Risk Of Arterial Thrombosis Research Articles

Prevalence and Risk Factors of Venous Thromboembolism in Critically Ill Patients with Severe COVID-19 and the Association between the Dose of Anticoagulants and Outcomes.

COVID-19 is characterized by a procoagulant state that increases the risk of venous and arterial thrombosis. The dose of anticoagulants in patients with severe COVID-19 pneumonia without suspected or confirmed thrombosis has been debated. We evaluated the prevalence, predictors, and outcomes of venous thromboembolism (VTE) in critically ill COVID-19 patients and assessed the association between the dose of anticoagulants and outcomes. This retrospective cohort included patients with COVID-19 who were admitted to the ICU between March and July 2020. Patients with clinically suspected and confirmed VTE were compared to those not diagnosed to have VTE. The study enrolled 310 consecutive patients with severe COVID-19 pneumonia: age 60.0±15.1 years, 67.1% required mechanical ventilation and 44.7% vasopressors. Most (97.1%) patients received anticoagulants during ICU stay: prophylactic unfractionated heparin (N=106), standard-dose enoxaparin (N=104) and intermediate-dose enoxaparin (N=57). Limb Doppler ultrasound was performed for 49 (15.8%) patients and chest computed tomographic angiography for 62 (20%). VTE was diagnosed in 41 (13.2%) patients; 20 patients had deep vein thrombosis and 23 had acute pulmonary embolism. Patients with VTE had significantly higher D-dimer on ICU admission. On multivariable Cox regression analysis, intermediate-dose enoxaparin versus standard-dose unfractionated heparin or enoxaparin was associated with lower VTE risk (hazard ratio, 0.06; 95% confidence interval, 0.01-0.74) and lower risk of the composite outcome of VTE or hospital mortality (hazard ratio, 0.42; 95% confidence interval, 0.23-0.78; p=0.006). Major bleeding was not different between the intermediate- and prophylactic-dose heparin groups. In our study, clinically suspected and confirmed VTE was diagnosed in 13.2% of critically ill patients with COVID-19. Intermediate-dose enoxaparin versus standard-dose unfractionated heparin or enoxaparin was associated with decreased risk of VTE or hospital mortality.

Abstract 12744: Outcomes of Patients With Myeloproliferative Neoplasms Admitted for Myocardial Infarction: Insights From National Inpatient Sample

Introduction: Myeloproliferative neoplasms (MPNs) are chronic clonal stem cell neoplasms with high risk of thrombosis and cardiovascular events. However, outcomes after acute myocardial infarction (AMI) and risk factors for cardiovascular events after AMI in patients with MPN have not been well characterized. Methods: Adult patients with a primary admission of AMI from September 2015 to December 2018 (N = 699,786) with (N = 3,156) and without (N = 696,586) a diagnosis of MPN were identified using the National Inpatient Sample. Primary outcome was composite inpatient major adverse cardiac events (MACE) of arterial and venous thrombosis, non-fatal cardiac arrest, and mortality. Patients with and without MPN were compared using propensity score estimation using Generalized Boosted Models(GBM). Outcomes between groups were compared using multivariable logistic regression. Results: Patient characteristics are described in Table 1. Patients with MPN were more likely to have a history of heart failure and less likely to have a history of coronary artery disease compared with patients without MPN. Patients with MPN were less likely to undergo revascularization despite similar rates of STEMI. After propensity score weighting with GBM and multivariable logistic regression, MPN patients had increased risk of MACE, arterial thrombosis, VTE and bleeding (Figure). Conclusions: Among patients hospitalized with AMI, those with MPN are at increased risk of MACE compared with patients without MPN. Revascularization is less utilized in patients with MPN. More investigation is needed in order to improve post-AMI outcomes in patients with MPN.

Abstract 12596: Comparison of the Efficacy and Safety of Direct Oral Anticoagulants With Vitamin K Antagonists in Patients With Thrombotic Antiphospholipid Syndrome: Systematic Review and Meta-analysis of Randomized Clinical Trials

Introduction: The efficacy and safety of direct oral anticoagulants (DOACs) as treatment alternatives for patients with thrombotic antiphospholipid syndrome (APS) remain controversial. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared the efficacy and safety of DOACs with vitamin-K antagonists (VKAs) in patients with thrombotic APS. We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials through April 9, 2022. Main efficacy outcomes were a composite of arterial thrombotic events, and a composite of venous thromboembolic events (VTE). The main safety outcome was major bleeding according to the International Society on Thrombosis and Hemostasis (ISTH) criteria. A random effects model with inverse variance was used for the primary analysis. Risk of bias was assessed using the Cochrane Collaboration criteria. Results: Our search retrieved 253 studies. Four RCTs involving 474 patients were included (Figure). All four RCTs were open-label but had proper random sequence generation and adequate allocation concealment. The DOACs used were rivaroxaban (3 trials) and apixaban (1 trial). The mean percent time in therapeutic range in the warfarin arm among the four studies was 60%. Overall, use of DOACs compared with VKAs was associated with increased odds of composite of arterial thrombotic events (OR 5.64, 95% confidence interval [CI] 1.96-16.27, p =0.001, I 2 = 0%). The odds of subsequent VTE events (OR 1.19, 95% CI 0.31-4.53, p =0.80, I 2 = 0%), or major bleeding (OR 1.02, 95% CI 0.42-2.47, p =0.97, I 2 = 0%) were not significantly different between the two groups. Conclusions: Patients with thrombotic APS randomized to DOACs compared to VKAs appear to have increased risk for arterial thrombosis. No significant differences were observed between patients randomized to DOACs vs VKAs in the risk of subsequent VTE or major bleeding.

Direct Oral Anticoagulants vs Vitamin K Antagonists in Patients With Antiphospholipid Syndromes: Meta-Analysis of Randomized Trials

BackgroundThe efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome remain controversial. ObjectivesThe authors performed a systematic review and meta-analysis of randomized controlled trials that compared DOACs with vitamin K antagonists (VKAs). MethodsWe searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through April 9, 2022. The 2 main efficacy outcomes were a composite of arterial thrombotic events and venous thromboembolic events (VTEs). The main safety outcome was major bleeding. Random effects models with inverse variance were used. ResultsOur search retrieved 253 studies. Four open-label randomized controlled trials involving 472 patients were included (mean control-arm time-in-therapeutic-range 60%). All had proper random sequence generation and adequate allocation concealment. Overall, the use of DOACs compared with VKAs was associated with increased odds of subsequent arterial thrombotic events (OR: 5.43; 95% CI: 1.87-15.75; P < 0.001, I2 = 0%), especially stroke, and the composite of arterial thrombotic events or VTE (OR: 4.46; 95% CI: 1.12-17.84; P = 0.03, I2 = 0%). The odds of subsequent VTE (OR: 1.20; 95% CI: 0.31-4.55; P = 0.79, I2 = 0%), or major bleeding (OR: 1.02; 95% CI: 0.42-2.47; P = 0.97; I2 = 0%) were not significantly different between the 2 groups. Most findings were consistent within subgroups. ConclusionsPatients with thrombotic antiphospholipid syndrome randomized to DOACs compared with VKAs appear to have increased risk for arterial thrombosis. No significant differences were observed between patients randomized to DOACs vs VKAs in the risk of subsequent VTE or major bleeding.

Predictors of increased risk of adverse cardiovascular outcomes among patients with myeloproliferative neoplasms and atrial fibrillation

BackgroundPatients with myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), have increased risk of cardiovascular (CV) disease. Atrial fibrillation (AF) is associated with adverse CV outcomes including arterial thrombosis, heart failure (HF), and CV death and coexists with MPN. Traditional risk scores (CHA2DS2-VASC and HAS-BLED) for estimating risks/benefits of anticoagulation to prevent thrombotic events in AF do not include MPN status. Therefore, we aimed to investigate CV outcomes in patients with MPN and AF and evaluate the predictive ability of traditional risk scores. MethodsWe conducted a single-center, retrospective cohort study of patients with MPN and AF. Primary outcome was composite of CV death and arterial thromboembolism; secondary outcomes were bleeding requiring emergency department visit or hospitalization, hospitalization for HF, and all-cause death. Multivariable competing-risk and Cox proportional hazards regression models were used to estimate risk of outcomes. Receiver operating characteristic (ROC) curve used to evaluate predictive ability of CHA2DS2-VASC and HAS-BLED of composite outcome and bleeding, respectively. ResultsA total 142 patients was included (62 ET, 54 PV, 26 MF). Composite outcome, bleeding, HF hospitalization and all-cause death occurred in 39 %, 30 %, 34 %, and 48 %, of patients respectively. After multivariable modeling, MF was associated with increased risk of composite outcome (SHR 2.70, 95 % CI 1.38–5.27) and all-cause mortality (HR 9.77, 95 % CI 4.88–19.54) but not bleeding (SHR 1.19, 95 % CI 0.51–2.80) or HF admissions (SHR 0.57, 95 % CI 0.19–1.72). CHA2DS2-VASC and HAS-BLED were poor predictors of composite outcome (C-statistic 0.52, 95 % CI 0.43–0.62) and bleeding (C-statistic 0.49, 95 % CI 0.40–0.58), respectively. ConclusionIn patients with MPN and AF, MF is associated with increased risk of CV death and arterial thrombosis and traditional risk scores do not accurately predict outcomes in this patient population. Further investigation is needed to refine risk scores in this patient population.

Optimal thromboprophylaxis and anticoagulant strategies in patients with COVID-19 pneumonia. The PROTHROMCOVID Trial

Abstract Introduction Hospitalized patients with COVID-19 are at increased risk of venous and arterial thrombosis, ARDS, and death. The optimal dosage of thromboprophylaxis in patients is unknown. Objective To evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia. Design, Setting, and Participants: The PROTHROMCOVID multicenter randomized clinical trial enrolled noncritical hospitalized adult patients with COVID-19 pneumonia from February 1, 2021, to September 30, 2021, at 18 centers in Spain. Methods Patients were randomized to prophylactic tinzaparin 4500IU or intermediate dose 100IU/kg or therapeutic tinzaparin 175IU/kg during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge. The patients were stratified at the time of randomization according to age, sex and the presence or absence of hypertension.The primary efficacy outcome was a composite endpoint of symptomatic systemic thrombotic events, need for invasive or non invasive mechanical ventilation or not, including high-flow nasal cannula oxygen, or death within 30 days. The main safety outcome was major bleeding at 30 days. Data were collected and adjudicated locally by non-blinded investigators through imaging, laboratory, and health record data. Results Of 311 patients randomized, 300 were included in the analysis (mean [SD]age, 56.7 [14.6] years; men, 182 [60.7%]; women, 118 [39.3%]). 106 patients (35.33%) were assigned to the prophylaxis group, 91 patients (30.33%) were allocated to the intermediate dose group and 103 patients (34.33%) were randomized to the anticoagulant dose group. The composite endpoint thrombotic event, need for invasive (IMV) or noninvasive mechanical ventilation (NIV) or HFT via nasal cannula or death at 30 days from randomization occurred in 58 patients (19.3%) of the whole population, 19 patients (17.09%) in prophylactic group, 20 (21.98%) in intermediate group and 19 (18.45%) in therapeutic group (P=0.72). No major bleeding were reported in the trial and non-major bleeding occurred in 5 patients (4.71%) in prophilactic, in 3 patients (3.2%) in intermediate arm and in 3 patients (2.9%) in therapeutic, without significant differences in each group (P=0.31). Conclusions In non-critically ill patients with COVID 19, intermediate or full-dose of tinzaparin do not appear to offer benefit over standard prophylactic doses IU in the likelihood of thrombotic event, non-invasive ventilation or high-flow oxygen, or death. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Leo Pharma

Antiphospholipid Antibodies in Pregnancy: Maternal and Neonatal Implications.

Antiphospholipid antibodies (aPL Abs) have long been associated with the occurrence of certain specific pregnancy morbidities, affecting both mother and fetus. Antithrombotic-based prophylactic regimens are the standard of care. Their intensity is modulated by the thrombotic history and has greatly improved the prognosis related to spontaneous morbidity. Observational studies show that this treatment is still associated with the persistence of excess of late-pregnancy placental diseases, calling for new or complementary developments, yet to be validated. Rigorous prospective multicentric validation of clinical and laboratory parameters capable of identifying those women and fetuses at a risk of pejorative evolution, thus early prognosis, is a priority issue. These will make it possible to develop customized treatments and test them. Furthermore, there are still concerns, particularly neurodevelopmental ones, about children born to aPL Ab-positive mothers, and clarification based on regular, more systematic evaluations is required. Even after pregnancy, women with a pure obstetrical antiphospholipid syndrome are at a greater risk of venous and arterial thrombosis over time, and prevention needs to be improved. These women also appear to develop more psychiatric and mood disorders. Central nervous system imaging using high-resolution techniques has shown subtle impairments in the white matter, associated with the most pathogenic aPL Abs and the clinical significance of this is under investigation. These mothers also seem to develop an excess of cancers. The systemic impact of aPL Abs is gradually being suspected, although this requires further evidence, and prevention should be envisaged.

Simultaneous Pulmonary Embolism and Carotid Thrombosis as a Presenting Manifestation of COVID-19

Although COVID-19 was initially described predominantly as a respiratory infection, subsequent reports noted that it can produce generalised inflammation with effects on multiple organ systems. As a result, it is possible for patients with COVID-19, including those with severe disease, to present initially with nonrespiratory signs and symptoms. Neurological manifestations, including ischaemic stroke, may be the first presenting issue and can result from carotid thrombosis. Similarly, the risk of both arterial and venous thrombosis is increased in COVID-19, which may result from hypercoagulability associated with systemic inflammation.

Preadmission Oral Anticoagulation for Atrial Fibrillation/Flutter and Death or Thrombotic Events During COVID-19 Admission

Atrial fibrillation/flutter (AF) and COVID-19 are associated with an elevated risk of arterial and venous thrombosis. Whether preadmission oral anticoagulation (OAC) for AF reduces the incidence of in-hospital death or thrombotic events among patients with COVID-19 is unknown. We identified 630 patients with pre-existing AF and a hospitalization diagnosis of COVID-19 and stratified them according to preadmission OAC use. Multivariable logistic regression was employed to relate preadmission OAC to composite in-hospital mortality or thrombotic events. Unadjusted composite in-hospital mortality or thrombotic complications occurred less often in those on than not on preadmission OAC (27.1% vs 46.8%, p <0.001). After adjustment, the incidence of composite in-hospital all-cause mortality or thrombotic complications remained lower with preadmission OAC (odds ratio 0.37, confidence interval 0.25 to 0.53, p <0.0001). Secondary outcomes including all-cause mortality (16.3% vs 24.9%, p = 0.007), intensive care unit admission (14.7% vs 29.0%, p <0.001), intubation (6.4% vs 18.6%, p <0.001), and noninvasive ventilation (18.6% vs 27.5%, p = 0.007) occurred less frequently, and length of stay was shorter (6 vs 7 days, p <0.001) in patients on than those not on preadmission OAC. A higher CHA2DS2-VASc score was associated with an increased risk of thrombotic events. In conclusion, among patients with baseline AF who were hospitalized with COVID-19, those on preadmission OAC had lower rates of death, arterial and venous thrombotic events, and less severe COVID-19.

Patients with myeloproliferative neoplasms and COVID‐19 have increased rates of arterial thrombosis

BackgroundBoth coronavirus disease‐2019 (COVID‐19) and myeloproliferative neoplasms (MPNs) are associated with systemic inflammation and risk of thrombosis. Risk of thrombosis in patients with COVID with and without MPNs has not been extensively studied. MethodsRetrospective cohort study of 44 patients with MPNs and 1114 patients without MPNs positive for SARS‐COV‐2. Outcomes were arterial thrombosis (AT), venous thromboembolism (VTE), bleeding, and death. Time‐to‐event analysis was performed using competing risk regression model and Cox proportional hazards. ResultsAT occurred more frequently in patients with MPN (7% vs. 1%, p = 0.03). Rates of VTE (7% vs. 5%, p = 0.73), bleeding (7% vs. 2%, p = 0.06), and death (9% vs. 6%, p = 0.32) were similar. MPN patients were older and had more cardiovascular comorbidities. After time‐to‐event competing‐risk regression adjusting for age, MPN patients had higher risk of AT (subdivision hazards ratio 3.95, 95% CI 1.09–14.39) but not VTE, bleeding, or death. ConclusionsAmong patients with COVID‐19, MPN patients had higher risk of arterial thrombosis but not VTE, bleeding, and death compared with non‐MPN patients. Larger studies are needed to confirm our findings given the limited sample size.

COVID-19-related thrombotic complications experience before and during delta wave.

ObjectiveHypercoagulability and thrombotic complications seen in SARS-CoV-2 patients, as well as the associated pathophysiology, have been reported extensively. However, there is limited information regarding the factors related to this phenomenon and its association with the COVID-19 delta variant.MethodsA retrospective review including patients admitted to a tertiary center with a COVID-19 positive test and at least one acute thrombotic event confirmed by imaging between June 2020 and August 2021 was performed. We compared the rates of thrombotic events in patients with COVID-19 before and during the Delta peak. We also analyzed the association of the thrombotic complications with demographic characteristics, comorbidities, anticoagulation strategies, and prothrombotic markers while describing other complications secondary to COVID-19 infection.ResultsOut of 964 patients admitted with COVID-19 diagnosis, 26.5% (n=256) had a thrombotic event evidenced by ultrasound (US) or computerized tomography (CT) scan. Venous thromboembolism was found in 60% (n=153), arterial thrombosis in 23% (n=60), and both venous and arterial thromboses in 17% (n=17) of the study cohort. Of all patients, 94% were not vaccinated. Delta variant wave patients (DW) had thrombotic episodes in 34.7% (n=50/144) of cases compared to 25% (n=206/820) of non-Delta wave (NDW) patients, posing an estimated risk 1.36 times higher in patients infected with COVID-19 during the DW than NDW. Overall, DW subjects were significantly younger (p<0.001) with lower BMI (p=0.021) compared to NDW patients. Statistical analyses showed African American patients were more likely to have arterial thrombosis compared to the other groups when testing positive for COVID-19 (OR: 1.78 [CI: 1.04 – 3.05], p=0.035), whereas immunosuppressed patients had less risk of arterial thrombosis (OR: 0.38 [CI: 0.15 – 0.96], p=0.042). Female gender (OR: 2.15 [CI: 1.20 – 3.85]. p=0.009) and patients with active malignancy (OR: 5.99 [CI: 2.14 – 16.78]. p=0.001) had an increased risk of having multiple thrombotic events at different locations secondary to COVID-19.ConclusionCOVID-19 infection is associated with elevated rates of thrombotic complications and an especially higher risk in patients infected during the Delta variant peak. We highlight the importance of vaccination and the development of new anticoagulation strategies for COVID-19 patients with additional hypercoagulable risk factors to prevent thrombotic complications caused by this disease.

Modeling of Competitive Flow in Aortofemoral Bypass

Competitive flow places surgical bypasses at risk for thrombosis in certain vascular beds, such as coronary bypass. However, the anatomic configurations that may lead to flow stagnation in aortofemoral bypass remain poorly characterized. We aimed to model competitive flow and determine parameters placing bypass patency at risk. We created an aortofemoral bypass flow dynamics computer model using MATLAB software (MathWorks). Our standard model (Fig 1) included a native iliac artery of 8 mm diameter with patent superficial femoral artery (SFA, 6 mm) and profunda femoris artery (4 mm) outflow and bypass conduit (8 mm) positioned over the profunda femoris artery. Models included native iliac stenosis ranging from 0% to 100% across four time points throughout the arterial impulse cycle. Sensitivity analyses were performed for SFA and profunda femoris arterial occlusion as well as varying arterial and graft diameters. We created a total of 40 models. Fig 2 shows our base model with increasing severity of stenosis. As the severity of native iliac stenosis increases, the arterial impulse in the graft arrives more briskly. With little or no native iliac stenosis, the arterial impulse in the graft limb is delayed, but stagnation of flow does not occur as shown by the aqua coloration moving through the graft limb across time points. Sensitivity analyses demonstrated similar findings. No model demonstrated stagnation of flow portending high risk of bypass graft or native arterial thrombosis. Computer modeling did not demonstrate flow stagnation in aortofemoral bypass across a range of anatomic configurations. Our models suggest that competitive flow of a native iliac artery may not put the bypass graft at risk of flow stagnation and thrombosis.Fig 2Flow dynamics of aortofemoral bypass overlying the profunda femoris artery with increasing stenosis of the native iliac inflow artery across four time points of arterial impulse.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The Mysterious Risk of Arterial Thrombosis With COVID-19: A Case Series and Systematic Review of Acute Limb Ischaemia.

Introduction: Coronavirus disease 2019 (COVID-19) generates a cytokine storm that predisposes patients to systemic complications including arterial thrombosis (AT) and acute limb ischaemia (ALI). This study reviews our understanding of the incidence and outcomes of patients with COVID-19 who develop AT.Methods: The case notes of all emergency patients with COVID-19 referred to the vascular services between March 2020 and March 2021 were reviewed. The study was undertaken to measure 30-day outcomes. Additionally, a literature search was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using the following search terms: acute limb ischaemia OR arterial thrombosis OR thrombectomy OR embolectomy AND COVID-19.Results: During March 2020 and March 2021, 60,000 people tested positive for COVID-19 in Norfolk. A total of 33 patients were referred to the vascular services, of which 15 had AT (estimated incidence of 0.03%). Of AT patients, 93% had ALI. Fourteen locations of AT were identified. Of ATs, 36% were infrainguinal. The 30-day mortality was 60%. Three patients underwent surgery: two embolectomies (one requiring subsequent below-knee amputation (BKA) and the other died) and one primary BKA requiring subsequent above-knee amputation. The 30-day amputation-free survival (AFS) rate was 29%. The literature search identified 361 studies prior to a thorough full-text review. Nine case series were included with more than 10 participants each. The incidence of AT was reported as high as 15%. In-hospital mortality was 40%, with a significant proportion undergoing amputation or palliative care. Approximately a third of patients undergoing revascularisation subsequently re-occluded. AFS remained as low as 25%.Conclusion: The incidence of AT within the vascular surgery territory in COVID-19 patients is low; however, it is associated with poor 30-day AFS. A computed tomography angiography protocol including the entire major vessels may be indicated in COVID-19 patients.

Risk of arterial and venous thromboses after COVID-19

Risk of arterial and venous thromboses after COVID-19

The association between whole blood viscosity and high thrombus burden in patients with non-ST elevation myocardial infarction.

Prior studies showed that patients with elevated whole blood viscosity (WBV) had a higher risk of arterial thrombosis, acute stent thrombosis, and left ventricular apical thrombus presence after acute coronary syndrome. This investigation aimed to determine the association between WBV and high thrombus burden (HTB) in non-ST elevation myocardial infarction (NSTEMI) patients treated with percutaneous coronary intervention (PCI). This retrospective cohort investigation included data from consecutive 290 NSTEMI patients who received PCI at a tertiary institution. Patients with grade 1-3 thrombus burden were categorized as having low thrombus burden (LTB) (n = 178), whereas those with grade 4-5 thrombus burden were classified as having HTB (n = 112). WBV at high shear rate (HSR) and low shear rate (LSR) were estimated using hematocrit (HTC) and total protein levels. Patients with HTB had higher WBV at both LSR and HSR. In HTB patients, the frequency of infarct-related artery (IRA) reference vessel diameter, distal embolization, and no-reflow was also higher. Multivariable logistic regression models indicated that WBV at LSR (odds ratio [OR], 1.028; 95% confidence interval [CI], 1.014-1.043; P < 0.001) and HSR (OR, 1.606; 95% CI, 1.334-1.953; P < 0.001) were independent predictors of HTB in NSTEMI patients. Notably, the area under the curve value of WBV at both shear rates was greater than that of its components, including total protein and HTC. This is the first study showing that WBV at both shear rates is a significant predictor of HTB in NSTEMI patients.

Association of Genetic Variability in Selected Genes with Platelet Hyperaggregability and Arterial Thrombosis

Abstract Introduction: Inherited platelet hyperaggregability, so called “Sticky platelet syndrome” (SPS), is a prothrombotic platelet disorder. The syndrome contributes more often to arterial than venous thrombosis. The most common localization of arterial occlusion involves cerebral or coronary arteries. However, SPS may also lead to thrombosis in the atypical sites of the circulation. This qualitative platelet alteration causes platelet hyperaggregability after a very low concentration of platelet inducers – adenosine diphosphate (ADP) and/or epinephrine (EPI). The precise genetic background of the syndrome has not been defined. In the present study we aimed to determine the association between selected single nucleotide polymorphisms (SNPs) within genes for platelet endothelial aggregation receptor 1 (PEAR1) and murine retrovirus integration site 1 (MRVI1) and the risk for arterial thrombosis in patients with SPS. The products of these selected genes play an important role in platelet aggregation. Patients and methods: We examined 69 patients with SPS and a history of arterial thrombosis and 69 healthy blood donors who served as controls. SPS was confirmed by a light transmission aggregometry (LTA) according to the method and criteria described by Mammen and Bick. We assessed two SNPs within PEAR1 gene (rs12041331, rs1256888) and two SNPs within MRVI1 gene (rs1874445, rs7940646). Results: Selected PEAR1 and MRVI1 polymorphisms seem not to be a risk factor for the development of SPS as the syndrome with an arterial thrombosis phenotype. However, in the subgroup of SPS1 patients there was found a decreased frequency of the minor A allele of SNP rs12041331 in PEAR1 gene (borderline p value, p=0.061) that can be hypothesized as protective against arterial thrombosis. In the same SPS1 subgroup the haplotype TA in PEAR1 gene also showed a decreased frequency with a borderline insignificance (p=0.056). We can theorize also about its protective role in SPS1 patients. We did not confirm the protective effect of polymorphism (T/T of rs 12566888) in PEAR1 against arterial thrombosis in SPS patients and SPS subgroups. Conclusion: Our results support the idea that examined genetic variability of the selected SNPs in PEAR1 and MRVI1 genes is not associated with platelet hyperaggregability manifested as arterial thrombosis. The possible protective role of the minor A allele of SNP rs12041331 as well as a role of haplotype TA in PEAR1 gene related to the arterial thrombosis found in the subgroup of SPS1 patients needs to be verified in further research.

JAK2V617F Is a Risk Factor for TIA/Stroke in Young Patients.

The objective of this study was to assess the risk of arterial thrombosis in patients who harbor the JAK2V617F allele burden ≥1% detected during workup for myeloproliferative neoplasms (MPNs). We conducted a large cross-sectional analysis consisted of 5,220 patients who were tested for JAK2V617F and 1,047,258 people matched in age from health care insurance provider, taking into account age, sex, hypertension, diabetes, atrial fibrillation. Compared with noncarriers, mutation carriers were older, less likely to be current or past smokers and had lower body mass index. There was no significant difference between the groups regarding myocardial infarction and peripheral vascular disease. However, JAK2V617F ≥1% at age 34 to 54 years was associated with eightfold more likely to have transient ischemic attack (TIA)/stroke history unrelated to hypertension, diabetes, or atrial fibrillation. Association of JAK2V617F with TIA/stroke was also observed in the older age group, albeit a weaker association and not statistically significant. Prevalence of TIA/stroke was higher in patients with JAK2V617F negative, with odds ratio of 3.93 when compared with the general population after confounder adjustments. Further research is warranted to verify the relation between allele burden of JAK2V617F mutation and TIA/stroke and the role of JAK2V617F per se as a risk factor for arterial thrombosis in the absence of overt MPN. Also, consideration should be paid to the screened group with JAK2V617F negative due to the high incidence of TIA/stroke among them in comparison to the general population.

Previously undiagnosed cancer in patients with arterial thrombotic events – A population‐based cohort study

BackgroundEmerging data suggest increased arterial thrombosis risk in the months preceding a cancer diagnosis. ObjectivesTo assess whether patients without documented vascular risk factors or pre‐existing cardiovascular disease have a higher relative risk of cancer 12 months after arterial thrombotic events (ATE), compared to unselected patients. Patients/MethodsA population‐based cohort study of Clalit Health Services (CHS) database included CHS members ≥25 years without prior cancer or ATE (n = 2 804 584). An iterative matching process selected 10 potential controls chronologically for each consecutive exposed, age‐ and sex‐matched (actual controls drawn 1:1 from a lot). Study exposure, ATE, was defined as ischemic stroke, transient ischemic attack, myocardial infarction or systemic arterial thromboembolism during hospitalization. The outcome was newly‐diagnosed cancer within 12 months, based on Israeli national cancer registry. Cox proportional hazards multivariate regression calculated hazard ratio (HR) for outcomes, adjusted for cancer risk factors. Analysis also performed for three subgroups: age ≤50 years; no cardiovascular risk factors; no prior cardiovascular disease. ResultsThe full ATE and matched control cohorts included 43 108 patients. The 12‐month cumulative incidence of cancer (95% confidence interval) was 0.020 (0.019–0.022) in the ATE cohort and 0.012 (0.011–0.013) in controls, corresponding to an adjusted HR of 1.665 (1.489–1.862). The relative risk of cancer was high in all subgroups up to a HR of 3.754 (1.912–7.372) in patients without cardiovascular risk factors. ConclusionThere is an increased risk of previously undiagnosed cancer at 12 months after ATE, especially in patients without documented vascular risk factors or pre‐existent cardiovascular disease.

Efficacy and safety of increased doses of anticoagulants in COVID-19 patients: a systematic review and meta-analysis

The aim of the study was to evaluate the efficacy and safety of increased doses of anticoagulants in comparison with standard doses in inpatients with COVID-19. Material and methods. A systematic review was carried out in October 2021 using the Pubmed database. The analysis included only randomized clinical trials with ≥200 participants that reported the death rate as the total number of cases or the percentage of patients. The primary outcome was all-cause mortality within the observation period. Additionally, the risk of arterial and venous thrombotic events, major and clinically relevant non-major bleeding was assessed. Results. Searching of Pubmed identified 8,903 references, of which the results of 6 randomized clinical trials (INSPIRATION, 3 platforms study in REMAP-CAP, ACTIV-4a, and ATTACC including stable and unstable patients, RAPID, ACTION and HEP-COVID) with the total of 5,228 patients were included in the final qualitative analysis and quantitative synthesis. Among all the patients, 2,660 received increased doses and 2,568 — standard doses of anticoagulants. The follow-up period varied from 21 to 30 days. The administration of increased doses did not affect the risk of death (OR, 0.95; 95 % CI, 0.73–1.24; I² = 59.14 %), but was associated with a reduced risk of thrombotic events (OR, 0.56; 95 % CI, 0.43–0.73; I² = 24.90 %), and an increased risk of major bleeding (OR, 1.86; 95 % CI, 1.23–2.80; I² = 0.00 %) or clinically relevant non-major bleeding (OR, 3.66; 95 % CI, 1.65–8.10; I² = 0.00 %). Within the sensitivity analysis, similar results were obtained in the subgroups of critically ill or stable patients and individuals with increased D-dimer. The maximal reduction in the risk of thrombotic events was found for the subgroup of patients with increased D-dimer (OR, 0.48; 95 % CI, 0.34–0.70; I² = 36.38 %). Conclusions. The use of increased doses of anticoagulants in inpatients with COVID-19 does not reduce the risk of death. Still, it is associated with a decrease in the risk of arterial and venous thrombosis and an increased risk of major bleeding.

Additional risk factors associated with thrombosis and pregnancy morbidity in a unique cohort of antiphospholipid antibody-positive patients.

Background:Antiphospholipid syndrome (APS) is an autoimmune prothrombotic condition with significant morbidity. The objective of this study was to identify additional clinical and epidemiological risks of arterial thrombosis, venous thrombosis, and pregnancy morbidities in a large cohort of persistent antiphospholipid antibodies (aPLs)-positive carriers.Methods:This was a cross-sectional cohort study of 453 consecutive patients with a documented positive aPL who attended Peking University People's Hospital. Among 453 patients screened, 297 patients had persistent positive aPL. We compared asymptomatic aPL carriers with thrombotic and obstetric APS patients. And the univariate analysis and multivariable logistic regression were used to evaluate the association between different risk factors and APS clinical manifestations. The levels of circulating markers of neutrophil extracellular traps (NETs) (cell-free DNA and citrullinated histone H3 [Cit-H3]) were assessed and compared among aPL-positive carriers with or without autoimmune disease and APS patients.Results:Additional risk factors associated with arterial thrombosis among aPL-positive carriers included: smoking (odds ratio [OR] = 6.137, 95% confidence interval [CI] = 2.408–15.637, P = 0.0001), hypertension (OR = 2.368, 95% CI = 1.249–4.491, P = 0.008), and the presence of underlying autoimmune disease (OR = 4.401, 95% CI = 2.387–8.113, P < 0.001). Additional risks associated with venous thrombosis among aPL carriers included: smoking (OR = 4.594, 95% CI = 1.681–12.553, P = 0.029) and the presence of underlying autoimmune disease (OR = 6.330, 95% CI = 3.355–11.940, P < 0.001). The presence of underlying autoimmune disease (OR = 3.301, 95% CI = 1.407–7.744, P = 0.006) is the additional risk, which demonstrated a significant association with APS pregnancy morbidity. Higher circulating levels of cell-free DNA and Cit-H3 were observed among APS patients and aPL patients with autoimmune diseases compared with those aPL carriers without underlying autoimmune diseases. Furthermore, control neutrophils that are conditioned with APS patients’ sera have more pronounced NET release compared with those treated with aPL carriers’ sera without underlying autoimmune diseases.Conclusion:We identified several potential additional risk factors for APS clinical manifestations among a large cohort of Chinese aPL carriers. Our data may help physicians to risk stratify aPL-positive Asian patients.