Hemophilia

Background

• TREAT FIRST, Diagnose second. Assume bleeding until proven otherwise.
• Two types (clinically indistinguishable):
  • Hemophilia A: Factor VIII deficiency
  • Hemophilia B: Factor IX deficiency
• Substantial proportion (~1/3) of both types arise from spontaneous mutations
• X-linked disorders (overwhelmingly a disease of men)
• ICH is most common cause of hemorrhagic death
• Do not give NSAIDs or IM injections
• Avoid invasive procedures (e.g. central lines, LP)

Prehospital Care

• Rapid transport to definitive care
• Apply pressure and achieve hemostasis in active bleeding patients
• Bring Factor therapy with patient and encourage use during transport
• Determine history of trauma or prior complications with hemophilia

Clinical Features

• Pt does not need objective exam finding to treat. Subjective complaints are a harbinger of serious issues.

Hemarthroses

1. Leads to joint destruction and chronic arthropathy if not adequately treated
2. Pts can reliably report when bleeding is occurring

Hematomas

1. Bleeding into soft tissues or muscle
   1. Neck (airway compromise)
   2. Limbs (compartment syndromes)
   3. Eye (retro-orbital hematoma)
   4. Spine (epidural hematoma)
   5. Retroperitoneum (iliopsoas bleeds and massive blood loss)

Mucocutaneous bleeding

1. Spontaneous bleeding uncommon from oropharynx, GI tract, epistaxis, or hemoptysis

CNS

1. Intracranial bleeding is most common cause of hemorrhagic death
2. Subdural hematomas occur spontaneously or with minimal trauma

Hematuria

1. Common, usually not serious, source is rarely found

Diagnosis

• Pain in soft tissue is bleeding until proven otherwise
• Paresthesias in legs - consider retroperitoneal bleed
• Easy bruising or bleeding out of proportion to the history of trauma
• Recurrent bleeding into joints and muscles
• Prolonged PTT; normal PT

Work-Up

1. Coags
   1. Only helpful for making the dx; once established unlikely to yield new information
   2. PT - normal
   3. PTT - abnormal (unless mild hemophilia)
   4. PTT s/p factor - should correct to normal
2. Factor VIII assay
   1. Consider before treatment (for heme to follow)
   2. Normal: 50-150%
      1. Mild: >5%
      2. Moderate: 1-5%
      3. Severe: < 1%
3. Head CT
   1. If HA, AMS, significant blunt head injury
4. CT A/P
   1. Back, thigh, groin, or abd pain
5. LP
   1. replete factor before attempting

Treatment

• Always inquire whether pt has known inhibitors - may be refractory to conventional tx
  • If so, obtain hematology consult before treatment
  • If no know inhibitors, and pt not improving after replacement, order mixing study
    • PTT will not correct if inhibitors present

Factor Replacement

1. Major bleeding (GI, CNS, large muscle, trauma) requires factor replacement level 80-100%
2. Moderate bleeding (soft tissue, small muscle, joint) requires 30-50%
3. Diagnosis unknown
   1. Give FFP (contains VIII and IX)
   2. Each bag raises factor levels by 3-5%

Hemophilia A

1. Dose of Factor VIII = weight (kg) x % increased desired x 0.5
   1. After initial correction give half this dose q8-12hr
   2. 1 IU/kg will increase the plasma concentration by 2%
2. Desmopressin
   1. May be sufficient in pts with mild bleeding
   2. 0.3mcg/kg IV over 15-30min

Hemophilia B

1. Dose of Factor IX = weight (kg) x % increase desired
   1. After initial correction give half this dose 24 hr later
   2. 1 IU/kg will increase the plasma concentration by 1%

Use the percentage as integer, not percentage (e.g. for 25% multiply by "25" not "0.25")

Desired Level Repletion

Type of Bleeding	Desired Factor Level	Factor VIII	Factor IX
Minor Bleed or prophylaxis	20-30%	10-15 U/kg	20-30 U/kg
Moderate Bleed	50%	25 U/kg	50 U/kg
Severe Bleed	100%	50 U/kg	100 U/kg

Inhibitors to Factors

• Antibody inhibitors to factor therapy more common in Factor concentrates and rare in recombinant factor therapy
• Treatment should be in consultation with hematologist
• In major bleeding, rVII has been suggested as potential salvage therapy for patients with inhibitors to recombinant factor

Disposition

• Admit:
  • Treatment requiring multiple factor replacement doses
• Bleeding in head, neck, pharynx, retropharynx, or retroperitoneum

See Also

• Coagulopathy (Main)

Source

• Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e (2010), Chapter 230. Hemophilias and Von Willbrand Disease
• Iorio A, Marchesini E, Marcucci M, Stobart K, Chan AK. Clotting factor concentrates given to prevent bleeding and bleeding-related complications in people with hemophilia A or B. Cochrane Database Syst Rev. Sep 7 2011;9:CD003429