antiplatelet therapy should not generally be added to full-dose anticoagulation. Optimization of blood pressure, low-density lipoprotein levels, glycaemic control, and lifestyle characteristics may also reduce stroke risk. Overall, a multifaceted approach is essential to best prevent stroke in patients with CCS/PAD.

Rates of Intracranial Hemorrhage in Mild Head Trauma Patients Presenting to Emergency Department and Their Management: A Comparison of Direct Oral Anticoagulant Drugs with Vitamin K Antagonists.

Background and objectives: Anticoagulants are thought to increase the risks of traumatic intracranial injury and poor clinical outcomes after blunt head trauma. The safety of using direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) after intracranial hemorrhage (ICH) is unclear. This study aims to compare the incidence of post-traumatic ICH following mild head injury (MHI) and to assess the need for surgery, mortality rates, emergency department (ED) revisit rates, and the volume of ICH. Materials and Methods: This is a retrospective, single-center observational study on all patients admitted to our emergency department for mild head trauma from 1 January 2016, to 31 December 2018. We enrolled 234 anticoagulated patients, of which 156 were on VKAs and 78 on DOACs. Patients underwent computed tomography (CT) scans on arrival (T0) and after 24 h (T24). The control group consisted of patients not taking anticoagulants, had no clotting disorders, and who reported an MHI in the same period. About 54% in the control group had CTs performed. Results: The anticoagulated groups were comparable in baseline parameters. Patients on VKA developed ICH more frequently than patients on DOACs and the control group at 17%, 5.13%, and 7.5%, respectively. No significant difference between the two groups was noted in terms of surgery, intrahospital mortality rates, ED revisit rates, and the volume of ICH. Conclusions: Patients with mild head trauma on DOAC therapy had a similar prevalence of ICH to that of the control group. Meanwhile, patients on VKA therapy had about twice the ICH prevalence than that on the control group or patients on DOAC, which remained after correcting for age. No significant difference in the need for surgery was determined; however, this result must take into account the very small number of patients needing surgery.

Use of vitamin K antagonists and risk of prostate cancer: Meta-analysis and nationwide case-control study.

Use of vitamin K antagonists (VKAs) has been suggested to reduce the risk of prostate cancer. We conducted a nested case-control study using Danish demographic and health data registries and summarized existing evidence in a meta-analysis. The case-control study included all Danish men aged 40-85 years with incident histologically verified prostate adenocarcinoma between 2005 and 2015 (cases). For each case, we selected 10 age-matched controls. We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CI) for prostate cancer associated with long-term VKA use adjusted for concomitant drug use, medical history and socioeconomic status. Among 38,832 prostate cancer cases, 1,089 (2.8%) had used VKAs for 3 or more years compared to 10,803 (2.8%) controls yielding a crude OR of 1.01 (95% CI, 0.95-1.08). Multivariable adjustment for covariates had limited influence on the association (OR, 1.03; 95% CI, 0.97-1.10). We observed no dose-response relationship (e.g. OR for 5-10 years of use, 1.06 95% CI, 0.97-1.16). We included 8 studies in the meta-analysis reporting effect estimates from 0.51 (95% CI, 0.23-1.13) to 1.10 (95% CI, 0.94-1.40). Using random effect methods, a pooled effect estimate of 0.86 (95% CI, 0.70-1.05) was obtained; however, there was considerable across-study heterogeneity (I2 : 93.9%). In conclusion, we did not observe a reduced risk of prostate cancer associated with VKA use in this nationwide study and, taken together with previous study findings, a major protective effect of VKAs against prostate cancer seems unlikely.

Rebleeding and Mortality After Lower Gastrointestinal Bleeding in Patients Taking Antiplatelets or Anticoagulants.

BACKGROUND & AIMS: Patients who develop lower gastrointestinal bleeding (LGIB) while receiving anticoagulants or anti-platelets have increased severity of bleeding and risk of rebleeding. We compared outcomes of patients receiving antiplatelets, anticoagulants, or direct oral anticoagulants (DOACs) who develop LGIB, as well as the effects of withholding these drugs on their course of bleeding. METHODS: We performed a retrospective study of 2528 consecutive adult patients with LGIB at 143 hospitals in the United Kingdom, from September through December 2015; 917 were taking anticoagulant or antiplatelet drugs and 1218 were taking neither (unexposed). We collected data on demographic features of patients, interventions or medications, outcomes, laboratory test results, and patient readmission until patient death, discharge, or 28 days after admission (whichever came first). Rebleeding was defined as additional transfusion requirements and/or a decrease in hematocrit ≥20% after 24 hrs of clinical stability. Multivariate regression was used to examine the relationship between drug class on presentation with LGIB and rebleeding, mortality, and cardiovascular events. Rates of rebleeding and cardiovascular complications in patients who had these drugs withheld were also analyzed. RESULTS: Patients receiving antiplatelets, but not those receiving warfarin (n = 232) or DOACs (n = 102), had a higher risk of in-hospital rebleeding (monotherapy hazard ratio [HR], 3.57; 95% CI, 1.13-11.28; n = 504 and dual antiplatelet therapy hazard ratio, 5.3; 95% CI, 1.56-18.54; n = 79) compared with the unexposed group. This risk was not lower in patients who received antiplatelets and had the drug withheld for fewer than 5 days, compared to those who continued the drug throughout admission (HR, 0.98; 95% CI, 0.45-2.17) No differences were observed in risk-adjusted mortality or readmission with further bleeding for patients receiving antiplatelets, DOACs, or warfarin. Cardiovascular events were too few to allow meaningful comparison. CONCLUSIONS: In patients with LGIB, antiplatelet drugs, but not warfarin or DOACs, are associated with an increased risk of rebleeding. Withholding antiplatelets during admission does not lead to reduction in rebleeding.

Incidence and endovascular treatment of severe spontaneous non-cerebral bleeding: a single-institution experience.

OBJECTIVES: To investigate the incidence and endovascular treatment of severe spontaneous non-cerebral hemorrhage (SSNCH) in a high-volume, tertiary university hospital. METHODS: All patients diagnosed with SSNCH between January 2016 and June 2017 were retrospectively analyzed. Endovascular treatment (group EVT) was offered only in patients demonstrating active bleeding at CT angiography (CTA). In cases without active bleeding at CTA, conservative management was decided (group CM). Outcome measures included the incidence of SSNCH, 6-month rebleeding, and survival rates in the two groups as well as EVT technical success and related complications. RESULTS: Within the 18-month period, 44 SSNCH cases were identified, resulting in an annual incidence of 29.3 cases. In 37/44 cases (84.1%), bleeding was attributed to the antithrombotic therapy. In total, 19/44 patients underwent EVT (43.2%), and 25/44 patients (56.8%) were managed conservatively. Two patients who were initially treated conservatively finally underwent EVT due to rebleeding (7.4%). The technical success of EVT was 100%, while rebleeding occurred in 1 case (5.2%) following lumbar artery embolization and was successfully re-embolized. According to the Kaplan-Meier analysis, the 1-, 3-, and 6-month survival rates were 68.4%, 63.2%, and 42.1% for group EVT and 87.5%, 75.0%, and 58.3% for group CM, respectively. There were no EVT-related complications. CONCLUSIONS: The annual incidence of SSNCH in our institution is substantial. EVT resulted in uncomplicated, high bleeding control rates. The mortality rate was similarly high following either EVT or conservative treatment and was mainly attributed to severe comorbidities. KEY POINTS: • This study demonstrates that the incidence of severe spontaneous non-cerebral hemorrhage (SSNCH) in our institution is substantial. • Endovascular treatment was offered only in patients with clinical signs of ongoing hemorrhage and active bleeding at CT angiography and resulted in effective and uncomplicated, minimal invasive hemostasis, in a population with severe comorbidities. • This is the first study to evaluate the outcomes of both endovascular hemostasis and conservative management. Rebleeding following either conservative or endovascular treatment was minimal.

Current Status and Clinical Outcomes of Oral Anticoagulant Discontinuation After Ablation for Atrial Fibrillation in Japan　- Findings From the AF Frontier Ablation Registry.

BACKGROUND: The safety of discontinuing oral anticoagulant (OAC) after ablation for atrial fibrillation (AF) in Japanese patients has not been clarified.Methods and Results:A study based on the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) was conducted. Data were collected from 3,451 consecutive patients (74.1% men; age, 63.3±10.3 years) who had undergone AF ablation at any of 24 cardiovascular centers in Japan between August 2011 and July 2017. During a 20.7-month follow-up period, OAC therapy was discontinued in 1,836 (53.2%) patients; 51 patients (1.5%) suffered a stroke/transient ischemic attack (TIA), 71 (2.1%) suffered major bleeding, and 36 (1.0%) died. Patients in whom OAC therapy was discontinued were significantly younger than those in whom OACs were continued, and their CHA2DS2-VASc scores were significantly lower. The incidences of stroke/TIA, major bleeding, and death were significantly lower among these patients. Upon multivariate adjustment, stroke events were independently associated with relatively high baseline CHA2DS2-VASc scores but not with OAC status. CONCLUSIONS: Although the incidences of stroke/TIA, major bleeding, and death were relatively low among patients for whom OAC therapy was discontinued, stroke/TIA occurrence was strongly associated with a high baseline stroke risk rather than with OAC status. Thus, discontinuation of OAC therapy requires careful consideration, especially in patients with a high baseline stroke risk.

Recognition and Conformational Properties of an Alternative Antithrombin Binding Sequence Obtained by Chemoenzymatic Synthesis.

Heparin is a highly sulfated glycosaminoglycan (GAG) of natural origin used as an anticoagulant and antithrombotic drug. These properties are principally based on the binding and activation of antithrombin (AT) through the pentasaccharide sequence GlcNAc/NS,6S-GlcA-GlcNS,3,6S-IdoA2S-GlcNS,6S (AGA*IA). Literature data show that the population of the 2 S0 ring conformation of the 2-O-sulfo-α-l-iduronic acid (IdoA2S) motif correlates with the affinity and activation of AT. It was recently demonstrated that two synthetic AGA*IA-containing hexasaccharides (one G unit added at the reducing end), differing in the degree of sulfation of the IdoA unit, show comparable affinity and ability to activate AT, despite a different conformation of the IdoA residue. In this paper, the binding of these two glycans to AT was studied by isothermal titration microcalorimetry (ITC), transferred (tr-) NOESY, saturation transfer difference (STD) NMR spectroscopy and molecular dynamics (MD) simulations. Results indicated that both the IdoA2S and the IdoA units assume a 2 S0 conformation when bound with AT, and so present a common binding epitope for the two glycans, centred on the AGA*IA sequence.

Catastrophic antiphospholipid syndrome: Lessons from 14 cases successfully treated in a single center. A narrative report.

The study aimed to evaluate the clinical significance of laboratory findings in patients with catastrophic antiphospholipid syndrome (CAPS) and to report the effects of a well-defined treatment protocol in 14 consecutive cases. Thirteen patients (12 presenting one and one presenting two episodes of CAPS) were consecutively treated and monitored between 1986 and 2017. Antiphospholipid antibody (aPL) characteristics of the patients were compared with those of 64 matched controls (45 antiphospholipid syndrome patients and 19 aPL carriers) who did not develop CAPS during the same mean follow-up period (12 years ±â€¯9.9 SD). Triple aPL positivity (IgG/IgM anticardiolipin + IgG/IgM anti-ß2Glycoprotein I + lupus anticoagulants) significantly prevailed in the CAPS patients with respect to the controls (p = 0.003). IgG anticardiolipin and IgG anti-ß2Glycoprotein I mean antibody titers of the CAPS patients were significantly higher than those of the controls (p = 0.0018 and p = 0.003, respectively). Triple therapy (anticoagulation + plasma exchange + steroids) was administered to all the CAPS cases except for one. Beginning in 2009, intravenous immunoglobulin infusion has also been included in the triple therapy protocol (six patients). All the patients recovered from CAPS; five showed renal failure and one a I-II class New York Heart Association (NYHA) dilated cardiomyopathy. Long-term outcomes of CAPS included a gradual worsening of renal failure in one patient who required hemodialysis 30 years after the acute episode. Renal function improved in the other four patients. The patient affected with dilated cardiomyopathy worsened to a II class NYHA over a five year period. Currently all the patients are alive. A specific antiphospholipid antibody profile could be considered a risk factor associated to CAPS. Early use of a defined treatment protocol based on triple therapy either or not associated with IVIG was associated with recovery in all CAPS patients.

Ultra-early hematoma growth in antithrombotic pretreated patients with intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Patients with acute intracerebral hemorrhage (ICH) pretreated with antithrombotic drugs may have increased early hematoma growth, which would increase mortality risk. The effect of antiplatelet (AP) and vitamin K antagonist (VKA) pretreatment on ultra-early hematoma growth (uHG) and its relationship with mortality in patients with acute supratentorial ICH was analyzed. METHODS: This is an observational retrospective study of a prospective register of 197 ICH patients with first computed tomography (CT) scan taken <6 h from ICH symptom onset. ICH volume was calculated by the ABC/2 formula and uHG by the baseline ICH volume/onset-to-CT time (ml/h) formula. The uHG analysis took into account the patient's pretreatment (none, AP or VKA) and the relationship between uHG and very-early (first 24 h) and 3-month mortality. RESULTS: In the pretreatment group, 50 (25.4%) patients were treated with AP and 37 (18.8%) with VKA. The median (interquartile range 25-75) uHG was 19.7 ml/h (2.9-44.8) for AP pretreated patients, 16.2 ml/h (5.1-42.5) for VKA pretreated patients and 8.4 ml/h (2.4-21.8) for non-pretreated patients, P = 0.019. The uHG was higher in patients with very-early [42.1 ml/h (20.1-79.6)] and total 3-month mortality [28.0 ml/h (15.8-52.5)] compared with survivors [3.9 ml/h (1.5-10.4)], P < 0.0001. Adjusted by ICH severity and previous functional status, uHG was an independent factor related to very-early (P = 0.028) and total 3-month mortality (P = 0.014). CONCLUSIONS: Patients pretreated with antithrombotics have much higher uHG, which would explain the increased mortality in these patients compared to untreated patients.

[Prevalence of oral anticoagulation and quality of its management in primary healthcare: A study by the Health Sentinel Network of the Region of Valencia (Spain)]. / Prevalencia de la anticoagulación oral y calidad de su seguimiento en el ámbito de la atención primaria: estudio de la Red Centinela Sanitaria de la Comunitat Valenciana.

OBJECTIVE: To estimate the prevalence of patients with oral anticoagulant therapy (OAT) in the Region of Valencia and to evaluate the quality of management of OAT with vitaminK antagonists (VKA) carried out in primary healthcare. DESIGN: Observational cross-sectional study conducted through the Health Sentinel Network of the Region of Valencia, which includes a survey and the retrospective analysis of OAT monitoring. SETTING: Primary healthcare, Region of Valencia, Spain. SUBJECTS: All patients aged 18years or older on OAT who consulted during the year 2014. The population covered by the 59 doctors of the Health Sentinel Network constitutes 2.2% of the adult population of the Region of Valencia, and it is representative of it. KEY MEASUREMENTS: Demographic, socioeconomic and health data as well as information concerning OAT. Quality of OAT management with VKA was assessed by means of the percentage of time in therapeutic range (TTR), computed using the Rosendaal method. RESULTS: A total of 1,144 patients were recorded (mean age 74.5±11 years; 49.7% women). Prevalence of OAT in the Region of Valencia is 1.3 cases per 100 population. The characteristic profile of these patients is an old person, with several comorbidities and a low level of education, who lives accompanied. Atrial fibrillation is the most common indication. 82.8% of patients on OAT with VKA were monitored in primary healthcare. The average TTR was 65.0%, and 53.9% of patients had a TTR ≥65%. Among inadequately controlled patients, 74.4% were perceived as well-controlled by their primary care doctor. CONCLUSIONS: Prevalence of OAT is high, and it is expected to increase. The degree of control achieved meets the generally accepted quality standard (mean TTR ≥65%), and it is comparable to that observed in other national and international studies. However, there is wide scope for improvement. It is crucial to optimize the management of this therapy in the most effective and cost-effective way. Among other measures, access of physicians to their patients' clinical information should be improved.

Pharmacological stroke prevention in the elderly with atrial fibrillation in Poland - Results of PolSenior study.

INTRODUCTION: Atrial fibrillation (AF) is the most frequent clinically significant arrhythmia, especially common in the elderly. As it is known, AF is associated with increased risk of stroke. Little is known about pharmacological cardiovascular prevention in the elderly with AF in Poland. OBJECTIVES: The purpose of the study was to evaluate the frequency of pharmacological stroke prevention among the elderly with AF in Poland and its association with clinical characteristics and concomitant cardiovascular risk factors. PATIENTS AND METHODS: The analysis included elderly (≥65 years) participants of the PolSenior study performed in years 2008-2012. RESULTS: The study group consisted of 4979 people (mean age: 79.3±8.7 years). Among them, there were 875 patients (18.7%) with documented history of AF. Pharmacological prevention with the use of vitamin K antagonists (VKA) was applied by 117 (13.4%) of the elderly with AF, including 15 (1.7%) on dual therapy. Additionally, 386 (45.3%) subjects with AF were using oral antiplatelet therapy (OAPs), mostly aspirin. Acenocoumarol was much more often used than warfarin. New oral anticoagulant drugs (NOACs) were not used at all. Only personal income was associated with the use of VKA. No significant correlation was found for the age, sex, place of residence and level of education. CONCLUSIONS: The study was unique to determine the frequency of pharmacological stroke prevention among elderly people with AF in Poland. It occurred that oral anticoagulant drugs were applied too rarely in this group of patients. Educational programs should be developed among general practitioners concerning current recommendations for patients with AF.