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Desmopressin (DDAVP) ameliorates the anti-platelet effects of clopidogrel and aspirin

Barlow AD, Nicholson ML
Dept of Transplant Surgery, Leicester General Hospital, UK

Correspondence to
Adam Barlow, E: adambarlow@doctors.net.uk

Comment on
Thapar A, Moore H, Golden D, Davies AH. Peri-operative antithrombotic therapy: bridging the gap. Ann R Coll Surg Eng 2012; 94: 142-145
doi: 10.1308/003588412X13171221590854

We read with interest the article by Thapar et al, which highlights an issue that is becoming increasingly familiar as more patients with drug eluting coronary stents are seen in surgical practice. However, their statement that there is no drug to reverse the effects of aspirin and clopidogrel is misleading.
Desmopressin, or DDAVP, is used in the treatment of von Willebrand disease and haemophilia A and acts by increasing plasma levels of factor VIII and von Willebrand factor. However, it has also been shown to ameliorate the effects of aspirin(1,2) and clopidogrel(3,4) induced platelet dysfunction. There are reports of its successful use to reduce bleeding in patients on aspirin undergoing cholecystectomy(5) and also to arrest life threatening clopidogrel induced bleeding in epistaxsis(6) and during carotid endarterectomy(4). It has a rapid onset of action and can be given on-table with almost immediate effect. We have personally used desmopressin to successfully obtain haemostasis in a patient on clopidogrel undergoing deceased donor renal transplantation where bleeding could not be controlled by conventional means.
We feel that it is important all surgeons are aware of this potentially life saving treatment for patients on clopidogrel or aspirin undergoing emergency surgery.

References
1. Schulz-Stübner S, Zielske D, Rossaint R. Comparison between nasal and intravenous desmopressin for the treatment of aminosalicylic acid-induced platelet dysfunction. Eur J Anaesthesiol 2002; 19: 647-651
2. Lethagen S, Rugarn P. The effect of DDAVP and placebo on platelet function and prolonged bleeding time induced by oral acetyl salicylic acid intake in healthy volunteers. Thromb Haemost 1992; 67: 185-6.
3. Leithäuser B, Zielske D, Seyfert UT, Jung F. Effects of desmopressin on platelet membrane glycoproteins and platelet aggregation in volunteers on clopidogrel. Clin Hemorheol Microcirc 2008; 39: 293-302.
4. Ranucci M, Nano G, Pazzaglia A, Bianchi P, Casana R, Tealdi DG. Platelet mapping and desmopressin reversal of platelet inhibition during emergency carotid endarterectomy. J Cardiothorac Vasc Anesth 2007; 21: 851-4.
5. Flordal PA, Sahlin S. Use of desmopressin to prevent bleeding complications in patients treated with aspirin. Br J Surg 1993; 80: 723-4.
6. Nácul FE, de Moraes E, Penido C, Paiva RB, Méier-Neto JG. Massive nasal bleeding and hemodynamic instability associated with clopidogrel. Pharm World Sci 2004; 26: 6-7.

We read this useful article with interest, but were concerned about guidance given regarding spinal and epidural anaesthesia. The article stated that following removal of an epidural catheter, an interval of 1-2 hours is recommended before restarting bridging therapy. This statement is misleading as an interval of 1 hour is deemed sufficient only if bridging therapy is a subcutaneous unfractionated heparin. However, low molecular weight heparins are increasingly favoured over unfractionated heparins and current guidance issued to anaesthetists states that an interval of at least 4 hours from catheter removal is required before the next dose of low molecular weight heparin. Neuraxial haematoma is a devastating complication if not recognised and treated immediately; it is therefore vital that we try to prevent this complication and observe the minimum suggested time intervals from neuraxial interventions and further dose of bridging, hence we feel it is important to clarify this issue.

References:
1. AAGBI 2012. Regional Anaesthesia in Patients with Abnormalities in Coagulation. http://www.aagbi.org/sites/default/files/RAPAC%20for%20consultation.pdf (accessed 08/05/2012)
2.Gogarten W, Vandermeulen E, Van Aken H, Kozek S, Llau JV, Samama CM Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology. Eur J Anaesthesiol 2010;27:999–1015