Late-Breaking Abstracts Address Thrombosis and COVID-19

A growing body of clinical evidence indicates that COVID-19 infection predisposes patients to arterial and venous thrombosis and thrombotic complications. At the International Society on Thrombosis and Haemostasis (ISTH) 2020 Virtual Congress, three late-breaking abstracts explored these associations by looking at the use of anticoagulation for patients admitted to the intensive care unit (ICU), the rate of venous thromboembolism (VTE) after hospital discharge, and the incidence of thrombotic complications in patients hospitalized with COVID-19 compared with patients hospitalized with influenza.

Anticoagulation and Survival

In the first study, researchers led by Hanny Al-Samkari, MD, associate director of the Hereditary Hemorrhagic Telangiectasia Center at Massachusetts General Hospital, explored the hypothesis that hypercoagulability contributes to death in patients with COVID-19, and whether therapeutic anticoagulation affects survival.1

This was the largest study to date evaluating thrombosis and bleeding in patients with COVID-19, Dr. Al-Samkari noted, with 3,239 critically ill adults enrolled from 67 centers. The researchers looked at the incidence of VTE and major bleeding within 14 days after ICU admission to determine risk factors for VTE, as well as the impact of anticoagulation on patient outcomes.

Patients were excluded if they had received therapeutic anticoagulation prior to hospitalization, had a major bleed within 2 days of admission, or had a platelet count less than 50×109/L within 2 days of admission.

A total of 2,809 people were included in the analysis. Patients’ median age was 61 years, and nearly two-thirds of the population were male.

During follow-up, 204 patients (6.3%) developed VTE, and 90 (2.8%) had a major bleeding event. Independent predictors of VTE were:

  • male sex (odds ratio [OR] = 1.70; 95% CI 1.05-2.77)
  • severe obesity (OR=2.08; 95% CI 1.17-3.70 for a body mass index [BMI] ≥40 vs. BMI <30)
  • higher D-dimer on ICU day 1 (OR=4.20; 95% CI 2.17-8.14 for >10,000 vs. ≤1,000 ng/mL)

Most of the patients (n=2,425) did not start therapeutic anticoagulation within 2 days of admission, with the remaining 384 starting anticoagulation on day 1 (n=231) or 2 (n=153) after ICU admission.

When comparing outcomes between the groups, “therapeutic anticoagulation initiated during the first 2 days of ICU stay did not improve 28-day survival in critically ill patients with COVID-19 in the U.S.,” Dr. Al-Samkari told ASH Clinical News. The 28-day mortality rate in the anticoagulated group was 46.6%, compared with 36.6% in the non-anticoagulated group (adjusted hazard ratio = 1.12; 95% CI 0.92-1.35).

He added that “bleeding was less common than thrombosis in these patients but was considerably more morbid.”

VTE After Discharge

The second late-breaking abstract related to COVID-19 discussed the incidence of VTE in patients discharged after being hospitalized for COVID-19.2 In his presentation, Matthias Engelen, MD, of University Hospitals Leuven in Belgium, noted that patients with COVID-19 have high D-dimer levels, which are predictive of mortality risk. Because of this association, his institution began administering low molecular weight heparin (LMWH) in prophylactic doses to all patients and in intermediate doses for patients admitted to the ICU.

However, it is unclear whether these patients had a residual risk and incidence of VTE after hospitalization. Therefore, with this study, Dr. Engelen and colleagues measured D-dimer levels and performed venous ultrasound screening for 6 weeks post-discharge to evaluate VTE risk and incidence. Any patients admitted to the ICU or who had D-dimer levels ≥2,000 ng/mL also had computed tomography pulmonary angiogram (CTPA) or ventilation/perfusion lung scan performed.

A total of 133 patients (median age = 58 years) who were hospitalized with COVID-19 were included in the analysis. The median hospital stay was 10 days, and 38% (n=50) had been admitted to the ICU. Most patients admitted to the ICU required mechanical ventilation (n=30; 60%).

Follow-up screening showed that D-dimer levels were significantly lower compared with those at discharge and during hospitalization (593 vs. 1,101 vs. 2,618 ng/mL). These lower levels might “indicate a lower thrombotic risk, but we don’t yet know,” Dr. Engelen said. He added that, although D-dimer levels were higher during hospitalization for patients admitted to the ICU, follow-up levels were similar between patients admitted to the ICU and those who were not.

Only 8% of patients received prophylactic LMWHs after discharge (mean 13 days) without major or clinically relevant bleeding events. There were no symptomatic VTE cases. Systematic screening with vascular ultrasound with or without CT pulmonary angiography (CTPA) or ventilation perfusion (V/Q) scans revealed only one asymptomatic VTE (deep vein thrombosis; 0.98%).

“There was a surprisingly low rate of extended thromboprophylaxis after discharge,” Dr. Engelen said. “More than half of ICU patients did not receive extended thromboprophylaxis at home.” In the 6 weeks following discharge, only 23% of patients received extended prophylactic LMWH – 13% of non-ICU patients and 38% of ICU patients.

Overall, the incidence of post-discharge VTE was 0.8%, with no cases of symptomatic VTE observed. The more intensive CTPA or lung scan found only one asymptomatic VTE.

“Despite widely reported higher incidence of in-hospital VTE, we report low rates of VTE in patients discharged after COVID-19 hospitalization in a center with a higher-dosed prophylactic strategy and asymptomatic screening for all patients at follow-up,” he said. “This implies we can reassure patients that despite high VTE risk in-hospital, the risk of VTE after hospitalization seems to be rather low.”

COVID-19 Versus Influenza

The third COVID-19–related late-breaking abstract compared venous and arterial thrombotic complications among patients hospitalized with COVID-19 or influenza.3 “COVID-19 may lead to thrombotic complications, aggravated by a stay at the ICU,” explained presenter Milou Stals, MD, from Leiden University Medical Center in the Netherlands, adding that the incidence of thrombotic complications in patients on general wards is understudied.

For this analysis, Dr. Stals and colleagues evaluated thrombotic complications in 579 patients who were admitted to the ICU or the general wards of three Dutch hospitals. Their outcomes were compared with those of patients hospitalized with influenza whose data were collected by Statistics Netherlands.

Of the COVID-19 population, 485 individuals were admitted to the general ward and 178 were admitted to the ICU (84 had been admitted to both). All patients received pharmacologic thromboprophylaxis and no screening strategies were performed.

67 patients were diagnosed with a total of 71 thrombotic complications (17 in the general ward and 50 in the ICU). Pulmonary embolism was the most common complication (n=54; 76%).

The 30-day cumulative incidence of thrombotic complications in patients admitted to the general wards was 5.3%. This was lower than in ICU admitted patients (34.1%), but the researchers noted that the incidence was still substantial (see TABLE). Also, while cumulative incidence of venous thrombotic complications was lower, at 17.8% (3.8% in the general ward and 18.7% in the ICU), the incidence in COVID-19 patients was much higher than in patients hospitalized with influenza (17.8% vs. 1.04% [ward and ICU combined]).

Dr. Stals and colleagues concluded that the considerably higher incidence of thrombotic complications in COVID-19 could suggest an effect specific to SARS-CoV-2 and that further studies should be done to explore explanations for this large difference between COVID-19 and influenza.

Study authors report no relevant conflicts of interest.

References

  1. Al-Samkari H, et al. Thrombosis, bleeding, and the effect of anticoagulation on survival in critically Ill patients with COVID-19 in the United States. Presented at ISTH 2020 Virtual Congress; July 12-14; LC/CO01.2
  2. Engelen MM, et al. Incidence of venous thromboembolism in patients discharged after COVID-19 hospitalisation. Presented at ISTH 2020 Virtual Congress; July 12-14; LC/CO01.3
  3. Stals MAM, et al. Higher incidence of thrombotic complications in hospitalized patients with SARS-COV-2 virus versus influenza virus infections. Presented at ISTH 2020 Virtual Congress; July 12-14; LC/CO01.4