What vitamins are coagulation factors?

November 15, 2025 •

3 min read

Blood clotting, a vital bodily process known as hemostasis, relies on a complex cascade of proteins called coagulation factors. While a vitamin is not a coagulation factor itself, a single fat-soluble vitamin plays an indispensable role as a necessary cofactor: Vitamin K.

Quick Summary

The coagulation process depends on several liver-synthesized proteins that require Vitamin K as a crucial cofactor. A deficiency in this vitamin can cause impaired clotting.

Key Points

Vitamin K is the Cofactor: Vitamin K is the single most essential vitamin involved in the production of specific coagulation factors, acting as a critical cofactor rather than a factor itself.
Key Coagulation Factors: Vitamin K is necessary for the activation of factors II (prothrombin), VII, IX, and X, which are all synthesized in the liver.
Mechanism of Action: Through a process called gamma-carboxylation, Vitamin K enables these proteins to bind calcium, allowing them to function correctly in the blood-clotting cascade.
Regulatory Proteins: In addition to procoagulant factors, Vitamin K is also required for the synthesis of anticoagulant proteins like Protein C and Protein S, which help regulate clotting.
Deficiency Risks: A lack of Vitamin K can lead to impaired blood clotting, causing excessive bleeding and bruising. This is a particular risk for newborns and individuals with malabsorption issues.
Warfarin Interference: The common anticoagulant drug warfarin works by inhibiting the Vitamin K cycle, thereby preventing the proper activation of the dependent clotting factors.
Dietary Sources: Vitamin K can be obtained from food sources such as leafy green vegetables (K1) and some fermented foods and animal products (K2), as well as being produced by intestinal bacteria.

The Essential Role of Vitamin K in Coagulation

Vitamin K is a fat-soluble vitamin famously known as the "clotting vitamin" due to its critical function in synthesizing key blood-clotting proteins. However, it is a common misconception that Vitamin K itself is a coagulation factor. Instead, it acts as a vital cofactor in a process called gamma-carboxylation. This post-translational modification is essential for the vitamin K-dependent coagulation factors to become biologically active and capable of binding calcium ions, which is a necessary step in the clotting cascade.

The Vitamin K-Dependent Coagulation Factors

In the liver, Vitamin K assists in the production and activation of a specific group of proteins. These are often referred to as the vitamin K-dependent factors and include both procoagulant (promoting clotting) and anticoagulant (inhibiting clotting) proteins.

Procoagulant Factors:

Factor II (Prothrombin): Precursor to thrombin, essential for converting fibrinogen to fibrin.
Factor VII: Involved in initiating the extrinsic coagulation pathway.
Factor IX: A key component of the intrinsic pathway.
Factor X: Where the intrinsic and extrinsic pathways merge.

Anticoagulant Proteins:

Protein C: Regulates clotting by degrading activated Factors V and VIII.
Protein S: Enhances Protein C's anticoagulant effects as a cofactor.

The Gamma-Carboxylation Process

Vitamin K enables the enzyme gamma-glutamyl carboxylase (GGCX) to modify specific glutamic acid residues on precursor proteins into gamma-carboxyglutamate (Gla) residues. These Gla domains bind calcium ions, crucial for the factors to function correctly on cell membranes during clotting. The vitamin K used is recycled through the vitamin K cycle, involving vitamin K epoxide reductase (VKOR). Warfarin inhibits VKOR, causing a functional vitamin K deficiency and hindering the production of active clotting factors.

Sources of Vitamin K

Vitamin K exists primarily as K1 (phylloquinone) and K2 (menaquinones).

Vitamin K1 (Phylloquinone): Primarily found in plant sources like green leafy vegetables (kale, spinach), broccoli, Brussels sprouts, and certain vegetable oils.

Vitamin K2 (Menaquinones): Found in animal products, fermented foods (meats, liver, eggs, cheeses), and is also synthesized by intestinal bacteria.

Consequences of Vitamin K Deficiency

Deficiency is uncommon in healthy adults with a balanced diet, partly due to bacterial synthesis in the gut. However, it can occur from poor diet, malabsorption, or long-term antibiotic use. Severe deficiency leads to the production of inactive clotting factors, resulting in bleeding disorders. Newborns are at higher risk due to limited stores and undeveloped gut flora, necessitating a vitamin K injection at birth to prevent Vitamin K deficiency bleeding (VKDB).

Comparison of Vitamin K-Dependent vs. Non-Dependent Clotting Factors


Feature	Vitamin K-Dependent Clotting Factors	Non-Dependent Clotting Factors
Specific Factors	Factors II, VII, IX, X, Proteins C, S, Z.	Factors I, III, IV, V, VIII, XI, XII, XIII.
Required Cofactor	Require Vitamin K for activation.	Do not require Vitamin K for activation.
Mechanism of Activation	Undergo gamma-carboxylation to bind calcium.	Activated through a series of enzyme cleavages.
Site of Synthesis	Synthesized in the liver.	Primarily synthesized in the liver (exceptions include Factor VIII and Tissue Factor).
Effect of Warfarin	Production is inhibited by warfarin therapy.	Production is not directly inhibited by warfarin.

Conclusion

While no vitamin is a coagulation factor itself, Vitamin K is an essential cofactor for the activation of a critical group of these proteins. This activation, through gamma-carboxylation, allows factors II, VII, IX, and X, along with regulatory proteins like C and S, to bind calcium and participate in the blood clotting cascade. Proper dietary intake of Vitamin K is therefore crucial for maintaining the body's ability to form clots. Newborns are particularly vulnerable to deficiency. Understanding this relationship is key to comprehending how blood clotting functions and how certain medications impact it. You can learn more about the role of Vitamin K and its dependent factors on the NCBI Bookshelf.

Frequently Asked Questions

No, Vitamin K does not directly participate in forming the blood clot. It acts as a necessary cofactor for the activation of several clotting factors synthesized in the liver, which then participate directly in the coagulation cascade.

Gamma-carboxylation is a post-translational modification that attaches an extra carboxyl group to certain proteins. It's crucial for coagulation factors to become active, as it allows them to bind calcium, which is essential for them to function correctly on cell membranes during clotting.

Vitamin K is required for the activation of coagulation factors II, VII, IX, and X, as well as the anticoagulant proteins C and S. All are produced in the liver.

For healthy individuals, consuming high doses of Vitamin K does not typically lead to excessive blood clotting because the body's metabolism is designed to prioritize the full carboxylation of existing clotting factors. There is no known toxicity associated with high Vitamin K1 or K2 intake.

Newborns have low Vitamin K status because placental transfer is limited, their gut bacteria have not fully developed, and breast milk contains low amounts of the vitamin. An injection prevents Vitamin K deficiency bleeding (VKDB), a serious and potentially fatal condition.

Warfarin is an anticoagulant drug that works by blocking the enzyme Vitamin K epoxide reductase (VKOR), which is responsible for recycling Vitamin K. This disruption creates a functional Vitamin K deficiency, preventing the activation of clotting factors and reducing the risk of abnormal blood clots.

Beyond its role in coagulation, Vitamin K is also essential for bone health. It is required for the production of proteins like osteocalcin and matrix Gla-protein (MGP), which are involved in bone mineralization and preventing arterial calcification.