Category: Letters

Desmopressin: a promising anti-platelet reversal?

Ornella Spagnolello1, Enrico Mirante2
 
1. Emergency Department, Emergency Medicine, Policlinico Umberto I Hospital, Sapienza University, Rome, Italy
2. Emergency Department, Emergency Medicine, Sant Eugenio Hospital, Rome, Italy
 
 
As a result of cardiovascular disease burden, anti-platelet agents exposition has widely spread all around the developed world. Moreover, based on the aging population, the estimated number of patients requiring anti-platelet therapy is expected to further rise in the years to come. However, alongside the overall benefit in preventing cardiovascularevents, platelet disfunction related to these drugsis undoubtedlyassociated with increasing bleeding risk. Therefore, a proper and well-shared protocol aiming to manage life-threatening bleeding or urgent surgery/invasive procedure indication among patients currently under anti-platelet therapy is strictly warranted in the emergency setting. 
Although many guidelines have formerly suggested platelet transfusionin the event of bleeding complication in patients exposed to anti-platelet agents, until now there is little evidence in support of this strategy. In addition, the use of platelet transfusion has been further questionedin the light of the PATCH trial results.(1) 
This randomized study comparing platelet transfusion to standard care in intracranial hemorrhagereported that platelet transfusion was of no benefit in reducing bleeding and led to a poorer outcome with increased mortality and poorer functional outcome in patient previouslyon anti-platelet therapy. Even though the results of this trial may not be applicable in all emergency settings, they raise crucialquestions about the safety profileof platelet transfusionin patients taking anti-platelet agents.  Desmopressin acetate (dDAVP) is a synthetic analog of antidiuretic hormone (ADH) with little vasopressin activity. Its administration increases plasma level of von Willebrand factor (vWD), factor VII, and tissue-type plasminogen activator (tPA) by enhancing their release from both platelets and endothelial cells. Therefore, along with the treatment of diabetes insipidus, its use has been approved by FDA also in prevention or management of bleedingof patients affected by mild Hemophilia A and von Willebrand’s Disease type I. According to its data sheet, desmopressin can be given either intravenouslyorsubcutaneouslyat a dose rangingfrom 0.1 to 0.4 micro/Kg, but intranasal use is also available. Side effects include facial flushing, hypervolemia, decreased urine output and hyponatremia.(2)
Cerebrovascular and cardiac thrombosis have been rarely reported, therefore, desmopressin should be cautiously administeredin patients reporting a recent ischemic ictus or myocardial infarction.(3) 
Since desmopressinhas also proved to safelyimprove platelet dysfunction in uremic patients,(4),(5) a number of guidelines have suggested its use for bleeding managementof patients taking anti-platelet therapy on the behalf of its potential reversal activity.(6),(7),(8),(9),(10)
Among them, the European guidelineson management of major bleeding and coagulopathy following traumarecommendeddesmopressin (0.3 micro/Kg) besides platelets transfusion in trauma patients currently treatedwith platelet-inhibiting drugs (Grade 2C). Moreover, the Neurocritical Care Society and Society of Critical Care Medicine suggested the consideration of a sigle dose of desmopressin (0.4 micro/Kg) in intracranial hemorrhage patients exposed to anti-platelet agents. However, the paucity of randomized studies carried out in the emergency setting underpowered the level of all these recommendations.  
In conclusion, taking into account the relevance of bleeding relied to anti-platelet agents, the potential harm of platelet transfusion, the lack of specific antidote along with the relative safety profile of desmopressin, further studies addressingthis issue are warranted.
References
  1. Baharoglu MI, Cordonnier C, Salman RA, de Gans K, Koop- man MM, Brand A, Majoie CB, Beenen LF, Marquering HA, Vermeulen M, Nederkoorn PJ, de Haan RJ, Roos YB. Platelet transfusion versus standard care after acute stroke due to spon- taneous cerebral haemorrhage associated with antiplatelet ther- apy (PATCH): a randomised, open-label, phase 3 trial. Lancet 2016; 387: 2605–13
  2. Van Herzeele C, De Bruyne P, Evans J, et al. Safety profile of desmopressin tablet for enuresis in a prospective study. Adv Ther. 2014;31:1306–16
  3. Byrnes JJ, Larcada A, Moake JL. Thrombosis following desmopressin for uremic bleeding.Am J Hematol. 1988;28(1):63
  4. Lee HK, Kim YJ, Jeong JU, Park JS, Chi HS, Kim SB (2010) Desmopressin improves platelet dysfunction measured by in vitro closure time in uremic patients. Nephron Clin Pract 114:c248–c252 
  5. Mannucci PM, Remuzzi G, Pusineri F et al (1983) Deamino-8-Darginine vasopressin shortens the bleeding time in uremia. N Engl J Med 308:8–12
  6. Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fer- nandez-Mondejar E, Filipescu D, Hunt BJ, Komadina R, Nardi G, Neugebauer EA, Ozier Y, Riddez L, Schultz A, Vincent JL, Spahn DR. The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Crit Care 2016; 20: 100 
  7. American Society of Anesthesiologists. Practice guidelines for perioperative blood management: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Management. Anesthesiology 2015; 122: 241–75 
  8. Ferraris VA, Brown JR, Despotis GJ, Hammon JW, Reece TB, Saha SP, Song HK, Clough ER, Shore-Lesserson LJ, Good- nough LT, Mazer CD, Shander A, Stafford-Smith M, Waters J, Baker RA, Dickinson TA, FitzGerald DJ, Likosky DS, Shann KG. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg 2011; 91: 944–82 
  9. Kozek-Langenecker SA, Afshari A, Albaladejo P, Santullano CA, De Robertis E, Filipescu DC, Fries D, Gorlinger K, Haas T, Imberger G, Jacob M, Lance M, Llau J, Mallett S, Meier J, Rahe-Meyer N, Samama CM, Smith A, Solomon C, Van der Linden P, et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2013; 30: 270–382
  10. Frontera JA, Lewin JJ 3rd, Rabinstein AA, Aisiku IP, Alexan- drov AW, Cook AM, del Zoppo GJ, Kumar MA, Peerschke EI, Stiefel MF, Teitelbaum JS, Wartenberg KE, Zerfoss CL. Guide- line for Reversal of Antithrombotics in Intracranial Hemorrhage: A Statement for Healthcare Professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care 2016; 24: 6–46
 

 

 

Itjem is the official italian scientific review for emergency medicine.

Publisher: Simeu, Società italiana della medicina di emergenza-urgenza, via Valprato, 68 Torino - www.simeu.it

Editorial coordination: Silvia Alparone.

Scientific Manager : Giuliano Bertazzoni; Operating Editorial Board: Paolo Balzaretti, Guido Borasi, Rodolfo Ferrari, Mauro Giordano, Paolo Groff, Emanuele Pivetta.

Advisory Board: Michele Gulizia, Riccardo Lubrano, Marco Ranieri, Maria Pia Ruggieri, Roberta Petrino, Francesco Violi, Ugo Loaisa, Lexie Asrow.

Editorial Board and Reviewers: Giancarlo Agnelli, Giancarlo Avanzi, Marco Baroni, Stefania Basili, Alessio Bertini, Francesco Buccelletti, Gian A. Cibinel, Roberto Cosentini, Fabio De Iaco, Andrea Fabbri, Paola Noto, Giovanni Ricevuti, Fernando Schiraldi, Danilo Toni.

Norme editoriali clicca qui.

  • Scientifici

  • Divulgativi

Loading
Loading