Bleeding diseases of unknown aetiology (BDUA)

Background

• BDUA may be assigned to patients with a history of severe and/or recurrent bleeding after invasive procedures or haemostatic challenges such as childbirth
• Dx assigned after the patient has had review in a specialist Coagulation centre and has had a full haemostatic work up done, including assessment of coagulation factor levels and platelet function
• Dx assigned when the patient is found to have a significant history of bleeding but no abnormalities are found on laboratory testing
• Patients are at risk of increased bleeding in the future and may require haemostatic treatment before invasive procedures or delivery

Clinical

• Severity of BDUA is variable and is determined by the patient's clinical bleeding Hx

Treatment Admin.

Prescribers must ensure that they prescribe the correct treatment. Treatment options include:

• Tranexamic Acid (TXA)
• DDAVP

If severe bleeding, consider random donor platelets or recombinant factor VIIa The patient's treatment of choice must be confirmed with the relevant CCC.

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

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

Links

• Irish Haemophilia Society
• National treatment guidelines (CUH Intranet only)
• HPRA
• Haemophilia A (VIII Defic.)
• Haemophilia B (IX Defic.)
• Von Willebrand Disease (VWD)
• PFDs
• RBDs