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Red blood cells adopt different shape while clotting

Red blood cells take on a different shape during clotting than originally believed, according to new research.

Known as the body's shape-shifters, red blood cells are perhaps the most flexible of all cell types. However, while Dr John W Weisel and his colleagues were researching how blood clots contract using magnetic resonance technology, they made a discovery that they were not expecting when they saw a sign of closely-packed red blood cells. 

The team discovered a previously unknown geometry that red blood cells assume when they're compressed during clot formation, which could reveal a new function for the malleable cells. It transpires that they can be compressed into many-sided, tightly-packed together structures instead of their traditional biconcave disc shape. 

Dr Weisel and his researchers also found that the aggregates of fibrin and platelets, which make up highly contracted clots, mainly sit on the clot exterior. In contrast, the red blood cells are crowded within the clot interior, although its contents are more homogeneous before contraction takes place.

Contracted clots may form an impenetrable seal and help prevent vascular obstruction, but resist penetration by drugs that break down fibrin - the structural component of clots and a potential treatment for strokes and heart attacks.

Dr Weisel, professor of cell and developmental biology at the Perelman School of Medicine, said: "The first time we saw this, we thought: 'This can't be biological.'"

"We found that contracted blood clots develop a remarkable structure, with a meshwork of fibrin and platelet aggregates on the exterior of the clot and a close-packed, tessellated array of compressed polyhedral erythrocytes within," he added.

For a blood clot to be formed, it must have the right amount of stiffness and plasticity so it stanches the blood flow when the tissue is damaged. However, it also needs to be flexible enough so that blood flow is not completely blocked. 

Clots are mainly made up of two aspects - the blood protein fibrinogen and platelets. Fibrinogen is converted to fibrin while clotting occurs, while platelets aggregate by binding to fibrin once they have been activated.

Once the clot has been formed, the platelets start contracting and reduce the clot to one-third of its original size - an important part of the process in stemming bleeding. It reduces obstruction in blood vessels and creates a matrix for the migration of cells which are involved in healing the wound. 

Red blood cells are involved in the contraction process and are pulled towards the clot's interior by the platelets. 

Such tightly-packed polyhedral erythocytes were also seen in human arterial thrombi, taken from patients who had heart attacks. Red blood cells adopt this shape when they're pushed together or contracted when the platelets compress a clot. This happens to reduce the volume, surface energy or bending energy. 

These new findings will potentially have clinical implications and may shed some light on the behaviour of thrombi. Thrombi need to be broken up quickly to treat a heart attack or a stroke, because they develop resistance if not tackled rapidly enough. IT is thought that the nearly impermeable barrier created by red blood cells within the contracted clots could be the reason behind this resistance. ADNFCR-438-ID-801681092-ADNFCR

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