[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Physiology](https://durgical.com/en/physiology/) › [Blood, hemostasis and basic immunity](https://durgical.com/en/physiology/#s-blood) › The coagulation cascade

[Physiology](https://durgical.com/en/physiology/) · [Blood, hemostasis and basic immunity](https://durgical.com/en/physiology/#s-blood)

# The coagulation cascade

- Mechanism
- Exam priority: high

A chain of blood proteins turns on one after another to make thrombin, which weaves fibrin threads that hold the platelet plug.

Updated 2026-11-01

Also called: Secondary hemostasis, Clotting factors, Cell-based model of coagulation

**See it in 3D:** [Liver](https://durgical.com/en/anatomy/liver/)

## Key points

- Tissue factor (exposed after injury) with factor VIIa is the physiological trigger.
- Vitamin K–dependent proteins: factors II, VII, IX, X and proteins C and S; they need γ-carboxylation to bind Ca²⁺ and phospholipid.
- PT/INR tests the extrinsic (VII) and common pathways (X, V, II, fibrinogen); aPTT tests the intrinsic (XII, XI, IX, VIII) and common pathways.
- Factor VII has the shortest half-life (~4–6 h), so the PT rises first when vitamin K is lacking or blocked.
- Hemophilia A = factor VIII, B = factor IX: deep bleeding into joints and muscles, long aPTT, normal PT.
- Factor XII deficiency prolongs the aPTT but does not cause bleeding.

## What it is

Coagulation is a series of enzymes (clotting factors) that activate each other on cell surfaces, amplifying a small signal into a burst of thrombin. Thrombin converts soluble fibrinogen into a fibrin mesh, which factor XIII cross-links into a stable clot. Today it is taught as a cell-based process: initiation on tissue-factor cells, amplification and propagation on activated platelets.

## Key facts

- Calcium is needed at several steps; citrate and EDTA tubes keep blood liquid by binding it.
- The liver makes almost all factors (factor VIII is made largely by endothelium), so liver failure prolongs the PT.
- Heparin boosts antithrombin; vitamin K antagonists block VKORC1 recycling; direct oral anticoagulants inhibit Xa or thrombin directly.
- Newborns have low vitamin K stores and a sterile gut, the basis of hemorrhagic disease of the newborn.

## How it works, step by step

- Injury exposes tissue factor (TF) on subendothelial cells → TF binds factor VIIa.
- TF–VIIa activates factor X (and IX) → Xa with Va makes a small amount of thrombin (initiation).
- That thrombin activates platelets and factors V, VIII and XI (amplification).
- On the platelet surface, IXa with VIIIa (tenase) activates large amounts of X.
- Xa with Va (prothrombinase) converts prothrombin into a burst of thrombin (propagation).
- Thrombin cleaves fibrinogen into fibrin monomers that polymerize into a mesh.
- Thrombin activates factor XIII → XIIIa cross-links fibrin → stable, insoluble clot.
- Thrombin bound to thrombomodulin switches to anticoagulant work by activating protein C (brakes).

## Factors to know

| Factor | Name | Pathway (test) | Note |
| --- | --- | --- | --- |
| I | Fibrinogen | Common (PT and aPTT) | Acute phase protein; consumed in DIC |
| II | Prothrombin | Common | Vitamin K–dependent; becomes thrombin |
| V | Proaccelerin | Common | Factor V Leiden resists protein C |
| VII | Proconvertin | Extrinsic (PT) | Shortest half-life; vitamin K–dependent |
| VIII | Antihemophilic factor | Intrinsic (aPTT) | Carried by vWF; hemophilia A |
| IX / X | Christmas factor / Stuart factor | Intrinsic / common | Vitamin K–dependent; hemophilia B is IX |

## Memory aid

Vitamin K counts down 'ten, nine, seven, two' (X, IX, VII, II), plus its two brakes, C and S.

## Test yourself

Think of the answer, then tap the question to see it.

## Why does the PT rise before the aPTT when vitamin K is deficient?

All vitamin K–dependent factors fall, but factor VII has the shortest half-life, so it drops first; VII is only in the extrinsic pathway, measured by the PT.

## Why does a child with factor XII deficiency have a long aPTT but no bleeding?

In the body, thrombin is generated through tissue factor and factor XI activation by thrombin, bypassing XII. The aPTT test tube, however, depends on contact activation through XII.

## What does the activated platelet surface contribute to coagulation?

Exposed phosphatidylserine binds Ca²⁺ and the γ-carboxylated factors, gathering tenase and prothrombinase complexes so thrombin is generated quickly and locally.

## How can thrombin act both as a procoagulant and as an anticoagulant?

Free thrombin makes fibrin and activates platelets, V, VIII, XI and XIII. Bound to thrombomodulin on intact endothelium, it activates protein C, which inactivates Va and VIIIa.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/physiology/the-coagulation-cascade/)

## See it in 3D

The structures of Durgical's 3D anatomy where it happens.

- [Liver](https://durgical.com/en/anatomy/liver/)

## Related topics

- [Primary hemostasis and platelets](https://durgical.com/en/physiology/primary-hemostasis-and-platelets/)
- [Coagulation tests: PT/INR, aPTT and platelets](https://durgical.com/en/physiology/coagulation-tests-pt-inr-aptt-and-platelets/)
- [Fibrinolysis and natural anticoagulants](https://durgical.com/en/physiology/fibrinolysis-and-natural-anticoagulants/)
- [Thrombosis and bleeding: Virchow's triad and hemostatic defects](https://durgical.com/en/physiology/thrombosis-and-bleeding-virchow-s-triad-and-hemostatic-defects/)
- [Functions of the liver](https://durgical.com/en/physiology/functions-of-the-liver/)

## Related conditions

- [Vitamin K deficiency bleeding of the newborn](https://durgical.com/en/conditions/vitamin-k-deficiency-bleeding-of-the-newborn/)
- [Cirrhosis](https://durgical.com/en/conditions/cirrhosis/)
- [Deep vein thrombosis](https://durgical.com/en/conditions/deep-vein-thrombosis/)

## In Biochemistry

- [Vitamin K (phylloquinone)](https://durgical.com/en/biochemistry/molecules/vitamin-k/)
- [Vitamin K epoxide reductase (VKORC1)](https://durgical.com/en/biochemistry/enzymes/vitamin-k-epoxide-reductase/)

## In Pharmacology

- [Heparins](https://durgical.com/en/pharmacology/classes/heparins/)
- [Warfarin](https://durgical.com/en/pharmacology/warfarin/)
- [Direct oral anticoagulants (DOACs)](https://durgical.com/en/pharmacology/classes/direct-oral-anticoagulants/)
- [Vitamin K antagonists](https://durgical.com/en/pharmacology/classes/vitamin-k-antagonists/)
- [Rivaroxaban](https://durgical.com/en/pharmacology/rivaroxaban/)
- [Dabigatran](https://durgical.com/en/pharmacology/dabigatran/)

[← All of physiology](https://durgical.com/en/physiology/)

Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: [18.5 Hemostasis](https://openstax.org/books/anatomy-and-physiology-2e/pages/18-5-hemostasis) (OpenStax (Rice University), 2022); [Prothrombin Time Test and INR (PT/INR)](https://medlineplus.gov/lab-tests/prothrombin-time-test-and-inr-ptinr/) (MedlinePlus (U.S. National Library of Medicine), 2024); [Partial Thromboplastin Time (PTT) Test](https://medlineplus.gov/lab-tests/partial-thromboplastin-time-ptt-test/) (MedlinePlus (U.S. National Library of Medicine), 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 37). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/physiology/the-coagulation-cascade/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/physiology/the-coagulation-cascade/