Hemophilia is a rare inherited bleeding disorder caused by a deficiency in specific blood-clotting proteins, known as clotting factors. This deficiency prevents blood from clotting properly, a process necessary to stop bleeding after an injury. This leads to prolonged and often spontaneous bleeding episodes, which can occur externally or internally. Management focuses on replacing the missing factors to allow for normal clot formation.
The Biological Basis of Hemophilia
The process of hemostasis, or blood clotting, involves a complex sequence of interactions between various proteins called clotting factors. These factors work together in a cascading fashion with platelets to form a stable fibrin clot that seals a damaged blood vessel. In hemophilia, a genetic mutation causes the body to produce too little of one of these specific factors, or an abnormal, non-functional version of it.
The two most common forms are Hemophilia A and Hemophilia B, which are distinguished by the factor that is missing. Hemophilia A, the more frequent type, results from a deficiency in clotting Factor VIII, while Hemophilia B involves a deficiency in Factor IX. Both of these factors are encoded by genes located on the X chromosome, which determines the inheritance pattern.
This location on the X chromosome makes Hemophilia an X-linked recessive disorder, explaining why it primarily affects males. Males have one X and one Y chromosome, meaning a single defective gene is enough to cause the condition. Females have two X chromosomes, so they typically need the defective gene on both X chromosomes to be fully affected, which is very rare. Females with one affected X chromosome are usually carriers who can pass the gene to their sons.
Recognizing the Signs of Bleeding Disorders
The severity of hemophilia is classified by the percentage of clotting factor activity in the blood. Individuals with severe hemophilia (less than 1% activity) often experience spontaneous bleeding episodes without apparent cause. Those with moderate hemophilia (1% to 5% activity) typically bleed after an injury. Mild hemophilia (5% to 40% activity) might only result in excessive bleeding following major trauma, surgery, or dental work.
One of the most characteristic and damaging types of internal bleeding is hemarthrosis, which is bleeding into the joints, most commonly the knees, elbows, and ankles. This bleeding causes pain, swelling, and tightness. If left untreated, repeated joint bleeds can lead to chronic joint damage and debilitating arthritis. Deep muscle bleeds, known as hematomas, can also occur, causing significant swelling that may press on nerves and result in pain or numbness.
Prolonged bleeding after a minor injury, excessive bruising, and frequent nosebleeds are common indicators of hemophilia. The most serious complication is bleeding into the brain, which can occur after a simple bump to the head. This requires immediate medical attention. Symptoms of intracranial bleeding include persistent, painful headaches, repeated vomiting, or sudden neurological changes.
Modern Management and Care
Diagnosis of hemophilia begins with a blood test, followed by specific factor assays that measure the percentage of Factor VIII or Factor IX activity. For individuals with a family history, testing can be performed shortly after birth using umbilical cord blood samples. The factor activity level determines the type and severity of the condition, guiding the treatment strategy.
The primary treatment involves Factor Replacement Therapy, which infuses the missing clotting factor directly into the patient’s bloodstream. The two main approaches are on-demand treatment, where the factor is infused only after a bleeding episode occurs, and prophylactic treatment, which involves regular, scheduled infusions to prevent bleeds from happening. Prophylaxis is now the standard of care for severe hemophilia, dramatically reducing joint damage and improving quality of life.
Recent advancements have introduced extended half-life factor concentrates, which require less frequent infusions, and non-factor therapies that work differently than traditional factor replacement. The most transformative development is gene therapy, which aims to provide a functional copy of the Factor VIII or IX gene to the patient’s liver cells. This can enable the body to continuously produce its own clotting factor, potentially changing a severe case of hemophilia into a mild or even normal state after a single treatment.