Hemophilia is a rare but serious genetic disorder in which the blood does not clot properly due to a lack or deficiency of specific clotting factors. This leads to prolonged bleeding after injuries, surgeries, or even spontaneous internal bleeding, especially into joints and muscles. While it is commonly known as a bleeding disorder, the underlying causes of hemophilia are often misunderstood.

Hemophilia is typically inherited and passed down through generations. However, it isn’t always hereditary. In some cases, people develop hemophilia later in life due to sudden genetic mutations or autoimmune responses, with no prior family history. Whether inherited from parents or developed spontaneously, understanding the root causes of hemophilia is crucial for early diagnosis, proper management, and informed family planning.

What Is Hemophilia?

Before diving into the causes, it is important to understand what hemophilia is. Hemophilia is a hereditary disorder characterized by the inability of blood to clot efficiently due to insufficient clotting factors, specifically factor VIII (Hemophilia A) or factor IX (Hemophilia B). These clotting proteins are essential in forming stable blood clots to stop bleeding. When they are missing or defective, even minor injuries can cause significant bleeding episodes.

Genetic Cause: The Primary Factor

The most common cause of hemophilia is a genetic mutation passed down from parent to child. Hemophilia is typically inherited in an X-linked recessive pattern, which means the defective gene is located on the X chromosome. Since males have only one X chromosome, a single faulty gene can result in hemophilia. Females have two X chromosomes, so they are usually carriers without showing symptoms, although in rare cases, they may have mild symptoms if one X chromosome is defective.

When a mother carries the hemophilia gene, there is a 50% chance that her son will have hemophilia and a 50% chance that her daughter will be a carrier. In contrast, if a father has hemophilia, none of his sons will inherit the condition, but all his daughters will be carriers.

Types of Genetic Mutations

There are several types of mutations that can affect the factor VIII or factor IX genes, leading to hemophilia. These include :-

Point mutations :- A single change in a DNA base can result in a faulty clotting factor protein.
Inversions :- A section of the gene is flipped or rearranged, particularly common in severe Hemophilia A.
Deletions :- Missing parts of the gene prevent proper production of the clotting factor.
Insertions :- Extra genetic material disrupts the gene’s normal function.

The type and severity of the mutation often determine whether the individual has mild, moderate, or severe hemophilia.

Causes of Hemophilia

Sporadic Mutation :- Although hemophilia is mostly inherited, about one third of cases occur in individuals with no family history of the disorder. These are known as sporadic mutations and happen due to spontaneous changes in the genes responsible for producing clotting factors. These mutations may occur during the formation of reproductive cells or early embryonic development. In such cases, a child is born with hemophilia despite both parents having normal genes.
Sporadic hemophilia is a reminder that the condition can arise unexpectedly and may not always follow typical genetic inheritance patterns.
Hemophilia in Females :- While hemophilia predominantly affects males, females can also experience symptoms, though rarely. This can happen in the following ways :-
- X-Inactivation (Lyonization) :- In some female carriers, the normal X chromosome is randomly inactivated in more cells than the faulty one, leading to insufficient clotting factor levels.
- Inheritance from Both Parents :- If a female inherits a hemophilia gene from both a carrier mother and a hemophilic father (extremely rare), she can have a form of hemophilia similar to males.
- Acquired Hemophilia :- In very rare cases, females can develop antibodies that attack their own clotting factors, leading to a condition known as acquired hemophilia (discussed more below).
Acquired Hemophilia :- Unlike congenital hemophilia, acquired hemophilia is not inherited. Instead, it occurs when the immune system mistakenly creates antibodies that target and neutralize clotting factor VIII. This condition is extremely rare and typically occurs in adults, particularly older individuals, postpartum women, or those with autoimmune diseases, cancers, or certain medications.
Acquired hemophilia presents with similar symptoms as inherited forms such as spontaneous bleeding, bruising, or prolonged bleeding after procedures but requires a different diagnostic and treatment approach.

Risk Factors That May Influence Hemophilia Expression

Although hemophilia is primarily genetic, certain factors may influence how it manifests :-

Severity of Mutation :- Some mutations lead to almost complete absence of the clotting factor, causing severe hemophilia, while others allow some function, leading to milder forms.
Carrier Status in Women :- Carriers may show bleeding tendencies, especially after surgeries, childbirth, or trauma.
Ethnicity and Family Background :- Hemophilia occurs in all ethnic groups but is more likely to be detected in populations with advanced genetic screening.

Diagnosing the Cause of Hemophilia

Diagnosis begins with a clinical evaluation of symptoms, followed by blood tests to measure clotting factor levels. If hemophilia is suspected, a genetic test can identify the specific mutation responsible. In sporadic or acquired cases, additional antibody tests and immune profiling may be needed.

Early and accurate diagnosis is crucial for managing hemophilia effectively and preventing complications like joint damage, internal bleeding, and prolonged wound healing.

Can Hemophilia Be Prevented?

Since hemophilia is usually inherited, it cannot be prevented in the traditional sense. However, genetic counseling can help families understand their risk and make informed decisions. Prenatal testing and carrier screening are also available for those with a family history of hemophilia. In the case of acquired hemophilia, managing underlying conditions and being aware of potential medication side effects may reduce the risk.

Conclusion

Hemophilia is a complex bleeding disorder rooted primarily in genetics but influenced by a range of mutations and, in rare cases, immune system dysfunctions. Understanding the causes of hemophilia helps individuals and families prepare for early diagnosis, better management, and treatment planning.