Factor IX Deficiency

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

1. Epidemiology
   1. Accounts for 15% of Hemophilia cases (remainder are Hemophilia A which is a Factor VIII Deficiency)
2. 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)
3. Symptoms
   1. Chronic history of Bleeding Diathesis since childhood
      1. Spontaneous bleeding
   2. Excessive Hemorrhage follows:
      1. Dental procedures
      2. Surgery
4. Signs
   1. Joint deformities
   2. Muscle contractures
5. Labs
   1. Partial Thromboplastin Time (PTT) prolonged
      1. Corrects with Factor IX supplementation
      2. Corrects with Normal serum
6. Management: Recombinant Factor IX replacement
   1. Consult Hematology
   2. Indications
      1. Acute Bleeding
      2. Preoperative prophylaxis
   3. 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
      2. Initial dose
         1. Factor IX 100 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
         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)
   4. 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
      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
   5. 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)
   6. Adjunctive Agents to Consider
      1. Consult Intervention Radiology and surgery for localized Hemorrhage source control
      2. Aminocaproic Acid (Amicar)
      3. Tranexamic Acid (TXA)
      4. Desmopressin (DDAVP)
7. 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. DiMichele (1996) Pediatr Clin North Am 43(3): 709-36 [PubMed]