Scientists in Birmingham have discovered a new blood coagulation puzzle

Scientists in Birmingham described a potential new target and strategy for antithrombotic therapy.

Their findings indicate a new platelet activation mechanism involving the binding protein S100 A8/A9 to the GPIbα platelet receptor, which has not previously been described as a target for anticoagulation therapy

These studies were conducted by Dr.

S100A8/A9 is expressed in white blood cells (neutrophils) and is a risk-related molecular pattern (DAMP), including a variety of molecular families that initiate inflammation during disease

S100 A8/A9, which is normally stored in cells, is released into the circulation during infection or inflammation, where it activates other immune cells

The concentration of S100 A8/A9 in the plasma of 87 severely ill patients extracted by the researchers from the blood of COVID-19 patients in the intensive care unit continued to be high (10-40 μg/ml)

After these findings, the researchers turned their attention to whether or how S100 A8/A9 affects platelet function, and found that recombinant human S100 A8/A9 induces the formation of procoagulant platelets in healthy human blood samples, which is a form of support for blood clotting The platelet population

The level of platelet activation is both significant and concentration-dependent, and has been confirmed in studies using a series of pro-coagulant markers

Surprisingly, their results showed that although recombinant S100 A8/A9 does not induce platelet aggregation, it does induce fibrin production in whole blood

Dr.

The researchers then tested whether S100 A8/A9-induced platelet activation can be reduced by antiplatelet drugs and non-steroidal anti-inflammatory drugs or by targeting the known receptors of S100 A8/A9

Studies using human platelets confirmed this, showing that recombinant GP1bα inhibits S100A8/A9 activation (measured by p-selectin expression, gpiibiia activation, and phosphatidylserine exposure)

Dr.

The University of Birmingham enterprise has filed a broad-based patent application involving the interaction of S100A8/A9 and GPIbα receptors in the treatment and prevention of inflammation and thrombotic diseases

Researchers are continuing to study the basic mechanisms and approaches.

The level of S100A8/A9 is elevated in COVID-19 patients, and it induces platelet coagulation in a gpib-dependent manner.