🩺 MedAtlax

Search

SearchSearch

Hemophilia

Aug 24, 20254 min read

Hemophilia

Types of Hemophilia

  • Hemophilia A & B: X-linked, recessive disorders caused by deficiency of functional plasma clotting factor VIII (A-8) (FVIII) or IX (9) (FIX), respectively. Can be inherited or acquired.

  • Hemophilia C: Autosomal recessive disorder, affecting both males and females, leading to a deficiency in factor XI(11).

  • Acquired Hemophilia A: Development of inhibitory antibodies to FVIII (8) complicates the treatment of genetic cases.

videocc

Hemophilia B

Hemophilia B, or Christmas disease, is an inherited, X-linked, recessive disorder that results in deficiency of functional plasma coagulation factor IX.

Hemophilia B accounts for 20% of hemophilia cases, and about 50% of those affected have factor IX levels greater than 1%.

Severity, Factor Activity, and Hemorrhage
Hemophilia AHemophilia B
Factor DeficiencyFactor VIIIFactor IX
InheritanceX-linked recessiveX-linked recessive
Incidence1/10,000 males (80% of cases)1/50,000 males

Coagulation Disorder Symptoms

Common Symptoms:

  • “Easy bruising”
  • Ecchymoses
  • Hemarthrosis
  • Deep tissue hematomas
  • Posterior epistaxis
  • GI bleeding
  • Urinary bleeding
  • Persistent bleeding after surgical procedures
  • Intracerebral hemorrhage (→ stroke / increased intracranial pressure)

Clinical Manifestations of Bleeding Disorders

Bleeding SymptomsPlatelet Defects (qualitative or quantitative)Clotting Factor Deficiencies (factor VIII or factor IX)
Overview of Bleeding EventsMucocutaneous bleeding (oral, nasal, GIT, vaginal, and genitourinary sites)Deep tissue bleeding (including joints and muscles)
Excessive Bleeding After Minor CutsYesNot usually
Epistaxisanteriorposterior
PetechiaCommonUncommon
Ecchymosessmall and superficiallarge subcutaneous and soft tissue hematomas
Hemarthroses, Muscle HematomasUncommonCommon (severe deficiency)
Bleeding with Invasive Procedures, Including Surgeryimmediate, dependent upon the severity of defect, ranging from mild to severeEither with procedural bleeding or delayed bleeding

Hemophilia Diagnosis

Laboratory Studies

  • CBC:
    • Hemoglobin/hematocrit: Normal or decreased
    • Platelet count: Normal
  • Coagulation Studies:
    • Bleeding time: Normal
    • Prothrombin time (PT): Normal (Intrinsic)
    • Activated partial thromboplastin time (aPTT): prolonged (mixed study)
  • FVIII, IX, XI Assays
  • Genetic Testing: Screening

Diagnostic Tests

  • Prolonged aPTT (High Yield) (Rule out von Willebrand disease)
  • Normal PT & platelet count (High Yield)
  • Mixing Study
    • aPTT prolongation due to true factor deficiency or presence of factor inhibitor
    • If aPTT normalizes after mixing with normal plasma → factor deficiency (hemophilia)
    • If aPTT does not normalize after mixing with normal plasma → factor inhibitor - Acquired

Hemophilia Management

Non-pharmacological Management

  • Physiotherapy
  • Hydrotherapy
  • Patient education on treatment and prevention of bleeding
  • Avoid non-steroidal anti-inflammatory drugs (NSAIDs) and intramuscular (IM) / joint injections

Pharmacological Management of different cases

  • Mild Hemorrhages:

    • Early hemarthrosis
    • Epistaxis
    • Gingival bleeding
    • FVIII level of at 30%

  • Major Hemorrhages:

    • Hemarthrosis
    • Muscle bleeding
    • Prophylaxis after head trauma with negative findings on examination
    • FVIII level of at least 50%

  • Life-threatening Bleeding:

    • Major trauma
    • Surgery
    • Advanced or recurrent hemarthrosis
    • FVIII level of 80-100%

Medications

  • Desmopressin (DDAVP): Vasopressin analog used for mild hemophilia A. Not effective for severe hemophilia. Peak effect observed in 30-60 minutes. Intranasal spray available for outpatient use.

  • Emicizumab: Humanized monoclonal bispecific antibody that reduces the risk of bleeding events in hemophilia A. Bridges activated factor IX and factor X by binding to both factors (thereby replacing the deficient factor VIII), leading to activation of factor X and restoration of the clotting cascade.

  • Antifibrinolytics (e.g., tranexamic acid): Used in conjunction with FVIII replacement for oral mucosal hemorrhage and prophylaxis.

  • Factor Replacement Therapy: IV InfusionZ

    • Hemophilia A: IV infusion of factor VIII concentrate.
    • Hemophilia B: IV infusion of factor IX concentrate (has a longer half-life than factor VIII, so transfusions are less frequent).
    • Hemophilia C: IV infusion of factor XI concentrate.

Note: Needed number of units of FVIII is calculated by the formula: (weight ÷ 4.4) × (factor level desired) = number of factor VIII units neededX

Inhibitors - Acquired hemophilia

Approximately 30% of people with hemophilia develop an antibody to the clotting factor they receive. These antibodies are known as inhibitors, often secondary to antiphospholipid syndrome (APS).

  • Testing for Inhibitors: Bleeding is not controlled after adequate amounts of factor concentrate are infused during a bleeding episode.
  • Treatment: High doses of FVIIa for bleeds or surgery. This overrides the defect in FVIII or FIX deficiency.
  • Long-term Management: Eradicate inhibitors by administering high-dose FVIII (or FIX) in a process called immune tolerance.

Prognosis

  • Prognosis is dependent on severity.
  • Up to 60% of individuals with hemophilia A have severe forms.
  • Prognosis is improved with proper treatment and prevention of injuries.
  • Genetic therapies are currently under development and may further improve prognosis.

Complications

  • Complications of Disease:

    • Degenerative joint disorders (arthritis)
    • Life-threatening hemorrhage

  • Complications of Treatment:

    • Viral infections (e.g., hepatitis, HIV) from transfusion
    • Development of antibodies against the administered coagulation factors
    • Opiate addiction

Graph View

Backlinks