Hemorrhage, Disseminated Intravascular Coagulopathy, and Thrombosis Complications Among Critically Ill Patients with COVID-19: An International COVID-19 Critical Care Consortium Study

Critical Care Medicine ():e005798, February 28, 2023.

Objectives: To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19.

Design: Prospective, observational study.

Setting: Two hundred twenty-nine ICUs across 32 countries.

Patients: Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021.

Interventions: None.

Measurements and Main Results: HECTOR complications occurred in 1,732 of 11,969 study eligible patients (14%). Acute thrombosis occurred in 1,249 patients (10%), including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial ischemia, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic strokes. Hemorrhagic complications were reported in 579 patients (4.8%), including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, 77 (13%) with pulmonary hemorrhage, and 68 (12%) with hemorrhage associated with extracorporeal membrane oxygenation (ECMO) cannula site. Disseminated intravascular coagulation occurred in 11 patients (0.09%). Univariate analysis showed that diabetes, cardiac and kidney diseases, and ECMO use were risk factors for HECTOR. Among survivors, ICU stay was longer (median days 19 vs 12; p < 0.001) for patients with versus without HECTOR, but the hazard of ICU mortality was similar (hazard ratio [HR] 1.01; 95% CI 0.92–1.12; p = 0.784) overall, although this hazard was identified when non-ECMO patients were considered (HR 1.13; 95% CI 1.02–1.25; p = 0.015). Hemorrhagic complications were associated with an increased hazard of ICU mortality compared to patients without HECTOR complications (HR 1.26; 95% CI 1.09–1.45; p = 0.002), whereas thrombosis complications were associated with reduced hazard (HR 0.88; 95% CI 0.79–0.99, p = 0.03).

Conclusions: HECTOR events are frequent complications of severe COVID-19 in ICU patients. Patients receiving ECMO are at particular risk of hemorrhagic complications. Hemorrhagic, but not thrombotic complications, are associated with increased ICU mortality.

 

Bleeding and thrombotic events in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study

 

Intensive Care Medicine volume 48, pages 1039–1052 (2022) Published: 13 July 2022

 

Purpose

To describe bleeding and thrombotic events and their risk factors in patients receiving extracorporeal membrane oxygenation (ECMO) for severe 

coronavirus disease 2019

 (COVID-19) and to evaluate their impact on in-hospital mortality.

Methods

The ECMOSARS registry included COVID-19 patients supported by ECMO in France. We analyzed all patients included up to March 31, 2022 without missing data regarding bleeding and thrombotic events. The association of bleeding and thrombotic events with in-hospital mortality and pre-ECMO variables was assessed using multivariable logistic regression models.

Results

Among 620 patients supported by ECMO, 29% had only bleeding events, 16% only thrombotic events and 20% both bleeding and thrombosis. Cannulation site (18% of patients), ear nose and throat (12%), pulmonary bleeding (9%) and intracranial hemorrhage (8%) were the most frequent bleeding types. Device-related thrombosis and pulmonary embolism/thrombosis accounted for most of thrombotic events. In-hospital mortality was 55.7%. Bleeding events were associated with in-hospital mortality (adjusted odds ratio (adjOR) = 2.91[1.94–4.4]) but not thrombotic events (adjOR = 1.02[0.68–1.53]). Intracranial hemorrhage was strongly associated with in-hospital mortality (adjOR = 13.5[4.4–41.5]). Ventilation duration before ECMO ≥ 7 days and length of ECMO support were associated with bleeding. Thrombosis-associated factors were fibrinogen ≥ 6 g/L and length of ECMO support.

Conclusions

In a nationwide cohort of COVID-19 patients supported by ECMO, bleeding incidence was high and associated with mortality. Intracranial hemorrhage incidence was higher than reported for non-COVID patients and carried the highest risk of death. Thrombotic events were less frequent and not associated with mortality. Length of ECMO support was associated with a higher risk of both bleeding and thrombosis, supporting the development of strategies to minimize ECMO duration.

 

Prevention of thrombotic risk in hospitalized patients with COVID-19 and hemostasis monitoring

Prevention of thrombotic risk in hospitalized patients with COVID-19 and hemostasis monitoring

by Sophie Susen, Charles Ambroise Tacquard, Alexandre Godon, Alexandre Mansour, Delphine Garrigue, Philippe Nguyen, Anne Godier, Sophie Testa, Jerrold H. Levy, Pierre Albaladejo and Yves Gruel

Critical Care volume 24, Article number: 364 (2020) 

Abstract

COVID-19 is an infection induced by the SARS-CoV-2 coronavirus, and severe forms can lead to acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) management. Severe forms are associated with coagulation changes, mainly characterized by an increase in D-dimer and fibrinogen levels, with a higher risk of thrombosis, particularly pulmonary embolism. The impact of obesity in severe COVID-19 has also been highlighted.

In this context, standard doses of low molecular weight heparin (LMWH) may be inadequate in ICU patients, with obesity, major inflammation, and hypercoagulability. We therefore urgently developed proposals on the prevention of thromboembolism and monitoring of hemostasis in hospitalized patients with COVID-19.

Four levels of thromboembolic risk were defined according to the severity of COVID-19 reflected by oxygen requirement and treatment, the body mass index, and other risk factors. Monitoring of hemostasis (including fibrinogen and D-dimer levels) every 48 h is proposed. Standard doses of LMWH (e.g., enoxaparin 4000 IU/24 h SC) are proposed in case of intermediate thrombotic risk (BMI < 30 kg/m2, no other risk factors and no ARDS). In all obese patients (high thrombotic risk), adjusted prophylaxis with intermediate doses of LMWH (e.g., enoxaparin 4000 IU/12 h SC or 6000 IU/12 h SC if weight > 120 kg), or unfractionated heparin (UFH) if renal insufficiency (200 IU/kg/24 h, IV), is proposed. The thrombotic risk was defined as very high in obese patients with ARDS and added risk factors for thromboembolism, and also in case of extracorporeal membrane oxygenation (ECMO), unexplained catheter thrombosis, dialysis filter thrombosis, or marked inflammatory syndrome and/or hypercoagulability (e.g., fibrinogen > 8 g/l and/or D-dimers > 3 μg/ml). In ICU patients, it is sometimes difficult to confirm a diagnosis of thrombosis, and curative anticoagulant treatment may also be discussed on a probabilistic basis. In all these situations, therapeutic doses of LMWH, or UFH in case of renal insufficiency with monitoring of anti-Xa activity, are proposed.

In conclusion, intensification of heparin treatment should be considered in the context of COVID-19 on the basis of clinical and biological criteria of severity, especially in severely ill ventilated patients, for whom the diagnosis of pulmonary embolism cannot be easily confirmed.

Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation

Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation

Daniel E. Leisman, Clifford S. Deutschman & Matthieu Legrand 

Intensive Care Medicine (2020)Cite this article Published: 28 April 2020

 Current management guidelines for COVID-19 reflect the assumption that critically ill patients infected with SARS-CoV-2 develop acute respiratory distress syndrome (ARDS). However, emerging data and clinical reports increasingly suggest an alternative view that severe COVID-19 reflects a confluence of vascular dysfunction, thrombosis, and dysregulated inflammation…