d-Dimer Testing in Laboratory Practice

BACKGROUND d-dimer is a reliable and sensitive index of fibrin deposition and stabilization. As such, its presence in plasma should be indicative of thrombus formation. There are many conditions unrelated to thrombosis in which d-dimer concentrations are high, however, making its positive predictive value rather poor. CONTENT Notwithstanding these limitations, d-dimer can be regarded as a most valuable laboratory tool to diagnose and manage a vast array of thrombosis-related clinical conditions, including (a) diagnosis of venous thromboembolism (VTE), (b) identification of individuals at increased risk of first thrombotic event (both arterial and venous), (c) identification of individuals at increased risk of recurrent VTE, (d) establishment of the optimal duration of secondary prophylaxis after a first episode of VTE, (e) pregnancy monitoring, and (f) diagnosis/monitoring of disseminated intravascular coagulation (DIC). This article is aimed at reviewing the merits and pitfalls of these applications. SUMMARY From my analysis of the literature, I draw the following conclusions. (a) d-dimer, as measured by a sensitive test, can be safely used to exclude VTE in symptomatic outpatients, provided that it is used in combination with the pretest clinical probability. (b) High concentrations of d-dimer are associated with an increased risk of recurrent VTE. (c) Patients who present with d-dimer above cutoff after stopping the regular course of oral anticoagulation benefit from extended prophylaxis. (d) Finally, d-dimer can be used as a fibrin-related degradation marker for the diagnosis/management of patients with DIC.

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Significantly enlarged varix in the free-loop of the umbilical cord during the second trimester

Case Reports in Perinatal Medicine ◽

10.1515/crpm-2019-0006 ◽

2020 ◽

Vol 9 (1) ◽

Author(s):

Akiko Kurasaki ◽

Junichi Hasegawa ◽

Natsumi Furuya ◽

Chika Homma ◽

Satoshi Harada ◽

...

Keyword(s):

Umbilical Cord ◽

Thrombus Formation ◽

Umbilical Vein ◽

Second Trimester ◽

Venous Flow ◽

Case Presentation ◽

Neonatal Blood ◽

High Concentrations ◽

Venous Varix ◽

D Dimer

Abstract Objectives Umbilical cord varix is an abnormal dilatation of the umbilical vein. There are two types of umbilical venous varix, of which the free-loop type is extremely rare, and the prognosis and etiology are unclear. In this report, we present a case of a significantly enlarged varix in the free loop of the umbilical cord found in the second trimester. Case presentation Cesarean section was performed at 28 weeks’ gestation due to enlargement of the varix and rapidly increased umbilical venous velocity at the outlet of the varix. Neonatal blood tests revealed anemia and high concentrations of D-dimer, and they were considered to be due to clot formation inside the umbilical cord venous varix. The neonate received blood transfusion but other neonatal course was generally favorable. Thrombus formation in the enlarged varix was due to the constriction of the umbilical cord. Conclusions This case showed that the assessment of umbilical venous flow velocity can be used for estimating the constriction of the umbilical vein and for determining the timing of delivery.

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937. Virally Suppressed PLH Switching From Abacavir to Tenofovir Alafenamide Did Not Have Changes in Immune Activation or Inflammation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy209.077 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S34-S34

Author(s):

Nicholas Funderburg ◽

Grace Mccomsey ◽

Manjusha Kulkarni ◽

Emily R Bowman ◽

Janelle Gabriel ◽

...

Keyword(s):

Immune Activation ◽

Platelet Reactivity ◽

Controlled Trial ◽

Increased Risk ◽

Persons Living With Hiv ◽

Grant Recipient ◽

High Concentrations ◽

Tenofovir Alafenamide ◽

D Dimer ◽

Research Grant

Abstract Background Abacavir (ABC) use has been associated with increased risk of myocardial infarction in persons living with HIV (PLH). Its mechanism is unknown, but may involve immune activation inflammation, and/or altered platelet reactivity. In the current analysis, we compared changes in biomarkers of immune activation and inflammation associated with increased cardiovascular (CV) mortality in virally suppressed PLH who switched off ABC to tenofovir alafenamide (TAF) to those who remained on ABC. Methods In a randomized, double-blinded, active-controlled trial (GS US 311–1717), virally suppressed PLH on a stable regimen containing ABC plus lamivudine (3TC) were randomly assigned (1:1) to maintain therapy or to switch to TAF plus emtricitabine (FTC) while continuing their third agent. At baseline (BL) and weeks 4, 12, 24, and 48 plasma markers (IL-6, hsCRP, D-Dimer, sCD14, sCD163, TNF-R1, and TNF-R2) were measured by ELISA; Lp-PLA2 levels were measured by the Plac assay. Differences between treatment groups overtime were assessed by 2-sided Wilcoxon rank-sum tests. Results Of 556 PLH randomized, 548 had samples available for biomarker assessments (TAF: 274; ABC: 274), both arms were of similar CD4 (median 671 cells/μL), age (median 52 years), race (73% white), but there were fewer women in the TAF arm (14% vs. 22%, P = 0.015) at baseline (BL). Mean BL ASCVD scores were 7.9 in both arms (>7.5 is increased CV risk). BL biomarker concentrations were similar between arms: most had high concentrations of Lp-PLA2 ≥200 ng/mL (94%) and one-third had elevated hsCRP levels >3 mg/L (34%). After switching from ABC to TAF, sCD14 had an early (W12) decreased (−3.4% vs. −0.1%, P = 0.023), while sCD163 increased at both W4 (2.5% vs. −1.2%, P = 0.02) and W24 (1.4% vs. −0.8%, P = 0.025) in the TAF arm; levels of sTNF-R1 also increased through W24 (3.2% vs. 0.2%, P = 0.003) (figure). There were no significant differences in percentage changes from BL between arms for levels of Lp-PLA2, hsCRP, IL-6, D-dimer, or TNF-R2. Conclusion Prior to switching from ABC to TAF, virally suppressed PLH with mean ASCVD scores of 7.9 had elevated levels of CV risk markers (Lp-PLA2 and hsCRP). Switching off ABC to TAF was not associated with any meaningful change in markers of immune activation or inflammation, suggesting that the ABC-associated increased MI risk may involve an alternative etiology. Disclosures G. Mccomsey, Merck: Consultant, Consulting fee. ViiV: Consultant, Consulting fee. Gilead: Consultant, Consulting fee. Astellas: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. P. Mallon, Gilead Sciences: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Grant recipient and Speaker honorarium. GSK Ireland: Grant Investigator and Scientific Advisor, Grant recipient. A. Winston, Gilead, ViiV Healthcare, BMS, Janssen and Merck: Consultant, Grant Investigator, Investigator and Speaker’s Bureau, Educational grant, Grant recipient, Research grant and Speaker honorarium. D. Sengupta, Gilead Sciences: Employee and Shareholder, Salary and Stock. M. Yan, Gilead Sciences: Employee and Shareholder, Salary and Stock. M. S. Rhee, Gilead Sciences: Employee and Shareholder, Salary and Stock. M. Das, Gilead Sciences: Employee and Shareholder, Salary and Stock.

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"ProC Global": A functional screening test that predicts recurrent venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th04-07-0445 ◽

2005 ◽

Vol 93 (03) ◽

pp. 600-604 ◽

Cited By ~ 7

Author(s):

Shannon Bates ◽

Marilyn Johnston ◽

Simon McRae ◽

Jeffrey Ginsberg ◽

Anne Grand’Maison

Keyword(s):

Venous Thromboembolism ◽

Protein C ◽

Specific Inhibitor ◽

Factor V Leiden ◽

First Episode ◽

Functional Screening ◽

Factor V ◽

Increased Risk ◽

Global Result ◽

Recurrent Vte

SummaryAbnormalities of the Protein C (PC) pathway are found in the majority of patients with thrombophilia. ProC Global is a coagulation assay that reflects the net effect of the PC pathway by measuring the activated partial thromboplastin time (APTT) of patient and control plasma, before and after activation of endogenous PC by Protac, a snake venom. Previous studies have suggested that abnormalities in this test are associated with an increased risk of venous thromboembolism (VTE). A retrospective analysis was performed using frozen plasma samples from 140 patients with confirmed VTE to determine whether an abnormal ProC Global result (in the presence and in the absence of known abnormalities in the PC pathway) is a predictor of initial and recurrent VTE. Patients were tested for the presence of activated protein C resistance, Factor V Leiden, PC and protein S (PS) deficiency, and non-specific inhibitor positivity. Mean ProC Global results were significantly lower in patients with recurrent VTE than in patients without recurrent VTE. The association between abnormal ProC Global result and recurrent VTE showed a strong trend, before (odds ratio, OR 3.6) and after (OR 3.1) exclusion of known thrombophilic abnormalities. Patients with a first episode of idiopathic VTE also expressed significant lower ProC Global results than those with secondary VTE. After exclusion of known PC pathway abnormalities, there was a statistically significant association between abnormal ProC Global and initial idiopathic VTE (p=0.04). These results suggest that ProC Global may serve as a predictor of recurrent VTE and potentially for first episode of idiopathic VTE. ProC Global may help identify patients at increased risk of initial and recurrent VTE.

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D-Dimer Levels and Risk of Recurrence Following Provoked Venous Thromboembolism: Findings from the Riete Registry

Blood ◽

10.1182/blood-2018-99-111190 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3810-3810

Author(s):

Martin Ellis ◽

Martin Mar ◽

Monreal Manuel ◽

Orly Hamburger-Avnery ◽

Alessandra Bura-Riviere ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Conflicts Of Interest ◽

Hazard Ratio ◽

Increased Risk ◽

Risk Patients ◽

Recurrent Vte ◽

D Dimer

Abstract Background. Patients with venous thromboembolism (VTE) secondary to transient risk factors or cancer may develop VTE recurrences after discontinuing anticoagulant therapy. Identifying at-risk patients could help to guide the ideal duration of anticoagulant therapy in these patients. Methods. We used the RIETE database to assess the prognostic value of d-dimer testing after discontinuing anticoagulation to identify patients at increased risk for recurrences. The proportion of patients with raised d-dimer levels was determined and the hazard ratio (HR) for VTE recurrences compared to those with normal levels was calculated. Univariate and multivariate analyses of factors associated with VTE recurrence were performed. Results. 3 606 patients were identified in the database in April 2018: 2 590 had VTE after a transient risk factor and 1016 had a cancer. D-dimer levels were measured after discontinuing anticoagulation in 1 732 (67%) patients with transient risk factors and 732 (72%) patients with cancer-associated VTE and these patients formed the cohort in which recurrent VTE rate was calculated. D-dimers and were elevated in 551 (31.8%) of patients with a transient risk factor and were normal in 1181 (68.2%). In the cancer-associated group, d-dimers were elevated in 398 (54.3%) and normal in 334 (45.7%) patients. The adjusted hazard ratio for recurrent VTE was: 2.32 (95%CI: 1.55-3.49) in patients with transient risk factors and 2.23 (95%CI: 1.50-3.39) in those with cancer. Conclusions. Patients with raised d-dimer levels after discontinuing anticoagulant therapy for provoked or cancer-associated VTE are at increased risk for recurrent VTE and death. Future studies could target these patients for extended anticoagulation. Disclosures No relevant conflicts of interest to declare.

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Post-Anticoagulation Cessation D-Dimer Testing and VTE Recurrence in Real-World Australian Audit

Blood ◽

10.1182/blood-2018-99-118661 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1227-1227

Author(s):

Julie Wang ◽

Rowena Brook ◽

Alison Slocombe ◽

Lisa Hong ◽

Prahlad Ho

Keyword(s):

Risk Factor ◽

Significant Risk ◽

Significant Risk Factor ◽

Risk Of Recurrence ◽

Increased Risk ◽

Recurrent Vte ◽

Residual Thrombus ◽

Repeat Imaging ◽

D Dimer

Abstract Aim Elevated D-dimer post-anticoagulation cessation is a recognised risk factor for recurrent venous thromboembolic events (VTE). In particular, raised D-dimer post cessation has been associated with increased risk of recurrence in unprovoked major VTE. Currently in Australia, D-dimer has not been widely used in practice to stratify the risk of VTE recurrence. This study aims to retrospectively analyse the effect of routine D-dimer testing and it's association with VTE recurrence. Methods A retrospective evaluation was performed on 1024 patients with a diagnosis of VTE at a tertiary hospital in Australia between January 2013 and December 2016. Data collected included demographics, results and timing of D-dimer testing and serial imaging results. Results 1024 patients were reviewed with a total median follow up of 12 months (range 0-59 months). D-dimer was tested in 189 patients (18.5%) within 90 days after cessation of anticoagulation. Of these patients, median age was 58 (18-92) and 55.3% (n=105) were female. 33.3% (n=63) had isolated distal deep vein thrombosis (IDDVT), 66.3% (n=126) had above knee DVT (AKDVT)/pulmonary embolus (PE), 54.5% (n=103) of VTE were provoked. Abnormal post cessation D-dimer (>500) was found in 72 patients (37.9%). Of these, 25 patients were restarted on anticoagulation; one had recurrent VTE whilst on low dose apixaban 2.5mg BD and one had recurrence after cessation of anticoagulation at a later date. Patients with elevated D-dimer post cessation had a higher rate of recurrence with the highest risk in patients with D-dimer >1000 (RR 7.38, p=<0.01) outlined in Table 1. Of the 164 patients with post cessation D-dimer testing who remained off anticoagulation there were a total of 24 (12.6%) episodes of recurrent VTE. Elevated D-dimer post anticoagulation cessation was a significant risk factor for recurrence in both provoked VTE (RR 4.21, p=0.01) and unprovoked VTE cohorts (RR 4.55, p=0.008) outlined in Table 2. When provoked VTE were sub-categorised, raised D-dimer demonstrated the most statistical significance in VTE provoked by travel (RR 13.5 p=0.06). Of the patients with post anticoagulation cessation D-dimer testing 170 patients (89.9%) had repeat imaging to assess for residual thrombus. In the subgroup of patients with no residual thrombus, elevated D-dimer was a significant risk factor for VTE recurrence (RR 6.4, p=<0.01). Patients with normal D-dimer and no residual thrombus had the lowest rate of recurrence 5.4% (n=4) see Table 3. When stratified by type of VTE, elevated D-dimer post anticoagulation cessation was significantly related to risk for recurrence in the overall IDDVT sub-cohort (RR 4.09, p=0.007). This was not significant for the AKDVT/PE sub cohort (RR 3.24, p=0.079). However, for patients with unprovoked AKDVT or PE, having D-dimer tested post anticoagulation, regardless of result, was associated with lower rates of VTE recurrence RR 0.30 (p=0.02) compared to those who had no D-dimer testing as part of follow-up. Conclusion Post treatment D-dimer testing may have a clinical role in stratifying the risk of VTE recurrence along with repeat imaging to detect residual thrombus. Elevated D-dimer post anticoagulation cessation is associated with increased risk of VTE recurrence for both provoked and unprovoked VTE with highest risk in patients with D-dimer >1000. Patients with no residual thrombus and a negative D-dimer post anticoagulation cessation had the lowest rate of recurrence. In the subgroup of patients with provoked VTE and IDDVT a positive D-dimer post cessation was associated with 4.21 and 4.09 relative risk of recurrence respectively, suggesting that the role of D-dimer testing can be extended to these subpopulations. Interestingly, in patients with unprovoked AKDVT or PE, having post-cessation D-dimer testing performed, regardless of result, was associated with a significantly lower rate of VTE recurrence compared to patients without D-dimer testing, which may be related to specialist review and recommencement of anticoagulation in high-risk patients. Disclosures No relevant conflicts of interest to declare.

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Markers Of Coagulation And Hemostatic Activation Identify COVID-19 Patients At High Risk For Thrombotic Events, ICU Admission and Intubation

10.1101/2020.10.04.20206540 ◽

2020 ◽

Author(s):

Darwish Alabyad ◽

Srikant Rangaraju ◽

Michael Liu ◽

Rajeel Imran ◽

Christine L. Kempton ◽

...

Keyword(s):

Thrombotic Event ◽

Anticoagulation Therapy ◽

Vascular Events ◽

Icu Admission ◽

Vein Thrombosis ◽

Coagulation Marker ◽

Increased Risk ◽

Patients At Risk ◽

Deep Vein ◽

D Dimer

ABSTRACTBackgroundCoronavirus disease 2019 (COVID-19) has been associated with a coagulopathy giving rise to venous and arterial thrombotic events. The objective of our study was to determine whether markers of coagulation and hemostatic activation (MOCHA) on admission could identify COVID-19 patients at risk for thrombotic events and other complications.MethodsCOVID-19 patients admitted to a tertiary academic healthcare system from April 3, 2020 to July 31, 2020 underwent standardized admission testing of MOCHA profile parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer) with abnormal MOCHA defined as ≥ 2 markers above the reference. Prespecified thrombotic endpoints included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, and access line thrombosis; other complications included ICU admission, intubation and mortality. We excluded patients on anticoagulation therapy prior to admission and those who were pregnant.ResultsOf 276 patients (mean age 59 ± 6.4 years, 47% female, 62% African American race) who met study criteria, 45 (16%) had a thrombotic event. Each coagulation marker on admission was independently associated with a vascular endpoint (p<0.05). Admission MOCHA with ≥ 2 abnormalities (n=203, 74%) was associated with in-hospital vascular endpoints (OR 3.3, 95% CI 1.2-8.8), as were admission D-dimer ≥ 2000 ng/mL (OR 3.1, 95% CI 1.5-6.6), and admission D-dimer ≥ 3000 ng/mL (OR 3.6, 95% CI 1.6-7.9). However, only admission MOCHA with ≥ 2 abnormalities was associated with ICU admission (OR 3.0, 95% CI 1.7-5.2) and intubation (OR 3.2, 95% CI 1.6-6.4), while admission D-dimer ≥2000 ng/mL and admission D-dimer ≥ 3000 ng/mL were not associated. MOCHA and D-dimer cutoffs were not associated with mortality. Admission MOCHA with <2 abnormalities (26% of the cohort) had a sensitivity of 88% and negative predictive value of 93% for a vascular endpoint.ConclusionsAdmission MOCHA with ≥ 2 abnormalities identified COVID-19 patients at increased risk of ICU admission and intubation during hospitalization more effectively than isolated admission D-dimer measurement. Admission MOCHA with <2 abnormalities identified a subgroup of patients at low risk for vascular events. Our results suggest that an admission MOCHA profile can be useful to risk-stratify COVID-19 patients.

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Predictive Value of Coagulation Markers Concerning Clinical Outcome 90 Days after Anterior Myocardial Infarction

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614557 ◽

1999 ◽

Vol 81 (05) ◽

pp. 701-704 ◽

Cited By ~ 11

Author(s):

Frederic Kontny ◽

Ulrich Abildgaard ◽

Carl-Erik Dempfle

Keyword(s):

Myocardial Infarction ◽

Clinical Outcome ◽

Predictive Value ◽

Thrombus Formation ◽

Left Ventricular ◽

Adverse Clinical Outcome ◽

Coagulation Activation ◽

Activation Markers ◽

Increased Risk ◽

D Dimer

SummaryTo study the predictive value of coagulation markers concerning clinical outcome, prothrombin fragment F1.2 (F1.2), fibrin monomer antigen (FM), D-Dimer (DD), and fibrinogen were measured in plasma samples drawn 2 and 7 days after acute myocardial infarction (AMI) in 314 consecutive patients randomized in a clinical trial of low molecular weight heparin (Dalteparin) (the FRAMI trial). Placebo-treated patients suffering death or new AMI within 90 days had significantly higher levels at day 2 of FM (Enzymun-Test FM), and DD (TINAquant D-dimer) (p = 0.001 and 0.02, respectively), but not F1.2 (Enzygnost F1.2 micro), relative to those without serious clinical events. At day 7 all three coagulation activation markers were significantly higher in patients with subsequent adverse clinical outcome. The Dalteparin group had significantly lower levels of these markers as compared to the placebo group. Left ventricular (LV) thrombus formation was not associated with changes in coagulation activation. However, patients with thrombus had significantly higher fibrinogen levels than those without thrombus (p = 0.004 day 2), independent of treatment group. Thus, markers of coagulation activation may be useful in stratification of patients when estimating risk for adverse clinical outcome after AMI. Furthermore, elevated fibrinogen levels are associated with increased risk of LV thrombus formation.

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Prevention of Recurrent Thrombotic Events in Children with Central Venous Catheter-Associated Venous Thrombosis

Blood ◽

10.1182/blood.2021013453 ◽

2021 ◽

Author(s):

Helen Havens Clark ◽

Lance Ballester ◽

Hilary B Whitworth ◽

Leslie Raffini ◽

Char Witmer

Keyword(s):

Risk Factors ◽

Significant Risk ◽

Venous Catheter ◽

Significant Risk Factor ◽

Bleeding Risk ◽

Secondary Prophylaxis ◽

Central Venous ◽

Full Dose ◽

Increased Risk ◽

Recurrent Vte

Central venous catheters (CVC) are the most significant risk factor for pediatric venous thromboembolism (VTE). After an index CVC-associated VTE (CVC-VTE), the role of secondary prophylaxis for subsequent CVC placement is uncertain. Aims of this single center retrospective study were to evaluate the efficacy of secondary prophylaxis for patients with a prior CVC-VTE and identify risk factors associated with recurrent VTE in patients less than 19 years with an index CVC-VTE between 2003 and 2013. Data collection included clinical and demographic factors, subsequent CVC placement, secondary prophylaxis strategy, recurrent VTE, and bleeding. Risk factors for recurrence and effectiveness of secondary prophylaxis were evaluated using survival and binomial models. Among 373 patients with an index CVC-VTE, 239 (64.1%) had subsequent CVC placement. 17.4% (65/373) of patients had recurrent VTE, 90.8% (59/65) were CVC-associated. On multivariable survival analysis, each additional CVC (HR 12.00; 95% CI 2.78 - 51.91), congenital heart disease (HR 3.70; 95% CI 1.97 - 6.95), and total parenteral nutrition dependence (HR 4.02; 95% CI 2.23 - 7.28) were associated with an increased hazard of recurrence. Full dose anticoagulation for secondary prophylaxis was associated with decreased odds of recurrent CVC-VTE (OR 0.35; 95% CI 0.19 - 0.65) but not prophylactic dosing (OR 0.61; 95% CI 0.28 - 1.30). Only 1.3% of CVCs experienced major bleeding with prophylactic or full dose anticoagulation. In summary, children with CVC-VTE are at increased risk for recurrent VTE. Secondary prophylaxis with full dose anticoagulation was associated with a 65% reduction in odds of thrombotic events.

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Low Rate of Thrombosis in Mexican Patients with COVID-19 Infection. a Benefit of Higher Doses Anticoagulants or a Sub Diagnosis?

Blood ◽

10.1182/blood-2020-136240 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 29-30

Author(s):

Félix Gibrant Marquez ◽

Santiago Riviello-Goya ◽

Angel Gabriel Vargas Ruiz ◽

Edgar Ortíz Brizuela ◽

Fernando Gil López ◽

...

Keyword(s):

Mechanical Ventilation ◽

Venous Thrombosis ◽

Critically Ill ◽

Major Bleeding ◽

Thrombotic Event ◽

Factors Associated ◽

Increased Risk ◽

Critical Patients ◽

D Dimer ◽

Low Rate

Background: Patients with COVID-19 have an increased risk of thromboembolic disease, this has been partly attributed to an excessive inflammatory response that is associated with hypercoagulability; patients develop thrombotic complications with rates of 6.4% in non-critically ill and 15 to 31 % in critically ill patients. With this data some clinicians have incorporated thromboprophylaxis with higher dose heparin into the management of this patients, to date there´s no information of the effect of this intervention. Methods: We conducted a prospective cohort, including consecutive critical and non-critical adults admitted to a referral center in Mexico City, between March 18 and May 19, all with a positive RT-PCR for SARS-CoV 2. Conventional coagulation test results were collected on admission and during hospitalization; use of anticoagulation, and patient outcomes were recorded, all patients had been discharged at the time of the final analysis. Thromboprophylaxis was administered according to institutional recommendations and individual medical criteria, we defined anticoagulant dose according to each medication. We compared the basal characteristics and outcomes in critical and non-critical patients. We evaluated the factors associated with thrombosis, bleeding, and mortality using the Cox Regression Model. Results: We evaluated 447 consecutive hospitalized patients with COVID-19, median age was 50 years (range,18-91), 62.6 % were male, 111 (24.8%) were critical. At admission 156 patients (34.9%) had D-dimer values above 3000 ng/mL, median fibrinogen was 651 mg/dL (range 130-1095), APTT was prolonged (> 3 seconds) in 179 patients (40%), and INR >1.2 in 26 patients (5.8%), median platelet value 215 X103/uL (range 33-666). Thromboprophylaxis' dosages were prophylactic in 267 (59.7%), intermediate in 75 (16.8%) and therapeutic in 91 (20.4%), 14 patients (3.1%) did not receive any medical thromboprophylaxis and 26 patients (5.8%) received aspirin during hospitalization. According to the International Society on Thrombosis and Hemostasis' criteria (ISTH criteria) 40 patients (8.9%) had overt-DIC, sepsis induced coagulopathy (SIC) was present in 28 patients (6.3%), and high risk for bleeding by IMPROVE score ≥7 points was found in 5 patients (1.1%). Overall thrombotic event (TE) was confirmed in five patients (1.1%), arterial thrombosis events in 0.4%, one stroke and one acute myocardial infarction; radiographically confirmed venous thrombosis in 0.67%, two with pulmonary embolism (PE) and one with deep venous thrombosis (DVT). The TE were more common in critical than in non-critical patients (3.6% vs 0.3%). The number of CT pulmonary angiogram or duplex ultrasounds performed when PE/DVT was suspected was eighteen (4%), eight (47%) non-critically ill and ten (53%) in the ICU; the rate of radiographically positive results was 22.2%. The overall major bleeding rate was 2.5%, of these 91% were in the ICU. Mortality was 23.5% in the cohort. Table 1. No factors were found to be associated with thrombosis. The factors associated with bleeding were an INR >1.2 (HR 9.0, 95% CI 1.2-67.3, p 0.03), IMPROVE score ≥7 (HR 81.3, 95% CI 11.9-555.6, p < 0.01), and mechanical ventilation (HR 33.1, 95% CI 4.1-262.2, p 0.01). Factors associated with mortality were: age >70 (HR 2.5, 95% CI 1.5-4.2, p <0.01), D-Dimer >3000 ng/mL (HR 2.0,95% CI 1.2-3.4, p <0.01), and mechanical ventilation (HR 1.7, 95% CI 1.01-2.8, p = 0.02). The presence of more than 450x109/L platelets was associated with reduced mortality (HR 0.31 95% CI 0.19-0.50). Figure 1 Discussion: The late outbreak of COVID-19 in Latin America had led to an empiric use of aggressive thromboprophylaxis. Our data shows a low TE rate as compared with other groups, nevertheless we cannot prove a direct impact of the aggressive thromboprophylaxis, firstly because of the low rate or events, and secondly, due to the limitations of an observational study. On the other hand, the incidence of PE/DVT is conditioned by the number of studies performed, yet radiological confirmation has proven difficult due to concerns about virus exposure. Regarding the security of the intervention, major bleeding rates were slightly higher to what has been otherwise reported, but with no bleeding related deaths. The benefit of higher anticoagulant doses most be shown in clinical trials before we can recommend their generalized use in COVID-19 patients. Disclosures No relevant conflicts of interest to declare.

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Brain Natriuretic Peptide, Troponin and D-Dimer Levels in Relation to Long-Term Functional Outcome after a First Episode of Pulmonary Embolism: Results from the E.L.O.P.E. Study

Blood ◽

10.1182/blood.v126.23.649.649 ◽

2015 ◽

Vol 126 (23) ◽

pp. 649-649

Author(s):

Susan R Kahn ◽

Andrew Hirsch ◽

Margaret Beddaoui ◽

Arash Akaberi ◽

David Anderson ◽

...

Keyword(s):

Pulmonary Embolism ◽

Relative Risk ◽

Brain Natriuretic Peptide ◽

First Episode ◽

Increased Risk ◽

The Relationship ◽

Acute Pe ◽

D Dimer ◽

Age And Sex

Abstract Background: Biomarkers such as brain natriuretic peptide (BNP), high-sensitivity cardiac troponin (hsTnT) and d-dimer (DD) are useful for acute or short-term risk stratification after pulmonary embolism (PE) to predict right ventricular dysfunction, recurrent PE or death. However, whether acute or convalescent levels of these biomarkers predict longterm functional limitation after PE has not been evaluated. To address this knowledge gap, we performed the ELOPE (Evaluation of Longterm Outcomes after PE) Study, a prospective, observational, multicenter cohort study of long-term outcomes after acute PE (www.clinicaltrials.gov NCT01174628). Objectives: To describe levels of NT-proBNP, hsTnT and d-dimer at baseline and 6 months in patients with acute PE, and to assess the relationship between biomarker levels and functional status at 1 year. Methods: Patients ³ 18 years old with a 1st episode of acute PE diagnosed within the previous 10 days screened at 5 Canadian recruiting centers were potentially eligible to participate. Exclusion criteria were subsegmental-only PE, preexisting severe cardiopulmonary comorbidity, previous proximal DVT, contraindication to CT pulmonary angiography (CTPA), life expectancy <1 year, unable to read questionnaire in English and French or to attend follow-up visits, and unable or unwilling to consent. Patients attended study visits at baseline, 1, 3, 6 and 12 months. Blood samples to assay NT-proBNP (serum), hsTnT (serum) and DD (plasma) were obtained at baseline and 6 months. NT-proBNP and hsTnT were measured using the cobas® 8000 modular analyzer (Roche Diagnostics, Laval, Quebec); cut-off for normal is <300pg/mL and <15ng/mL, respectively. DD was measured with the immune-turbidimetric STA®-Liatest® assay run on a STA® analyser (DiagnosticaStago, Asnieres, France); cut off for normal is <500ug FEU/L. The primary outcome for the ELOPE Study was maximal aerobic capacity as defined by peak oxygen uptake (VO2) as a percent of predicted maximal VO2 (VO2max) on a cardiopulmonary exercise test (CPET) performed at the 1-year visit, with <80% predicted VO2max considered abnormal, as per American Thoracic Society guidelines. For each biomarker at baseline and 6 months, we calculated median (IQR) values, % of values above the cutoff, and univariate relative risk (RR) for VO2max <80% predicted on 1-year CPET (see Table). Multivariate logistic regression analysis (multiple log-binomial regression) was done, adjusted for age and sex, to assess the relationship between NT-proBNP, hsTnT, DD and 1-year CPET result. Results: 984 patients were screened for participation; of these, 150 were eligible and 100 (67%) consented to participate. Mean (SD) age was 50 (15) years, 57% were male, 80% were outpatients, and 33% had concomitant DVT. PE was provoked in 21% and unprovoked in 79%; none were cancer-related. Table. Median biomarker values, % of values above cutoff, and univariate RR for VO2max <80% predicted on 1-year CPET Variable NT-proBNP (pg/mL) hsTroponin T (ng/L) D-Dimer (ug FEU/L) Visit Date Baseline 6 months Baseline 6 months Baseline 6 months Median (IQR) 46 (21, 98) 37 (21, 81) 6 (3, 11) 5 (3, 8) 1230 (550, 2050) 200 (110, 370) N (%) > cut-off* 8 (10.1%) 4 (5.8%) 8 (10.1%) 5 (7.2%) 62 (78.5%) 8 (11.6%) Univariate RR for VO2 max <80% predicted at 1 year 1.74(0.99, 3.04) 1.15(0.41, 3.18) 1.34(0.66, 2.71) 0.44(0.07, 2.57) 1.42(0.66, 3.06) 0.84(0.33, 2.14) *Cut-offs: see Methods In a multiple model adjusted for age and sex, baseline NT-proBNP >300 pg/mL was associated with a relative risk (RR) of 2.31 (95% CI 1.10, 4.86; p=0.027) for VO2max <80% predicted on 1-year CPET, whereas DD and hsTnT did not influence this risk. Conclusion: In a prospective cohort of patients with a first episode of PE without preexisting severe cardiopulmonary comorbidity, baseline NT-proBNP >300 pg/mL predicted a greater than 2-fold increased risk of abnormal CPET at 1 year after PE. This finding may allow early identification of PE patients at increased risk of poor longterm outcome after PE. Further analyses are in progress to assess the relationship between changes in biomarker levels from baseline to 6 months and 1-year CPET result. Funding: Canadian Institutes of Health Research (MOP-93627) Disclosures Wells: BMS/Pfizer: Research Funding; Bayer: Honoraria.

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