What do the intrinsic and extrinsic (coagulation) pathways reflect?

From the Guidelines

The intrinsic and extrinsic pathways reflect two distinct mechanisms of initiating blood coagulation, with the intrinsic pathway starting within the bloodstream and the extrinsic pathway beginning outside the blood vessels, both ultimately converging to form a stable clot.

Key Points

• The intrinsic pathway is triggered by an activating surface, such as contact activation by glass, which activates factor XII to factor XIIa 1.
• The extrinsic pathway is initiated by tissue factor from damaged cells contacting factor VII in the blood, forming a complex that activates factor X directly 1.
• Both pathways converge into a final common pathway, where factor X is activated into factor Xa, and factors Xa and factor Va together form the prothrombinase complex, which catalyses thrombin formation from prothrombin 1.
• The formation of tenase and prothrombinase complexes requires a surface, which is present as membranes (platelets, EVs) that expose negatively charged phospholipids (PL) as phosphatidylserine 1.
• Certain anticoagulants inhibit coagulation by chelating Ca2+ ions, thereby impeding the formation of the tenase and prothrombinase complexes 1.

Clinical Importance

• Understanding the intrinsic and extrinsic pathways is crucial for diagnosing and managing coagulation disorders, as well as interpreting laboratory tests such as the activated partial thromboplastin time (aPTT) and prothrombin time (PT) 1.
• The intrinsic pathway is assessed by the aPTT, while the extrinsic pathway is evaluated by the PT 1.
• In reality, these pathways do not function independently but work together in a complex, interconnected system to achieve hemostasis when blood vessel injury occurs 1.

From the Research

Intrinsic and Extrinsic Pathways

The intrinsic and extrinsic pathways are part of the coagulation cascade, which is a complex process that helps to prevent excessive bleeding when a blood vessel is injured.

• The intrinsic pathway is activated by damage inside the vascular system and is mediated by platelets and other substances in the blood.
• The extrinsic pathway is activated by external trauma that leads to blood vessel damage and is mediated by tissue factor, a protein that is released from damaged tissue.

Reflection of Intrinsic and Extrinsic Pathways

The provided studies do not directly discuss the intrinsic and extrinsic pathways of coagulation. However, they do discuss the treatment and prevention of deep vein thrombosis and pulmonary embolism, which are conditions related to coagulation disorders.

• According to 2, the treatment of deep vein thrombosis or pulmonary embolism with low-molecular-weight heparin (LMWH) or warfarin can help to prevent recurrences.
• The study 3 discusses the use of apixaban, a direct oral anticoagulant, for the treatment and prevention of venous thromboembolism.
• The review 4 focuses on the pharmacology and clinical trial data of apixaban for the prevention and treatment of deep vein thrombosis and pulmonary embolism.
• The study 5 examines the relationship between anticoagulation intensity and the risk of recurrence after deep vein thrombosis or pulmonary embolism.
• The review 6 discusses the use of rivaroxaban, another direct oral anticoagulant, for the treatment and prevention of deep vein thrombosis and pulmonary embolism.

Coagulation Cascade

While the provided studies do not directly discuss the intrinsic and extrinsic pathways, they do highlight the importance of coagulation in the development and treatment of thrombotic disorders.

• The coagulation cascade is a complex process that involves the activation of various clotting factors, including those involved in the intrinsic and extrinsic pathways.
• Understanding the coagulation cascade is essential for the development of effective treatments for thrombotic disorders, such as deep vein thrombosis and pulmonary embolism.