The complex process of blood clotting
When a blood vessel is injured, the body's hemostatic system initiates a complex, multi-step process known as the coagulation cascade to stop the bleeding. This cascade involves a series of reactions that activate proteins called clotting factors, which work with platelets to form a fibrin clot. A deficiency in any one of these clotting factors can disrupt the process, leading to excessive bleeding. Deficiencies can be inherited genetically or acquired later in life due to other medical conditions or nutritional issues.
Major inherited bleeding disorders
Deficiencies in certain clotting factors are some of the most well-known causes of inherited bleeding disorders. The two most common are hemophilia A and B, which are primarily inherited by males through the X chromosome, and von Willebrand disease, which affects both males and females.
Hemophilia A: Factor VIII deficiency
- Cause: Hemophilia A is caused by a deficiency in factor VIII, a critical protein in the coagulation cascade.
- Symptoms: Bleeding severity depends on the level of factor VIII in the blood. Severe cases can result in frequent spontaneous bleeding into joints and muscles, which can cause significant pain and permanent joint damage if left untreated.
Hemophilia B: Factor IX deficiency
- Cause: Also known as Christmas disease, hemophilia B results from a deficiency of factor IX.
- Symptoms: Like hemophilia A, the severity of bleeding is related to the amount of factor IX present. Symptoms range from mild, often only noticed after a major injury or surgery, to severe, with frequent spontaneous bleeding episodes.
Von Willebrand Disease (VWD): vWF deficiency
- Cause: As the most common inherited bleeding disorder, VWD is caused by a deficiency or defect of von Willebrand factor (vWF). VWF acts as a glue, helping platelets stick to the site of injury and carrying factor VIII, which protects it from breakdown.
- Types: VWD has several types, with Type 1 being the most common. The severity of symptoms can vary widely depending on the type and amount of functional vWF.
- Symptoms: Symptoms often include easy bruising, frequent nosebleeds, and heavy menstrual bleeding in women.
Rare inherited bleeding disorders
Besides hemophilia A, B, and VWD, deficiencies in other factors can also lead to bleeding disorders. These are often less common and are typically inherited in an autosomal recessive manner, meaning a person inherits two defective genes.
- Factor I (Fibrinogen) Deficiency: The complete absence (afibrinogenemia) or low levels (hypofibrinogenemia) of this protein can prevent proper clot formation.
- Factor VII Deficiency: A lack of this factor, also known as Alexander's disease, can cause easy bruising, nosebleeds, and excessive bleeding after injury or surgery.
- Factor X Deficiency: This rare deficiency, also called Stuart-Prower deficiency, can lead to severe bleeding episodes, including joint bleeds and intracranial hemorrhage.
- Factor XI Deficiency (Hemophilia C): Most common among people of Ashkenazi Jewish descent, this deficiency typically causes milder bleeding problems that often only become apparent after trauma or surgery.
- Factor XIII Deficiency: This very rare deficiency can cause delayed but significant bleeding episodes, as the initial clot is unstable and breaks down.
Acquired conditions affecting clotting factors
While many factor deficiencies are inherited, several conditions can cause acquired bleeding disorders by affecting the production or function of clotting factors.
Vitamin K deficiency bleeding (VKDB)
- Cause: Vitamin K is essential for the liver to produce several key clotting factors (II, VII, IX, X). A deficiency, especially common in newborns who haven't received a preventative shot, can cause serious bleeding.
- Symptoms: VKDB can manifest as bruising, bleeding from the umbilical cord, or, most dangerously, intracranial hemorrhage, with few to no warning signs.
Other acquired causes
- Liver Disease: Since most clotting factors are synthesized in the liver, severe liver disease can impair their production, leading to bleeding.
- Vitamin C Deficiency (Scurvy): While not directly impacting clotting factors, a lack of vitamin C weakens blood vessels and impairs collagen formation, causing bleeding gums and easy bruising.
- Medications: Certain blood-thinning medications, like warfarin, work by interfering with vitamin K and can cause acquired factor deficiencies.
Comparing common bleeding disorders
| Feature | Hemophilia A | Hemophilia B | Von Willebrand Disease (VWD) | Vitamin K Deficiency |
|---|---|---|---|---|
| Deficient Factor | Factor VIII | Factor IX | von Willebrand Factor (vWF) | Factors II, VII, IX, X |
| Cause | Inherited (X-linked) | Inherited (X-linked) | Inherited (Autosomal Dominant) | Acquired (poor diet, liver disease) |
| Prevalence | Approximately 1 in 5,000 live male births | Approximately 1 in 25,000 live male births | Most common inherited bleeding disorder, affecting up to 1% of the population | More common in infants not given prophylactic Vitamin K; can occur in adults with risk factors |
| Typical Symptoms | Joint and muscle bleeds, deep bruising | Joint and muscle bleeds, deep bruising | Easy bruising, frequent nosebleeds, heavy periods | Internal/external bleeding, especially in newborns (VKDB) |
When to seek medical help
If you or a loved one experience unexplained or excessive bleeding, easy bruising, frequent nosebleeds, or prolonged bleeding after a minor injury, it is crucial to consult a healthcare provider. Diagnosis involves specific blood tests, such as prothrombin time (PT), partial thromboplastin time (PTT), and specific factor assays, to identify the underlying deficiency. Early diagnosis is vital for preventing life-threatening bleeds and managing the condition effectively. For more information on the types of bleeding disorders, visit the NHLBI website.
Conclusion
Numerous factor deficiencies, both inherited and acquired, can cause abnormal bleeding. Conditions like hemophilia A, hemophilia B, and von Willebrand disease are common inherited causes, while vitamin K deficiency can lead to a potentially severe acquired form. A proper diagnosis from a healthcare professional is the first step toward understanding and managing these complex conditions to prevent complications and improve quality of life.
