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 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)

Clinical Features

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

1. Hemarthroses
   1. Leads to joint destruction and chronic arthropathy if not adequately treated
   2. Pts can reliably report when bleeding is occurring
2. 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)
3. Mucocutaneous bleeding
   1. Spontaneous bleeding uncommon from oropharynx, GI tract, epistaxis, or hemoptysis
4. CNS
   1. Intracranial bleeding is most common cause of hemorrhagic death
   2. Subdural hematomas occur spontaneously or with minimal trauma
5. 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%
4. 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
5. 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%

^As integer, not percentage (e.g. for 25%, "25" not "0.25")

Specific Therapy (Factor VIII)

TYPE OF BLEEDING	INITIAL DOSAGE	DURATION	COMMENT
SKIN
Abrasion	None	None	Treat with local pressure and topical thrombin
Laceration	Usually none; if necessary, treat as minor	None	Local pressure and anesthetic with epinephrine may benefit; watch 4 hours after suturing; reexamine in 24 hours
Deep	Minor bleeding (12.5 mg/kg)	Single-dose coverage	May need hospitalization for observation; repeat may be necessary for suture removal
EPISTAXIS
Spontaneous	Usually none; may need to be treated as mild bleeding	None	Uncommon; consider platelet inhibition; treat in usual manner
Traumatic	Moderate bleeding (25 mg/kg)	Up to 5–7 days	Trauma-related bleeding can be significant
ORAL
Mucosa or tongue bites	Usually none; treat as minor if persists	Single dose	Commonly seen
Traumatic (laceration) or dental extraction	Moderate (25 U/kg) to severe (50 U/kg)	Single dose; may need more	Saliva rich in fibrin lytic activity; oral ε-aminocaproic acid (Amicar) may be given at 100 mg every 6 hr for 7 days to block fibrinolysis; check contraindications; hospitalize patients with severe bleeding
Soft tissue/muscle hematomas	Moderate (25 U/kg) to severe (50 U/kg)	2–5 days	May be complicated by local pressure on nerves or vessels (e.g., iliopsoas, forearm, calf)
Hemarthrosis
Early	Mild (12.5 U/kg)	Single dose	Treat as earliest symptom (pain); knee, elbow, ankle more common
Late or unresponsive cases of early hemarthrosis	Mild to moderate (25 U/kg)	3–4 days	Arthrocentesis rarely necessary and only with 50% level coverage; immobilization is critical point of therapy
Hematuria	Mild (12.5 U/kg)	2–3 days	Urokinase, the fibrinolytic enzyme, is in urine; with persistent hematuria an organic cause should be ruled out
Major Bleeding	Major bleeding (50 U/kg)	7–10 days or 3–5 days after bleeding ceases	In head trauma, therapy should be given prophylactically; early CT scan of head recommended for all

Disposition

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

See Also

• Coagulation Disorders
• Bleeding Treatment

Source

• Tintinalli
• Rosen's