What are the causes and symptoms of bleeding disorders, such as Hemophilia (Hemophilia A and Hemophilia B) or Von Willebrand disease?

From the Guidelines

Bleeding disorders, such as hemophilia A and B, should be managed with factor replacement therapy, including recombinant factor VIII products for hemophilia A, and consideration of non-replacement therapies like emicizumab for severe cases with inhibitors, as recommended by the International Society on Thrombosis and Haemostasis clinical practice guideline 1. The treatment of bleeding disorders depends on the specific disorder, with hemophilia A and B being managed differently.

• Hemophilia A is more common, accounting for about 80% to 85% of all hemophilia cases, and results from deficiency of functional coagulation factor VIII, while hemophilia B results from deficiency of functional factor IX 1.
• The estimated prevalence of hemophilia A and B at birth is 24.6 and 5.0 cases per 100,000 males, respectively, and individuals with hemophilia live with an increased risk of excessive bleeding, which varies according to the baseline factor plasma levels 1.
• Treatment with FVIII and FIX concentrates may lead to the development of antibodies against the infused clotting factor concentrate, of which some may neutralize the factor activity, and bypassing agents such as recombinant activated FVII and activated prothrombin complex concentrate can be used to treat patients with inhibitors whose bleeding does not respond to replacement of the deficient factor 1.
• Non-replacement therapies, such as emicizumab, have emerged as new treatment options for hemophilia A, and are recommended for the prophylactic treatment of patients with severe hemophilia A with and without inhibitors 1.
• Patients with bleeding disorders should carry medical identification indicating their condition, avoid medications that affect clotting, and seek immediate medical attention for serious bleeding episodes.
• The International Society on Thrombosis and Haemostasis clinical practice guideline provides recommendations for the treatment of congenital hemophilia A and B, including the use of plasma-derived FVIII and FIX concentrates, standard and extended half-life recombinant FVIII and FIX concentrates, bypassing agents, and emicizumab 1.

From the FDA Drug Label

Desmopressin Acetate Injection is a vasopressin analog used for:

• Hemophilia A- for patients with factor VIII coagulant activity levels greater than 5% to maintain hemostasis during surgical procedures and postoperatively or reduce bleeding with episodes of spontaneous or traumatic injuries such as hemarthroses, intramuscular hematomas, or mucosal bleeding.
• von Willebrand's disease (Type I) - for patients with mild to moderate disease with factor VIII levels greater than 5% to maintain hemostasis during surgical procedures or traumatic injuries such as hemarthroses, intramuscular hematomas, or mucosal bleeding.

Bleeding Disorders: Desmopressin acetate is used to manage bleeding disorders such as Hemophilia A and von Willebrand's disease (Type I) by increasing factor VIII coagulant activity levels.

• Key Indications:
  • Hemophilia A: maintain hemostasis during surgical procedures, postoperatively, or reduce bleeding with spontaneous or traumatic injuries
  • von Willebrand's disease (Type I): maintain hemostasis during surgical procedures or traumatic injuries
• Important Considerations:
  • Factor VIII coagulant activity levels should be greater than 5% for desmopressin acetate to be effective
  • Desmopressin acetate is not indicated for severe Type I von Willebrand's disease or when there is evidence of an abnormal molecular form of factor VIII antigen 2

From the Research

Bleeding Disorders Overview

• Bleeding disorders, such as hemophilia A and von Willebrand's disease, are conditions that affect the blood's ability to clot, leading to prolonged bleeding 3, 4.
• These disorders can be managed with various treatments, including desmopressin, a synthetic vasopressin analogue that increases plasma concentrations of factor VIII and von Willebrand factor 3, 4, 5.

Desmopressin Treatment

• Desmopressin is a safe and effective agent in the management and prophylaxis of bleeding tendency in patients with mild hemophilia A and von Willebrand's disease 3, 4, 5.
• The treatment involves administering desmopressin intravenously or subcutaneously, which can increase factor VIII and von Willebrand factor concentrations, providing normal hemostasis in patients with mild or moderate hemophilia and von Willebrand's disease 3, 4, 5.
• However, some patients may not respond to desmopressin, and a test-infusion or injection should be carried out to assess the future usefulness of the compound 5.

Emergency Management

• Emergency department physicians play a crucial role in managing patients with bleeding disorders, requiring accurate diagnosis, appropriate investigations, and timely management of bleeding symptoms 6.
• A thorough history and physical examination are essential in identifying the cause of bleeding and assessing the severity of the condition 6.
• In patients with diagnosed bleeding disorders, emergency care cards can outline the initial treatment, which should be administered before pursuing investigations or imaging studies 6.

Management and Prophylaxis

• Proper prophylactic or early treatment with appropriate hemostatic agents can minimize morbidity and functional disability, improving quality of life in patients with bleeding disorders 7.
• DDAVP is the drug of choice for patients with mild hemophilia or type 1 or 2 von Willebrand's disease, whose response to DDAVP has been found to be adequate 7.
• Recombinant products and virally inactivated plasma-derived products are recommended for therapeutic blood components, with dosages varying according to specific indications 7.