Identification Of Venous Thromboembolism Research Articles

Cohort study of prediction of venous thromboembolism in emergency department patients with extremity symptoms.

Despite diagnostic algorithms, identification of venous thromboembolism (VTE) in emergency departments (ED) remains a challenge. We evaluated symptoms, background, and laboratory data in 27,647 ED patients presenting with pain, swelling, or other symptoms from the extremities, and identified predictors of VTE diagnosis within one year. Predictors of a clinical decision to perform phlebography, ultrasound, or computer tomography (CT) angiography of pelvic, lower, or upper extremity veins, CT of pulmonary arteries, or pulmonary scintigraphy at the ED or within 30days, and the results of such investigations were also evaluated. A total of 3195 patients (11.6%) were diagnosed with VTE within one year. In adjusted analysis of patients in whom all laboratory data were available, a d-dimer value ≥ 0.5mg/l (odds ratio [OR]: 2.602; 95% confidence interval [CI] 1.894-3.575; p < 0.001) at the ED and a previous diagnosis of VTE (OR: 6.037; CI 4.465-8.162; p < 0.001) independently predicted VTE within one year. Of diagnosed patients, 2355 (73.7%) had undergone imaging within 30days after the ED visit and 1730 (54.1%) were diagnosed at this examination. Lower age (OR: 0.984; CI 0.972-0.997; p = 0.014), higher blood hemoglobin (OR: 1.023; CI 1.010-1.037; p < 0.001), C-reactive protein (OR: 2.229; CI 1.433-3.468; p < 0.001), d-dimer (OR: 8.729; CI 5.614-13.574; p < 0.001), and previous VTE (OR: 7.796; CI 5.193-11.705; p < 0.001) predicted VTE on imaging within 30days, whereas female sex (OR 0.602 [95% CI 0.392-0.924]; p = 0.020) and a previous diagnosis of ischemic heart disease (OR 0.254 [95% CI 0.113-0.571]; p = 0.001) were negative predictors of VTE. In conclusion, analysis of 27,647 ED patients with extremity symptoms confirmed the importance of well-established risk factors for VTE. Many patients developing VTE within one year had initial negative imaging, highlighting the importance of continued symptom vigilance.

Design and validation of algorithms to identify venous thromboembolism in the French National Healthcare Database.

This paper aims to introduce an algorithm designed to identify Venous Thromboembolism (VTE) in the French National Healthcare Database (SNDS) and to estimate its positive predictive value. A case-identifying algorithm was designed using SNDS inpatient and outpatient encounters, including hospital stays with discharge diagnoses, imaging procedures and drugs dispensed, of French patients aged at least 18 years old to whom baricitinib or Tumor Necrosis Factor Inhibitors (TNFi) were dispensed between September 1, 2017, and December 31, 2018. An intra-database validation study was then conducted, drawing 150 cases identified as VTE by the algorithm and requesting four vascular specialists to assess them. Patient profiles used to conduct the case adjudication were reconstituted from de-identified pooled and formatted SNDS data (i.e., reconstituted electronic health records-rEHR) with a 6-month look-back period prior to the supposed VTE onset and a 12-month follow-up period after. The positive predictive value (PPV) with its 95% confidence interval (95% CI) was calculated as the number of expert-confirmed VTE divided by the number of algorithm-identified VTE. The PPV and its 95% CI were then recomputed among the same patient set initially drawn, once the VTE-identifying algorithm was updated based on expert recommendation. For the 150 patients identified with the first VTE-identifying algorithm, the adjudication committee confirmed 92 cases, resulting in a PPV of 61% (95% CI = [54-69]). The final VTE-identifying algorithm including expert suggestions showed a PPV of 92% (95% CI = [86-98]) with a total of 87 algorithm-identified cases, including 80 retrieved from the 92 confirmed by experts. The identification of VTE in the SNDS is possible with a good PPV.

#5401 REAL-WORLD STUDY BETWEEN NEPHROTIC SYNDROME AND VENOUS THROMBOEMBOLISM

Abstract Background and Aims Nephrotic syndrome (NS) is a recognized risk factor of venous thromboembolism (VTE), however, there have been limited comprehensive epidemiologic data on VTE among NS patients. Therefore, we designed our study to assess the epidemiology and clinical correlates of VTE among hospitalized adults with NS in China. Method In this nationwide real-world study of 78,797 hospitalized patients with NS from 18 medical centers across China, VTE was identified by International Classification of Diseases, 10th revision (ICD-10) codes or imagological examinations during hospitalization. Multivariable logistic regression analysis was used to investigate the association between clinical variables and VTE through the R Programming software. Results A total of 1227 VTE cases were identified in the hospitalized NS population and the detection rate was 1.56%. Detection rate of VTE varied significantly in patients with different pathologic types of NS. Patients with membranous nephropathy (MN) had a significantly increased risk of VTE {Odds ratio [OR] 2.11 [95% confidence interval (CI) 1.12–4.36]}. While patients with focal segmental glomerulosclerosis (FSGS) did not show a significant high risk [OR 0.93 (95% CI 0.29–2.60)] compared with minimal change disease. We also found that male [OR 1.44 (95% CI 1.15–1.80)], age [OR 1.09 (95% CI 1.02–1.17)], anemia [OR 1.50 (95% CI 1.15–1.95)], cerebral bleeding [OR 3.23 (95% CI 1.69–6.16)], respiratory tract infection [OR 2.05 (95% CI 1.60–2.63)], respiratory failure [OR 2.24 (95% CI 1.42–3.53)], use of proton pump inhibitors (PPIs) [OR 2.19 (95% CI 1.54–3.12)], use of glucocorticoids [OR 1.46 (95% CI 1.03–2.09)] and immunosuppressants [OR 1.48 (95% CI 1.14–1.93), orthopedic operations [OR 1.97 (95% CI 1.22–3.18)], high-level D-dimer (&amp;gt;0.55 mg/L) [OR 2.62 (95% CI 1.87–3.65)] were associated with increased risk of VTE detection. While 24-hour urine protein quantification &amp;gt;10 g/d [OR 1.24 (95% CI 0.90–1.70)] showed little significant correlation with VTE. Hypertension [OR 0.74 (95% CI 0.58–0.95)] and the use of diuretics [OR 0.72 (95% CI 0.53–0.97)] were found to have a negative correlation with VTE detection. Conclusion The detection rate of VTE among patients with NS during hospitalization was 1.56%. Male, age, MN, anemia, cerebral bleeding, respiratory tract infection, respiratory failure, and use of PPIs, glucocorticoids and immunosuppressants, high D-dimer concentration were associated with VTE detection in NS. While 24-hour proteinuria did not show a significant association with VTE identification.

Utilization of Natural Language Processing in Venous Thromboembolism Identification

Introduction: Capturing venous thromboembolism (VTE) outcomes using only International Classification of Disease (ICD) codes can lead to misclassification of events and to inaccurate conclusions. Manual chart review, the gold standard, is labor intensive and not always feasible. The current study aims to validate an improved computable VTE phenotype algorithm combining ICD with natural language processing (NLP) in patients undergoing hematopoietic cell transplantation (HCT). Methods: All patients undergoing first allogeneic HCT at Fred Hutchinson Cancer Center (FHCC) from 2006-2019 were included in the current study. To capture as many as possible VTE events, we used a sensitive screening method within one year before and after the transplant date that encompassed 1) all patients with ICD-9 and ICD-10 codes for acute, chronic, or historical pulmonary embolism (PE), deep venous thrombosis (DVT), and phlebitis and thrombophlebitis, and 2) all patients with at least 1 radiology report with a pertinent VTE-related keyword from venous doppler ultrasound, contrast computed tomography, or ventilation perfusion scans. All patients from this screened subset were then reviewed by chart abstractors (JA, KM) to establish the gold standard of incident VTE events, which was defined as the new onset of radiologically confirmed PE, lower extremity DVT, or upper extremity/catheter related DVT within 1-year post-transplant. We then tested the performance of the acute VTE ICD-9/10 codes (selective codes from 415, 451, 453; I26, I80, I82) from inpatient or outpatient encounters from stem cell infusion until 1-year post-transplant. We also tested the utility of a NLP algorithm, a method that has been previously validated in a separate cancer cohort using unstructured radiology impressions (PMID: 35647478). Finally, we compared the performance of combining these two algorithms against the gold standard to report positive predictive value (PPV) and sensitivity (Sn). Results: Among 2,879 patients who underwent allogeneic HCT over 15 years, 740 (26%) met study inclusion criteria. Based on the gold standard of detailed medical record review, 275 (10%) were found to have a radiologically confirmed VTE event within 1-year post-transplant (Figure 1). A further 389 (14%) historical VTE events were confirmed before transplant. The acute VTE ICD-9/10 codes identified 339 patients and the NLP algorithm predicted 245 patients to have VTE (including 155 overlap). The ICD codes alone for acute VTE had an estimated Sn of 73% and PPV of 59%. The NLP radiology algorithm alone for VTE had an estimated Sn of 73% and PPV of 82%. Approximately 3 in 10 VTE events were missed in each algorithm. However, the combination of ICD or NLP identified 245/275 of all VTE events (Sn 89%). The PPVs for ICD+/NLP+, ICD-/NLP+, and ICD+/NLP- were 89%, 64%, and 27%, respectively (Table 1). In summary, those with concordant ICD/NLP prediction had excellent PPVs, and approximately 8% of patients with discordant ICD/NLP (n=234/2,879) would require additional chart review to achieve a final PPV >90% and Sn >90%. Conclusion: In the current study, we found that the sensitivity for either the acute ICD codes or the NLP algorithm alone was sub-optimal (missing 3 in 10), and a combined screen should be considered (missing 1 in 10). The use of ICD-9/10 codes alone for new VTE had poor accuracy in our cohort (PPV of 59%), suggesting that additional features are needed, such as concurrent anticoagulation medications. In contrast, the NLP algorithm was validated with high PPV 82% (89% when combined with positive acute ICD screen) in the current cohort and may not require additional confirmation, though caution should be taken for its usage in other studies without dedicated follow-up where radiology reports are captured and stored in one unified healthcare system. One limitation of the study is the lack of review of patients initially screened negative by either ICD codes or radiology keyword searches. While the initial screen was designed to be highly sensitive, we may have missed small number of true VTE events and the reported Sn in this study represents the best-case scenario. In conclusion, while computable phenotype algorithms represent a promising future for the identification of VTE, a hybrid approach involving manual chart review (for only cases where the ICD and NLP screens disagree) may provide the highest yield and help minimize the labor intensive manual review. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

AB0809 PADUA PREDICTION SCORE COMBINED WITH SERUM ALBUMIN FOR THE IDENTIFICATION OF VENOUS THROMBOEMBOLISM OF HOSPITALIZED PATIENTS IN THE DEPARTMENT OF RHEUMATOLOGY

Background:Venous thromboembolism (VTE) includes thrombotic disease of venous system, but primarily includes lower extremity deep vein thrombosis (DVT) and pulmonary embolism (PE). Population-based epidemiological studies have shown an association between systemic autoimmune diseases and VTE[1]. The Padua prediction score(PPS) is a new 20-point risk assessment model proposed by Professor Barbar et al[2] in 2010. A large number of researches have shown that low serum albumin concentration is associated with an increased risk of VTE [3],but there is a lack of studies on serum albumin in VTE, and there are no reports on PPS in rheumatology inpatients.Objectives:To investigate the status of VTE in patients in the department of rheumatology, and to explore the value of PPS combined with serum albumin in the identification of VTE in this patient population.Methods:Baseline data of inpatients in rheumatology department were collected at Sichuan Provincial People’s Hospital from September 2018 to September 2020. Occurrence of VTE was compared between high and low risk groups. PPSs were analyzed in VTE and non-VTE patients. Multivariate logistic regression was used to analyze the independent risk factors of VTE. The receiver operating characteristic curve was used to evaluate the probablity of value of rheumatic inpatients with VTE assessed by PPS,serum albumin and PPS with serum albumin. P&lt;0.05 indicates that the difference was statistically significant.Results:A total of 2282 patients were included in this study, and 50(2.2%) had symptomatic VTE. Among the symptomatic VTE cases,38(1.6%) had DVT only,8(0.4%) had PE only, and 4(0.2%) were diagnosed with DVT and PE. PPSs in VTE and non-VTE groups were 3.00(2.00~6.00) and2.00(1.00~2.00) respectively (P&lt; 0.05). One hundred and eighty-eight cases was divided into high-risk group of VTE (PPS≥4), while 2094 cases (PPS&lt;4) were in the low-risk group. Logistic regression analysis showed that known thrombophilic condition, history of VTE, reduced mobility, and D-dimer were independent risk factors of VTE in rheumatology patients, the odd ration(OR) values were 161.90, 26.08, 8.73,and1.04. Serum albumin was the independent protection factor [OR= 0.92(95%CI:0.87~0.98)]. The AUC of PPS model, serum albumin model and the combined predictive model were 0.77, 0.75, 0.84, respectively. The difference between the combined prediction model and PPS model was statistically significant (Z=3.813, P&lt;0.05). The optimal sensitivity of PPS and serum albumin models is 60%, 82%, respectively, and the optimal specificity of is 82.5%,58.6%, respectively. The combination model corresponds to a sensitivity of 62% and a specificity of 90.4%.Conclusion:The incidence of symptomatic VTE was relatively higher in hospitalized patients in rheumatology department. Serum albumin was the protective factor. The combination of albumin and PPS can improve the accuracy of screening for VTE in rheumatology in-patients.

Tromboprofilaxis durante el embarazo

Introducción. En mujeres, el riesgo de desarrollar enfermedad tromboembólica venosa (ETV) es 5 a 6 veces mayor durante el embarazo, riesgo que puede aumentar considerablemente si existen antecedentes personales o familiares de otros estados protrombóticos. La ETV es una de las principales causas de morbimortalidad en esta población, por lo que para evaluar la pertinencia de usar tromboprofilaxis, ya sea farmacológica o no farmacológica, es necesario reconocer oportunamente los factores de riesgo clínico asociados a esta condición.Objetivo. Describir el uso de pruebas de tamizaje de estados protrombóticos y de la tromboprofilaxis farmacológica y no farmacológica para prevenir la ETV durante la gestación, durante el parto y durante el puerperio.Materiales y métodos. Se realizó una revisión de la literatura en Embase, ClinicalKey, ScienceDirect, Access Medicine, Scopus, ProQuest, PubMed y LILACS. Se buscaron estudios sobre trombofilia y trombofilaxis en el embarazo publicados entre enero de 2004 y marzo de 2018 en inglés y en español.Resultados. En la búsqueda inicial se identificaron 128 artículos, de los cuales 54 cumplieron los criterios de inclusión. La mayoría de estudios correspondió a revisiones narrativas (n=16), guías de práctica clínica (n=13) y revisiones sistemáticas (n=8).Conclusión. Se recomienda el uso de pruebas de tamizaje de estados protrombóticos durante la gestación, el parto y el puerperio, ya que la identificación oportuna de la ETV permitirá disminuir las tasas de morbimortalidad en esta población mediante la implementación de medidas tromboprofilácticas, sean o no farmacológicas.

Risk Stratification for Postoperative Venous Thromboembolism after Endoscopic Sinus Surgery.

Objectives Venous thromboembolism (VTE) contributes to significant patient morbidity, yet the incidence of VTE following endoscopic sinus surgery (ESS) is unknown. Quality improvement criteria are prompting increased standardization of perioperative VTE prophylaxis. Risk stratification for VTE may better define best practice measures to balance limiting VTE development with avoiding unnecessary chemoprophylaxis. Study Design Retrospective cohort study. Setting Tertiary institution. Subjects and Methods Adult patients who underwent ESS without perioperative chemoprophylaxis from 2008 to 2016 were evaluated. Identification of VTE was performed via screening diagnosis and procedure codes and clinical records, with subsequent confirmation of true-positive VTE. Data for individual Caprini scores were abstracted from electronic medical records. The primary outcome was development of VTE within 30 days following ESS relative to the Caprini score. Results A total of 2369 ESS cases were evaluated. While initial screening identified multiple potential VTE events, in-depth medical record review confirmed only 4 true VTE (0.17%). The VTE rate among cases with a Caprini score of <8 (0.09%, 2/2278) was significantly less ( P = .008) than the rate with a score of ≥8 (2.2%, 2/91). Beyond overall score, specific risk factors associated with development of postoperative VTE included stroke, central venous access, sepsis, and inpatient status (all P < .025), while prior VTE and hypercoagulability were not associated with postoperative VTE (all P > .5). Conclusions In the absence of perioperative chemoprophylaxis, postoperative VTE following ESS is extremely rare, particularly for patients carrying low-to-moderate Caprini scores. Risk stratification based on these data can assist in the design of VTE prophylaxis guidelines for ESS patients.

Identification of Venous Thromboembolism (VTE)-Associated Novel Variants in the ABO Gene Using Targeted Deep Sequencing

Abstract 709 Background:A recent analysis of merged genome-wide and candidate gene genotypes in VTE cases and controls identified multiple tag SNPs that were strongly associated with VTE. Objective:To identify rare and/or novel functional variants by sequencing the implicated genes. Methods:Cases (n=1488) were Mayo Clinic European-American patients of non-Hispanic ancestry with objectively-diagnosed VTE in the absence of active cancer, venous catheter or antiphospholipid antibodies. Controls (n=1439) were Mayo Clinic outpatients without VTE who were frequency-matched on case age, gender, race, MI/stroke status and state of residence. For this analysis, we selected a subset of these cases and controls for sequencing to take advantage of the joint configuration of two ABO SNPs of primary interest, rs8176719 (ABO exon 6 deletion determining type O blood group) and rs2519093 (ABO intron 1 tag SNP), which were previously shown to be strongly associated with VTE (p=5.7E-12 and p=3.0E-16, respectively). We randomly sampled 82 cases and 14 controls within 3 of the 9 potential allele frequency cells (Figure). The rs8176719 alleles are -−/−- (double deletion is the common allele), –/G, and G/G (the rare allele). The rs2519093 alleles are GG (G is the common allele), AG, and AA (A is the rare allele). For each SNP, the genotypes are represented as 0, 1, or 2 copies of the minor allele. We represented the joint allelic configuration of the two SNPs with the number of copies of the rs8176719 given first as 0/0 (both with 0 copies of the minor allele), 0/1, 0/2 (0 copies of the rs8176719 SNP), 1/0 (1 copy of the rare rs8176719 SNP), 1/1/, and 1/2, and 2/0 (2 copies of the rare allele for the rs8176719 SNP and 0 copies of the rare allele of the rs2519093 SNP), 2/1, and 2/2. From the Figure one observes discrepancies between cases and controls at the 0/0, 1/1 and 2/2 combinations. We randomly sampled from these three combinations, taking one third of the case series. For each SNP, we had 28 cases with 0/0 copies of the rare allele, 27 cases with 1/1 copies of the rare allele; and 27 cases with the combination of 2/2 copies of the rare allele. We compared these 82 cases with 14 controls that do not have any of these combinations. Sixteen genes were selected for deep sequencing, including 5 genes harboring SNPs significantly associated with VTE (F5, SLC19A2, ABO, NME7, ATP1B1), 10 genes with SNPs marginally associated with VTE (C1orf114, KLKB1, SELP, F11, SCUBE1, PRKCB1, CD44, ITPR1, GFRA1, BLZF1), and CYP4V2 which reportedly confounds F11 and KLKB1. Agilent SureSelect probes were designed to capture and enrich the ∼2 Mb genomic regions of these 16 genes. Samples were multiplexed (12-plex) and sequenced using Illumina HiSeq 2000. The sequence reads were aligned to the human genome build 36 using Burrows-Wheeler Aligner, and the single nucleotide variants (SNVs) and small INDELs were called using SNVMix and GATK, respectively. For this analysis, novel ABO SNVs were tested for an association with VTE using age-, sex-adjusted logistic regression and Fisher’s Exact Test. [Display omitted] Results:98% of the targeted regions were sequenced with > 20X coverage. On average, ∼2500 SNVs and ∼200 INDELs were detected in each sample. Fifteen novel SNVs in intron 6 and 3’ of the ABO gene were associated with VTE (p<E-06) and belonged to 3 distinctive LD blocks; none were in LD with the coding or tag ABO SNPs (rs8176719; rs2519093). SNVs inside the middle LD block at the 3’ of ABO are located within an enhancer and promoter histone marked with putative transcription factor binding sites. In addition, strong evidence from both ENCODE and dbEST support the middle LD block as lying within a novel transcript, probably an extension of the 3’ of ABO. In addition, we discovered a novel, significant, protective, frame-shifting single base (G) deletion at ABO chr9:135120877. Conclusion:Novel ABO functional variants that are associated with VTE were identified by deep sequencing. Disclosures:Heit:Daiichi Sankyo: Consultancy, Honoraria.

An Emergency Department Guideline for the Diagnosis of Pulmonary Embolism: An Outcome Study

Objective: To assess the clinical outcome of patients suspected of pulmonary embolism (PE) following implementation of an emergency department (ED) diagnostic guideline. Methods: A prospective observational study of all patients suspected of PE who presented to the ED during a four-month study period. The authors' modification of the Charlotte criteria recommended D-dimer testing in those younger than 70 years of age with a low clinical suspicion of PE and no unexplained hypoxemia, unilateral leg swelling, recent surgery, hemoptysis, pregnancy, or prolonged duration of symptoms. The primary outcome was the identification of venous thromboembolism during a three-month follow-up period. The negative predictive value of the overall diagnostic strategy and the test characteristics of D-dimer were calculated. Results: A total of 1,207 consecutive patients were evaluated for suspected PE; 71 (5.8%) were diagnosed with venous thromboembolism. One missed case of PE was identified on follow-up, yielding a negative predictive value of 99.9% (95% confidence interval [CI] = 99.5% to 100%). The missed case was a patient who presented with pleuritic chest pain and shortness of breath; a chest radiograph revealed pneumothorax, and the physician decided not to pursue the positive D-dimer result. The patient returned six weeks later with PE. Subgroup analysis of patients having D-dimer performed (n= 677) yields a sensitivity of 0.93 (95% CI = 0.77 to 0.98) and a specificity of 0.74 (95% CI = 0.70 to 0.77). Conclusions: Implementation of a PE diagnostic guideline in a community ED setting is safe and has improved the specificity of the enzyme-linked immunosorbent assay D-dimer test when compared with previous studies.

An Emergency Department Guideline for the Diagnosis of Pulmonary Embolism: An Outcome Study

To assess the clinical outcome of patients suspected of pulmonary embolism (PE) following implementation of an emergency department (ED) diagnostic guideline. A prospective observational study of all patients suspected of PE who presented to the ED during a four-month study period. The authors' modification of the Charlotte criteria recommended D-dimer testing in those younger than 70 years of age with a low clinical suspicion of PE and no unexplained hypoxemia, unilateral leg swelling, recent surgery, hemoptysis, pregnancy, or prolonged duration of symptoms. The primary outcome was the identification of venous thromboembolism during a three-month follow-up period. The negative predictive value of the overall diagnostic strategy and the test characteristics of D-dimer were calculated. A total of 1,207 consecutive patients were evaluated for suspected PE; 71 (5.8%) were diagnosed with venous thromboembolism. One missed case of PE was identified on follow-up, yielding a negative predictive value of 99.9% (95% confidence interval [CI] = 99.5% to 100%). The missed case was a patient who presented with pleuritic chest pain and shortness of breath; a chest radiograph revealed pneumothorax, and the physician decided not to pursue the positive D-dimer result. The patient returned six weeks later with PE. Subgroup analysis of patients having D-dimer performed (n = 677) yields a sensitivity of 0.93 (95% CI = 0.77 to 0.98) and a specificity of 0.74 (95% CI = 0.70 to 0.77). Implementation of a PE diagnostic guideline in a community ED setting is safe and has improved the specificity of the enzyme-linked immunosorbent assay D-dimer test when compared with previous studies.