Prevention Of Thrombotic Events Research Articles

Thromboelastography with Platelet Mapping Identifies High Platelet Reactivity is Associated with Obesity, Diabetes, and Thrombotic Events

Metabolic comorbidities such as diabetes and obesity are considered pro-inflammatory states which theoretically increase the risk of perioperative thrombotic events across many surgical disciplines. Currently, there is a paucity of objective metrics to determine such risk and ideal pharmacologic targets. Thromboelastography with Platelet Mapping (TEG-PM) provides a comprehensive profile of coagulation and may provide insight into clot dysregulation. Patients undergoing lower extremity revascularization underwent serial TEG-PM analysis. The relationship between the TEG-PM metrics and thrombosis was evaluated. Preoperative TEG-PM samples of patients with body mass index (BMI)≥25 were compared to those of patients with a normal BMI, and between patients with diabetes mellitus (DM) and those without. 218 TEG-PM samples from 202 patients were analyzed. The BMI≥25 cohort showed significantly greater platelet aggregation [81.9% (±20.9) vs. 68.6% (±27.7), P<0.01]. Patients with DM were more frequently on full-dose anticoagulation [47.7% vs. 29.7% P=0.01] yet demonstrated increased clot strength, or adenosine diphosphate (ADP)-Maximum Clot Amplitude (MA) [49.1 (±16.1) vs. 41.5 (±17.1) and 37.7 (±19.6) vs. 31.6 (±17.4) P<0.01]. 49 patients experienced thrombosis and exhibited greater platelet aggregation [76.6% (±17.8) vs. 66.8% (±30.4) P=0.03] and greater ADP/arachidonic acid MA [47.1 (±16.6) vs. 41.9 (±18.8) and 38.2 (±17.8) vs. 32.5 (±19.9) both P=0.05]. Patients who thrombosed were more often diabetic [69.5% versus 51.0% P=0.03] and on full-dose anticoagulation [75.0% vs. 56.8% P=0.02]. Patients with a BMI≥ 25 and those with diabetes demonstrated TEG-PM profiles similar to patients with thrombosis. Diabetes was independently associated withthrombosis, and full-dose anticoagulation was not protective. This suggests the potential utility of TEG-PM for thrombotic risk stratification based on metabolic factors and suggests antiplatelet agents may be effective at prevention of thrombotic events in this population.

The Association between Blood Cell Counts and Thrombotic Events in Japanese Patients with Polycythemia Vera: A Retrospective Database Study

Introduction: The primary goal of therapy for polycythemia vera (PV) is the prevention of thrombotic events (TE). Several studies conducted in the United States and Europe have indicated that elevated hematocrit (HCT) and white blood cell count (WBC) are associated with an increased risk of TE in patients with PV. However, these associations have not been reported in Japanese patients with PV. In this study, we aimed to evaluate the association between blood cell counts and TE in Japanese patients with PV using a real-world database. Methods: This retrospective cohort study was performed using the RWD database (Real World Data Co., Ltd) which is a large-scale electronic medical records database collected between 1987 and 2022. Patients who met the following criteria were included: 1) PV (ICD-10, D45) initially diagnosed at ≥18 years of age (index date is the date of initial diagnosis); 2) at least one hospital visit within 180 days after the index date; 3) no history of myelofibrosis or acute myeloid leukemia before the index date; 4) ≥2 HCT measurements since the index date, and 5) no phlebotomy or hydroxyurea therapy before the index date. The outcome was the time from the index date to the first TE or to the last day of follow-up for censored cases. The primary analysis evaluated the association between HCT and TE using a univariate time-dependent Cox proportional hazards (PH) model. In the secondary analysis, WBC, platelet count (PLT), hematocrit-to-hemoglobin ratio (HHR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), basophil-to-lymphocyte ratio (BLR), phlebotomy were used as time-dependent exposures, whereas age, sex, risk factors for cardiovascular disease, and Barbui's risk stratification were used as baseline variables to evaluate their associations with TE. A multivariable-adjusted Cox PH model with each time-dependent exposure and baseline variables was also conducted. Results: Of 1,796 patients diagnosed with PV, 1,259 met the eligibility criteria. The median age (interquartile range [IQR]) of the patients was 66 (55-74) years; 63.1% were male; 23.1% had a history of TE; 71.9% were in the high-risk group according to Barbui's stratification; and 37.5% had one or more comorbidities (diabetes mellitus, hypertension, or dyslipidemia). The median (IQR) follow-up period was 1.3 (0.1-4.6) years. Of the 1259 patients, 45.0% (566) developed TE during the follow-up period and the incidence rate was 14.4 (95% confidence interval [CI], 13.2-15.6) per 100 person-years. The median HCT at the time of the first TE was 49.5% (HCT &amp;lt;45%: 157 [32.4%], ≥45%: 328 [ 67.6%]); the median WBC and PLT were 10.2×10 9/L and 335.0×10 9/L, respectively. In the primary analysis, the hazard ratio (HR) and 95% CI for TE in patients with HCT ≥45% compared with patients with HCT &amp;lt;45% was 0.96 (0.77-1.21), with no significant association. Age, history of TE and Barbui's risk stratification were associated with the risk of TE (HR [95% CI]: 1.02 [1.01-1.03], 1.25 [1.02-1.54], 1.78 [1.39-2.27], respectively). Compared with patients with WBC &amp;lt;10×10 9/L, patients with WBC ≥15×10 9/L and 10-≤15×10 9/L were associated with an increased TE risk (multivariable-adjusted HR [95% CI]: 2.10 [1.65-2.68] and 2.05 [1.59-2.64], respectively). Compared with patients with PLT &amp;lt;400×10 9/L, patients with PLT ≥1000×10 9/L, 600-&amp;lt;1000×10 9/L, and 400-&amp;lt;600×10 9/L were associated with an increased TE risk (multivariable-adjusted HR [95% CI]: 1.98 [1.35-2.89], 2.18 [1.67-2.85], and 1.59 [1.20-2.12], respectively). High HHR, NLR, PLR, BLR values and phlebotomy were associated with an increased TE risk (multivariable-adjusted HR [95% CI]: 3.93 [2.37-6.51], 1.05 [1.03-1.06], 2.33 [1.46-3.73], 4.92 [2.27-10.71] and 1.99 [1.36-2.91]). Conclusions: This is the largest and first real-world cohort study to demonstrate the association between blood cell counts and TE in Japanese patients with PV. The results did not show that maintaining an HCT &amp;lt;45% is associated with a reduced risk of TE in Japanese patients with PV. In contrast, the risk of TE was associated with phlebotomy, Barbui's risk stratification, and elevated WBC, PLT, HHR, PLR, and BLR. These data support the need to consider blood cell counts other than HCT in treatment strategies for Japanese patients with PV in clinical practice. Furthermore, follow-up studies are required to identify the specific levels of blood cell counts associated with an increased TE risk.

Recurrent bleeding during standard anticoagulant therapy in comorbid patients with atrial fibrillation: a clinical case report

The question of the safety of direct oral anticoagulants (DOACs), despite their high efficacy in the prevention of thrombotic events in atrial fibrillation (AF), remains relevant due to the risk of developing hemorrhagic events while taking standard doses, which requires a thorough personalized approach. The article presents a clinical case of the development of spontaneous hematomas on the skin of the upper and lower extremities and hemarthrosis of the knee joint while taking 20 mg of rivaroxaban in a 72-year-old patient with AF without impaired renal and hepatic function. Due to the increase in the residual plasma concentration of rivaroxaban, a pharmacogenetic study and the Thrombodynamics (TD) test were performed. A pharmacogenetic study did not reveal significant gene polymorphisms associated with the metabolism of rivaroxaban. However, TD allowed us to confirm the presence of significant hypocoagulation at the peak of the residual blood concentration of the drug in the blood, which could cause recurrent hemorrhagic events in the patient. In addition, the patient is taking amiodarone at a dosage of 200 mg per day, which does not allow us to rule out drug-drug interaction, despite the inconsistency of the literature data.

Flow-Mediated Dilation Can be used as an Indicator for Assessing Severity and Deaths by Covid-19 at the Initial Hours of Hospitalization

Assessment of Flow-Mediated Dilation (FMD) in patients hospitalized for COVID-19 will assist with regard to early identification of markers at the onset of SARS-CoV-2 infection. Therefore, the early evaluation of simple markers, obtained at the bedside before the most serious manifestations are already installed, can help health professionals to act preventively to save lives, direct care in the initial stage of infection, helping in the prognosis and diagnosis. Given the importance and relevance of this technique in this population at this time and the need to better understand the pathophysiology of COVID-19 as well as its damage to the endothelium, we performed an evaluation of FMD in different severity of COVID-19 in recently hospitalized patients. A total of 100 patients were enrolled in the study and were divided into two groups according to the severity of COVID- 19. The results provide new evidence that patients with COVID-19 classified as severe/critical have greater endothelial dysfunction and that FMD may be a simple marker, helping in the prognosis and diagnosis and, consequently, in the prevention of thrombotic events.

Antithrombotic therapy in peripheral arterial disease

BackgroundPatients with peripheral arterial disease (PAD) are at increased risk for major adverse cardiovascular events (MACE) such as cardiovascular death, myocardial infarction, and stroke as well as major adverse limb events (MALE) such as amputation and acute limb ischemia. Therefore, prevention of thrombotic events is crucial to improve the prognosis of PAD patients. This review article concludes current evidence and guideline recommendations about antithrombotic therapy in PAD patients.Antithrombotic therapy is highly effective to reduce MACE and MALE events in PAD patients. Recently, the concept of dual pathway inhibition (low-dose rivaroxaban plus acetylic salicylic acid (ASA) has been tested in the COMPASS and VOYAGER-PAD trial. Compared to ASA alone dual pathway inhibition was superior to prevent MACE and MALE. After peripheral revascularization, in particular the risk for acute limb ischemia was reduced. In contrast, the risk for major bleeding is increased. Therefore, current guidelines recommend the combination of low-dose rivaroxaban and ASA in PAD patients with low bleeding risk. In patients with high bleeding risk, a single antiplatelet drug (preferable clopidogrel) is indicated. In patients with atherosclerotic vascular disease and indication for oral anticoagulation, no additional antiplatelet drug is necessary, as this would increase the risk of bleeding without improving the prognosis.ConclusionAntithrombotic treatment reduces MACE and MALE and is recommended in all patients with PAD. Individual bleeding risk should always be considered based on the current data situation and an individual benefit-risk assessment must be carried out.

COVID-19-Associated Pulmonary Embolism: Review of the Pathophysiology, Epidemiology, Prevention, Diagnosis, and Treatment.

COVID-19 is associated with endothelial activation in the setting of a potent inflammatory reaction and a hypercoagulable state. The end result of this thromboinflammatory state is an excess in thrombotic events, in particular venous thromboembolism. Pulmonary embolism (PE) has been of special interest in patients with COVID-19 given its association with respiratory deterioration, increased risk of intensive care unit admission, and prolonged hospital stay. The pathophysiology and clinical characteristics of COVID-19-associated PE may differ from the conventional non-COVID-19-associated PE. In addition to embolic events from deep vein thrombi, in situ pulmonary thrombosis, particularly in smaller vascular beds, may be relevant in patients with COVID-19. Appropriate prevention of thrombotic events in COVID-19 has therefore become of critical interest. Several changes in viral biology, vaccination, and treatment management during the pandemic may have resulted in changes in incidence trends. This review provides an overview of the pathophysiology, epidemiology, clinical characteristics, and risk factors of COVID-19-associated PE. Furthermore, we briefly summarize the results from randomized controlled trials of preventive antithrombotic therapies in COVID-19, focusing on their findings related to PE. We discuss the acute treatment of COVID-19-associated PE, which is substantially similar to the management of conventional non-COVID-19 PE. Ultimately, we comment on the current knowledge gaps in the evidence and the future directions in the treatment and follow-up of COVID-19-associated PE, including long-term management, and its possible association with long-COVID.

A Description of Apixaban Dosing Patterns for Treatment or Prevention of Thrombotic Events in Hospitalized Patients on Dialysis.

Introduction: Apixaban is currently the only oral direct factor Xa inhibitor approved for treatment and prevention of venous thromboembolism (VTE) in patients on hemodialysis. Exclusion of dialysis patients from major clinical trials results in prescriber uncertainty regarding the optimal dose of apixaban for VTE treatment in this population. This study sought to characterize the variance in apixaban prescribing patterns for thrombotic indications other than atrial fibrillation. Methods: This retrospective, multi-center, descriptive study analyzed apixaban dosing patterns for hospitalized chronic dialysis patients with history of thrombosis. The primary outcome was incidence of deviation from manufacturer recommendations for dosing, assessed for either a new start or receipt prior to hospitalization. Secondary outcomes included observation of recurrent thrombotic and bleeding event rates during subsequent hospitalizations. Patients were analyzed into subgroups according to type of thrombotic indication for treatment. Data are reported with descriptive statistics. Results: A total of 101 patients were included. Deviations in recommended dosing were observed in 53 of 80 (66.2%) patients receiving apixaban for treatment of acute or chronic thrombosis. Of 44 patients started on apixaban during hospitalization for the indication of acute VTE, a dose deviation was observed in 79.5% of patients. Rates of rehospitalization for recurrent thrombotic events and bleeding were 11.8% and 9.9%, respectively. Conclusion: Variation in apixaban prescribing practices for the treatment of VTE in dialysis patients is common, suggesting an urgent need for prospective studies and updated dosing guidance to optimize safety with apixaban use in this population.

Formulation, Optimization and Evaluation of Ticagrelor Loaded Self Microemulsifying Chewable Tablets

Abstract: Ticagrelor is a new generation Adenosine diphosphate receptor inhibitor drug which is highly lipohilic having poor aqueous solubility used in the treatment of Acute Coronary Syndrome and prevention of Thrombotic events like Stroke and Heart Attack. An approach has been made to develop Chewable tablets of drug loaded on Self-microemulsifying drug delivery systems (SMEDDS), screen suitable adsorbent for solidification of formulated SMEDDS and to study the effect of superdisintegrants in chewable tablets. Methods: On basis of Pseudoternary diagrams constructed for selected oil, surfactant and cosurfactant, SMEDDS formulation was formulated using Capmul MCM EP oil with surfactant (Cremophor RH 40) and co-surfactant (PEG 400) which was solidified using selected adsorbent. Chewable tablets were compressed by direct compression method using superdisintegrants. Results: IR Studies and DSC studies revealed compatibility and stability of drug in formulation. Compression blend containing Solidified SMEDDS possessed good flow and compressibility. Chewable tablets compressed using Soy Polysaccharides as super disintegrant showed least wetting and disintegration time, drug release of 97.68% within 30 min. Short term stability studies revealed no significant change in physical and chemical properties. Conclusion: These results suggest that the Ticagrelor loaded self microemulsifying chewable tablets can be a promising oral drug delivery system to improve the solubility and dissolution profile of Ticagrelor. Key words: Ticagrelor, SMEDDS, Adsorbents, Chewable tablets, Acute coronary syndrome.

Pulmonary embolism in patients with the Coronavirus Disease 2019

Coronaviruses are RNA viruses causing infectious diseases. They had been responsible for 15% cases of a common cold before December 2019. With the new strain of coronavirus SARS CoV2 which causes COVID-19 disease, the ongoing pandemic surprised with the severity of symptoms and its course compared to the previously known mild respiratory tract infections. In the end of December 2021, over 274 million people were diagnosed with COVID-19 disease, and the total mortality amounted to nearly 5.4 million deaths in more than 200 countries. One of the potentially fatal complications of COVID-19 is pulmonary embolism (PE). It appears that PE has been associated with several coagulation abnormalities as well as with frequent significantly elevated concentration of D‑dimer's. A higher D‑dimer concentration in blood serum, in turn, has been associated with an increased risk of premature death. Moreover, inflammation, typical in the course of COVID-19, is considered a prothrombotic condition; higher interleukin 6 (Il-6) and C‑reactive protein concentrations have been found in patients with more severe forms of COVID-19. So far, none specific for COVID-19 studies have been available with regard to the diagnosis and treatment of PE. Therefore, the practical approach is based on the experience of other groups of patients. Prevention of thrombotic events seems reasonable, at least in COVID-19 patients with the risk factors of developing venous thromboembolism. Low‑molecular‑weight heparins are most commonly prescribed (e.g. enoxaparin, dalteparin). Following the confirmed definite PE diagnosis, proper anticoagulation or, if necessary, thrombolytic treatment must be introduced.

Antiplatelet Activity of Cucurbita maxima.

Natural extracts constitute an important source in the prevention of noncommunicable diseases, such as cardiovascular diseases. The pumpkin, Cucurbita maxima, is widely consumed in Chile. Pumpkin seeds, despite having crude protein, lipids, and carbohydrates, are regarded as agro-industrial waste. In this work, we correlated the antiplatelet activity of aqueous, ethanolic, and methanolic extracts from pumpkin seeds with their bioactive compounds. In vitro platelet aggregation and activation studies were performed by turbidimetry and flow cytometry, respectively. Results reveal that the extracts inhibited, in a dose-dependent manner, platelet aggregation induced by adenosine diphosphate, thrombin receptor activator peptide 6 (TRAP-6), and collagen. Pumpkin seed extracts inhibited P-selectin secretion and glycoprotein IIb/IIIa activation on TRAP-6-activated platelets. They were found to be rich in fatty acids and a powerful source of plant-based protein, which could be related to the high antiplatelet potential identified in extracts. This research demonstrated that pumpkin seed extracts could be a candidate in the prevention of thrombotic events.

The Safety of Aspirin Vs. Direct Oral Anticoagulants: A Meta-Analysis of Currently Published Clinical Trials

Introduction:Several prior analyses have suggested that the use of warfarin leads to no observable difference in bleeding events when compared to aspirin. Although direct oral anticoagulants (DOACs) have been shown to be consistently safer than warfarin, data comparing the safety and efficacy of DOACs vs. aspirin has been sparse until recently. To date, two large randomized trials, EINSTEIN CHOICE and AVERROES, have compared DOACs to aspirin for secondary VTE prevention and prevention of thrombotic events in patents with atrial fibrillation respectively. Although DOACs were proven more effective then aspirin for both indications, the comparative bleeding risk between the two interventions remained unclear. In order to evaluate the safety of aspirin vs. DOACs we performed a meta-analysis of patients receiving aspirin vs. full dose DOAC within the two aforementioned trials.Methods:Using data from two recently-published, phase III trials– EINSTEIN CHOICE and AVERROES– we performed a meta-analysis using a Mantel-Haenszel random-effects model. Odds Ratios (OR) were generated along with forest plots. All analysis was performed with Review Manager (version 5.3 The Nordic Cochrane Centre, The Cochrane Collaboration, 2014).Results:In total, 3854 patients were treated with a therapeutic dose DOAC (apixaban 5mg BID or rivaroxaban 20mg daily) and 3876 were treated with varied doses of aspirin (81mg [46.9%], 100mg [27.6%], 162mg [18.5%], 243mg [1.9%], 324mg [5.0%], and unknown dose [0.2%]). Our analysis detected no statistically significant difference in major bleeding events (1.27% vs. 1.07%; p=0.4) or clinically-relevant, non-major bleeding events (3.22% vs. 2.65%; p=0.14) between the two groups (Table 1).Conclusion:This analysis suggests that aspirin is not appreciably safer than full dose DOACs in terms of bleeding risk. Given the size of this analysis, if a true difference in bleeding risk does exist, it is likely small and not clinically relevant. In addition to being significantly less effective, these results contradict any notion that aspirin is a safer alternative in terms of bleeding risk. Therefore, given the superior efficacy of DOACs for secondary VTE prevention and stroke prevention in atrial fibrillation, DOACs should always be preferentially used over aspirin in these populations. Future guidelines for clinical practice should reflect the evidence that aspirin is neither safer nor more effective for either indication. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prevention of thrombotic events in pregnant women with myeloproliferative neoplasms

Prevention of thrombotic events in pregnant women with myeloproliferative neoplasms

4423 Impact of Gender on High On-Treatment Platelet Reactivity (HPR) and Major Adverse Cardiovascular Events (MACEs) in Caribbean Hispanic patients using Clopidogrel

OBJECTIVES/GOALS: The use of P2Y12 receptor inhibitors like Clopidogrel is crucial in the prevention of thrombotic events in patients with coronary artery disease, peripheral arterial disease, and cerebrovascular disease. Variation in the level of platelet inhibition is present in many patients, and it is associated with the occurrence of major adverse cardiovascular events (MACEs). The term High-on treatment platelet reactivity (HTRP) is used to describe impaired antiplatelet inhibition while on Clopidogrel. Multiple factors have been associated with the presence of HTPR in patients with CAD and PAD, including CYP2C19 loss of function polymorphism, drug-drug interactions, and medical comorbidities. Gender differences are another factor that might influence the levels of platelet inhibition while on Clopidogrel and hence, HTPR. Differences by Gender exist in platelet biology, count, and activation. The evidence for the influence of Gender in HTPR is limited, but a possible association has been described. In this study, we described the association of Gender with HTPR and Major Adverse Cardiovascular Events (MACEs) occurrence. The data is from a sample of Hispano-Caribbean patients on Clopidogrel therapy alone or in combination with Aspirin that were retrospectively evaluated from an ongoing trial in Puerto Rico. The result of this study provided evidence of the influence that Gender has on antiplatelet therapy function and MACEs occurrence. METHODS/STUDY POPULATION: The population in the study consisted of Hispano-Caribbean patients using Clopidogrel alone or in combination with Aspirin for coronary artery disease, peripheral arterial disease, or cerebrovascular disease. The sample was obtained from multiple hospital institutions with cardiovascular services in Puerto Rico during the years 2016-2019. Patients were part of the ongoing trial, “Adopting a precision medicine paradigm in Puerto Rico: leveraging ancestral diversity to identify predictors of Clopidogrel response in Caribbean Hispanics.” The sample size consisted of 150 patients. Participants were recruited during routine medical care, pre-admission evaluation for elective cardiac procedures, or during hospitalization in the participating institutions. Platelet reactivity testing was performed with the system Verify Now® to determine PRU values, and High on-treatment platelet reactivity was defined as PRU ≥208. One year after recruitment, the patients were re-evaluated for the occurrence of MACEs. The association of the variables HTPR, occurrence of MACEs, and Gender were assessed using logistic regression in addition to the role of HTPR and Gender for predicting MACE occurrence. The analysis was done using the statistic software Intellectus ©. RESULTS/ANTICIPATED RESULTS: The sample consisted of 67 females and 83 males with and Mean age of 67.87 years and 61.11 years, respectively. The prevalence of HTPR in the sample was 32.67 % (n = 49) with 36% (n = 24) for females, and 30%(n = 25) for males. The mean PRU values were 179.54 for females and 170.81 for males. The percentage of MACEs one year after recruitment was 29.33 % (n = 44) with 43% on females (n = 19), and 57% on males (n = 25). Logistic regression for Gender predicting HTPR was non-significant with a χ2(2) = 0.55, p = .758, and McFadden R2 = 0.00. Also, logistic regression for the effects of Gender and HTPR on the Odds of MACEs occurrence was not significant based on a model with an alpha of 0.05, χ2(2) = 1.99, p = .370, and McFadden R2 = 0.01. DISCUSSION/SIGNIFICANCE OF IMPACT: The sample consisted of 67 females and 83 males with and Mean age of 67.87 years and 61.11 years, respectively. The prevalence of HTPR in the sample was 32.67 % (n = 49) with 36% (n = 24) for females, and 30%(n = 25) for males. The mean PRU values were 179.54 (±70.42) for females and 170.81(±64.89) for males. The percentage of MACEs one year after recruitment was 29.33 % (n = 44) with 43% on females (n = 19), and 57% on males (n = 25). Logistic regression for Gender predicting HTPR was non-significant with a χ2(2) = 0.55, p = .758, and McFadden R2 = 0.00. Also, logistic regression for the effects of Gender and HTPR on the odds of MACEs occurrence was not significant based on a model with an alpha of 0.05, χ2(2) = 1.99, p = .370, and McFadden R2 = 0.01.

P0227VITAMIN K ANTAGONIST-ASSOCIATED MICROSCOPIC HEMATURIA: ASSOCIATION WITH INR LEVELS AND PROTECTIVE EFFECT OF RAAS BLOCKADE

Abstract Background and Aims Vitamin K antagonists (VKA) are the most widely used anticoagulants in the daily clinical practice for the prevention of thrombotic events. Several renal adverse effects have been associated with the use of VKA, from hemodynamic effects due to massive urological hemorrhage associated with VKA overdose, to non-hemodynamic effects that include glomerular hemorrhage and renal tubular obstruction due to red cell casts. The main aim of our study was to establish an association between INR levels and microscopic hematuria in patients with VKA, and identify possible risk and protective factors associated with development of microscopic hematuria in these patients. Method We performed a transversal study that included patients with oral anticoagulation with coumarin derivatives (warfarin or acenocoumarol), that attended the Hematology outpatient clinic from October to December 2019 for routine INR control. A urine specimen was collected on the day of the INR control. We performed a simple urinalysis to all patients and quantified the precise number of red cells in the urine sediment by flow cytometry. Demographic data, kidney function tests including serum creatinine and albuminuria, comorbidities, anticoagulant dose and concomitant treatment were registered. Results 337 patients were included in the study, with an average age of 68.6 ± 12.2 years, 51% were females, 95% were treated with acenocoumarol and 5% with warfarin. Median INR levels were 2.6 (IQR 2.1-3.3) and the median number of urine red cells in the sediment were 11 RBCs/µl (IQR 0-13). 11.9% of the patients presented microscopic hematuria (≥14 RBCs/µl). There was a significant correlation between INR levels and the number of RBCs in the urine sediment (Spearman’s rho= 0.119, p= 0.029), independent from the type of anticoagulant used. This correlation was stronger after excluding those patients who had concomitant bacteriuria (Spearman’s rho= 0.201, p= 0.024). We found no correlation between time elapsed from start of anticoagulation or total weekly dose with the intensity of microscopic hematuria. In the univariate analysis, microhematuria was associated with having an INR &amp;gt;3.5 (19% vs. 10.2%, p=0.046), bacteriuria (15.2% vs. 3.6%, p=0.015), leukocyturia (14.8% vs. 6.6%, p= 0.026), hypertension (16.2% vs. 9.5%, p=0.053), and the use of RAAS blockers (17.2% vs. 6.9%, p=0.004). After performing a multivariate logistic regression that included the aforementioned variables, the association between microhematuria and RAAS blockade with either an ACE inhibitor or ARB was maintained (OR 0.38, CI 95% 0.163-0.886, p=0.025), independent from INR levels, hypertension, leukocyturia or bacteriuria. We found no association between serum creatinine, albuminuria or antiplatelet treatment with the presence of microscopic hematuria. Conclusion INR overdose is significantly associated with the presence of microscopic hematuria, independent from the type of VKA used or the total weekly dose. RAAS blockade is an independent protective factor for the presence of microscopic hematuria in anticoagulated patients.

Repurposing a platelet aggregation inhibitor ticagrelor as an antimicrobial against Clostridioides difficile

Drug resistance in Clostridioides difficile becomes a public health concern worldwide, especially as the hypervirulent strains show decreased susceptibility to the first-line antibiotics for C. difficile treatment. Therefore, the simultaneous discovery and development of new compounds to fight this pathogen are urgently needed. In order to determinate new drugs active against C. difficile, we identified ticagrelor, utilized for the prevention of thrombotic events, as exhibiting potent growth-inhibitory activity against C. difficile. Whole-cell growth inhibition assays were performed and compared to vancomycin and metronidazole, followed by determining time-kill kinetics against C. difficile. Activities against biofilm formation and spore germination were also evaluated. Leakage analyses and electron microscopy were applied to confirm the disruption of membrane structure. Finally, ticagrelor’s ability to synergize with vancomycin and metronidazole was determined using checkerboard assays. Our data showed that ticagrelor exerted activity with a MIC range of 20–40 µg/mL against C. difficile. This compound also exhibited an inhibitory effect on biofilm formation and spore germination. Additionally, ticagrelor did not interact with vancomycin nor metronidazole. Our findings revealed for the first time that ticagrelor could be further developed as a new antimicrobial agent for fighting against C. difficile.

Use of Direct Oral Anticoagulants in Children and Adolescents.

While the need for anticoagulation in children has increased over the last decades, dose regimens of currently used anticoagulants, including low-molecular-weight heparin (LMWH) and vitamin K antagonist (VKA), are still extrapolated from adult guidelines because well-designed clinical trials were never performed in children. This approach is not optimal due to specific pediatric features of the hemostatic system and pathophysiology of thrombosis. These anticoagulants also present several disadvantages that further hamper optimal anticoagulation of pediatric patients, especially newborns and infants. The new direct oral anticoagulants (DOACs), which have the potential to overcome these disadvantages, were extensively investigated in adults and have become a valid alternative to LMWH and VKA for anticoagulation in the adult population. Several pediatric trials on all approved DOACs are currently ongoing, providing specific pediatric formulations and age- and weight-adjusted dose guidelines. First results of phase III trials indicate that DOACs are at least as efficient and safe as LMWH and VKA for the treatment and prevention of thrombotic events in children with different clinical conditions. This review article summarizes available data from terminated and ongoing controlled trials on DOACs in children and adolescents.

Do the Benefits of Routine Perioperative Chemoprophylaxis for Prevention of Thrombotic Events in Multilevel Posterior Surgery of the Cervical or Thoracic Spinal Cord Outweigh the Risks?

Do the Benefits of Routine Perioperative Chemoprophylaxis for Prevention of Thrombotic Events in Multilevel Posterior Surgery of the Cervical or Thoracic Spinal Cord Outweigh the Risks?

Ticagrelor: AReversible P2Y12 Inhibitor in Prevention of Thrombotic Events

Ticagrelor: AReversible P2Y12 Inhibitor in Prevention of Thrombotic Events

НУЖЕН ЛИ ЦЕНТРАЛИЗОВАННЫЙ КОНТРОЛЬ АНТИКОАГУЛЯНТНОЙ ТЕРАПИИ В ДОНБАССЕ?

В представленном обзоре освещаются показания, побочные эффекты и возможные стратегии ведения пациентов, принимающих антикоагулянты. Показанием к длительной или пожизненной терапии антикоагулянтами являются тромботическое событие и профилактика тромботических событий у пациентов с высоким риском, включая послеоперационные состояния, фибрилляцию предсердий и пациентов с искусственными клапанами. В этой терапии наиболее распространены антагонисты витамина К, такие как варфарин, которые блокируют витамин К-эпоксидредуктазу, предотвращая тем самым образование активной формы витамин К-зависимых факторов свертывания крови. Наиболее значимым и опасным побочным эффектом, связанным с приемом варфарина, является кровотечение, развитие которого напрямую связано с уровнем МНО. Осложнениями такой терапии могут быть также и тромботические осложнения при недостаточной дозе препарата. Это и объясняет необходимость строгого контроля МНО у пациентов, принимающих препараты соответствующего действия. В статье проанализирован опыт работы антикоагулянтных кабинетов в некоторых регионах Российской Федерации. Количество пациентов, требующих проведения такого лечения в Донбассе, достаточно велико, что диктует необходимость создания антикоагулянтных кабинетов на территории нашего региона.

Risk factors for venous thromboses in patients with rheumatoid arthritis

Objective: to determine risk factors (RFs) for venous thromboembolic events (VTE) in patients with rheumatoid arthritis (RA).Subjects and methods: The investigation enrolled 374 patients (311 women and 63 men) with a reliable diagnosis of RA who met the 2010 ACR/EULAR classification criteria. The patients' mean age was 53.7±13.6 years; the disease duration was 12.1±10.7 years. All the patients were treated at the V.A. Nasonova Research Institute of Rheumatology Clinic during the period from 2014 to 2017. A standard clinical examination of the peripheral joints was performed. RA activity was measured using DAS28. A survey was made using a questionnaire including questions on traditional RFs for VTE and RFs that might be caused by RA and its therapy. Results and discussion. VTE were recorded in 45 (12%) out of the 374 patients. Group 1 included 45 patients with VTE; Group 2 consisted of 329 patients without VTE. Multidimensional analysis showed an increased risk of developing VTE in RA under the influence of the following factors: high inflammatory activity; lower extremity varicose veins; hypercholesterolemia; and hypertension. Their weighted coefficients were 1.1, 2.5, 1.0, and 0.9, respectively. According to the obtained model (p&lt;0.001), the risk of VTE in RA can be predicted by the following formula: Z = 1.1 • high RA activity (Yes = 1/No = 0) + 2.5 • lower extremity varicose veins (Yes = 1/No = 0) + 1.0 • hypercholesterolemia (Yes = 1/No = 0) + 0.9 • hypertension (Yes = 1 / No = 0).Conclusion: The increased risk for VTE in RA patients determines the need for its timely assessment, by taking into account the known risk factors as both standard ones and those caused by the disease itself and its therapy. This risk assessment is necessary for the timely adequate treatment and prevention of thrombotic events in RA.