# The Antithrombotic Potential of Sulfated-Polysaccharides from Red Seaweed Hypnea musciformis (Wulfen) J.V. Lamouroux: An In Vitro, In Silico and In Vivo Study

## TL;DR

This study explores anticoagulant properties of sulfated polysaccharides from red seaweed as a safer alternative to heparin for treating thrombosis.

## Contribution

The study introduces sulfated polysaccharides from Hypnea musciformis as a novel anticoagulant with reduced bleeding risk.

## Key findings

- Intact polysaccharide and one hydrolysate prolonged activated partial thromboplastin time in vitro.
- In vivo tests showed lower hemorrhagic tendency compared to heparin.
- Computational simulations revealed stronger interaction between ATIII and the intact polysaccharide.

## Abstract

Thrombosis has emerged as a significant concern during
the Coronavirus
Disease 2019 (COVID-19) pandemic, with patients experiencing increased
venous thromboembolism due to prolonged immobilization and inflammation.
In Brazil, studies show a higher thrombosis risk among COVID-19 patients,
emphasizing the need for effective thromboprophylaxis. Heparin (HEP),
commonly used in hospitals, enhances antithrombin III (ATIII) activity
to inhibit thrombin and factor Xa, thus reducing thrombosis risk.
However, it can cause adverse effects like bleeding and HEP-induced
thrombocytopenia, complicating its use and prompting the search for
safer anticoagulant alternatives. This study aimed to evaluate the
anticoagulant properties of sulfated polysaccharides (SP) derived
from the red seaweed Hypnea musciformis, particularly their hydrolysates with different molecular weights.
Additionally, computational analyses were conducted to investigate
their interaction with ATIII, compared to HEP, to determine if the
mechanism of action is similar. In vitro, the assays
assessed the antithrombotic activity using activated partial thromboplastin
time (APTT) and prothrombin time (PT) tests, with low-molecular-weight
HEP CLEXANE (LMWH) as a positive control. Results showed that the
intact polysaccharide and one hydrolysate (EX 5) prolonged activated
partial thromboplastin time, while no samples affected prothrombin
time. The in vivo bleeding time test revealed that
these samples had a significantly lower hemorrhagic tendency than
the positive control. Computational simulations indicated a stronger
interaction between ATIII and the intact polysaccharide compared to
its hydrolysate. These findings suggest that SP from H. musciformis could offer a promising anticoagulant
therapy with reduced bleeding risk for clinical application in thrombotic
conditions.