Disease Description (Causes and Symptoms)
- Definition: Hemophilia is a bleeding disorder caused by a congenital deficiency of blood-clotting factors (mainly VIII or IX).
- Causes and genetic types
- Hemophilia A: factor VIII deficiency, X-linked recessive inheritance (mainly affects males; females are usually carriers). Some cases result from mutations. Incidence: approximately 1 in 4,000–10,000 male births (varies by source).
- Hemophilia B: factor IX deficiency, X-linked recessive inheritance, with an incidence of approximately 1 in 20,000–25,000 male births.
- Hemophilia C: factor XI deficiency, mainly autosomal (recessive) inheritance; rare.
- Pathophysiology: VIII/IX deficiency weakens the intrinsic coagulation pathway, resulting in insufficient thrombin generation and clot formation. On testing, aPTT (activated partial thromboplastin time) is prolonged, while PT and platelet count are generally normal.
- Main symptoms
- Recurrent hemarthroses (hemophilic arthropathy, joint pain and decreased joint function), intramuscular hematomas
- Persistent bleeding after trauma, surgery, or tooth extraction
- Mucosal bleeding (gums, nosebleeds), easy bruising
- In patients with severe disease, increased risk of spontaneous bleeding within the first few months of life and serious bleeding (e.g., intracranial hemorrhage)
Treatment Methods
- General principles: replacement of the deficient clotting factor (treatment of acute bleeding and prevention [prophylaxis]), management of complications (joint damage, inhibitors), education, rehabilitation, and genetic counseling.
- Acute bleeding
- Replacement of the causative factor: Hemophilia A → factor VIII concentrates (fresh frozen plasma and cryoprecipitate are supplementary options); Hemophilia B → factor IX concentrates or combination products.
- Mild hemophilia A: desmopressin (DDAVP, a vasopressin analog) can temporarily increase VIII levels (indications must be confirmed).
- Adjunctive hemostasis: compression, rest, ice; consider orthopedic treatment and imaging in cases of joint dislocation or large hematomas.
- Prevention (prophylaxis)
- In severe hemophilia (blood factor activity ≤1%), regular intravenous injections (e.g., factor VIII 2–3 times per week, factor IX 1–2 times per week, etc.) are used to prevent joint bleeding and protect the joints.
- Education on self-injection at home enables early intervention and reduces medical expenses.
- When inhibitors (antibodies) develop
- When alloantibodies are present, standard factor administration is ineffective → use bypassing therapy (activated prothrombin complex concentrate, aPCC; recombinant activated factor VII [rFVIIa]) and consider immune tolerance induction (ITI).
- Additional treatment and management
- Pain: replace the deficient factor first; nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (aspirin) are not recommended because of the bleeding risk. Acetaminophen is preferred.
- Orthopedic treatment and physical therapy: rehabilitation and surgery for joint damage (consultation as needed).
- New and investigational treatments: AAV-based gene therapy and other treatments are actively being applied clinically and researched, but indications and availability vary by region and time (consult a specialist).
- Precautions for vaccinations and procedures: avoid intramuscular injections whenever possible (if necessary, administer replacement factor beforehand) and establish a plan to prevent and manage bleeding.
Precautions (Major Contraindications and Points to Note)
- NSAIDs (ibuprofen, indomethacin, etc.), aspirin, anticoagulants, and antiplatelet agents should be avoided because of the bleeding risk.
- A plan for factor replacement before dental or surgical procedures is essential.
- Immediate emergency medical care is required when symptoms suggest intracranial hemorrhage, such as severe headache, vomiting, decreased consciousness, or focal neurological symptoms.
Checklist Before an Outpatient Visit (Including Example Questions)
- Items to bring/prepare
- A list of currently used medications (including prescriptions, OTC medicines, and supplements)
- Copies of previous test results (coagulation tests, factor activity, inhibitor [Bethesda] test results), if available
- Records of previous injections, transfusions, and treatments (type and dose of factor product, response) and a bleeding log
- Family history (whether there is hemophilia or another bleeding disorder) and clinical photographs (such as joint deformity), if available
- Health insurance information, emergency contact information, and primary physician information
- Symptoms and changes to organize in advance for the outpatient visit
- Recent bleeding frequency, location, and cause (spontaneous vs. trauma), and the time required for healing
- Presence of joint pain, swelling, or decreased motor function
- Whether surgery or dental treatment is planned (date and type)
- Situations to inform the medical staff about in advance during the visit
- Whether you have recently received vaccinations or transfusions or received treatment at another hospital
- Allergies (especially those related to blood products or vaccines) and possibility of pregnancy (in female carriers)
Example Questions (for Preparation Before an Outpatient Visit)
- What was my factor level on my most recent test? (Or present previous test records.)
- Do I have any previous inhibitor test results? What method was used and what were the levels?
General Example Questions to Ask the Doctor
- What is the current severity and prognosis of my disease?
- What treatment (prophylaxis or self-injection) is recommended in my case? When should it be started, and what is the target treatment level?
- Which available factor product (recombinant vs. plasma-derived) is appropriate? What are the side effects?
- How should I provide emergency first aid at home if bleeding occurs? When should I go to the emergency room?
Examples of Disease-Specific Questions
- (Example: severe disease) When should regular preventive factor injections (prophylaxis) be started, and how frequently should they be given? How should the target trough factor level be set?
- If an inhibitor is detected, what are my treatment options? What are the advantages and disadvantages of immune tolerance induction (ITI) and bypassing therapy?
If necessary, discuss with your doctor the specific items for diagnostic testing and treatment planning (e.g., precise factor testing and Bethesda testing) and information on connecting with a regional hemophilia treatment center (HTC).