The word “hemo” is a prefix derived from the ancient Greek word haîma, meaning blood. Hemophilia refers to a specific, inherited condition that affects the blood’s ability to clot effectively. This inherited genetic disorder is characterized by a deficiency in certain proteins, known as clotting factors, necessary for stopping bleeding. This deficiency results in prolonged or excessive bleeding after injury.
Understanding the Prefix and the Disease
Hemophilia is fundamentally a disorder of hemostasis, the body’s natural process for preventing and stopping blood loss. The condition is defined by a missing or defective protein, known as a clotting factor, which impairs the formation of a stable blood clot. This critical process of forming a clot involves a series of steps called the coagulation cascade.
The coagulation cascade can be understood as a chain reaction, much like a set of dominoes falling in sequence, where the activation of one clotting factor triggers the next. At the end of this complex chain, the final step is the conversion of a soluble protein called fibrinogen into insoluble fibrin strands. These fibrin strands create a mesh-like structure that stabilizes the initial, weak platelet plug, forming a strong, lasting clot to seal the injured blood vessel.
In individuals with hemophilia, one of the essential factors in the middle of this cascade is absent or dysfunctional. The two most common forms involve Factor VIII or Factor IX, both of which are required to activate the subsequent factors in the chain reaction. Without the proper function of Factor VIII or Factor IX, the coagulation cascade breaks down, preventing the formation of sufficient fibrin mesh. This failure means that while an initial plug may form, the resulting clot is unstable and prone to breaking open, leading to continued or recurrent bleeding.
Genetic Basis and Classification
The inheritance pattern of the two main types of the disease, Hemophilia A and Hemophilia B, is defined as X-linked recessive. The genes responsible for producing Factor VIII and Factor IX are located on the X chromosome, one of the two sex chromosomes. Males possess one X and one Y chromosome, meaning that if their single X chromosome carries the altered gene, they will express the disorder because they lack a second, healthy copy to compensate.
Females, who have two X chromosomes, are typically carriers of the disorder when they inherit one altered gene. A carrier female generally has enough functional clotting factor from her healthy X chromosome to prevent severe bleeding symptoms. However, in rare cases where the process of X-chromosome inactivation is skewed, a female carrier may have lower-than-normal factor levels and experience mild bleeding symptoms.
Hemophilia is classified into three levels of severity based on the concentration of the deficient clotting factor in the blood plasma. Severe hemophilia is diagnosed when the factor level is less than 1% of the normal amount, often leading to spontaneous bleeding episodes. Moderate hemophilia is characterized by factor levels between 1% and 5%, typically resulting in bleeding only after minor trauma. Individuals with mild hemophilia have factor levels between 5% and 40% and may only experience significant bleeding following major surgery or severe injury.
Symptoms and Treatment Options
The clinical presentation of hemophilia varies significantly with the severity of the factor deficiency, ranging from mild bruising to life-threatening internal hemorrhage. The most common and defining symptom is prolonged bleeding after an injury, surgery, or dental procedure. However, the most significant medical issues arise from spontaneous internal bleeding, which may occur without any discernible trauma.
One of the most frequent and damaging types of spontaneous internal bleeding is hemarthrosis, which involves bleeding directly into the joints, particularly the knees, elbows, and ankles. This joint bleeding causes a tingling sensation, pain, swelling, and warmth. If left untreated, the repeated episodes can severely damage the joint cartilage and bone. Over time, chronic joint disease, known as hemophilic arthropathy, can develop, leading to debilitating pain and loss of mobility.
The most dangerous complication of hemophilia is an intracranial hemorrhage, or bleeding into the brain, which is a leading cause of death and disability for patients. Even a minor head bump can trigger this serious event in those with severe hemophilia. Symptoms may include a persistent, severe headache, repeated vomiting, or changes in consciousness, requiring immediate medical intervention.
The standard of care for hemophilia treatment is factor replacement therapy, which involves infusing the missing clotting factor, Factor VIII or IX, directly into the bloodstream. This is administered in two primary approaches: on-demand treatment or prophylaxis. On-demand therapy is used episodically to treat a bleed after it has occurred. Prophylactic treatment involves regularly scheduled infusions to maintain a factor level high enough to prevent bleeding from happening in the first place.
Prophylaxis, often started in childhood, is the preferred approach for those with severe hemophilia, as it significantly reduces the incidence of joint bleeding and subsequent joint damage. Modern factor products include standard half-life concentrates, which require frequent intravenous infusions, and extended half-life products, which allow for less frequent dosing. A newer approach for Hemophilia A involves non-factor therapies, such as Emicizumab, a bispecific monoclonal antibody. This drug works by binding to both Factor IXa and Factor X, effectively mimicking the function of Factor VIII to bridge these two factors together, thus bypassing the Factor VIII deficiency and restoring the coagulation cascade.