D-Dimer Analysis in COVID-19 Patients

The COVID-19 incidence is increasing around the world. Some countries are experiencing worsening conditions, evendeaths. One coagulation marker that noticeably increases in COVID-19 patients is D-dimer. This study aimed to analyzeD-dimer levels of COVID-19 patients. Retrospective study using medical records of 84 COVID-19 patients, conducted fromApril to August 2020 at UNHAS Hospital. Patients were grouped based on the severity of the disease as non-severe andsevere. D-dimer levels were measured using the Alere Triage® D-dimer with the fluorescent immunoassay method. Thestatistical test used was Mann-Whitney, D-dimer prognostic levels were calculated with ROC analysis to get the cut-off.Significant if the p < of 0.05. The sample consisted of 74 non-severe and ten severe COVID-19 patients, mostly in the 30-39age group. D-dimer levels in non-severe (0.31±0.38 μg/L) significantly differ from severe group (3.09±2.56 μg/L) (p<0.001).The Receiver Operating Characteristics (ROC) curve showed D-dimer sensitivity and specificity of 90.0% and 89.2%,respectively at the ≥ 0.80 μg/L cut-off, Negative Predictive Value (NPV) of 98.5%, and Positive Predictive Value (PPV) of52.9%. D-dimer levels increased in severe COVID-19 patients due to an increased inflammatory response resulting inexcessive thrombin. The ROC D-dimer curve indicated a cut-off rate of 0.80 μg/L, providing optimal sensitivity andspecificity. D-dimer has a significant difference in non-severe and severe COVID-19 patients and shows good value todetermine the severity of COVID-19 disease with a cut-off value ≥ 0.80 μg /L.

Abstract P112: Markers of Coagulation and Hemostatic Activation Identify Covid-19 Patients at High Risk for Thrombotic Events

Introduction: COVID-19 has been associated with venous and arterial thrombotic complications. 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. Methods: COVID-19 patients admitted to a tertiary academic healthcare system from April 3, 2020 to July 31, 2020 underwent admission testing of MOCHA profile parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer). For this analysis we excluded patients on outpatient anticoagulation therapy preceding admission. Prespecified endpoints monitored during hospitalization included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke and access line thrombosis. Results: During the study period, 276 patients were included in the analysis cohort (mean age 59 ± 6.3 years, 47% female, 83% non-white race). Arterial and venous thrombotic events occurred in 43 (16%) patients (see Table). Each coagulation marker was independently associated with the composite endpoint (p<0.05). Admission MOCHA with ≥ 2 abnormalities was associated with the composite endpoint (OR 3.1, 95% CI 1.2-8.3), ICU admission (OR 3.2, 95% CI 1.8-5.5) and intubation (OR 2.8, 95% CI 1.5-5.5). Admission MOCHA with < 2 abnormalities (26% of the cohort) had sensitivity of 88% and a negative predictive value of 93% for an in-hospital endpoint. Conclusion: Admission MOCHA with ≥ 2 abnormalities identified COVID-19 patients at risk for a thrombotic event, ICU admission and intubation while < 2 abnormalities identified a subgroup of patients who were at low risk for thrombotic events. Our results suggest that an admission MOCHA profile can be useful to risk stratify COVID-19 patients. Further studies are needed to determine whether an admission MOCHA profile can guide anticoagulation therapy and improve overall clinical outcomes.

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

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.

Clinical Significance of Soluble Fibrin in Coagulopathy caused by Highly Invasive Surgery

The clinical use of soluble fibrin (SF) as a coagulation marker is increasing. However, its diagnostic role in critical coagulopathy during invasive abdominal surgery has not been examined. In the present study, we evaluated of changes in SF and other conventional markers, and statistical examination of risk factors in the Disseminated intravascular coagulation (DIC). 44 highly invasive surgeries (segmental hepatectomy or more, 28; pancreaticoduodenectomy, 9; distal pancreatectomy, 5; splenectomy, 2) were included. After excluding 7 patients who did not develop DIC, 37 patients were classified into 2 groups: the SAC group, in which SAC remained after surgery (n = 16), and the DIC group, which developed DIC (n = 21). All patients were diagnosed with SIRS triggers a hypercoagulable condition (SAC) on POD1 and with DIC on POD2. Multivariate analysis revealed significant differences only in the SF level and FDP (odds ratio at 14.4 and 7.8). A prediction formula was then prepared based on the β value: P = 1 / [1 + exp {-(2.665 × SF + 2.049 × FDP - 1.309)}]. The sensitivity and specificity of the prediction formula were 71% and 94%, respectively. These results showed that the risk factors in the DIC group were SF and FDP on POD1, with SF being the stronger risk factor. Operative stress can be quantified using the SF level on POD1, enabling more specific perioperative management from the perspective of postoperative coagulopathy control.

Coagulation Factors, Postmenopausal Hormone Replacement Therapy and the Risk of Venous Thrombosis: The WHI Clinical Trials of Postmenopausal Hormone Therapy.

Background. Postmenopausal estrogen (E) therapy, especially in combination with progestin (P) doubles the relative risk of venous thrombosis (VTE). Risk with hormones is higher with increasing age, obesity and with factor V Leiden. We studied coagulation markers as susceptibility factors for postmenopausal hormone-related VTE. Methods. The Women’s Health Initiative program included two placebo-controlled double-blind randomized trials of two E regimens, E (conjugated equine estrogens) or E+P (E + medroxyprogesterone acetate), in 16,608 postmenopausal women aged 50–79. We performed a nested case control study that measured baseline levels of coagulation markers in 215 women who developed VTE during follow up and 867 age-matched controls. The joint effects of treatment assignment to either E regimen vs placebo and prespecified abnormal levels of each coagulation factor on relative risk of VTE were estimated by logistic regression adjusting for age, race, body-mass index and type of E regimen. Results. Low levels of protein C and free protein S (<5th percentile), high D-dimer (top quartile), and high plasmin antiplasmin complex (PAP) and prothrombin fragment 1–2 (top decile) were all associated with risk of VTE with adjusted odds ratios (95% CI) of 2.0 (1.0–4.1), 2.9 (1.5–5.6), 2.8 (2.0–4.0), 2.5 (1.6–4.0) and 1.9 (1.2–3.1), respectively. Elevated factors II, VIII, IX and fibrinogen were not VTE risk factors. Compared to women with normal coagulation marker levels assigned to placebo, the joint odds of VTE with either E regimen plus an abnormal coagulation marker were more than additive compared to the separate effects of hormones and coagulation abnormalities for low protein C, low free protein S, and elevated D-dimer, PAP and F1–2. The odds ratios of VTE with the combination of an abnormal coagulation factor and assignment to hormones were (in order listed in prior sentence), 4.5 (95% CI 2.0–10.2), 6.7 (3.0–14.5), 6.1 (3.7–10), 5.8 (3.2–10.5) and 4.4 (2.4–7.7). Conclusions. We report new findings of elevated F1-2 and PAP as VTE risk factors in women in this prospective study nested in trials of E or E+P versus placebo. Protein C or S values below the 5th percentile were also clinically relevant even though they do not represent inherited deficiency. Lower protein C and free protein S, and higher D-dimer, F1-2 and PAP all identified women at increased risk of VTE with hormones. If our findings are confirmed in management studies, measurement of these factors might assist women with decision-making on safety of E or E+P.