Desmopressin for Bleeding Disorders

Desmopressin is a synthetic analogue of arginine vasopressin that raises plasma factor VIII and von Willebrand factor two to six-fold within an hour. It is used for mild haemophilia A, type 1 and some type 2 von Willebrand disease, and selected platelet function defects, and is effective only in patients whose individual response has been shown.

Classification. Vasopressin analogue; haemostatic agent.

Mechanism. Stimulates V2 receptors on vascular endothelium, releasing stored von Willebrand factor and factor VIII from Weibel-Palade bodies. It has minimal V1 pressor activity. Antidiuresis through renal V2 receptors causes water retention.

Pharmacokinetics. Intravenous half-life is 3 to 4 hours, though factor effect lasts 6 to 12 hours. Subcutaneous bioavailability is about 85% of the intravenous dose; intranasal bioavailability is about 3 to 10%. Peak factor levels occur 30 to 60 minutes after intravenous use and 60 to 90 minutes after subcutaneous or intranasal use. Repeated doses give a smaller response (tachyphylaxis) as stores deplete.

Mild haemophilia A (factor VIII 5 IU/dL or more) and type 1 von Willebrand disease with a proven response; selected type 2A, 2M and 2N.

• Intravenous: 0.3 µg/kg diluted in 0.9% sodium chloride (50 mL for adults and children 10 kg or over; 10 mL for under 10 kg) infused over 20 to 30 minutes. Maximum: 20 µg for each dose.
• Subcutaneous: 0.3 µg/kg once.
• Intranasal (high-strength spray, 150 µg for each spray): 150 µg (one spray) for under 50 kg; 300 µg (one spray in each nostril) for 50 kg or more.
• Frequency: repeat every 12 to 24 hours if needed. Limit to 3 to 4 consecutive days because the response falls by about 30% after the first doses. Loading dose and titration: none.
• Example: a 70 kg adult receives 21 µg, capped at 20 µg (5 mL of a 4 µg/mL ampoule).

Response testing. Give a test dose of 0.3 µg/kg intravenously or subcutaneously when the patient is well. Measure factor VIII and von Willebrand factor activity before the dose, at 1 hour and at 4 hours. A response is a rise to at least 2-fold and to over 30 to 50 IU/dL; for major surgery the target is 50 IU/dL or more.

Adjunct. Add tranexamic acid, 15 to 20 mg/kg (maximum 1 g) intravenously every 8 hours or 1 to 1.5 g orally three times daily, for mucosal bleeding, but not for bleeding from the upper urinary tract.

Uraemic and drug-related platelet dysfunction (specialist use). 0.3 µg/kg intravenously once, repeated daily for up to 3 days.

Adjustments. Kidney: avoid when eGFR is under 50 mL/min, as clearance falls and hyponatraemia risk rises. Liver: no adjustment. Children: avoid under 2 years; extreme caution to age 5 years. Older adults: caution because of hyponatraemia and cardiovascular risk.

Contraindications. Type 2B von Willebrand disease (platelet aggregation and thrombocytopenia), type 3 disease, severe haemophilia A, haemophilia B, hyponatraemia or history of it, psychogenic polydipsia, syndrome of inappropriate antidiuresis, heart failure, uncontrolled hypertension, unstable angina or recent arterial thrombosis, and concurrent loop or thiazide diuretics.

Boxed-warning-level risk. Severe hyponatraemia, with seizures, coma, respiratory arrest or death, especially in young children and with excess fluid intake.

Adverse effects. Facial flushing, headache, tachycardia, mild hypotension (infusion too fast), nausea, abdominal cramps, fluid retention. Serious: hyponatraemia, arterial thrombosis (rare), seizures.

Interactions. Hyponatraemia risk rises with selective serotonin reuptake inhibitors, tricyclic antidepressants, carbamazepine, oxcarbazepine, lamotrigine, chlorpropamide, opioids, non-steroidal anti-inflammatory drugs and diuretics. Tranexamic acid adds a prothrombotic effect in at-risk patients.

Pregnancy and breastfeeding. Used in von Willebrand disease and carriers with mild disease at delivery when needed, with fluid restriction and sodium monitoring; transient oxytocic effects occur. Compatible with breastfeeding.

Regional points. Low cost and availability make desmopressin the main treatment for mild haemophilia A and type 1 von Willebrand disease in East Africa, where concentrate is scarce. Do not confuse the high-strength haemostatic nasal spray (150 µg for each spray) with the low-strength spray for diabetes insipidus.

Common errors. Using in an unproven responder, in type 2B disease or in severe haemophilia; repeating beyond 4 days; fast infusion causing hypotension; no fluid restriction.

Administration. Intravenous infusion over 20 to 30 minutes; do not give as rapid bolus. Restrict fluids to about 1 L in 24 hours for adults after each dose, and avoid hypotonic fluids. Ampoules are stored at 2 to 8°C.

Baseline. Factor VIII, von Willebrand factor antigen and activity, platelet count, sodium, creatinine, blood pressure, and cardiovascular risk review.

Monitoring. Blood pressure and pulse during the infusion. Sodium at baseline and at 24 hours after repeated doses; stop if sodium falls under 130 mmol/L or symptoms appear. Factor VIII and von Willebrand factor activity at 1 hour and before surgery. Platelet count in suspected type 2B disease.

Referral and escalation. Sodium under 125 mmol/L, seizures or reduced consciousness: stop desmopressin and fluids and start hyponatraemia treatment urgently. Refer major bleeding, major surgery, non-responders and pregnancy to a haemophilia centre.