Platelet, Neutrophil Activation Linked to Venous Thromboembolism Risk in COVID-19 Patients

Among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), key features of platelet and neutrophil activation may predict worsening venous thromboembolism (VTE) and guide heparin treatment intensity. These findings were published in The Journal of Infectious Diseases.

Researchers from Italy compared data from patients infected with SARS-CoV-2 (n=36) and healthy volunteers (n=31) matched for age and gender. Venous blood was assessed by flow-cytometry and associated with clinical outcomes.

Patients had a mean age of 70.6 (±2.8) years, and 55.5% were men. Platelet (209.1±22.3 vs 220.0±15.7 x10³/mL) and neutrophil (4.3±0.8 vs 3.4±0.1 x10³/mL) concentrations did not differ significantly between patients with SARS-CoV-2 and healthy patients, respectively. The groups differed significantly for neutrophil to lymphocyte ratio (P =.0001), D-dimer concentration (P <.0001), von Willebrand factor antigen (P <.0001), von Willebrand factor ristocetin cofactor activity (P <.0001), rates of hypertension (P <.01), type 2 diabetes mellitus (P <.05), and heparin use (P <.0001).

Six patients were admitted to the intensive care unit (ICU) and 14 required mechanical ventilation. Patients requiring ventilation or transfer to the ICU had higher sequential organ failure assessment (SOFA) scores. SOFA scores were also correlated with D-dimer (r, 0.35; P =.04), neutrophil to lymphocyte ratio (r, 0.54; P =.001), and arterial oxygen partial pressure to fractional inspired oxygen (PO₂/FiO₂; r, -0.53; P =.02).

Thrombotic events developed among 22.2% of patients (pulmonary embolism [n=6], deep vein thrombosis [n=2], vena cava thrombosis [n=1]). These patients were under prophylactic low-molecular weight heparin (LMWH; n=6) and therapeutic LMWH (n=2). Thrombotic events were associated with high SOFA scores (8.2±1.2 vs 5.5±0.3; P <.05).

Patients who were infected with SARS-CoV-2 had higher circulating platelet-leukocyte, platelet-neutrophil, and platelet-monocyte complexes than healthy controls. Soluble P-selectin was correlated with PO₂/FiO₂ (r, -0.52; P =.032) and neutrophil to lymphocyte ratios (r, 0.36; P =.047), which were related with disease severity.

Patients infected with SARS-CoV-2 had higher circulating myeloperoxidase-DNA complexes and citrullinated histone H3. Myeloperoxidase-DNA complexes were associated with plasma soluble P-selectin (r, 0.39; P =.027), neutrophil to lymphocyte ratio (r, 0.55; P =.001), and SOFA scores (r, 0.63; P =4.8×10^–4).

Myeloperoxidase-DNA complexes could be used to distinguish patients more likely to develop a thrombotic event (area under the curve [AUC], 0.769; P <.001) from those patients less likely to have an event (AUC, 0.791; P <.001). The best cut-offs were greater than 0.12 OD for myeloperoxidase-DNA complexes and greater than 3.9 ng/mL for citrullinated histone H3.

This study was limited by the small number of patients who had a thrombotic event; observations need to be confirmed among a larger cohort.

These data indicated circulating platelet and neutrophil markers may allow for stratifying patients at increased risk for severe SARS-CoV-2 infection and for thrombotic events.

Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Petito E, Falcinelli E, Paliani U, et al; COVIR study investigators. Neutrophil more than platelet activation associates with thrombotic complications in COVID-19 patients. J Infect Dis. Published online December 6, 2020. doi:10.1093/infdis/jiaa756