Hemophilia

Hemophilia is a rare inherited bleeding disorder that impairs the body's ability to form blood clots. People with hemophilia bleed longer after injuries, may have spontaneous internal bleeding, and often experience bleeding into joints and muscles. While once life-threatening, modern treatments have dramatically improved outcomes, allowing most people with hemophilia to live full, active lives with proper management.

🚨 Bleeding Emergency

Seek immediate emergency care for: head injury or severe headache, neck/throat bleeding, severe abdominal pain, excessive bleeding that won't stop, loss of consciousness, or signs of intracranial bleeding (severe headache, vomiting, confusion, seizures). Time is critical - inform medical staff about hemophilia immediately.

Medical Disclaimer: This information is for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for diagnosis and treatment of any medical condition.

Understanding Hemophilia

Hemophilia is caused by mutations in genes that provide instructions for making clotting factors. These proteins work together in a complex cascade to form blood clots. When one factor is missing or deficient, the clotting process is disrupted.

Types of Hemophilia

  • Hemophilia A (Classic Hemophilia):
    • Factor VIII deficiency
    • 80-85% of cases
    • 1 in 5,000 male births
  • Hemophilia B (Christmas Disease):
    • Factor IX deficiency
    • 15-20% of cases
    • 1 in 25,000 male births
  • Hemophilia C:
    • Factor XI deficiency
    • Rare, milder form
    • Not X-linked (affects both sexes)

Severity Classification

  • Severe: <1% normal factor activity
    • Spontaneous bleeding episodes
    • Frequent joint/muscle bleeds
  • Moderate: 1-5% normal factor activity
    • Occasional spontaneous bleeds
    • Prolonged bleeding after trauma
  • Mild: 5-40% normal factor activity
    • Bleeding mainly after surgery/trauma
    • May go undiagnosed until adulthood

Inheritance Pattern

X-Linked Recessive Inheritance

Hemophilia A and B are inherited in an X-linked recessive pattern. The genes for factors VIII and IX are located on the X chromosome.

For Males (XY):

  • One altered X chromosome causes hemophilia
  • Affected males cannot pass to sons
  • All daughters will be carriers
  • 30% of cases are new mutations

For Females (XX):

  • Usually carriers with one affected X
  • May have mild symptoms (lyonization)
  • 50% chance of passing to each child
  • Rare to have hemophilia (requires two affected X chromosomes)

Genetic Counseling

  • Important for family planning
  • Carrier testing available
  • Prenatal diagnosis possible
  • Preimplantation genetic diagnosis option

Signs and Symptoms

Common Bleeding Manifestations

  • Joint bleeds (hemarthrosis):
    • Most common in severe hemophilia
    • Knees, elbows, ankles most affected
    • Warmth, swelling, pain
    • Limited range of motion
  • Muscle bleeds:
    • Deep muscle hematomas
    • Iliopsoas bleeds particularly serious
    • Can compress nerves
  • Easy bruising:
    • Large, deep bruises
    • From minor bumps
  • Prolonged bleeding:
    • After cuts, dental work, surgery
    • May restart days later

Serious Bleeding Complications

  • Intracranial hemorrhage:
    • Life-threatening emergency
    • Can occur spontaneously or after minor head trauma
    • Leading cause of death
  • Gastrointestinal bleeding:
    • Blood in stool
    • Black, tarry stools
  • Hematuria:
    • Blood in urine
    • Usually painless
  • Retroperitoneal bleeding:
    • Back/flank pain
    • Can be life-threatening

Age-Related Presentations

Newborns:

  • Bleeding after circumcision
  • Intracranial hemorrhage (2-4%)
  • Cephalohematoma
  • Prolonged bleeding from heel sticks

Toddlers:

  • Increased bruising when learning to walk
  • Oral bleeding from falls
  • First joint bleeds

Children/Adults:

  • Recurrent joint bleeds
  • Chronic arthropathy
  • Muscle hemorrhages

Diagnosis

Clinical Suspicion

  • Family history of bleeding
  • Excessive bleeding in males
  • Unexplained bruising/bleeding
  • Joint swelling in children

Laboratory Tests

Screening Tests:

  • PT (Prothrombin Time): Normal
  • aPTT (activated Partial Thromboplastin Time): Prolonged
  • Platelet count: Normal
  • Bleeding time: Normal

Specific Factor Assays:

  • Factor VIII activity level
  • Factor IX activity level
  • Confirms diagnosis and severity
  • Distinguishes hemophilia A from B

Additional Tests:

  • Von Willebrand factor testing
  • Inhibitor screening
  • Genetic testing
  • Carrier testing for females

Prenatal Diagnosis

  • Chorionic villus sampling (10-12 weeks)
  • Amniocentesis (15-20 weeks)
  • Fetal blood sampling (18+ weeks)
  • Non-invasive prenatal testing emerging

Treatment

Factor Replacement Therapy

The cornerstone of hemophilia treatment is replacing the missing clotting factor.

Types of Factor Products:

  • Plasma-derived factors:
    • From donated human plasma
    • Viral inactivation processes
    • Contains other proteins
  • Recombinant factors:
    • Genetically engineered
    • No human/animal proteins
    • Reduced infection risk
    • Standard half-life or extended half-life

Treatment Approaches:

  • On-demand treatment:
    • Given at time of bleeding
    • For mild/moderate hemophilia
  • Prophylaxis:
    • Regular infusions to prevent bleeds
    • Standard for severe hemophilia
    • Usually 2-3 times per week
    • Extended half-life products allow less frequent dosing

Non-Factor Therapies

Emicizumab (Hemlibra):

  • Bispecific antibody for Hemophilia A
  • Mimics factor VIII function
  • Subcutaneous injection
  • Weekly to monthly dosing
  • Works with inhibitors

Desmopressin (DDAVP):

  • For mild Hemophilia A only
  • Releases stored factor VIII
  • Temporary effect
  • Cannot use repeatedly

Antifibrinolytic Agents:

  • Tranexamic acid
  • Aminocaproic acid
  • For mucosal bleeding
  • Dental procedures

Gene Therapy

  • FDA-approved for Hemophilia A and B
  • Single infusion of modified virus
  • Delivers functional gene to liver
  • Can achieve normal factor levels
  • Long-term durability being studied
  • High cost but potentially curative

Managing Inhibitors

20-30% of severe Hemophilia A patients develop inhibitors (antibodies against factor VIII).

  • Bypassing agents:
    • Activated prothrombin complex concentrate
    • Recombinant factor VIIa
  • Immune tolerance induction:
    • High-dose factor exposure
    • Can eliminate inhibitors
  • Emicizumab: Effective with inhibitors

Comprehensive Care

Hemophilia Treatment Centers

  • Multidisciplinary team approach
  • Hematologists
  • Specialized nurses
  • Physical therapists
  • Social workers
  • Genetic counselors

Home Treatment

  • Self-infusion training
  • Factor storage and handling
  • Venous access devices if needed
  • Treatment logs
  • Emergency supplies

Physical Therapy

  • Maintain joint function
  • Strengthen muscles
  • Prevent contractures
  • Improve balance and proprioception
  • Aquatic therapy beneficial

Pain Management

  • Acetaminophen preferred
  • Avoid NSAIDs (affect platelets)
  • Ice for acute bleeds
  • Physical therapy
  • COX-2 inhibitors with caution

Living with Hemophilia

Activity Guidelines

  • Recommended activities:
    • Swimming
    • Walking/hiking
    • Cycling with helmet
    • Golf
    • Table tennis
  • Avoid high-contact sports:
    • Football
    • Hockey
    • Boxing
    • Wrestling
  • With precautions:
    • Basketball
    • Soccer
    • Baseball

Travel Considerations

  • Carry factor and supplies
  • Letter from physician
  • Know nearest treatment centers
  • Travel insurance coverage
  • Factor storage requirements

Dental Care

  • Preventive care crucial
  • Inform dentist of hemophilia
  • Factor coverage for procedures
  • Antifibrinolytics for extractions
  • Avoid nerve blocks if possible

Surgery Preparation

  • Coordinate with hemophilia team
  • Factor levels 80-100% for surgery
  • Maintain levels postoperatively
  • Monitor for inhibitors
  • Physical therapy planning

School/Work

  • Educate teachers/employers
  • Emergency action plan
  • Factor storage if needed
  • Activity modifications
  • Know rights under disability laws

Complications

Joint Disease (Hemophilic Arthropathy)

  • Most common long-term complication
  • Repeated bleeds damage cartilage
  • Progressive joint destruction
  • Chronic pain and disability
  • May require joint replacement

Inhibitor Development

  • 20-30% in severe Hemophilia A
  • 3-5% in Hemophilia B
  • Usually within first 50 exposures
  • Makes treatment challenging
  • Risk factors include:
    • Severe mutations
    • Family history
    • Intensive treatment

Viral Infections (Historical)

  • HIV/AIDS in 1980s
  • Hepatitis C before 1992
  • Current products very safe
  • Screening and viral inactivation

Pseudotumors

  • Encapsulated hematomas
  • Can erode bone
  • Require surgical removal
  • Rare with prophylaxis

Prognosis

Modern Outlook

  • Near-normal life expectancy with treatment
  • Prophylaxis prevents most complications
  • Quality of life dramatically improved
  • Most can participate in normal activities
  • Career options less limited

Factors Affecting Prognosis

  • Access to treatment: Critical factor
  • Prophylaxis adherence: Prevents joint damage
  • Inhibitor development: Complicates treatment
  • Early diagnosis: Better outcomes
  • Comprehensive care: Reduces complications

Future Directions

  • Gene therapy offering potential cure
  • Longer-acting factors
  • Non-factor therapies expanding
  • Improved inhibitor management
  • Better joint preservation strategies