- Hypofibrinogenemia is a rare blood disorder characterised by low fibrinogen levels, a protein crucial for effective clot formation and bleeding control.
- Both congenital mutations and acquired conditions, such as liver damage or massive blood transfusions, can cause hypofibrinogenemia.
- Clinical manifestations typically include excessive bleeding, prolonged clotting time, and sometimes spontaneous bruising.
- Diagnostic tests measure plasma fibrinogen concentration and help differentiate between congenital and acquired hypofibrinogenemia.
- Treatment involves administering fibrinogen concentrate and addressing underlying causes to restore hemostasis.
- Complications may include unusual bleeding or, less commonly, thromboembolic events; early diagnosis is essential.
Introduction
Hypofibrinogenemia is a blood disorder characterised by a reduced level of fibrinogen, a protein necessary for blood clotting and preventing excessive bleeding. When fibrinogen levels fall below normal, the body has difficulty forming stable clots, increasing the risk of abnormal bleeding. This condition can be caused by inherited genetic mutations or develop later in life due to other health problems. Early diagnosis and treatment are crucial, as hypofibrinogenemia carries significant risks if left untreated. Considering the causes and symptoms will help you better manage your health.
Understanding Hypofibrinogenemia
Hypofibrinogenemia is a condition within the broader category of fibrinogen disorders that affects the blood’s ability to stop bleeding. This condition results from inherited (congenital) mutations or external (acquired) factors that lead to a deficiency of fibrinogen, disrupting normal clot formation.
Unlike other fibrinogen disorders, hypofibrinogenemia means that some fibrinogen remains in the plasma, but not enough for adequate hemostasis. Recognising the differences between congenital and acquired hypofibrinogenemia is critical for precise diagnosis and conduct planning.
Now we will examine the primary function of fibrinogen in the body and how hypofibrinogenemia differs from other fibrinogen-related conditions.
Definition and Fibrinogen’s Role in the Body
Fibrinogen is a large, complex protein found in plasma, with a molecular weight of approximately 340 kDa. It is produced in the liver and is one of the most abundant blood proteins after albumin and immunoglobulins. In case of injury, thrombin converts fibrinogen into fibrin, which forms the necessary network that holds the blood clot together.
Fibrinogen also:
- Binds to platelets, promoting their aggregation at sites of injury.
- Acts as an acute-phase protein during inflammation.
- Helps regulate fibrinolysis and maintain hemostasis.
When fibrinogen levels are low, blood loses its ability to form stable clots, increasing the risk of further bleeding. Hypofibrinogenemia, in particular, means a plasma fibrinogen level below normal (usually less than 2 g/dL), which disrupts the balance necessary for effective clot formation and wound healing.
Differences from Other Fibrinogen Disorders
Disorders of fibrinogen levels manifest in various forms, each with distinct characteristics. Low fibrinogen levels characterise hypofibrinogenemia, though fibrinogen levels are not absent, whereas other related disorders involve multiple defects.
| Disorder | Fibrinogen Levels | Cause | Clinical Features |
| Hypofibrinogenemia | Low (but detectable) | Congenital mutation or acquired | Bleeding, mild-moderate |
| Afibrinogenemia | Absent/Undetectable | Genetic mutation | Severe bleeding |
| Dysfibrinogenemia | Normal/Low | Dysfunctional protein (mutation) | Bleeding or clotting |
Congenital hypofibrinogenemia is a consequence of inherited genetic defects, while acquired hypofibrinogenemia is caused by external factors such as liver damage, massive blood transfusions, or certain diseases. Dysfibrinogenemia is characterised by the presence of fibrinogen with an abnormal structure, which may function incorrectly even if present in normal quantities. Understanding these differences helps physicians choose the most appropriate diagnostic tests and treatment strategies.
Causes and Risk Factors
Hypofibrinogenemia can be genetic or acquired, and each has distinct risk factors. Congenital hypofibrinogenemia is inherited and is usually caused by mutations in genes that encode fibrinogen. On the other hand, acquired hypofibrinogenemia typically develops as a result of situations such as severe liver damage, massive blood transfusions, or certain types of cancer that deplete or reduce fibrinogen levels. Knowing your family history and the presence of any co-existing liver or blood disorders can help determine your own risk level.
Genetic (Congenital) Causes
Congenital causes are often due to genetic mutations affecting fibrinogen levels. Congenital hypofibrinogenemia, a rare disorder, is characterised by significantly low levels of fibrinogen in the plasma, which impairs effective clot formation. These genetic abnormalities can disrupt normal hemostasis, increasing the risk of bleeding even with minor injuries. Understanding the molecular weight of different fibrinogen variants can be helpful for diagnosis. Fibrinogen disorders can also manifest as dysfibrinogenemia, in which impaired fibrinogen function affects overall blood clotting, underscoring the potential use of fibrinogen concentrates in treatment.
Acquired Causes and Contributing Conditions
Acquired hypofibrinogenemia results from factors that increase fibrinogen consumption or decrease its production. Common conditions include:
- Liver damage or insufficiency that impairs fibrinogen synthesis.
- Massive blood transfusions or dilution, in which red blood cells and plasma are replaced, reducing the concentration of fibrinogen.
- Certain cancers, infections, or disseminated intravascular coagulation (DIC) can increase fibrinogen degradation.
For example:
- Intensive plasma transfusions or episodes of bleeding can quickly dilute or deplete existing fibrinogen.
- Chronic diseases or treatments affecting the liver can also lead to acquired hypofibrinogenemia.
According to official government websites, early detection and handling of the underlying cause of the disease are crucial for current treatment and preventing further complications.
Symptoms and Clinical Manifestations
The clinical manifestations of hypofibrinogenemia can range from mild to severe and often include unexpected or prolonged bleeding. Some individuals may experience frequent nosebleeds, easy bruising, or unusually heavy bleeding during surgery or after an injury. In more severe cases, spontaneous hematomas—extensive collections of blood under the skin—may develop. Because the symptoms can overlap with those of other blood-clotting disorders, recognising these warning signs is crucial for early diagnosis and treatment.
Common Signs and Bleeding Events
Hypofibrinogenemia can manifest with various symptoms caused by low fibrinogen levels and impaired blood clotting. The most common symptoms include:
- Frequent nosebleeds or bleeding gums
- Excessive bleeding after minor cuts or procedures
- Easy bruising
After dental treatment, you may also experience heavy menstrual bleeding or prolonged bleeding. In some cases, bleeding from joints and muscles may occur, especially with a further decrease in fibrinogen levels. Platelet function may remain normal, but the inability to form a stable fibrin clot makes you vulnerable to further blood loss.
With persistent bleeding, the number of red blood cells may decrease over time, leading to anaemia. For these reasons, it is essential to inform your doctor of any episodes of unexplained bleeding so that they can examine you promptly.
Complications: Thromboembolism and Spontaneous Hematomas
Although bleeding is the primary concern in hypofibrinogenemia, complications can extend beyond simple blood loss. In particular, spontaneous hematomas—large, painful swellings caused by the accumulation of blood under the skin or in the muscles—can occur even without trauma. These can be uncomfortable and dangerous, especially if they occur near vital organs.
In rare cases, individuals with hypofibrinogenemia may develop thromboembolic complications, in which abnormal clot formation blocks blood vessels. As explained by De Moerloose P. and other experts, these events are infrequent but highlight the complex interplay between fibrinogen, clot formation, and the body’s regulatory systems.
Early detection and management of bleeding and clotting risks provide the best prognosis for individuals with this condition.
Diagnosis and Laboratory Assessment
Diagnosing hypofibrinogenemia involves a combination of clinical examination and specialised laboratory tests. Your medical team will measure fibrinogen concentration in your plasma using validated methods, and if bleeding is present, they may also assess platelet count and red blood cell levels. Additional diagnostic tests help differentiate between congenital and acquired forms. Based on the fallouts, your doctor will determine the optimal course of treatment. Categorising the underlying cause is crucial for effective treatment and preventing future complications.
Diagnostic Tests and Processes
To confirm hypofibrinogenemia, the doctor will order special laboratory tests. The most common is the Clauss fibrinogen test, which determines plasma fibrinogen concentration by measuring clot formation. Other tests may include:
- Fibrinogen antigen tests assess the amount of fibrinogen present.
- Viscoelastic tests (such as ROTEM or TEG) assess clot strength and stability.
- Prothrombin time (PT) and started partial thromboplastin time (aPTT) are used to determine overall blood clotting function.
Blood samples are analysed to determine platelet count and red blood cell levels to assess the degree of bleeding or consumption of blood clotting factors. The results of these diagnostic tests, described in peer-reviewed scientific literature (see [PMC, DOI, and Google Scholar]), help determine the severity of fibrinogen deficiency and the need for replacement therapy or further investigation.
Differentiating Congenital vs. Acquired Hypofibrinogenemia
The distinction between congenital and acquired hypofibrinogenemia is based on laboratory test results and the patient’s medical history. Congenital cases usually manifest at a young age and may include a family history of bleeding disorders or genetic mutations identified through molecular testing.
Acquired cases, on the other hand, typically develop suddenly, triggered by liver dysfunction, massive blood transfusions, cancer, or severe infections. Diagnostic tests help to clarify the clinical picture.
- Genetic testing for mutations in the FGA, FGB, or FGG genes confirms the diagnosis of congenital hypofibrinogenemia.
- Medical history, recent surgeries, injuries, or co-existing conditions may indicate an acquired form of the disease.
Taking these differences into account helps doctors choose appropriate therapy, addressing the underlying cause in acquired cases and offering long-term alternative solutions in congenital forms.
Conclusion
Hypofibrinogenemia is a serious condition that requires attention and understanding. By recognising its causes, symptoms, and potential complications, individuals can better manage their health. Early verdict and appropriate treatment are essential to reduce the risks related to this condition, such as thromboembolism and spontaneous bruising. If you suspect you have similar symptoms or have any worries about your health, please do not hesitate to consult a doctor for further examination. Your well-being is of paramount importance, and being informed is the first step towards proper medical care.