Thrombotic Events and Anticoagulation-Related Bleeding Complications in Critically Ill Patients with Coronavirus Disease 2019.

Background: Thrombosis (T) is common in coronavirus disease 2019 (COVID-19) patients, and d-dimer concentrations correlate with outcomes. Controversy exists with regards to anticoagulation (AC) for patients. We implemented a full-heparinization AC protocol from the onset of the pandemic and hypothesized that a safety signal would be undetectable. Patients and Methods: Prospective evaluation of 111 patients with COVID-19 critical illness hospitalized from March to June 2020. All patients received therapeutic heparinoid-based AC from admission. Incidences of T, bleeding (B), or both (BT) were noted. The primary outcome was mortality. Kruskal-Wallis test and logistic regression were performed. Results are expressed as n (%), median (interquartile range) and odds ratios with 95% confidence intervals. Alpha was set at 0.05. Results: Thirty-two patients (28%) had T, 23 (20%) had B, and 14 (12%) had BT; 42 (40%) patients were unaffected. Two logistic regression models (outcome = mortality) evaluated BT as T, or BT as B. For BT as T, neither T, B, nor male gender predicted mortality; similarly, for BT as B, neither T, B, nor male gender predicted mortality. Factors associated with higher odds of death included higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00-1.13; p = 0.0045), higher d-dimer concentration (OR, 1.00; 95% CI, 1.00-1.01; p = 0.043), and higher activated partial thromboplastin time (aPTT; OR, 1.09; 95% CI, 1.02-1.16; p = 0.010). Conclusions: Neither T nor B predicted mortality in this prospective cohort of anticoagulated patients with COVID-19 critical illness. These data support continued full-dose heparinoid prophylaxis.

Rotational thromboelastometry in patients with acute respiratory distress syndrome owing to coronavirus disease 2019: Is there a viscoelastic fingerprint and a role for predicting thrombosis?

OBJECTIVES: We evaluated rotational thromboelastometry tracings in 44 critically ill coronavirus disease 2019 patients, to determine whether there is a viscoelastic fingerprint and to test the hypothesis that the diagnosis and prediction of venous thromboembolism would be enhanced by the addition of rotational thromboelastometry testing. RESULTS: Rotational thromboelastometry values reflected an increase in clot strength for the EXTEM, INTEM, and FIBTEM assays beyond the reference range. No hyperfibrinolysis was noted. Fibrinolysis shutdown was present but did not correlate with thrombosis; 32% (14/44) of patients experienced a thrombotic episode. For every 1 mm increase of FIBTEM maximum clot formation, the odds of developing thrombosis increased 20% (95% confidence interval, 0-40%, P = .043), whereas for every 1,000 ng/mL increase in D-dimer, the odds of thrombosis increased by 70% (95% confidence interval, 20%-150%, P = .004), after adjustment for age and sex (AUC 0.96, 95% confidence interval, 0.90-1.00). There was a slight but significant improvement in model performance after adding FIBTEM maximum clot formation and EXTEM clot formation time to D-dimer in a multivariable model (P = .04). CONCLUSIONS: D-dimer concentrations were more predictive of thrombosis in our patient population than any other parameter. Rotational thromboelastometry confirmed the hypercoagulable state of coronavirus disease 2019 intensive care unit patients. FIBTEM maximum clot formation and EXTEM clot formation time increased the predictability for thrombosis compared with only using D-dimer. Rotational thromboelastometry analysis is most useful in augmenting the information provided by the D-dimer concentration for venous thromboembolism risk assessment when the D-dimer concentration is between 1,625 and 6,900 ng/dL, but the enhancement is modest. Fibrinolysis shutdown did not correlate with thrombosis.

Cervical spinal cord infarction associated with coronavirus infectious disease (COVID)-19.

Coronavirus disease (COVID-19) has a number of emerging neurological manifestations in addition to pneumonia and respiratory distress. In what follows, we describe a case of a previously healthy young man with severe COVID-19 who subsequently developed an acute flaccid paralysis. Work up revealed a lesion in his cervical spinal cord concerning for spinal infarction or transverse myelitis. He received empiric pulsed steroids without improvement. Taken together, we felt his presentation was most consistent with spinal cord infarction in the setting of critical illness with COVID-19. We believe this is a rare case of spinal cord stroke associated with COVID-19.

Probative Value of the D-Dimer Assay for Diagnosis of Deep Venous Thrombosis in the Coronavirus Disease 2019 Syndrome.

OBJECTIVES: To describe the predictive utility of the D-dimer assay among patients with the coronavirus disease 2019 syndrome for unprovoked lower extremity deep venous thrombosis. DESIGN: Prospective observational study with retrospective data analysis. SETTING: Academic medical center surgical ICU. PATIENTS: Seventy-two intubated patients with critical illness from coronavirus disease 2019. INTERVENTIONS: Therapeutic anticoagulation after imaging diagnosis of the first three deep venous thrombosis cases was confirmed; therapeutic anticoagulation as prophylaxis thereafter to all subsequent ICU admissions. MEASUREMENTS AND MAIN RESULTS: Seventy-two patients with severe coronavirus disease 2019 were screened for deep venous thrombosis after ICU admission with 102 duplex ultrasound examinations, with 12 cases (16.7%) of lower extremity deep venous thrombosis identified. There were no differences between groups with respect to age, renal function, or biomarkers except for D-dimer (median, 12,858 ng/mL [interquartile range, 3,176-30,770 ng/mL] for lower extremity deep venous thrombosis vs 2,087 ng/mL [interquartile range, 638-3,735 ng/mL] for no evidence of deep venous thrombosis; p < 0.0001). Clinical screening tools (Wells score and Dutch Primary Care Rule) had no utility. The C-statistic for D-dimer concentration was 0.874 ± 0.065. At the model-predicted cutoff value of 3,000 ng/mL, sensitivity was 100%, specificity was 51.1%, positive predictive value was 21.8%, and negative predictive value was 100%. CONCLUSIONS: Lower extremity deep venous thrombosis is prevalent in coronavirus disease 2019 disease and can be present on ICU admission. Screening has been recommended in the context of the pro-inflammatory, hypercoagulable background milieu. D-dimer concentrations are elevated in nearly all coronavirus disease 2019 patients, and the test appears reliable for screening for lower extremity deep venous thrombosis at or above a concentration of 3,000 ng/mL (more than 13-fold above the normal range). Full anticoagulation is indicated if the diagnosis is confirmed, and therapeutic anticoagulation should be considered for prophylaxis, as all coronavirus disease 2019 patients are at increased risk.