Clotting factors are proteins in the blood that control bleeding. When a blood vessel is injured, the walls of the blood vessel contract to limit the flow of blood to the damaged area. Then, small blood cells called platelets stick to the site of the injury and spread along the surface of the blood vessel to stop the bleeding.

At the same time, chemical signals are released from small sacs inside the platelets that attract other cells to the area and make them clump together to form what is called a platelet plug.

On the surface of these activated platelets, many different clotting factors work together in a series of complex chemical reactions (known as the coagulation cascade) to form a fibrin clot. The clot acts like a mesh to stop the bleeding.

Coagulation factors circulate in the blood in an inactive form. When a blood vessel is injured, the coagulation cascade is initiated, and each coagulation factor is activated in a specific order to lead to the formation of the blood clot. Coagulation factors are identified with Roman numerals (e.g. factor I or FI), although the coagulation cascade does not follow numerical sequencing. An ‘a’ is added to the name to indicate that the protein has been activated; for example, FX (factor X) gets activated to FXa. 

If any of the clotting factors in the cascade are missing or do not function correctly,  the chain reaction of activated factors is extremely slowed down, and the fibrin mesh is very weak. In afibrinogenemia, the fibrin mesh is not generated at all. 

Beyond clotting factor deficiencies, bleeding can also occur if there are problems with von Willebrand factor or the platelets themselves—components responsible for the initial step of blood clotting (primary hemostasis).

von Willebrand Disease (vWD)

• Mechanism: As the most common inherited bleeding disorder, vWD occurs due to a deficiency or dysfunction in von Willebrand factor (vWF).
• Role in Clotting: vWF acts as the essential molecular “glue” that anchors platelets to subendothelial collagen at the injury site. It also serves as a protective carrier protein for Factor VIII in the bloodstream.
• Impact: Without sufficient or functional vWF, platelets cannot stick to the damaged blood vessel, preventing the initial platelet plug from forming efficiently and destabilising Factor VIII levels.

Platelet Disorders: Platelet-related bleeding disorders are broadly divided into two categories based on whether the issue is the number of platelets or how well they function:

• Quantitative Defects (Thrombocytopenia): Occurs when the body has too few platelets to form an effective plug. This can stem from reduced bone marrow production, increased destruction (e.g., Immune Thrombocytopenia / ITP), or splenic sequestration.
• Qualitative Defects (Platelet Dysfunction): Occurs when platelet counts are normal, but the platelets fail to adhere, activate, or aggregate properly.
  • Inherited: Conditions like Bernard-Soulier syndrome (defects in platelet adhesion receptors) or Glanzmann thrombasthenia (defects in platelet aggregation receptors).
  • Acquired: Frequently caused by medications like aspirin and antiplatelet agents, which inhibit chemical signals needed for aggregation, or underlying conditions like kidney dysfunction.