Your browser doesn't support javascript.
HIV-1 and SARS-CoV2 both cause protein s, but through different mechanisms
Research and Practice in Thrombosis and Haemostasis ; 5(SUPPL 2), 2021.
Article in English | EMBASE | ID: covidwho-1509117
ABSTRACT

Background:

The anticoagulant protein S (PS) circulates in two plasma pools free (functional) or bound to complement factor 4-binding protein (c4bp). PS deficiency commonly occurs in Human Immunodeficiency Virus-1 (HIV-1)+ patients and is associated with thrombosis. We hypothesized a similar process contributes to thrombosis in COVID-19.

Aims:

To assess the regulation of PS in viral coagulopathies.

Methods:

This study was approved by the Institutional Review Board. Citrated plasma was collected from consenting HIV-1+ (19 naïve, 11 on antiretroviral therapy, ART) or SARS-CoV-2+ (28 inpatients, 49 outpatients) and healthy controls for both populations (10, 31, respectively).

Results:

HIV-1+ patients had lower total PS than controls (94.12 ± 8.71% vs 133.77 ± 10.45%, P = 0.008), in both naïve (42%) and ART-treated (27%) patients. Total PS negatively correlated with endogenous thrombin potential ( P = 0.01), suggesting PS deficiency contributes to increased thrombin generation in these patients. Total PS was not reduced in SARS-CoV-2+ patients, but free PS was (Table). To determine the cause of free PS deficiency, we measured known PS-binding proteins C4bp, protein C (PC), and Mer, and found no differences between patients and controls. By native gel, we identified PS bound to C4bp, Mer, PC, tissue factor pathway inhibitor (TFPI), and von Willebrand Factor (VWF). VWF was markedly elevated in inpatients. Purified VWF dose-dependently decreased free, but not total, PS when added to control plasma, and blocked the TFPI cofactor activity of PS. PS was also identified as a plasma binding partner of VWF by mass spectrometry, and this interaction increased 10-million-fold with shearing. Finally, despite anticoagulation, plasma thrombin generation in inpatient samples was comparable to controls, suggesting a profound hypercoagulability, possibly exacerbated by PS deficiency.

Conclusions:

In HIV-1, PS consumption leads to total PS deficiency. In SARS-CoV-2, VWF increases and binds PS, reducing the free pool. Thus, viruses can cause PS deficiency through multiple mechanisms, promoting thrombosis by shifting the procoagulant-anticoagulant balance.

Full text: Available Collection: Databases of international organizations Database: EMBASE Language: English Journal: Research and Practice in Thrombosis and Haemostasis Year: 2021 Document Type: Article

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: Databases of international organizations Database: EMBASE Language: English Journal: Research and Practice in Thrombosis and Haemostasis Year: 2021 Document Type: Article