In the intrinsic pathway of coagulation, which factor is activated by the contact of blood with negatively charged surfaces?

Explanation

## The Intrinsic Pathway: Contact Activation **Key Point:** The intrinsic pathway is initiated when blood comes into contact with negatively charged surfaces (in vitro) or exposed collagen and tissue factor pathway inhibitor (TFPI) in vivo. The first factor activated in this cascade is Factor XII (Hageman factor). ### The Contact Cascade (Intrinsic Initiation) ```mermaid flowchart TD A[Negatively charged surface<br/>Collagen, kaolin, glass]:::outcome --> B[Factor XII<br/>Hageman factor]:::action B --> C[Factor XIIa<br/>Serine protease]:::action C --> D[Factor XI activation]:::action D --> E[Factor IXa<br/>Christmas factor]:::action E --> F[Tenase complex<br/>IXa + VIIIa + PL + Ca2+]:::action F --> G[Factor X activation]:::action G --> H[Common pathway]:::outcome ``` ### Intrinsic vs. Extrinsic Pathway Initiation | Pathway | Initiator | First Factor Activated | Clinical Test | |---------|-----------|------------------------|---------------| | **Intrinsic** | Negative surface / Collagen | **Factor XII** | aPTT (activated partial thromboplastin time) | | **Extrinsic** | Tissue Factor (TF) + Factor VII | **Factor VII** | PT (prothrombin time) | | **Common** | Factor X activation | **Factor X** | PT, aPTT, Thrombin time | ### Why Factor XII? **High-Yield:** Factor XII (Hageman factor) is the **contact factor**. When blood encounters negatively charged surfaces (glass, kaolin, or in vivo: collagen, phosphatidylserine on apoptotic cells), Factor XII undergoes autoactivation to Factor XIIa. Factor XIIa is a serine protease that then activates Factor XI, which activates Factor IX, leading to the amplification cascade. **Clinical Pearl:** Factor XII deficiency does **NOT** cause bleeding, despite a prolonged aPTT. This is because the extrinsic pathway (Factor VII) can still generate sufficient thrombin. However, Factor XII deficiency increases the risk of thrombosis (paradoxically) and is associated with angioedema (via bradykinin generation through the kallikrein-kinin system). ### Why the Other Options Are Wrong - **Factor VIII:** Activated downstream by Factor IXa; it is a cofactor, not the initiator. - **Factor IX:** Activated by Factor XIa; it comes after Factor XII in the cascade. - **Factor X:** Part of the common pathway; it is activated by both intrinsic (tenase) and extrinsic (TF-VIIa) complexes, but it is not the initiator of the intrinsic pathway.