What is fibrinogen? Functions, classifications, and its role in the pharmaceutical industry

Fibrinogen is a plasma protein that plays a key role in blood clotting and coagulation. As the precursor to fibrin, it is responsible for forming stable clots and stopping bleeding. Beyond its importance in controlling bleeding in the body, fibrinogen is also a valuable diagnostic tool and can be isolated for use as a medication. But what exactly is fibrinogen, and why is it so important?

What is fibrinogen?

Fibrinogen is a soluble protein produced by the liver and transported into the bloodstream. It is known as “clotting factor I”, and during the formation of a blood clot, the enzyme thrombin converts fibrinogen into fibrin - a fibrous protein that forms the backbone of a stable blood clot. Fibrin assembles into a mesh-like structure that stabilizes clots and supports wound healing.

Without enough fibrinogen, the body cannot properly form blood clots, leading to excessive bleeding - even from minor injuries. Clinically, fibrinogen levels are monitored to assess the risk of bleeding, inflammation and liver function. High levels can signal inflammation, infection or an increased risk of cardiovascular events like heart attacks and strokes. Low levels may indicate liver disease or clotting disorders.

Fibrinogen concentrates are used to treat bleeding episodes and fibrin sealants are used in surgical procedures to control bleeding. 
 

Why fibrinogen matters: Clinical and industrial importance

1. Blood clotting and hemostasis

Fibrinogen is essential in the final step of the coagulation process, the series of steps that occur during the formation of a blood clot. When activated by thrombin, it transforms into fibrin, which forms the insoluble mesh that stabilizes blood clots. This not only stops bleeding but also supports wound healing and tissue repair. Fibrinogen deficiencies, whether inherited (congenital deficiency) or the result of another illness or condition (acquired deficiency), can lead to severe bleeding disorders.

2. Inflammation and cardiovascular risk

Fibrinogen also serves as a key inflammatory marker. Levels can increase in response to inflammation, infection, trauma and chronic diseases. High levels are associated with systemic inflammation, atherosclerosis and increased cardiovascular risk, including stroke and heart attack, making fibrinogen a useful tool to evaluate a patient’s condition.

3. Fibrinogen concentrates for therapy

Fibrinogen can be isolated from plasma and concentrated for use as a medication. Concentrates are used as replacement therapies for individuals with congenital and acquired fibrinogen deficiencies due to surgery, trauma or liver disease. These concentrates are highly purified and standardized for safe, fast administration.

4. Surgical applications

Fibrinogen is used intravenously to control bleeding during major procedures such as cardiac surgery, liver transplants and obstetric emergencies. Fibrin sealants, which combine fibrinogen with thrombin, are used at bleeding sites during surgery to speed up clot formation and minimize blood loss improving surgical results.

Native Fibrinogen: This is the functional form of fibrinogen naturally circulating in the plasma. In healthy adults, normal plasma levels typically range from 2-4 g/L. These levels are routinely measured in coagulation tests to assess clotting ability and monitor various clinical conditions.

Fibrinogen Disorders

High Fibrinogen Levels: Higher fibrinogen levels are often observed during systemic inflammation, pregnancy or in individuals who smoke or are obese. High fibrinogen is also recognized as a risk factor for cardiovascular diseases, including stroke and heart attack, due to the increased risk of blood clots.

Fibrinogen deficiency

• Hypofibrinogenemia: Low fibrinogen levels in blood can result from a variety of conditions such as severe liver disease, other coagulation or congenital disorders. Clinically, hypofibrinogenemia presents as an increased bleeding tendency, especially in surgical or trauma settings. Treatment options include cryoprecipitate (a frozen blood product prepared from blood plasma) or fibrinogen concentrates, which are used in emergencies and perioperative care. 
• Afibrinogenemia is characterized by a complete absence of fibrinogen, leading to severe bleeding disorders from birth. 
• Dysfibrinogenemia involves the presence of structurally abnormal fibrinogen that doesn’t function properly, which can cause either bleeding or clotting complications. These are rare genetic conditions that affect the production or structure of fibrinogen. Genetic testing and blood clotting tests are essential for diagnosis and management of these conditions.

Fibrinogen Activation and Function: Step-by-Step

Step 1: Synthesis in the liver:

Fibrinogen is produced by hepatocytes and circulates in plasma, remaining inactive until the coagulation cascade is triggered. This liver-dependent production highlights fibrinogen’s relevance in evaluating liver function.

Step 2: Activation by thrombin:

When a blood vessel is injured, the coagulation cascade is activated. Thrombin, a key enzyme in this pathway, cleaves two small peptides - fibrinopeptides A and B - from the fibrinogen molecule. This cleavage transforms soluble fibrinogen into insoluble fibrin, initiating clot formation at the site of injury.  

Step 3: Fibrin polymerization:

Fibrin is aligned and forms a polymer of long fibrin strands. These strands form a fibrous, three-dimensional network that traps red blood cells and platelets, creating the structural scaffold of a blood clot.

Step 4: Crosslinking by Factor XIII:

To enhance clot stabilization, activated Factor XIII (Factor XIIIa) creates bonds between adjacent fibrin strands, which results in a dense, insoluble fibrin mesh that resists mechanical stress and protects against premature clot breakdown. All these steps are essential for effective wound healing.

Step 5: Clot resolution (Fibrinolysis):

Once tissue repair is underway, the clot must be removed. The process of fibrinolysis dissolves the fibrin mesh. The plasmin enzyme degrades fibrin into soluble fragments, restoring normal blood flow. 

Clinical and Industrial Applications

Diagnostic testing

Fibrinogen is routinely tested using functional methods (the Clauss test) to check clotting ability and detect increased risk of blood clots.

Replacement therapies

Fibrinogen is used in congenital and adquired deficiencies.

Surgery and trauma management

Fibrinogen reduces blood loss and transfusion needs in complex procedures like liver transplantation, cardiac surgery, and obstetric hemorrhage.

Wound healing and tissue repair

Fibrinogen (in sealants) accelerates healing, promotes tissue adhesion, and locally reduces bleeding postoperatively.

Biologics and regenerative medicine

Pharma-grade fibrinogen is integral to developing biocompatible products like tissue scaffolds and drug delivery platforms.