Factor IX Deficiency

Aka: Factor IX Deficiency, Factor 9 Deficiency, Christmas Disease, Hemophilia B, Plasma Thromboplastin Component Deficiency

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II. Epidemiology

  1. Accounts for 15% of Hemophilia cases (remainder are Hemophilia A which is a Factor VIII Deficiency)

III. Pathophysiology

  1. Inherited sex linked trait
  2. Factor IX Deficiency
  3. Clinically indistinguishable from Hemophilia A (which is the much more common Factor VIII Deficiency)

IV. Symptoms

  1. Chronic history of Bleeding Diathesis since childhood
    1. Spontaneous bleeding
  2. Excessive Hemorrhage follows:
    1. Dental procedures
    2. Surgery

V. Signs

  1. Joint deformities
  2. Muscle contractures

VI. Labs

  1. Partial Thromboplastin Time (PTT) prolonged
    1. Corrects with Factor IX supplementation
    2. Corrects with Normal serum
  2. Factor IX assay decreased
    1. Factor IX is considered 100% when measured at 1 unit factor/ml plasma
    2. Normal Hemostasis occurs when activity 50-150% (0.5 to 1.5 units/ml)

VII. Management: Recombinant Factor IX replacement

  1. Consult Hematology
  2. Indications
    1. Acute Bleeding
    2. Preoperative prophylaxis
  3. Contraindications to Factor IX replacement
    1. Anaphylaxis to Factor IX
      1. Severe Anaphylaxis occurs in 5% of severe Hemophilia B patients
      2. Treat with combination (thrombosis risk)
        1. Factor VIII inhibitor-bypassing activity (FEIBA) AND
        2. Recombinant activated Factor VII
  4. Dosing basic regimen
    1. Background
      1. Active Factor IX rises 1% for every Factor IX unit/kg given
      2. Example: 100% replacement = 100 units/kg (up to 140 units/kg)
    2. Initial dose
      1. Factor IX 100 units/kg (up to 140 units/kg) every 8-12 hours OR
      2. Factor IX (desired concentration - current concentration) * wtKg every 8-12 hours
    3. Factor IX Infusion
      1. Load: 100 units/kg (up to 140 units/kg)
      2. Infusion: 4-5 units/hour (directed by Factor IX levels)
    4. Modifiers
      1. Subtract patient's weekly maintenance dose already given (last few days) from the acutely required units
      2. Additional factor dose is needed to overcome inhibitors (if present)
  5. Dosing in major bleeding (directed by involved region and target Factor IX levels)
    1. Major injury with active bleeding or preoperative and perioperative prophylaxis and management
      1. Target: 100% initially, then 80-100% until wound healed, then 30% of normal Factor IX Level until Suture removal
      2. Recombinant Factor IX 100 units/kg initially and then 50 units/kg daily (adjusted for healing)
    2. Joint bleeding (hemarthrosis)
      1. Target: 80% in acute period, then 40% every other day of normal Factor IX Level
      2. Recombinant Factor IX 80 units/kg initially, then 40 units/kg every other day (or every third day) until healed
    3. Gastrointestinal Bleeding
      1. Target: 100% initially, then 50% of normal Factor IX Level until healed
      2. Recombinant Factor IX 100 units/kg initially, then 30-40 units/kg daily
    4. Genitourinary bleeding
      1. Target: 100% initially, then 30% of normal Factor IX Level until healed
      2. Recombinant Factor IX 100 units/kg initially, then 30-40 units/kg daily
      3. Avoid antifibrinolytic medications (TXA, EACA) in Hematuria (risk of thrombotic ureteral obstruction)
    5. CNS Bleeding
      1. Target: 80-100% initially, then 50-100% of normal Factor IX Level for 14 days
      2. Recombinant Factor IX 100 units/kg initially, then 50 units/kg daily
    6. Oral Bleeding
      1. Target: 100% of normal Factor IX Level
      2. Recombinant Factor IX 100 units/kg
      3. Consider topical Fibrinolytic agents
    7. Epistaxis
      1. Target: 80-100% initially, then 30% of normal Factor IX Level until healed
      2. Recombinant Factor IX 80-100 units/kg then 35-40 units/kg daily
    8. Muscle bleeding
      1. Target: 50% of normal Factor IX Level
      2. Recombinant Factor IX 40-60 units/kg daily then 20-30 units/kg every other day until healed
  6. Moderate Bleeding
    1. Dosing
      1. Factor IX 25 units/kg
    2. Indications
      1. Hematomas with dissection or involving soft tissue or Muscle
      2. Traumatic Epistaxis
      3. Oral Mucosal or Tongue Lacerations
      4. Dental extractions
      5. Hemarthrosis with late presentations (or unresponsive to treatment)
      6. Severe Hematuria
  7. Mild Persistent Bleeding
    1. Dosing
      1. Factor IX 12.5 units/kg
    2. Indications
      1. Deep Lacerations
      2. Major spontaneous Epistaxis
      3. Major Oral Mucosa or Tongue bites
      4. Mild Hematuria
      5. Early hemarthrosis
      6. Muscle Hematoma
  8. Mild Intermittent Bleeding
    1. No factor replacement needed
    2. Indications
      1. Abrasions and mild Lacerations
      2. Minor, controlled spontaneous Epistaxis
      3. Superficial Oral Mucosal or Tongue bites
      4. Minor Hematoma
  9. Alternative agents when Factor IX is not available
    1. Fresh Frozen Plasma (FFP) 4 units
      1. Increases Factor IX to only 5%
    2. Prothrombin Complex Concentrate (PCC) 100 units
      1. Risk of thrombosis (reserve only for very serious bleeding such as CNS Hemorrhage)
  10. Adjunctive Agents to Consider
    1. Consult Intervention Radiology and surgery for localized Hemorrhage source control
    2. Avoid antifibrinolytic medications (TXA, EACA) in Hematuria (risk of thrombotic ureteral obstruction)
    3. Tranexamic Acid (TXA, preferred)
      1. See Tranexamic Acid for IV dosing
      2. Oral: Take 1 g four times daily for 3-8 days
    4. E-aminocaproic acid (EACA, Amicar, adult dosing)
      1. Less potent than TXA, with greater toxicity and a shorter Half-Life
      2. IV: 4-5 g load IV, then 1 g/h infusion
      3. Oral: 4 g every 4-6 hours orally for 2-8 days
    5. Desmopressin 0.3 mcg/kg IV over 30 minutes (or via nasal spray)
      1. Only effective in mild Hemophilia (will not work in moderate to severe)
      2. Triggers release of VWF into plasma from cellular stores
        1. Immediately increases Factor VIII by 2-3x
      3. Strong Diuretic effect
        1. Risk of hypnatremia (avoid in age <2 years due to cerebral edema risk)
        2. Decrease total fluid fluid intake if >1 dose taken in a day (typically restrict to once daily)

VIII. Prevention

  1. Medical alert bracelet
  2. Treatment plan from Hemophilia treatment center
  3. Patients may carry their own factor replacment (preferred)

IX. References

  1. Deloughery and Orman in Majoewsky (2013) EM:Rap 13(9): 1-4
  2. Guest and Herbert in Swadron (2022) EM:Rap 22(4): 9
  3. Hoag, Jundoria, Dave and Lopez (2026) Crit Dec Emerg Med 40(7): 4-13
  4. DiMichele (1996) Pediatr Clin North Am 43(3): 709-36 [PubMed]
  5. Jones (2024) Am Fam Physician 110(1): 58-64 [PubMed]

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