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1.
Ann Intern Med ; 177(1): JC11, 2024 01.
Article in English | MEDLINE | ID: mdl-38163369

ABSTRACT

SOURCE CITATION: Villiger R, Juillard P, Darbellay Farhoumand P, et al. Prediction of in-hospital bleeding in acutely ill medical patients: external validation of the IMPROVE bleeding risk score. Thromb Res. 2023;230:37-44. 37634309.


Subject(s)
Hemorrhage , Inpatients , Humans , Risk Factors , Hospitals
2.
Am J Hematol ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816957

ABSTRACT

Prognostication in acute pulmonary embolism (PE) requires reliable markers. While cellular indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) appear promising, their utility in PE prognostication needs further exploration. We utilized data from the RIETE registry and the Loyola University Medical Center (LUMC) to assess the prognostic value of NLR, PLR, and SII in acute PE, using logistic regression models. The primary outcome was 30-day all-cause mortality. We compared their prognostic value versus the simplified Pulmonary Embolism Severity Index (sPESI) alone. We included 10 085 patients from RIETE and 700 from the LUMC. Thirty-day mortality rates were 4.6% and 8.3%, respectively. On multivariable analysis, an elevated NLR (>7.0) was associated with increased mortality (adjusted odds ratio [aOR]: 3.46; 95% CI: 2.60-4.60), outperforming the PLR > 220 (aOR: 2.36; 95% CI: 1.77-3.13), and SII > 1600 (aOR: 2.52; 95% CI: 1.90-3.33). The c-statistic for NLR in patients with low-risk PE was 0.78 (95% CI: 0.69-0.86). Respective numbers were 0.66 (95% CI: 0.63-0.69) and 0.68 (95% CI: 0.59-0.76) for intermediate-risk and high-risk patients. These findings were mirrored in the LUMC cohort. Among 9810 normotensive patients in RIETE, those scoring 0 points in sPESI and with an NLR ≤ 7.0 (35% of the population) displayed superior sensitivity (97.1%; 95% CI: 95.5-98.7) and negative predictive value (99.7%; 95% CI: 99.5-99.8) than sPESI alone (87.1%; 95% CI: 83.9-90.3, and 98.7%; 95% CI: 98.4-99.1, respectively) for 30-day mortality. The NLR is a significant prognostic marker for 30-day mortality in PE patients, especially useful to identify patients with very low-risk PE.

3.
Lancet ; 399(10319): 50-59, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34921756

ABSTRACT

BACKGROUND: Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. METHODS: In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2-3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04662684. FINDINGS: From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2-3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12-0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group. INTERPRETATION: In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. FUNDING: Bayer.


Subject(s)
Aftercare , Blood Coagulation/drug effects , COVID-19/complications , Factor Xa Inhibitors/pharmacology , Factor Xa Inhibitors/therapeutic use , Rivaroxaban/pharmacology , Rivaroxaban/therapeutic use , Venous Thromboembolism/prevention & control , Adult , Aged , Female , Heparin/administration & dosage , Heparin/therapeutic use , Hospitalization , Humans , Male , Middle Aged , Patient Discharge , Treatment Outcome , COVID-19 Drug Treatment
4.
J Healthc Manag ; 68(4): 284-297, 2023.
Article in English | MEDLINE | ID: mdl-37326622

ABSTRACT

GOAL: Readmissions are a significant financial burden for payers. Cardiovascular-related discharges are particularly prone to readmission. Posthospital discharge support can impact patient recovery and probably reduce patient readmissions. This study aimed to address the underlying behavioral and psychosocial factors that can negatively affect patients after discharge. METHODS: The study population was adult patients admitted to the hospital with a cardiovascular diagnosis who had a plan to discharge home. Those who consented to participate were randomized to intervention or control groups on a 1:1 basis. The intervention group received behavioral and emotional support, whereas the control group received usual care. Interventions included motivational interviewing, patient activation, empathetic communication, addressing mental health and substance use, and mindfulness. PRINCIPAL FINDINGS: Observed total readmission costs were significantly lower in the intervention group than in the control group ($1.1 million vs. $2.0 million) as was the observed mean cost per readmitted patient ($44,052 vs. $91,278). The mean expected cost of readmission after adjustment for confounding variables was lower in the intervention group than in the control group ($8,094 vs. $9,882, p = .011). PRACTICAL APPLICATIONS: Readmissions are a costly spend category. In this study, posthospital discharge support addressing the psychosocial factors contributing to patients' readmissions resulted in a lower total cost of care for those with a cardiovascular diagnosis. We describe an intervention that is reproducible and can be scaled broadly through technology to reduce readmission costs.


Subject(s)
Hospitalization , Patient Readmission , Adult , Humans , Patient Discharge , Patient Outcome Assessment
5.
Stroke ; 52(6): e217-e223, 2021 06.
Article in English | MEDLINE | ID: mdl-33902301

ABSTRACT

Background and Purpose: Antiplatelet therapy is key for preventing thrombotic events after transient ischemic attack or ischemic stroke. Although the role of aspirin is well established, there is emerging evidence for the role of short-term dual antiplatelet therapy (DAPT) in preventing recurrent stroke. Methods: We conducted a systematic review and study-level meta-analyses of randomized controlled trials comparing outcomes of early initiation of short-term DAPT (aspirin+P2Y12 inhibitor for up to 3 months) versus aspirin alone in patients with acute stroke or transient ischemic attack. Primary efficacy outcome was risk of recurrent stroke and primary safety outcome was incidence of major bleeding. Secondary outcomes studied were risk of any ischemic stroke, hemorrhagic stroke, major adverse cardiovascular events, and all-cause death. Pooled risk ratios (RRs) and CIs were calculated using a random-effects model. Results: Four trials with a total of 21 459 patients were included. As compared to aspirin alone, DAPT had a lower risk of recurrent stroke (RR, 0.76 [95% CI, 0.68­0.83]; P<0.001; I2=0%) but a higher risk of major bleeding events (RR, 2.22 [95% CI, 1.14­4.34], P=0.02, I2=46.5%). Patients receiving DAPT had a lower risk of major adverse cardiovascular events (RR, 0.76 [95% CI, 0.69­0.84], P<0.001, I2=0%) and recurrent ischemic events (RR, 0.74 [95% CI, 0.67­0.82], P<0.001, I2=0%). Conclusions: As compared to aspirin alone, short-term DAPT within 24 hours of high-risk transient ischemic attack or mild-moderate ischemic stroke reduces the risk of recurrent stroke at the expense of higher risk of major bleeding.


Subject(s)
Aspirin/administration & dosage , Dual Anti-Platelet Therapy/methods , Ischemic Attack, Transient/drug therapy , Platelet Aggregation Inhibitors/administration & dosage , Randomized Controlled Trials as Topic/methods , Stroke/drug therapy , Aspirin/adverse effects , Dual Anti-Platelet Therapy/adverse effects , Hemorrhage/chemically induced , Hemorrhage/diagnosis , Humans , Ischemic Attack, Transient/diagnosis , Platelet Aggregation Inhibitors/adverse effects , Stroke/diagnosis , Time-to-Treatment
6.
Am Heart J ; 242: 115-122, 2021 12.
Article in English | MEDLINE | ID: mdl-34480880

ABSTRACT

BACKGROUND: The devastating Coronavirus disease (COVID-19) pandemic is associated with a high prothrombotic state. It is unclear if the coagulation abnormalities occur because of the direct effect of SARS-CoV-2 or indirectly by the cytokine storm and endothelial damage or by a combination of mechanisms. There is a clear indication of in-hospital pharmacological thromboprophylaxis for every patient with COVID-19 after bleed risk assessment. However, there is much debate regarding the best dosage regimen, and there is no consensus on the role of extended thromboprophylaxis. DESIGN: This study aims to evaluate the safety and efficacy of rivaroxaban 10 mg once daily for 35 ± 4 days versus no intervention after hospital discharge in COVID-19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization. The composite efficacy endpoint is a combination of symptomatic VTE, VTE-related death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35 ± 4 posthospital discharge and symptomatic arterial thromboembolism (myocardial infarction, nonhemorrhagic stroke, major adverse limb events, and cardiovascular death) up to day 35 ± 4 posthospital discharge. The key safety outcome is the incidence of major bleeding according to ISTH criteria. SUMMARY: The MICHELLE trial is expected to provide high-quality evidence around the role of extended thromboprophylaxis in COVID-19 and will help guide medical decisions in clinical practice.1.


Subject(s)
COVID-19/complications , Factor Xa Inhibitors/administration & dosage , Rivaroxaban/administration & dosage , Thrombosis/prevention & control , Adult , Brazil , Drug Administration Schedule , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage/chemically induced , Humans , Male , Prospective Studies , Pulmonary Embolism/etiology , Pulmonary Embolism/prevention & control , Rivaroxaban/adverse effects , Thromboembolism/etiology , Thromboembolism/prevention & control , Thrombosis/etiology , Venous Thrombosis/etiology , Venous Thrombosis/prevention & control
7.
Semin Thromb Hemost ; 47(4): 351-361, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33086403

ABSTRACT

Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). However, limited data exist on patient characteristics, treatments, and outcomes. To describe the clinical characteristics, treatment patterns, and short-term outcomes of patients diagnosed with VTE during hospitalization for COVID-19. This is a prospective multinational study of patients with incident VTE during the course of hospitalization for COVID-19. Data were obtained from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. All-cause mortality, VTE recurrences, and major bleeding during the first 10 days were separately investigated for patients in hospital wards versus those in intensive care units (ICUs). As of May 03, 2020, a total number of 455 patients were diagnosed with VTE (83% pulmonary embolism, 17% isolated deep vein thrombosis) during their hospital stay; 71% were male, the median age was 65 (interquartile range, 55-74) years. Most patients (68%) were hospitalized in medical wards, and 145 in ICUs. Three hundred and seventeen (88%; 95% confidence interval [CI]: 84-91%) patients were receiving thromboprophylaxis at the time of VTE diagnosis. Most patients (88%) received therapeutic low-molecular-weight heparin, and 15 (3.6%) received reperfusion therapies. Among 420 patients with complete 10-day follow-up, 51 (12%; 95% CI: 9.3-15%) died, no patient recurred, and 12 (2.9%; 95% CI: 1.6-4.8%) experienced major bleeding. The 10-day mortality rate was 9.1% (95% CI: 6.1-13%) among patients in hospital wards and 19% (95% CI: 13-26%) among those in ICUs. This study provides characteristics and early outcomes of patients diagnosed with acute VTE during hospitalization for COVID-19. Additional studies are needed to identify the optimal strategies to prevent VTE and to mitigate adverse outcomes associated.


Subject(s)
COVID-19 , Heparin, Low-Molecular-Weight/administration & dosage , Hospital Mortality , Registries , Venous Thromboembolism , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , Female , Follow-Up Studies , Hemorrhage/etiology , Hemorrhage/mortality , Hemorrhage/therapy , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , Venous Thromboembolism/diagnosis , Venous Thromboembolism/etiology , Venous Thromboembolism/mortality , Venous Thromboembolism/therapy
8.
Vasc Med ; 25(3): 210-217, 2020 06.
Article in English | MEDLINE | ID: mdl-32000631

ABSTRACT

Gastric cancer is the fifth most common malignancy worldwide. Venous thromboembolism is an independent predictor of death among patients with gastric cancer. We aimed to describe the factors associated with mortality, thrombosis recurrence, and bleeding complications in patients with gastric cancer who develop venous thromboembolism. We included 612 patients with gastric cancer and venous thromboembolism in the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry from 2001 to 2018. We used Cox proportional hazard ratios and a Fine-Gray model to define factors associated with outcomes. The overall mortality at 6 months was 44.4%. Factors associated with increased 6-month mortality included immobility (HR 1.8, 95% CI 1.3-2.4; p < 0.001), anemia (HR 1.4, 95% CI 1.1-1.8; p < 0.02), and leukocytosis (HR 1.8, 95% CI 1.4-2.3; p < 0.001). Recurrent thrombosis occurred in 6.5% of patients and major bleeding complications in 8.5% of the cohort. Male sex was the main factor associated with thrombosis recurrence (HR 2.1, 95% CI 1.1-4.0; p < 0.02) and hemoglobin below 10 g/dL (HR 1.6, 95% CI 1.05-2.50; p = 0.03) the main factor associated with bleeding. In conclusion, patients with gastric cancer who develop venous thrombosis have a very high likelihood of death. Low hemoglobin in this population is associated with poor outcomes.


Subject(s)
Stomach Neoplasms/epidemiology , Venous Thromboembolism/epidemiology , Aged , Aged, 80 and over , Anemia/blood , Anemia/epidemiology , Biomarkers/blood , Databases, Factual , Female , Hemoglobins/metabolism , Hemorrhage/epidemiology , Humans , Male , Middle Aged , Prognosis , Recurrence , Registries , Risk Assessment , Risk Factors , Stomach Neoplasms/blood , Stomach Neoplasms/mortality , Time Factors , Venous Thromboembolism/blood , Venous Thromboembolism/mortality
9.
Semin Thromb Hemost ; 45(8): 793-801, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31614388

ABSTRACT

Patients with cirrhosis are not only at an increased risk of bleeding but also at risk of venous thromboembolism (VTE). We sought to determine the clinical characteristics, management, and outcomes after VTE in patients with cirrhosis. We used the data from RIETE (Registro Informatizado de la Enfermedad TromboEmbolica), an international registry of patients with VTE, to compare the outcomes in patients with and without cirrhosis. Main outcomes included all-cause mortality, pulmonary embolism (PE)-related mortality, recurrent VTE, and bleeding. Among 43,611 patients with acute VTE, 187 (0.4%) had cirrhosis. Of these, 184 (98.4%) received anticoagulation for a median of 109 days (interquartile range [IQR]: 43-201 days), most commonly with enoxaparin (median dose: 1.77 [IQR: 1.38-2.00] mg/kg/day). Compared with patients without cirrhosis, those with cirrhosis had a higher rate of all-cause mortality (10.7 vs. 3.4%; odds ratio [OR]: 3.41; 95% confidence interval [CI]: 2.03-5.46) and fatal bleeding (2.1 vs. 0.2%; OR: 13.94; 95% CI: 3.65-37.90) but similar rates of fatal PE (0.5 vs. 0.5%; OR: 1.17; 95% CI: 0.03-6.70). Patients with cirrhosis had a higher rate of all-cause mortality per 100 patient-years of follow-up (58.9 vs. 16.0; hazard ratio [HR]: 3.70; 95% CI: 2.69-4.91). One-year hazard ratio of clinically relevant bleeding (HR: 2.86; 95% CI: 1.91-4.27), fatal bleeding (HR: 8.51; 95% CI: 3.5-20.7), or recurrent VTE (HR: 2.08; 95% CI: 1.00-4.36) was higher in patients with cirrhosis. Cirrhosis is a challenging comorbidity in patients with VTE. Most patients were treated with anticoagulation and had an elevated risk of recurrence, similar risk of fatal PE, and a very high risk of bleeding including fatal bleeds.


Subject(s)
Liver Cirrhosis/etiology , Venous Thromboembolism/complications , Aged , Female , Humans , Male , Registries
10.
J Surg Oncol ; 120(3): 494-500, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31222842

ABSTRACT

BACKGROUND AND OBJECTIVES: Pancreatic cancer is strongly associated with thrombosis. We investigated early postoperative venous thromboembolism (PVTE) mortality among patients with pancreatic surgery and compared outcomes in adenocarcinoma pancreatic cancer (ACPC) to non-adenocarcinoma pancreatic neoplasm (NACPN). METHODS: We analyzed a prospectively collected database of patients who underwent pancreatic cancer or neoplasm-related surgery. As NACPN is underrepresented in other studies, we selected NACPN patients and a random sample of ACPC patients. PVTE was defined as VTE occurring within 3 months of surgical intervention. Statistical analysis was performed using Cox proportional hazards regression. RESULTS: A total of 441 pancreatic surgery patients were included, with 331 ACPC and 110 NACPN. Median follow-up was 449 days during which 90 (20.4%) patients developed VTE. PVTE occurred in 53 (12.0%) patients, including 41 (12.4%) ACPC patients and 12 (10.9%) NACPN patients. Those with PVTE had 60% higher mortality rate. A multivariable analysis found that PVTE is an independent predictor of increased mortality (HR Adj, 1.6; 95% CI, 1.1-2.2; P < .01). The mortality impact was not consistent between ACPC (HR, 3.2; 95% CI, 1.3-7.9) and NACPN groups (HR, 1.3; 95% CI, 0.9-1.8). CONCLUSIONS: Postoperative venous thromboembolism is an independent predictor of increased mortality in pancreatic surgery, specifically in adenocarcinoma pancreatic cancer surgery.


Subject(s)
Carcinoma, Pancreatic Ductal/mortality , Pancreatic Neoplasms/mortality , Venous Thromboembolism/mortality , Aged , Carcinoma, Pancreatic Ductal/blood , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/surgery , Cohort Studies , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Postoperative Complications/blood , Postoperative Complications/etiology , Postoperative Complications/mortality , Postoperative Complications/pathology , Prospective Studies , Retrospective Studies , Venous Thromboembolism/pathology , Venous Thromboembolism/physiopathology
11.
Vasc Med ; 24(4): 341-348, 2019 08.
Article in English | MEDLINE | ID: mdl-30915913

ABSTRACT

Venous thromboembolism (VTE) and coronary artery disease are major health issues that cause substantial morbidity and mortality. New data have emerged suggesting that these two conditions could have a close relationship. Thus, we sought to determine the trends in annual rate of VTE occurrence in patients with ST-segment elevation myocardial infarction (STEMI) and measure its impact on in-hospital mortality, bleeding complications, and cost and length of hospitalization. We queried the 2003-2013 Nationwide Inpatient Sample databases to identify adults with primary diagnosis of STEMI. VTE events were then allocated. Inpatient outcomes of patients with VTE were compared to those without VTE. Out of 2,495,757 hospitalizations for STEMI, VTE was diagnosed in 25,149 (1%) hospitalizations. Patients who experienced VTE were older (mean age: 67.5 vs 64.8, p < 0.01) and had a higher proportion of black patients (10.1% vs 7.7%, p < 0.001) and females (40.1% vs 35%, p < 0.001) compared to patients without VTE. There was an increasing trend in the rate of VTE during the study period (2003: 0.8% vs 2013: 1.0%, p < 0.001). Patients with VTE had a prolonged hospitalization (median: 9 vs 3 days, p < 0.001), increased cost, higher risk of gastrointestinal bleeding (OR: 2.13, p < 0.001), intracranial hemorrhage (OR: 2.14, p < 0.001), blood transfusions (OR: 1.94, p < 0.001), and mortality (OR: 1.39, p < 0.001). The rate of VTE occurrence in patients with STEMI in our study was 10 per 1000 admissions. VTE was associated with more bleeding complications, longer hospital stays, higher costs, and mortality. These findings suggest that a more aggressive approach for VTE prophylaxis may be warranted in this population.


Subject(s)
Coronary Artery Disease/therapy , Hospitalization , Inpatients , ST Elevation Myocardial Infarction/therapy , Venous Thromboembolism/epidemiology , Aged , Aged, 80 and over , Coronary Artery Disease/economics , Coronary Artery Disease/mortality , Databases, Factual , Female , Hemorrhage/epidemiology , Hospital Costs , Hospital Mortality , Hospitalization/economics , Hospitalization/trends , Humans , Length of Stay , Male , Middle Aged , Retrospective Studies , Risk Assessment , Risk Factors , ST Elevation Myocardial Infarction/economics , ST Elevation Myocardial Infarction/mortality , Time Factors , Treatment Outcome , United States/epidemiology , Venous Thromboembolism/economics , Venous Thromboembolism/mortality , Venous Thromboembolism/therapy
12.
J Cardiovasc Electrophysiol ; 29(3): 412-420, 2018 03.
Article in English | MEDLINE | ID: mdl-29377394

ABSTRACT

INTRODUCTION: Reticulated platelet (RP) content is increased in nonvalvular atrial fibrillation (NVAF). The purpose of this study was to determine if platelet content, morphology, and RP proportion are modulated by platelet genes. METHODS AND RESULTS: Expression of six platelet-predominate genes impacting platelet formation and release, platelet count, and RP content was assessed in NVAF patients before and 3-4 months after pulmonary veins isolation (PVI) and compared to normal sinus rhythm (NSR) controls. RNA from isolated platelets was reverse-transcribed assayed against selected genes utilizing real-time qPCR, and expressed as mean cycle threshold (ΔCt) using beta-2-microglobulin as endogenous control. RP content was assessed by flow cytometry. A fourfold lower expression of CFL1 gene coding for nonmuscle cofilin (7.8 ± 0.9 vs. 5.7 ± 1.6, P < 0.001) and twofold lower expression of four other genes were associated with similar platelet counts but fourfold higher (28.7+7.0 vs. 6.7+5.4, P < 0.001) RP content (%) in 97 NVAF cases compared to 51 NSR controls. Three to 4 months after PVI, RP decreased by 28%, while CFL1 gene expression increased over twofold but TUBA4A gene expression decreased almost twofold; NFE2 and MYL6 gene expression remained unchanged. CONCLUSIONS: NVAF is associated with notable downregulation of genes directing platelet production and size but increased RP content. PVI impacts the expression of many of these genes, implying a direct relationship between atrial fibrillation and platelet biogenesis.


Subject(s)
Atrial Fibrillation/surgery , Blood Platelets/metabolism , Catheter Ablation , Pulmonary Veins/surgery , Action Potentials , Aged , Atrial Fibrillation/blood , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Blood Platelets/pathology , Case-Control Studies , Catheter Ablation/adverse effects , Cofilin 1/blood , Cofilin 1/genetics , Female , Gene Expression Regulation , Heart Rate , Humans , Male , Membrane Proteins/blood , Membrane Proteins/genetics , Middle Aged , Myosin Light Chains/blood , Myosin Light Chains/genetics , NF-E2 Transcription Factor, p45 Subunit/blood , NF-E2 Transcription Factor, p45 Subunit/genetics , Platelet Count , Pulmonary Veins/physiopathology , Receptors, Progesterone/blood , Receptors, Progesterone/genetics , Time Factors , Treatment Outcome , Tubulin/blood , Tubulin/genetics
13.
Eur J Haematol ; 98(6): 615-621, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28306170

ABSTRACT

AIMS: Platelets retain cytoplasmic messenger RNA and are capable of protein biosynthesis. Several diseases are known to impact the platelet transcriptome but the effect of non-valvular atrial fibrillation (NVAF) on platelet RNA transcript is essentially unknown. The aim of this study was to evaluate the impact of NVAF on platelet RNA transcript by measuring platelet genes expression in consecutive NVAF patients before and 3-4 months after pulmonary vein isolation (PVI) and compared to normal sinus rhythm controls (NSR). METHODS AND RESULTS: RNA from isolated platelets were reverse transcribed, assayed against 15 genes using real-time qPCR, and expressed as mean cycle threshold (ΔCt) using beta-2-microglobulin as endogenous control. Expression of all evaluated genes, except cathepsin A gene, was significantly lower (higher ΔCt) in 103 NVAF patients compared to 55 NSR controls. Insulin-like growth factor binding protein acid labile subunit gene (IGFALS) had expression more than 16 fold-lower (17.0±2.8 vs 12.5±3.8, P<.001), follow by genes encoding for prostacyclin receptor, and for von Willebrand factor which had fourfold lower expression compared to NSR controls. Gender, type of atrial fibrillation, heart failure, hypertension, prior stroke, diabetes mellitus, and atherosclerosis were associated with different gene expression. Following PVI, expression of four genes significantly increased, particularly IGFALS gene (increased 256-fold) and ADAMT gene increased 16-fold); expression of three genes significantly decreased, and expression of eight genes has not changed. CONCLUSIONS: Platelets are capable to respond to the circulatory environment of NVAF by altering transcript and changing prothrombotic status. This shows platelet potential for molecular "reprogramming" possibly induced by flow disturbances of NVAF.


Subject(s)
Atherosclerosis/blood , Atrial Fibrillation/blood , Blood Platelets/metabolism , Diabetes Mellitus/blood , Heart Failure/blood , Hypertension/blood , ADAMTS13 Protein/blood , ADAMTS13 Protein/genetics , Aged , Atherosclerosis/physiopathology , Atherosclerosis/surgery , Atrial Fibrillation/physiopathology , Atrial Fibrillation/surgery , Blood Platelets/pathology , Carrier Proteins/blood , Carrier Proteins/genetics , Case-Control Studies , Diabetes Mellitus/physiopathology , Diabetes Mellitus/surgery , Female , Gene Expression , Glycoproteins/blood , Glycoproteins/genetics , Heart Failure/physiopathology , Heart Failure/surgery , Humans , Hypertension/physiopathology , Hypertension/surgery , Male , Middle Aged , Pulmonary Veins/surgery , Receptors, Epoprostenol/blood , Receptors, Epoprostenol/genetics , Sex Factors , von Willebrand Factor/genetics , von Willebrand Factor/metabolism
14.
Eur Respir J ; 48(5): 1360-1368, 2016 11.
Article in English | MEDLINE | ID: mdl-27660517

ABSTRACT

Current guidelines suggest treating cancer patients with incidental pulmonary embolism comparably to patients with symptomatic pulmonary embolism.We used the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry to compare the rate of major bleeding and symptomatic pulmonary embolism during the course of anticoagulation and after its discontinuation in cancer patients with incidental pulmonary embolism.As of March 2016, 715 cancer patients with incidental pulmonary embolism had been enrolled in RIETE. During the course of anticoagulant therapy (mean 235 days), the rate of major bleeding was higher than the rate of symptomatic pulmonary embolism (10.1 (95% CI 7.48-13.4) versus 3.17 (95% CI 1.80-5.19) events per 100 patient-years, respectively), and the rate of fatal bleeding was higher than the rate of fatal pulmonary embolism (2.66 (95% CI 1.44-4.52) versus 0.66 (95% CI 0.17-1.81) deaths per 100 patient-years, respectively). After discontinuing anticoagulation (mean follow-up 117 days), the rate of major bleeding was lower than the rate of symptomatic pulmonary embolism (3.00 (95% CI 1.10-6.65) versus 8.37 (95% CI 4.76-13.7) events per 100 patient-years, respectively); however, there were no differences in the rate of fatal events at one death each.The risk/benefit ratio of anticoagulant therapy in cancer patients with incidental pulmonary embolism is uncertain and must be evaluated in further studies.


Subject(s)
Anticoagulants/therapeutic use , Neoplasms/complications , Neoplasms/drug therapy , Pulmonary Embolism/complications , Pulmonary Embolism/drug therapy , Aged , Anticoagulants/adverse effects , Female , Hemorrhage , Humans , Incidental Findings , Male , Middle Aged , Pulmonary Embolism/prevention & control , Registries , Risk Assessment , Thrombolytic Therapy , Treatment Outcome
15.
Vasc Med ; 21(5): 437-444, 2016 10.
Article in English | MEDLINE | ID: mdl-27155290

ABSTRACT

The aim of this study was to determine if galectin-3 levels were different between participants with peripheral artery disease (PAD) and controls, and to describe its relationship with markers of early atherosclerosis. Sixty participants were recruited into two groups: a PAD group (n=31), ankle-brachial index (ABI) ⩽0.90 and a normal ABI group (n=29), ABI 1.0-1.4. PAD participants were older (68.6 vs 61.8 years, p=0.037), more commonly men (68% vs 38%, p=0.02), and with more cardiovascular risk factors (p<0.001). Galectin-3 was 22% higher in PAD participants (mean±SD: 17.6±4.7 vs 14.4±4.1 ng/mL, p<0.01). The odds ratio for galectin-3 in PAD to be 1 ng/mL higher than the participants with normal ABI was 1.19, after adjusting by age and gender (p=0.014). High-sensitivity C-reactive protein (hs-CRP) and homeostatic model assessment (HOMA) were positively associated with galectin-3 in the age- and gender-adjusted model, while arterial elasticity and microalbuminuria were not. In conclusion, galectin-3 levels were higher in participants with PAD.


Subject(s)
Ankle Brachial Index , Galectin 3/blood , Peripheral Arterial Disease/blood , Age Factors , Aged , Aged, 80 and over , Biomarkers/blood , Blood Proteins , C-Reactive Protein/analysis , Case-Control Studies , Female , Fibrosis , Galectins , Humans , Insulin Resistance , Linear Models , Logistic Models , Male , Middle Aged , Odds Ratio , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/physiopathology , Predictive Value of Tests , Risk Factors , Sex Factors , Up-Regulation , Vascular Stiffness
16.
Stroke ; 46(6): 1525-32, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25953368

ABSTRACT

BACKGROUND AND PURPOSE: It is not known whether racial or ethnic disparities observed with other revascularization procedures are also seen with carotid artery stenting (CAS) and endarterectomy (CEA). METHODS: We compared the utilization and outcomes of CAS and CEA across racial/ethnic groups within the CARE Registry between May 2007 and December 2012. RESULTS: Between 2007 and 2012, of the 13 129 patients who underwent CAS, majority were non-Hispanic whites (89.3%), followed by blacks (4.4%), Hispanics (4.3%), and other groups (2.0%). A similar distribution was observed among the 10 953 patients undergoing CEA (non-Hispanic whites, 92.6%; blacks, 3.5%; Hispanics, 2.8%; and other groups, 1.1%). During this time period, a trend toward proportionate increase in CAS utilization was observed in non-Hispanic whites and other groups, whereas the opposite was observed among Hispanics and blacks. This trend persisted even when hospitals performing both CAS and CEA were exclusively analyzed. Adherence to antiplatelet and statin therapy was significantly lower among blacks post CEA. In-hospital major adverse cardiac and cerebrovascular events remained comparable across groups post CAS and CEA. At 30 days, the incidence of stroke (7.2%) and major adverse cardiac and cerebrovascular events (8.8%) was higher among blacks post CEA (P<0.05), after risk adjustment. CONCLUSION: During the study period, utilization of CAS and CEA was highest among non-Hispanic whites. There was a trend toward increased CAS utilization over time among non-Hispanic whites and other groups, and a trend toward increased CEA utilization among Hispanics and blacks. In-hospital major adverse cardiac and cerebrovascular events remained comparable between groups, whereas 30-day major adverse cardiac and cerebrovascular events were significantly higher in blacks.


Subject(s)
Black or African American , Cerebral Revascularization/adverse effects , Endarterectomy, Carotid/adverse effects , Heart Diseases , Hispanic or Latino , Registries , Stroke , White People , Adult , Aged , Aged, 80 and over , Female , Heart Diseases/epidemiology , Heart Diseases/ethnology , Heart Diseases/etiology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Incidence , Male , Medication Adherence , Middle Aged , Platelet Aggregation Inhibitors/administration & dosage , Stents , Stroke/epidemiology , Stroke/ethnology , Stroke/etiology , United States
17.
Catheter Cardiovasc Interv ; 86(7): 1219-27, 2015 Dec 01.
Article in English | MEDLINE | ID: mdl-26308961

ABSTRACT

OBJECTIVE: The aim of the study was to assess the utilization of catheter-directed thrombolysis (CDT) and its comparative effectiveness against systemic thrombolysis in acute pulmonary embolism (PE). BACKGROUND: Contemporary real world data regarding utilization and outcomes comparing systemic thrombolysis with CDT for PE is sparse. METHODS: We queried the Nationwide Inpatient Sample from 2010 to 2012 using the ICD-9-CM diagnosis code 415.11, 415.13, and 415.19 for acute PE. We used propensity score analysis to compare outcomes between systemic thrombolysis and CDT. Primary outcome was in-hospital mortality. Secondary outcome was combined in-hospital mortality and intracranial hemorrhage (ICH). RESULTS: Out of 110,731 patients hospitalized with PE, we identified 1,521 patients treated with thrombolysis, of which 1,169 patients received systemic thrombolysis and 352 patients received CDT. After propensity-matched comparison, primary and secondary outcomes were significantly lower in the CDT group compared to systemic thrombolysis (21.81% vs. 13.36%, OR 0.55, 95% CI 0.36-0.85, P value = 0.007) and (22.89% vs. 13.36%, OR 0.52, 95% CI 0.34-0.80, P value = 0.003), respectively. The median length of stay [7 days, interquartile range (IQR) (5-9 days) vs. 7 days, IQR (5-10 days), P = 0.17] was not significant between the two groups. The CDT group had higher cost of hospitalization [$17,218, IQR ($12,272-$23,906) vs. $23,799, IQR ($17,892-$35,338), P < 0.001]. Multivariate analysis identified increasing age, saddle PE, cardiopulmonary arrest, and Medicaid insurance as independent predictors of in-hospital mortality. CONCLUSIONS: CDT was associated with lower in-hospital mortality and combined in-hospital mortality and ICH.


Subject(s)
Catheterization, Swan-Ganz , Fibrinolytic Agents/administration & dosage , Practice Patterns, Physicians' , Pulmonary Embolism/drug therapy , Thrombolytic Therapy/methods , Adult , Aged , Catheterization, Swan-Ganz/adverse effects , Catheterization, Swan-Ganz/mortality , Catheterization, Swan-Ganz/statistics & numerical data , Catheterization, Swan-Ganz/trends , Chi-Square Distribution , Databases, Factual , Female , Fibrinolytic Agents/adverse effects , Hospital Mortality , Humans , Intracranial Hemorrhages/chemically induced , Logistic Models , Male , Medicaid , Medicare , Middle Aged , Multivariate Analysis , Odds Ratio , Practice Patterns, Physicians'/trends , Propensity Score , Pulmonary Embolism/diagnosis , Pulmonary Embolism/mortality , Risk Factors , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/mortality , Thrombolytic Therapy/statistics & numerical data , Thrombolytic Therapy/trends , Time Factors , Treatment Outcome , United States
18.
Stroke ; 45(10): 2995-3001, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25184360

ABSTRACT

BACKGROUND AND PURPOSE: Coated-platelets, a subset of procoagulant platelets observed on dual agonist stimulation with collagen and thrombin, support a robust prothrombinase activity and provide a unique measure of platelet thrombotic potential. Coated-platelet levels are increased in large artery stroke, and higher levels are associated with early stroke recurrence, suggesting a potential role for risk stratification in asymptomatic patients with carotid artery stenosis. METHODS: Three-hundred twenty-nine consecutive patients with technically adequate carotid Doppler evaluation without stroke or transient ischemic attack (TIA) in the previous 6 months were enrolled as part of a prospective cohort study conducted during a 40-month period. The main outcome was occurrence of stroke or TIA according to coated-platelet levels and internal carotid stenosis severity at enrollment. The optimal cutoff value of coated-platelet levels was determined by recursive partitioning analysis. Event-free survival was estimated using Kaplan-Meier and Cox proportional hazards regression analyses. RESULTS: A cutoff of ≥45% for coated-platelet levels in combination with stenosis≥50% yielded a sensitivity of 0.78 (95% confidence interval, 0.51-1.0), specificity of 0.92 (0.89-0.95), positive predictive value of 0.21 (0.07-0.34), and a negative predictive value of 0.99 (0.98-1.0) for ipsilateral stroke or TIA. The incidence rate of ipsilateral stroke or TIA for patients with ≥50% stenosis and ≥45% coated-platelets was 21.5 per 100 person-years versus 1.27 per 100 person-years for patients with ≥50% stenosis and <45% coated-platelets (P<0.0001). CONCLUSIONS: Coated-platelet levels identify asymptomatic carotid stenosis patients at high risk for stroke or TIA, which suggests a role for coated-platelets in risk stratification before revascularization.


Subject(s)
Blood Platelets/cytology , Carotid Stenosis/complications , Ischemic Attack, Transient/diagnosis , Stroke/diagnosis , Aged , Cohort Studies , Female , Flow Cytometry , Hematologic Tests/methods , Humans , Ischemic Attack, Transient/mortality , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Sensitivity and Specificity , Stroke/mortality
19.
J Thromb Thrombolysis ; 38(2): 241-9, 2014.
Article in English | MEDLINE | ID: mdl-24233387

ABSTRACT

Venous thromboembolism (VTE) is a leading cause of death among outpatient chemotherapy patients. However the VTE preventive measures for outpatients are not widely advocated. We did a meta-analysis to evaluate the outpatient VTE prevention's effectiveness and safety. We searched electronic databases until the end of December 2012 and reviewed the abstracts and manuscripts following the PRISMA guidelines. Occurrence of first VTE event was the efficacy outcome. The safety end point was major bleeding. We calculated Q statistic and a homogeneity formal test. The odds ratio (OR) estimates were pooled by using the Mantel-Haenszel fixed-effects method in the absence of heterogeneity. Data were analyzed using the R META package). We identified 1,485 articles and reviewed 37 articles based on initial screening. The number of patients included in 11 selected trials was 7,805. The odds of VTE was lower in the prophylaxis group (OR 0.56; 95% CI 0.45-0.71) and improved when heparin-based prevention was analyzed (OR 0.53; 95% CI 0.41-0.70). We found strong prevention among patients with lung cancer (OR 0.46; 95% CI 0.29-0.74) and pancreatic cancer (OR 0.33; 95% CI 0.16-0.67). Major bleeding events were frequent in the intervention group (OR 1.65; 95% CI 1.12-2.44). Thromboprophylaxis reduced VTE episodes. The VTE events were reduced by 47% in heparin-based prophylaxis trials compared to placebo. The patients receiving heparin-based prophylaxis had a 60% increase in bleeding events. Improving risk stratification tools to personalize prevention strategies may enhance the VTE prevention applicability in cancer patients.


Subject(s)
Neoplasms/therapy , Venous Thromboembolism/prevention & control , Female , Humans , Male , Neoplasms/epidemiology , Randomized Controlled Trials as Topic , Risk Factors , Venous Thromboembolism/epidemiology
20.
J Thromb Haemost ; 22(3): 613-619, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38184204

ABSTRACT

Pulmonary embolism (PE) is a leading preventable cause of death in surgical patients, and rates of fatal PE are increasing. Individual assessment, to balance the risks of thrombosis and bleeding, is the key to providing appropriate prophylaxis. The risk assessment process includes use of evidence-based guidelines, literature published since the latest guidelines, large registries, and risk scoring systems together with clinical experience and judgment. Risk assessment is a dynamic process and needs to be updated both during the hospital stay and just prior to discharge since clinical events may change the level of risk. The final assessment may identify patients who require ongoing anticoagulant prophylaxis after discharge. The Caprini risk score is widely used in surgical patients and is a composite of the number of risk factors and their relative weights. The Caprini risk score set point for risk levels requiring anticoagulant prophylaxis varies depending on the type of surgical procedure, surgical population, and number of risk factors. Mandatory implementation of evidence-based care pathways is helpful in lowering PE-related mortality. This review presents several challenging cases, emphasizing the importance of employing all available assessment tools, including dynamic assessment of risk during hospitalization. Finally, the limitations of evidence-based guidelines in complex scenarios and the need to employ all available tools to properly protect very high-risk patients are emphasized.


Subject(s)
Pulmonary Embolism , Thrombosis , Venous Thromboembolism , Humans , Anticoagulants/adverse effects , Venous Thromboembolism/epidemiology , Pulmonary Embolism/etiology , Pulmonary Embolism/prevention & control , Pulmonary Embolism/drug therapy , Thrombosis/drug therapy , Risk Assessment , Risk Factors
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