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. 2020 Aug 4;20(5):393–403. doi: 10.1007/s40256-020-00431-z

Table 2.

Studies published on hypercoagulability in COVID-19

Authors; type of study Country Living/autopsy No. of patients Sex Age, years Comorbidities/predisposing factors Anticoagulation Outcome Major findings/comments
Menter et al. [11]; cohort Switzerland Autopsy 21 81% male Mean 76

HTN: 100%

CAD: 71%; obesity: 19%

DM: 35%

Smoker: 40%

Anticoagulation: 52%

Alveolar microthrombi: 45%

Glomerular microthrombi: 16.7%

Patients with blood group A may have a lower threshold of tolerance for COVID-19
Wichmann et al. [15]; prospective cohort Germany Autopsy 12 75% male Median 73

DM: 25%

Obesity: 25%

CAD: 50%

COPD/asthma: 33%

Anticoagulation: 91.6%

DVT: 58%

Mortality due to massive PE: 33%

Extremely high D-dimer: 25% (> 20,000 ng/mL; normal < 500 ng/mL)

Prolonged PT/aPTT: 33%

Klok et al. [16]; prospective cohort Netherlands

Living,

all ICU patients

184 76% male Mean 64 Cancer: 2.7% Prophylactic anticoagulation: 100%

VTE: 27%

Ischemic stroke: 3.7% (13% mortality)

Predictor of thrombotic complications:

Age: aHR 1.05/year (95% CI 17–37%)

Prolongation of PT > 3 s or aPTT > 5 s: aHR 4.1, 95% CI 1.9–9.1

Helms et al. [17]; multicenter prospective cohort France Living, all ICU patients 150 81.3% male Mean 63

CAD: 48%

DM: 20%

Respiratory disease: 14%

Prophylactic: 70%

Therapeutic: 30%

PE and DVT: 18.7%

Ischemic stroke: 1.3%

Mesenteric and limb ischemia: 0.7% each

PE in COVID vs. non-COVID ARDS: 11.7% vs. 2.1% (OR 6.2, 95% CI 1.6–23.4; p < 0.008)

Elevated D-dimer and fibrinogen (> 95%)

Elevated vWF activity and factor VIII also seen

Lupus anticoagulant: 87.7%

Poissy et al. [18]; case series France Living, all ICU patients 107 59.1% male Median 57 Median BMI: 30 kg/m2

When PE was diagnosed: prophylactic anticoagulation: 91%

Therapeutic anticoagulation: 9%

PE in COVID ICU (2020) vs. non-COVID ICU (2019): 20.6% vs. 6.1%

AR: 14.4% (95% CI 6.1–22.8%)

PE in COVID ICU (2020) vs. influenza ICU (2019): 20.6% vs. 7.5%

AR: 13.1%, 95% CI 1.9–24.3%

Risk factors for PE:

D-dimer: SHR 1.81 (95% CI 1.03–3.16)

Factor VIII activity: SHR 1.73 (95% CI 1.10–2.72)

vWF Ag levels: SHR 1.69 (95% CI 1.12–2.56)

Middeldorp et al. [19]; single-center cohort Netherlands Living 74 66% male Mean 61

Obesity: 14%

Cancer: 3.5%

Prophylactic anticoagulation: 100%

VTE: 20%

Cumulative incidence of VTE at 7, 14, and 21 days: 16% (95% CI 10–22), 33% (95% CI 23–43), and 42% (95% CI 30–54), respectively

Cumulative incidence of VTE was higher in the ICU

VTE associated with mortality: aHR 2.4 (95% CI 1.02–5.5)

Risk factors for VTE:

Higher WBC Count: SHR 1.9 (95% CI 1.1–3.2)

Higher neutrophil-to-lymphocyte ratio: SHR 2.0 (95% CI 1.3–3.1)

Higher D-dimer: SHR 1.6 (95% CI 1.2–2.1)

Cui et al. [27]; retrospective China Living, all ICU patients 81 46% male Mean 59.9

HTN: 25%

DM: 10%

CAD: 12%

Smoking: 43%

Prophylactic anticoagulation: 0% VTE: 25% (10% mortality) Patients with VTE were older, had lower lymphocytes, longer aPTT, and higher D-dimer (all significant)
Artifoni et al. [22]; retrospective cohort France Living, all non-ICU patients 71 61% male Median 64

HTN: 41%

DM: 20%

Cancer: 6%

Smoking: 9%

Prophylactic anticoagulation: 99%

VTE: 22.5% (1.4% mortality)

PE: 10%

D-dimer, ICU admission, and need for invasive ventilation were significantly higher in patients with VTE
Lodigiani et al. [21]; retrospective cohort Italy Living 388 68% male Median 66

HTN: 47.2%

Smoking: 11.6%

DM: 22.7%

Obesity: 24.1%

CAD: 13.9%

Cancer: 6.4%

Prophylactic anticoagulation: 100% in ICU and 75% in non-ICU

VTE: 4.4%

Ischemic stroke: 2.5%

MI: 1.1%; all higher in ICU patients

93.7% of VTE patients have elevated D-dimer ranging from 1620 to 40,905 ng/mL
Llitjos et al. [20]; retrospective cohort France Living, all ICU patients 26 77% male Mean 68

HTN: 85%

Smoking: 27%

Median BMI: 30.2 kg/m2

Prophylactic anticoagulation: 31%

Therapeutic: 69%

VTE: 69% (12% mortality)

PE: 23%

VTE was significantly higher in the prophylactic anticoagulation group

High rate of thromboembolic events in patients receiving therapeutic anticoagulation
Nahum et al. [37]; prospective cohort France Living, all ICU patients 34 78% male Mean 62.2

HTN: 38%

DM: 44%

CAD: 9%

COPD: 6%

Cancer: 3%

BMI mean: 31.4 kg/m2

Prophylactic anticoagulation: 100% VTE: 79% (65% at admission and 14% more at 48 h of ICU admission) despite prophylactic anticoagulation High levels of D-dimer, fibrinogen, and C-reactive protein are found in patients with VTE

Ag antigen, aHR adjusted hazard ratio, aPTT activated partial thromboplastin time, AR absolute risk, ARDS acute respiratory distress syndrome, BMI body mass index, CAD coronary artery disease, CI confidence interval, COPD chronic obstructive pulmonary disease, COVID-19 coronavirus disease 2019, DM diabetes mellitus, DVT deep vein thrombosis, HTN hypertension, ICU intensive care unit, MI myocardial infarction, OR odds ratio, PE pulmonary embolism, PT prothrombin time, SHR subhazard ratio, VTE venous thromboembolism, vWF von Willebrand factor, WBC white blood cell