Anaphylactic shock to defibrotide


  • Immediate hypersensitivity to defibrotide.

Defibrotide, a polydeoxyribonucleotide with antithrombotic and profibrinolytic properties, was originally used in patients with chronic venous insufficiency (CVI), but was recently shown to have protective effects during cardiac arrest (1), to resolve or prevent thrombotic microangiopathy and hepatic veno-occlusive disease after allogenic stem cell and/or bone marrow transplantation (2, 3). Finally, defibrotide was successfully used in cases of catastrophic antiphospholipid syndrome (4).

Several adverse reactions to this drug have been described: vomiting and diarrhoea, thrombophlebitis at infusion site and cutaneous reaction (5).

We present a case of reaction to defibrotide with different clinical manifestation: anaphylactic shock. We studied a 66-year-old woman who suffered from CVI and experienced anaphylactic shock (generalized urticaria, vomiting, fall in blood pressure, collapse, loss of consciousness) within 15 min after intravenous administration of the first dose (200 mg) of Prociclide® (defibrotide, Prociclide, Crinos SpA, Milan, Italy). After treatment with anti-shock therapy in the emergency department, her symptoms were considerably reduced within 2 h and completely resolved after 24 h.

Eight months earlier, she had tolerated oral defibrotide. The patient had no personal or family history of allergic disease.

Four months later she was referred to our Allergy Unit for allergologic investigation.

After obtaining informed consent, we investigated the patient and five healthy nonatopic control subjects. All these patients underwent skin test (prick and intradermal) with defibrotide diluted in 0.9% NaCl and administered at increasing concentration every 15–20 min, as previously described (6).

The patient responded positively to prick testing with defibrotide (wheal 3 × 10 mm) as undiluted drug (200 mg/ml) and to intradermal testing at concentration of 2 mg/ml (wheal 13 × 20 mm).

Control intradermal tests with defibrotide were also administered to five healthy subjects without any adverse effect.

Clinical findings and positive skin test with defibrotide imply that the patient developed type-1 hypersensitivity. To the best of our knowledge, this is the first documented case of immediate hypersensitivity to defibrotide: this shows that also drugs potentially nonallergenic as deoxyribonucleic acid derivative can induce severe allergic reaction.