Haemophilia A (factor VIII defic.)

Management

Treatment Administration

• Prescribers must ensure that they prescribe the correct clotting factor concentrate e.g. Elocta for FVIII deficiency
• Not all patients with mild FVIII deficiency require clotting factor concentrate, and the use of alternative treatments may be indicated e.g. DDAVP and/or TXA
• The patient's treatment of choice must be confirmed with the relevant CCC

Clotting Factor Concentrate – Elocta

• Elocta is the factor used in the treatment and prophylaxis of bleeding in patients with congenital factor VIII deficiency
• Elocta comes as a powder and solvent in a pre-filled syringe that must be reconstituted for solution
• Tt is administered as a bolus infusion

Pre filled glass syringes are not compatible with clave connectors, therefore if administering Elocta via a clave connector, PICC line or CVAD the reconstituted solution should be drawn into a plastic syringe prior to administration.

Elocta administration

• Elocta should be administered as a slow IV push at a rate not exceeding 10mls per minute
• A post treatment factor level should be drawn 20 minutes post administration (two coagulation samples send to lab. for forwarding to the CCC for analysis)
• Liaise with CCC regarding the post treatment level result in case further treatment is required

DDAVP / Desmopressin

DDAVP® solution for injection (Desmopressin Acetate) is a synthetic analogue of the natural hormone arginine vasopressin. It is indicated for use in managing bleeds in some persons with Factor VIII deficiency and Von Willebrand disease/Low VWF by increasing plasma levels of FVIII and VWF.

DDAVP dose calc.

• DDAVP is administered intravenously at a dose of 0.3 micrograms/kg
• The max. total dose for any patient is 27 micrograms
• Example: A 60kg patient requiring DDAVP, the dose should be calculated as 60 kg x 0.3 micrograms = 18 micrograms

DDAVP dose Administration

• DDAVP comes in 1ml ampoule which contains Desmopressin acetate 4 micrograms per ml in a sterile, aqueous solution for injection
• DDVAP should be added to 100mls of normal saline
• The 100ml solution should be administered intravenously over 30 minutes
• Example: A 60kg patient requiring DDAVP - The intravenous preparation has a concentration of 4 micrograms /ml. Therefore, the intravenous dose for a 60kg patient (18 micrograms) will be prepared by diluting 4.5mls of DDAVP in 100mls of normal saline and this will be administered IV over 30 minutes

Contraindications/Cautions - DDAVP

DDAVP is contraindicated in patients with:

• Hypersensitivity to the active substance or to any of the excipients listed in the SPC
• Habitual or psychogenic polydipsia
• Hx of unstable angina and/or known or suspected cardiac insufficiency and other conditions requiring treatment with diuretics
• Known hyponatraemia
• SIADH
• Von Willebrands disease type II B where Desmopressin may result in pseudothrombocytopenia due to the release of clotting factors which cause platelet aggregation

DDAVP/Desmopressin precautions

Fluid balance

• DDAVP should only be administered under the supervision of a specialist with appropriate laboratory facilities available for monitoring of the patient
• Maintain fluid and electrolyte balance. Treatment without concomitant reduction of fluid intake may lead to fluid retention and/or hyponatraemia with or without accompanying warning signs or symptoms. Local practice is to ensure no more than 1.5 litres total fluid intake in adults in 24 hours post DDAVP infusion
• Infants, elderly and patients with serum sodium levels in the lower range of normal may have increased risk of hyponatraemia. Treatment with DDAVP should be interrupted or carefully adjusted during acute intercurrent illnesses characterised by fluid and/or electrolyte imbalance (such as systemic infections, fever, gastroenteritis) as well as in excessive bleeding, and the fluid and electrolyte balance should be carefully monitored
• Special attention should be given when Desmopressin is co-administered with other drugs affecting water and or sodium homeostasis. In patients with chronic therapy with drugs affecting water and/or sodium homeostasis, DDAVP/Desmopressin Injection should be administered after confirmation of normal baseline sodium
• Bewrae fluid overload (re-condiser IV fluids, daily patient weight), monitor serum Na⁺ and osmolalitys

Thrombotic Risk

• DDAVP is not recommended for patients >55 years (thrombotic risk)

Other conditions

• Beware ↓renal fxn., CVS disesase or cystic fibrosis
• Get advice (CCC) in post-op/vairceal bleeding/cirrhosis
• Beware ↑ ICP

TXA - Tranexamic Acid (Cyklokapron)

TXA (PO or IV) is an anti-fibrinolytic agent, indicated in patients with haemophilia for short-term use (2-8 days), to reduce or prevent haemorrhage.

TXA dose

• PO (500mg tablets) given as 1g q8h
• IV (500mg in 5ml ampoule) given as 10mg/kg q8h

PO TXA contraindications/cautions

IV TXA contraindications/cautions

Patients w F-VIII deficiency & inhibitors

• These are very complex cases. Managment should be by the CCC/Haematologists on call
• Inhibitors (antibodies against infused FVIII concentrate) are a common occurrence in FVIII deficiency (Haemophilia A)
• The incidence of inhibitor development is approximately 30% and a FVIII inhibitor may be present at low levels ("low responding", inhibitor titre <5 Bethesda Units (BU)) or high levels ("high responding", inhibitor titre ≥ 5BU)
• Not all inhibitors are persistent, as low responding inhibitors may wane with continued regular factor infusions or high responding inhibitors may be cleared with immune tolerance therapy
• A small number of patients have persistent, high responding inhibitors and these patients cannot receive FVIII concentrate to treat or prevent bleeding but should receive alternative treatments such as bypassing agents or Hemlibra
• Patients with FVIII deficiency have a life-long risk of developing an inhibitor although the majority of inhibitors occur before the first 50 (and often before the first 20) exposure days
• It is important to identify patients with FVIII deficiency that have a current or past history of inhibitors. Please note:
  • Is inhibitor present currently or in past?
  • What is patient's current treatment of choice?
  • Has patient ever received Immune tolerance treatment? If yes, when was this given and did the patient achieve eradication of the inhibitor?
• More details at National treatment guidelines (CUH Intranet)

Links

• Irish Haemophilia Society
• National treatment guidelines (CUH Intranet)
• HPRA
• Bleeding disorders
• Haemophilia B (IX Defic.)
• Von Willebrand Disease (VWD)
• PFDs
• RBDs
• BDUA