Hemophilia is associated with various clotting factors. Patients with hemophilia can receive replacement therapy for the specific clotting factor in which they are deficient. Replacement therapy involves infusing clotting factors intravenously. It is effective in combating bleeding episodes, and patients can receive continuous replacement therapy. The replacement clotting factor can involve donor blood or recombinant clotting factors that are not related to human blood but are prepared in labs. Other therapies like desmopressin are effective for mild hemophilia. Desmopressin stimulates hormones to release more clotting factors. It can be administered via nasal spray or injected into the vein. Clot-preserving medications are effective in protecting clots from breaking down. Fibrant sealants can be applied directly over the wound site as they promote clotting and healing for patients with hemophilia. Internal bleeding can cause significant damage to the joints. Physical therapy is critical in reducing the impact of bleeding into joint spaces. Surgery may be required in severe cases. First aid involving pressure bandages can be helpful for minor cuts to reduce bleeding. Ice packs are helpful for areas beneath the skin, and ice pops help in slowing down bleeding in the mouth. Patients diagnosed with hemophilia are recommended to get immunization against both hepatitis A and B as there is a chance of contracting these diseases through donated blood products.¹
Patients diagnosed with moderate or severe hemophilia A are treated with factor VIII concentrates. Most patients with mild hemophilia A are treated with desmopressin (1-Deamino-8-D-ArgininVasoPressin). DDAVP® (desmopressin) is preferred over factor VIII concentrates as the treatment of choice because DDAVP is generally cheaper, depending upon the country. Patients treated with DDAVP do not have the risk of developing inhibitors due to the use of allogeneic (exogenous) sources of factor VIII present in clotting factor concentrates. Endogenous factor VIII increases with desmopressin in patients with hemophilia A. In previous studies, large inter-individual variation in response to desmopressin was observed. Desmopressin is less frequently used in patients with moderate hemophilia A as patients with lower baseline factor VIII levels show reduced response.²
Blood Clotting Intervention
Various studies have been conducted to understand the randomized or quasi-randomized clinical trials involving children and adults with congenital hemophilia A and B. They included patients with varying degrees of severity and ages. Patients with factor VIII or IX inhibitors were excluded from the study. These trials included various clotting factor concentrates administered intravenously as prophylactic treatment. Prophylaxis can be administered in many formulations, such as clotting factor concentrates, recombinant clotting factor concentrates, fresh frozen plasma, cryoprecipitate, or lyophilized plasma-derived clotting factor concentrates. The comparison groups in the studies were prophylaxis versus on-demand treatment, prophylaxis versus placebo, and prophylaxis versus alternate prophylaxis.³
Treatment Centers and Factor Concentrates
Hemophilia treatment centers are equipped with doctors and nurses who are capable of providing good quality medical care for patients with hemophilia. They provide comprehensive care that can help patients to prevent serious issues related to hemophilia and address major concerns related to a bleeding disorder. The team consists of blood specialists and hematologists, physical therapists, social workers, and other healthcare professionals who are specialized in the care of patients with bleeding disorders. Plasma-derived factor concentrates are part of the treatment. The liquid part of the blood contains clotting factors, albumin, and antibodies. Human plasma protein is part of clotting factor products, which are collected from donors and tested for viruses. The collected plasma undergoes several processes to separate the freeze-dried clotting factors components into clotting factor products, and it is treated to kill any potential viruses and packaged for use.⁴
Treatment Products – Emicizumab and DDAVP
Emicizumab replaces the function of factor VIII rather than replacing the deficient factor VIII directly. It is also known as Hemlibra® or ACE910. It has the potential to reduce bleeding episodes in patients with hemophilia A. It is administered as an injection under the skin and acts as prophylaxis by treating breakthrough bleeds. It uses clotting factor concentrates, but inhibitors can still develop. The maintenance dose of emicizumab is given every 1, 2, or 4 weeks. It is well tolerated by patients and acts as an effective alternative to conventional factor VIII replacement products. Chromogenic Bethesda assay is required to test for inhibitors as traditional laboratory inhibitor testing methods do not work.⁴,⁵
DDAVP or desmopressin acetate (Stimate®) triggers the release of factor VIII in patients with hemophilia A. It is similar to natural hormones in the body. Factor VIII is released from the body tissues where it is stored. DDAVP can be administered intravenously, subcutaneously, or intranasally. It increases factor VIII levels in the body to stop the bleeding. The drug releases factor VIII from Weibel-Palade bodies (WPBs) in the endothelial cells. Factor VIII is primarily synthesized in the liver and the extrahepatic form of factor VIII is produced in the spleen, lymphatic tissue, and endothelial cells. It is dependent upon vasopressin type 2 receptors, which are expressed in lung endothelial cells.⁴,⁶
Epsilon Aminocaproic Acid (Amicar®)
Epsilon aminocaproic acid (EACA) can prevent perioperative bleeding in patients with congenital bleeding disorders. It is effective for patients suffering from congenital bleeding disorders such as hemophilia. It acts as an alternative method to prevent bleeding complications in oral or dental procedures. Minor surgical procedures can be hazardous for patients with hemophilia because of bleeding, which depends on the severity of the disease. Several local and systematic patient factors are involved, such as platelet dysfunction, vasculopathy, and periodontal inflammation. EACA is an antifibrinolytic agent that can prevent bleeding complications for people with inherited bleeding disorders.⁶
- Hemophilia. Mayo Clinic. August 7, 2020. Accessed August 3, 2021.
- Loomans JI, Kruip MJHA, Carcao M, et al.; RISE Consortium. Desmopressin in moderate hemophilia A patients: a treatment worth considering. Haematologica. 2018;103(3):550-557. doi:10.3324/haematol.2017.180059
- Iorio A, Marchesini E, Marcucci M, Stobart K, Chan AK. Clotting factor concentrates given to prevent bleeding and bleeding‐related complications in people with hemophilia A or B. Cochrane Database Syst Rev. 2011;(9):CD003429. doi:10.1002/14651858.CD003429.pub4
- Treatment of hemophilia. Centers for Disease Control and Prevention. Accessed August 3, 2021.
- Blair HA. Emicizumab: a review in haemophilia A. Drugs. 2019;79(15):1697-1707. doi:10.1007/s40265-019-01200-2
van Galen KP, Engelen ET, Mauser-Bunschoten EP, van Es RJ, Schutgens RE. Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions.Cochrane Database Syst Rev. 2019;4(4):CD011385. doi:10.1002/14651858.CD011385.pub3
Reviewed by Harshi Dhingra, MD, on 8/11/2021.