An Introduction to
Understanding Thrombosis

What is haemostasis?

• Haemostasis is the normal physiological response preventing significant blood loss after vascular injury
• The process depends on an intricate series of events involving platelets, other cells, and the activation of specific blood proteins, known as coagulation factors
• When blood vessel injury occurs, physiological haemostasis is triggered and the coagulation process begins. Haemostasis serves to maintain the integrity of the circulatory system; however, the process can become imbalanced, leading to significant morbidity and mortality
• Knowledge of the haemostasis process is important in understanding the major disease states associated with thrombosis

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The coagulation cascade

• The coagulation process that leads to haemostasis involves a complex set of reactions involving approximately 30 different proteins
• These reactions convert fibrinogen to fibrin, which, together with platelets, forms a stable thrombus. Several coagulation cascade models have been proposed, including the intrinsic and extrinsic pathway model and the more recent cell-based model
• Building on these models, research has elucidated a role for other components of the coagulation process, including microparticles and the protein P-selectin
• An inherited or acquired imbalance in the coagulation system that leads to an increased risk of thrombosis is called thrombophilia
• Approximately one in three patients with VTE has an inherited thrombophilia

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Venous thrombi

• Formation of a thrombus within a vein is known as a venous thrombosis
• If the thrombus breaks loose and travels through the circulatory system, it is known as an embolus
• Venous thrombi manifest mainly as DVT and PE
• DVT is the most common type of VTE, but patients with DVT are also at risk of PE, which can potentially be life-threatening
• VTE is associated with cancer, trauma and surgery, and several pre-disposing risk factors, including pregnancy, obesity and immobility, have been identified
• VTE can also lead to serious long-term complications, including PTS and CTEPH

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Thrombus formation

• Haemostasis is necessary for survival, but the pathological formation of a thrombus poses significant health risks
• A pathological thrombus, formed when there is an imbalance in the blood coagulation system, can potentially obstruct blood flow, leading to a number of serious health conditions
• Two different types of thrombi can be formed:
  • Arterial thrombi
  • Venous thrombi
• The pathologist Rudolph Virchow postulated that thrombus formation and propagation resulted from abnormalities in three areas, collectively known as Virchow’s triad
• It is now possible to quantify some of the factors that are associated with an increased risk of VTE and other cardiovascular diseases, and of stroke in patients with AF