Desmopressin in Bleeding Disorders

Desmopressin (DDAVP) is a synthetic analogue of vasopressin that raises plasma factor VIII and von Willebrand factor (VWF) for several hours. It treats mild haemophilia A, type 1 von Willebrand disease and some platelet function disorders, and avoids the cost and infection risk of plasma products. It does not work in severe haemophilia A, haemophilia B or type 3 von Willebrand disease.

Mechanism. Desmopressin acts on V2 receptors on endothelial cells and releases stored VWF and factor VIII. Platelet adhesion improves, so bleeding time shortens. V1 effects are minimal, so it causes little vasoconstriction.

Pharmacokinetics. Peak factor rise follows 30 to 60 minutes after intravenous or subcutaneous dosing; effect lasts 6 to 12 hours. Stores deplete after repeated doses, so response falls (tachyphylaxis) after the second or third dose. Intranasal bioavailability is about 10%.

Dosing for bleeding disorders.

• Intravenous or subcutaneous: 0.3 micrograms/kg, diluted in 50 mL of sodium chloride 0.9% and infused over 20 to 30 minutes when given intravenously.
• Intranasal (concentrated 150 micrograms a spray): 300 micrograms for adults over 50 kg (one spray in each nostril); 150 micrograms under 50 kg.
• Repeat every 12 to 24 hours for up to 3 days; response weakens with each dose.
• Oral tablets are not used for bleeding disorders.

Response test. Give a test dose when the diagnosis is made. Measure factor VIII, VWF antigen and VWF activity before and at 1 hour (and 4 hours) after. A good response is a factor level at least double the baseline and over 50 IU/dL.

Combined use. Add tranexamic acid 15 to 20 mg/kg three times daily (or 1 g orally three times daily) for mucosal bleeding, dental procedures and menorrhagia.

• First-line. Mild haemophilia A and type 1 von Willebrand disease with a documented response; minor bleeding and minor surgery.
• Alternative. Platelet function disorders and uraemic bleeding (0.3 micrograms/kg once); drug-induced platelet dysfunction with major bleeding.
• Specialist. Carriers of haemophilia A with low factor VIII; type 2 von Willebrand disease only after a proven response (not type 2B, where platelets fall).
• Emergency. Not a first choice for life-threatening bleeding; give factor concentrate.

Selection. Use when the response test is adequate and the bleed or procedure is minor. Choose factor concentrate for major surgery, severe disease and when a second dose within 24 hours will not reach the target.

Contraindications. Hyponatraemia or a history of it; type 2B von Willebrand disease; type 3 disease; unstable coronary or cerebrovascular disease; polydipsia; heart failure needing diuretics; hypersensitivity; infants under 2 years (relative).

Serious adverse effects.

• Hyponatraemia from water retention, causing headache, confusion and seizures. Restrict fluid to about 1 litre in the 24 hours after a dose.
• Facial flushing, headache and tachycardia with rapid infusion.
• Hypotension if infused quickly; thrombosis in at-risk patients (rare).

Major interactions. Loop and thiazide diuretics, SSRIs, carbamazepine, tricyclic antidepressants, NSAIDs and other drugs causing hyponatraemia; additive antifibrinolytic thrombotic risk with tranexamic acid in high-risk patients.

Common prescribing errors.

• Giving without a prior response test.
• Repeating doses for more than 3 days.
• Free fluid intake after the dose.
• Giving in type 2B disease.
• Using it in severe haemophilia A.

Special groups.

• Pregnancy: used for bleeding in selected carriers; monitor sodium; avoid in pre-eclampsia.
• Breastfeeding: small amounts in milk; acceptable.
• Children: 0.3 micrograms/kg; avoid under 2 years because of hyponatraemia risk; fluid restriction.
• Older adults: higher risk of hyponatraemia and cardiovascular events; reduce use.
• Kidney: avoid in moderate and severe impairment.
• Liver: no adjustment.
• East Africa: factor concentrate is often unavailable, so desmopressin is valuable in mild haemophilia A and von Willebrand disease where diagnosed; confirm local stock, since nasal spray strengths differ.

Monitoring. Serum sodium before the second dose and at 24 hours; blood pressure and pulse during infusion; factor VIII and VWF levels; weight and fluid balance.

Referral and escalation. Sodium under 130 mmol/L or neurological symptoms; failure to respond to the test dose; bleeding in severe disease; major surgery.

Comparison with alternative classes. Desmopressin is cheap and avoids plasma-derived infection risk, but works only in mild disease and weakens with repeat doses. Factor concentrates are reliable and dose-adjustable, and antifibrinolytic drugs add benefit for mucosal bleeding.