This booklet is intended as a guide for healthcare personnel who might not be familiar with haemophilia. People with haemophilia (PWH) and their physicians should be advised by a Comprehensive Haemophilia Treatment Centre staffed by a multidisciplinary team skilled in the care of this uncommon chronic bleeding disorder.

Parents of patients with severe haemophilia are usually trained in home infusion of the clotting Factor when their child is about four years old and self infusion is normally accomplished by 12 – 14 years of age. However, infants and boys with mild haemophilia must rely on a Haemophilia Centre or other medical facility for clotting Factor infusions.

Please contact your nearest Haemophilia Treatment Centre if you have any uncertainty regarding management.

Acknowledgement is made of all the past and current members of MASAC, who have produced the previous edition, and reviewed the current edition.

Haemophilia is an inherited, x-linked, lifelong bleeding disorder which affects males almost exclusively. Most frequently haemorrhage involves joints or muscles. Bleeding patterns differ with age: infants usually bleed into soft tissues or from the mouth but as the boy grows, characteristic joint bleeding becomes more common.

Haemophilia A is the most common form of haemophilia and is due to a deficiency of clotting Factor VIII.

Haemophilia B is due to a deficiency of clotting Factor IX.

Haemophilia is classified as severe, moderate, or mild according to the levels of circulating Factor VIII or IX and indicates the expected frequency of bleeding:

Inhibitors may develop in 10 – 15% of persons with haemophilia A but are much less common in haemophilia B (1 – 3%). Inhibitors are neutralising antibodies that limit the effectiveness of Factor infusions.

Risk Factors for the development of inhibitors:

• severe haemophilia
• family history of inhibitor development
• more frequent in black patients

If an individual is going to develop an inhibitor, this usually happens within the first 50 exposure days after starting Factor VIII replacement therapy.

Inhibitors titres are measured in Bethesda units (BU)

1. Monitor all patients every 3 – 6 months for the development of inhibitors. This is particularly important and should be done more frequently in newly diagnosed black patients with severe haemophilia A, who are at greater risk.
2. Never undertake a surgical procedure or joint aspiration in a person with haemophilia without checking for inhibitors.
3. If there is no response to appropriate replacement therapy, test for inhibitors.
4. Call a Haemophilia Treatment Centre for advice on patient management.

Refer to Factor VIII inhibitor management options section.

• Minor surgery, which includes endoscopy, skin biopsy, bronchoscopy, lumbar puncture, dental procedures, etc.
• Major surgery, which includes laparotomy, arthroplasty.

• Consultation between surgeon, haematologist and blood centre.
• Check FBC, liver function, renal function and inhibitor level.
• Do Factor recovery studies.
• Prepare a written management plan and communicate this to all stakeholders.

• Raise Factor level to 50 – 80% for minor surgery and 80 – 100% for major surgery
• Maintain Factor level at 50% for major surgery for at least 7 – 14 days.
• Avoid intraoperative and postoperative blood loss.

• Haemophilia A:
  • for major surgery, give 40 – 50 IU/kg FVIII
  • for minor surgery give 20 – 40 IU/kg FVIII, 30 minutes before surgery, 6 hours postoperatively and then 12-hourly thereafter.
• Haemophilia B:
  • for major surgery, give 60 – 80 IU/kg FIX
  • for minor surgery 20 – 40 IU/kg, 30 minutes before surgery.
• Repeat the same dose 6 hours postoperatively and then daily thereafter.
• Factor infusion for major surgery should continue for 7 – 14 days.
• Venous thromboembolism (VTE) prophylaxis using elastic stockings should be considered in all high-risk surgery.
• Keep peak maintenance Factor level at 50% until healing has started.
• Introduce postoperative rehabilitation and mobilisation gradually under Factor prophylaxis.
• Continuous infusion of Factor with a pump may be used.
• Use of antibiotics postoperatively is mandatory.
• Ensure that patient receives adequate analgesia
  – NB avoid intramuscular analgesia.

Genetic testing for haemophilia A and B is important for:

• Definitive carrier testing
• Prenatal counselling and testing

• Haemophilia A: give 25 – 40 IU/kg 2 – 3 times per week
• Haemophilia B: give 25 – 40 IU/kg twice per week

Dose depends on bleeding severity
Minor bleed: 20 – 40 IU/kg
Major bleed: 40 – 50 IU/kg
Expected response: 1 IU/kg = 2% rise in Factor VIII level
Half life Factor VIII: 8-12 hr
For serious bleeding Factor VIII assay may be required to monitor the response to the infusion.
If there is no response to appropriate replacement therapy, test for inhibitors.

Dose depends on bleeding severity
Minor bleed: 20 – 40 IU/kg
Major bleed: 60 – 80 IU/kg
Expected response: 1 IU/kg = 1% rise in Factor IX level
Half life Factor IX: 16-24 hr
For serious bleeding Factor IX assay may be required to monitor the response to the infusion.
If there is no response to appropriate replacement therapy, test for inhibitors.

See section on the products available in South Africa

Ice/cold pack – 5 minutes on, 10 minutes off
Immobilise joint with a splint
Low Responder (< 5 BU)

• Give Factor VIII at 2 – 3 times the normal dose
• Monitor response clinically
• Frequent factor recovery levels

High Responder (> 5 BU)
Both APCC and rVIIa are effective for treatment of acute bleeding episodes in patients with Factor VIII inhibitors.

• Activated Prothromibin Complex Concentrate (APCC)
  Dose: 50 – 100 IU/kg q12 – 24h for 3 days or until clinical improvement Infuse at 2 IU/kg/min
  Do not exceed a single dose of 200 IU/kg
  • Do not use antifibrinolytic drugs (e.g. tranexamic acid) concurrently because of the risk of thromboembolism

• Recombinant Factor VIIa (rFVIIa)
  90 μg per kg q2 – 3 h or by continuous infusion (at 20 μg/kg/hr) until clinical improvement.
  Factor VIIa activates Factor X and leads to the formation of a haemostatic plug.
  New single dose of 270 μg/kg may be used

• Tranexamic acid 15 – 25 mg/kg/dose po/IV q6- 8h may be used concurrently with recombinant Factor VIIa.

• IT should be initiated at a Haemophilia Treatment Centre
• Successful therapy (eliminating the inhibitor) may take months.
• Several regimens are effective – the Dutch regime
  (25 IU Factor VIII/kg 3 times per week) is the most affordable.

• An aPCC should be carefully monitored for anaphylaxis and anamnestic reaction. Therefore patients with haemophilia B and inhibitors are best treated with rFVIIa, the only bypassing agent that does not contain FIX.
• There is no evidence to guide tolerisation procedures in patients with haemophilia B and inhibitors. Plasma-derived FIX may be used for tolerisation with careful monitoring of anaphylactic reactions

• Give dose of 90 – 120 μg/kg IV every 2 – 3 hours as bolus or 20 IU/kg/hour as continuous infusion. Single dose of 270 μg/kg may be used.
• Antifibrinolytic can be given concurrently with rFVIIa.

Rehabilitation after a bleed is essential to maintain strength and range of motion.

Any person with haemophilia and related bleeding disorders may have transfusion acquired infection.

• Test annually for HAV, HBV, HCV.
• Antibody/antigen negative patients should be immunised, and response assessed.
• Active infection should be excluded in positive patients.
• Patients with chronic active hepatitis should be referred to a Hepatologist for management.

NB. Patients with hepatic dysfunction may have other Factor deficiencies (test PT or INR) or a low platelet count.