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The clotting problem in hemophilia

Introduction

Blood is carried throughout the body within a network of blood vessels. When tissues are injured, damage to a blood vessel may result in leakage of blood through holes in the vessel wall. The vessels can break near the surface, as in a cut. Or they can break deep inside the body, making a bruise or an internal hemorrhage.

Platelets are small cells circulating in the blood. Each platelet is less than 1/10,000 of a centimetre in diameter. There are 150 to 400 billion platelets in a normal litre of blood. The platelets play an important role in stopping bleeding by clumping together and forming a plug, thereby beginning the repair of injured blood vessels. Clotting factors like factor VIII and IX are then needed to glue the plug in place thus forming a clot.

When a blood vessel is damaged, there are four stages in the normal formation of a clot. See Figure 1.


Figure 1


Stage 1: The blood vessels are damaged and the bleedings starts.

Stage 2: The blood vessels constrict to slow the flow of blood to the injured area.

Stage 3: Platelets stick to, and spread on, the walls of damaged blood vessels. This is called platelet adhesion. These spreading platelets release substances that activate other nearby platelets which clump at the site of injury to form a platelet plug. This called platelet aggregation.

Stage 4: The surface of these activated platelets then provides a site for blood clotting to occur. Clotting proteins like factor VIII and IX circulating in the blood are activated on the surface of the platelets to form a mesh-like fibrin clot.

These proteins (factors I, II, V, VII, VIII, IX, X, XI, XII, XIII and von Willebrand factor) work like dominos, in a chain reaction. This is called the coagulation cascade. (See Figure 2.)


Figure 2


What is the clotting problem in hemophilia?

When one of the proteins, for example, factor VIII, is absent, the dominos stop falling, and the chain reaction is broken. Clotting does not happen, or it happens much more slowly than normal. The platelets at the site of the injury do not mesh into place to form a permanent clot. (See Figure 1, stage 4.) The clot is 'soft' and easily displaced. Without treatment, bleeding will continue until the pressure outside the broken vessel is equal to the pressure inside. This can take days and sometimes weeks.