Understanding Hemophilia and Its Types
Hemophilia is an inherited bleeding disorder where the blood does not clot properly [1.9.1]. This is due to a deficiency in specific proteins called clotting factors. The two most common types are:
- Hemophilia A: Caused by a lack of clotting factor VIII (FVIII) [1.9.1].
- Hemophilia B: Caused by a lack of clotting factor IX (FIX) [1.9.1].
The severity of the disease—mild, moderate, or severe—is determined by the amount of active clotting factor in the blood [1.9.3]. People with severe hemophilia can experience spontaneous bleeding into joints and muscles, which can lead to chronic pain and joint damage if not treated effectively [1.7.2, 1.7.4].
The Traditional Drug of Choice: Factor Replacement Therapy
The long-standing standard of care for both hemophilia A and B is factor replacement therapy [1.2.4]. This treatment involves intravenously infusing commercially prepared factor concentrates to replace the missing clotting factor, allowing the blood to clot properly [1.3.2]. These concentrates are made from either human plasma or through recombinant DNA technology [1.2.4].
Treatment can be administered in two ways:
- On-Demand Therapy: Factor is infused to stop an active bleeding episode [1.3.2]. While effective for acute bleeds, this approach does not prevent them and is no longer recommended as a long-term strategy because it fails to prevent long-term joint damage [1.8.1, 1.8.3].
- Prophylactic Therapy: Factor is infused on a regular schedule (e.g., two or three times a week) to prevent bleeds from occurring in the first place [1.3.2]. Prophylaxis is superior to on-demand treatment, significantly reducing the annual number of bleeds and preserving joint health [1.8.2, 1.8.4]. Children with hemophilia A on prophylaxis may need infusions three times a week, while those with hemophilia B may need them twice a week [1.2.2].
Complications of Factor Therapy
A significant complication of factor replacement therapy is the development of inhibitors, which are antibodies that the body produces against the infused clotting factor [1.7.2]. These inhibitors can neutralize the treatment, making it less effective at stopping bleeds [1.2.2]. Up to 30% of people with severe hemophilia A may develop inhibitors [1.2.2].
A New Era: Non-Factor Replacement Therapies
In recent years, the treatment paradigm has shifted with the introduction of non-factor therapies. These innovative drugs work by rebalancing the coagulation system or mimicking the function of missing factors, rather than directly replacing them [1.4.3, 1.4.4].
Emicizumab (Hemlibra®) for Hemophilia A
Emicizumab is a bispecific monoclonal antibody that has become a game-changer for individuals with hemophilia A, both with and without inhibitors [1.5.2, 1.5.4]. It works by mimicking the function of activated factor VIII, bridging activated factor IX and factor X to restore the blood's ability to clot [1.5.1, 1.5.5].
Key advantages of Emicizumab include:
- Subcutaneous administration: It is given as an injection under the skin, which is far less burdensome than intravenous infusions [1.4.3].
- Less frequent dosing: After initial loading doses, it can be administered weekly, every two weeks, or every four weeks [1.5.1].
- Effectiveness with inhibitors: It is effective in patients who have developed inhibitors to factor VIII [1.5.4].
It is important to note that Emicizumab is a prophylactic treatment to prevent bleeds and is not used to treat active bleeding episodes [1.5.1].
Rebalancing Agents for Hemophilia A & B
Other non-factor therapies, known as rebalancing agents, are in development or newly approved. These drugs work by inhibiting the body's natural anticoagulant proteins, thereby rebalancing hemostasis. Examples include:
- Marstacimab: An antibody targeting tissue factor pathway inhibitor (TFPI) that was approved in England in May 2025 for severe hemophilia B. It is administered as a once-weekly subcutaneous injection [1.3.5].
- Fitusiran and Concizumab: These are other rebalancing agents that have shown promise in clinical trials for both hemophilia A and B [1.4.1, 1.4.2].
| Feature | Factor Replacement Therapy | Non-Factor Therapy (Emicizumab) |
|---|---|---|
| Mechanism | Replaces missing clotting factor (FVIII or FIX) [1.2.4]. | Mimics the function of FVIII [1.5.5]. |
| Administration | Intravenous (IV) infusion [1.3.2]. | Subcutaneous (SQ) injection [1.5.1]. |
| Frequency | 2-3 times per week for prophylaxis [1.2.2]. | Weekly, bi-weekly, or monthly for prophylaxis [1.5.1]. |
| Use Case | Prophylaxis and on-demand treatment of bleeds [1.3.2]. | Prophylaxis only [1.5.1]. |
| Inhibitors | Can be neutralized by inhibitors [1.2.2]. | Effective in patients with inhibitors [1.5.4]. |
Adjuvant and Alternative Therapies
- Desmopressin (DDAVP): For people with mild hemophilia A, this synthetic hormone can be used to stimulate the body to release its own stored factor VIII and von Willebrand factor [1.2.3, 1.10.4]. It can be given as a nasal spray or injection before procedures to prevent bleeding [1.10.1].
- Antifibrinolytic Agents: Medications like tranexamic acid and aminocaproic acid help prevent blood clots from breaking down [1.11.2]. They are particularly useful for bleeding in mucous membranes, such as the mouth or nose [1.11.3].
The Future: Gene Therapy
The ultimate goal in hemophilia treatment is a cure, and gene therapy offers a path toward that. The approach involves a one-time intravenous infusion of a viral vector carrying a functional copy of the FVIII or FIX gene into the liver cells, enabling the body to produce its own clotting factor [1.6.5].
- For Hemophilia B: Hemgenix® (etranacogene dezaparvovec) was approved by the FDA in November 2022 [1.3.2]. Studies have shown it can significantly reduce the rate of annual bleeds after a single infusion [1.3.4].
- For Hemophilia A: Roctavian® (valoctocogene roxaparvovec-rvox) was approved by the FDA in June 2023 for severe hemophilia A [1.2.4].
While promising, the uptake of these therapies has been slow, and there are ongoing questions about long-term durability and safety [1.6.1, 1.6.2]. However, long-term follow-up from early trials shows sustained benefit for over a decade in some patients [1.6.3].
Conclusion
There is no single "drug of choice" for hemophilia; treatment is multifaceted and evolving. Factor replacement therapy remains a cornerstone, especially for treating active bleeds. However, for prophylaxis, non-factor therapies like Emicizumab have become a preferred option for many with hemophilia A due to their convenience and effectiveness. For hemophilia B, newer agents like Marstacimab are expanding options [1.3.5]. Looking ahead, gene therapy holds the potential to provide a long-lasting, functional cure, fundamentally changing the lives of people with severe hemophilia [1.6.5]. The best treatment is determined through a collaborative decision between the patient and their hematologist, considering the type of hemophilia, its severity, the presence of inhibitors, and the patient's lifestyle.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Consult with a qualified healthcare professional for diagnosis and treatment. For more information, you can visit the CDC's page on Hemophilia Treatment.
