Hemophilia Treatment Protocols

Factor VIII Deficiency

Initial half life:  6-8 hours.
Subsequent half life:  8-12 hours.

* Some patients have demostrated lower recovery and require higher doses of factor.  Such families should be instructed to notify treaters of need for higher doses.

Factor VIII Deficiency with Inhibitors

Many children with low level inhibitors are treated with higher doses of factor VIII (check their chart).  If inhibitors are greater than 5 Bethesda units, they are unlikely to respond to standard treatment.

Alternative Products

• Prothrombin complex concentrate (Konyne 80, Bebulin, Prophiline):  Dose is 75 i.u./kg q 12 hours.  Do not exceed 200 i.u./kg/day.
• FEIBA and Autoplex (activated prothrombin complex concentrates):  Dose is 50-75 i.u./kg every 12 hours (use with direction from attending hematologist).
• Recombinant factor VIIa (NovoSeven) 90 mcg/kg q 2-3 hours.  Use only after discussing with hematology attending.
• Porcine factor VIII (must check porcine inhibitor titer).  Use only after discussing with hematology attending.

Factor IX Deficiency

Initial half life:  4-6 hours
Subsequent half life: 18-24 hours

von Willebrand Disease

Use DDAVP (desmopressin) IF trial has been completed and von Willebrand has been typed (may be contraindicated in type IIB).  Patients unresponsive to iv DDAVP or those with severe (type III) disease, usually receive Humate-P or Alphanate.

IV DDAVP dosing:  0.3 mcg/kg in 50 cc saline (10 cc if wt < 10 kg) over 20-30 minutes IV.

Intranasal DDAVP (Stimate) may be used for mild clinical bleeding.  Check with the hemophilia program staff.  Stimate must be ordered by name, it is the only effective intranasal formulation.

Treatment Plans

• On Demand Therapy:  Traditional method of hemophilia management; treatment with factor replacement materials at first sign of bleeding episode.
• Prophylaxis:  It is recommended that prophylaxis begin after a child has established a pattern of repeated bleeding but before frequent joint bleeds occur.
• Primary Prophylaxis:  Initiation of regular factor replacement therapy soon after diagnosis of severe hemophilia (1-2 years of age).  Intention is to prevent joint bleeding.

Secondary Prophylaxis:  Initiation of regular factor replacemnt therapy to prevent further bleeding or progression of joint disease in a patient with recurrent joint bleeds or a target joint.

Prophylactic Doses

• Factor VIII:  Treatment with recombinant factor VIII
• 3 x week at 25-30 i.u./kg on Monday and Wednesday, and an increased dose of 40-50 i.u./kg on Fridays or;
• 20-40 i.u./kg qod
• Factor IX
• 45-50 i.u./kg twice per week is usually sufficient, but actual dose should be calculated based on the patient's recovery with the chosen product.
• The goal is to keep trough levels of VIII or IX above 1%
• Morning infusions are recommended as peak levels occur during waking, active time of the day.

Treatment of Bleeding Episodes

Head Trauma:  Every reported head injury in a child with severe hemophilia should be treated with a 100% correction, even without symptoms or external bruising, unless trama is considered to be trivial.

• Mild Trauma:  If neurologic examination is normal and family is able to observe carefully, one 100% correction may be given with a telephone follow-up arranged.
• Significant Trauma (e.g., down stairs, unwitnessed fall, falling on playground, MVA), even without symptoms requires evaluation and/or admission.  Treatmen:  100% correction and CAT scan.  Retreat with 30-50% correction q 12 hours x 1 or 2.  If hospitalized, discharge at 24-36 hours if studies and examination remain normal.  Always err on the side of caution in determining the treatment plan for patients with head trauma.


Children with mild hemophilia:  Treatment is required only for significant trauma only (100% correction followed by 30-50% correction q 12 hours x 1-2).

Children with severe hemophilia and a history of intracranial bleeding should be considered a candidate for prophylaxis.

For children on prophylaxis  who have already been treated earlier in the day, dosage and follow-up may be altered if their level of VIII or IX are calculated to be > 30% at the time of injury.  However, even children on prophylaxis should receive replacement therapy if they have significant head trauma.

Flank or Abdominal Pain or Swelling:  These symptoms must be evaluated by the physician, even for patients who are on home therapy.

Compartment Syndrome:  If any evidence of current or potential nerve compression exists in a child with a muscle or soft tissue bleed, especially in the arm, immediate correction is important.  Treat with 70-100% correction, repeating q 12 hours with 30-50% and admit.
 

Hemarthrosis:  Current recommendations for treatment of joint bleeding in children are more intensive therapy than previously.  Every hemarthrosis warrants at least two infusions of factor replacement.  Clinic staff should be notified of every joint bleed to provide appropriate follow-up.  The guidelines include the following:

• Severe hemophilia


Minor or early bleeds in joints:  50-70% correction initially.  Repeat correction with 30% in 12 hours.  If re-treatment in 12 hours is not convenient for family, increase the initial dose to 100% and re-treat in 24 hours.  A third treatment at 36-48 hours after initial treatment may be recommended.

Chronic, late or significant joint bleeds in target joints:  70% correction and repeat in 12 hours and 24 hours with 30% for factor VIII patients.  For factor IX patients not on regular therapy, second infusion should be given in 4-8 hours and repeated 24 hours later.
 

• Moderate or Minor Hemophilia


Every joint bleed in a patient with moderate or mild hemophilia is considered a significant bleed and should be treated with the more aggressive approach described above.

Management of a Target Joint:  A target joint is defined as one in which 3 or more bleeding episodes are reported in a six month period.  This is an indication for secondary prophylaxis.  Obtain radiographs of the joint, consult PT and initiate regular replacement therapy for 6-12 weeks to interrupt the cycle of bleeding.  Many families will decide to continue on prophylaxis for longer periods of time, maybe indefinitely.

Soft Tissue Bleeds:  Usually do not rquire infusion unless located in a critical area or an open space (neck, thigh).

Muscle Bleeds:  Most early muscle bleeds: 30% correction, immobilize area and follow-up contact in 12-24 hours.  If nerve compression evident or likely: 70-100% with follow-up treatments of 30% q 12 hours.  Admit.

• Thigh bleeds:  70% correction.  Maintain above 30% for 2-3 days; may need several additional days.  Admit.  Check hemoglobin.  Loss of 2-4g/dL is common with minimal swelling.
• Iliopsoas bleeds:  70% initial correction, maintain above 30% until muscle heals.  May be difficult to differentiate from hip bleed, but initial treatment is the same.


For iliopsoas and other retroperitoneal bleeds, bedrest is usually required.  Factor levels should be maintained above 30% with strict immobilization until there is no pain on deep palpation.  Otherwise, there is a high likelihood of rebleeding.  Initial ambulation should also be covered with a 30% correction daily for 2 days.

Check hemoglobin often in retroperitoneal bleeds, for continued bleeding can be asymptomatic and ultimately life-threatening.

• Amicar dose:  100 mg/kg q 6 hours (400 mg/kg/day) x 5 days.  Not to exceed 24 gm/day.  Liquid contains 1.24 gm/5 cc; tablets are 500 mg each.
• Amicar is contra-indicated: if hematuria is present, when using Prothrombin Complex Concentrates, or APCCs (Konyne 80) within 12 hours.
• Topical thrombin is applied, dry, with firm pressure to the oozing site in the mouth, after the large, unstable clot has been removed.
• Replacement of factor: 30% correction to be repeated if bleeding persists (q 12 hours in VIII; q 24 hours in IX).
• If tongue or lingual swelling is present, correct to 70% and admit for observation of airway and 30% corrections q 12 hours.
• Instruct families of children with mouth bleeds to maintain a soft diet for the child, without straws.  Pacifiers and bottles should be discouraged whenever possible, as sucking will dislodge the clot.

Hematuria:  Hematuria, if accompanied by pain, if after trauma to abdomen or back, or if occurring in patients with mild hemophilia, requires ultrasound or other imaging studies and aggressive replacement therapy.

• If no trauma is reported and the patient denies pain, recommend bed rest, force fluids for 24 hours.
• If hematuria persists on bedrest, use bedrest for 24 hours with 30% correction and repeat dose if necessary.
• Persistent hematuria should be evaluated.

• Local infiltration or any procedure which may initiate bleeding should be proceeded by a 30% correction.
• Mandibular blocks are discouraged but may be used with a 70% correction, if necessary.
• Dental extractions require initiation of Amicar the evening prior to the procedure (100 mg/kg/dose, not to exceed 24 gm/day).  Infuse with a 70% correction one hour prior to the procedure.  Obtain a PTT 15 minutes after infusion.  If PTT is within normal limits, proceed.  Repeat treatments may be necessary.

Surgery:  Prior to surgery:

• Notify the hemophilia program nurse who will coordinate plans, including:
• Notify pharmacy of anticipated factor requirements
• Arrange a factor yield and survival study.  Hemophilia nurses will help set this up in outpatients.
• Notify coagulation lab of yield and survival study and expected needs for factor assays during admission.
• Calculate doses, based on results of the yield and survival study, with the attending physician.
• Order initial dose to be on-call to the OR