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Vol 28, No 6 (2021)
Review Article
Published online: 2020-11-09

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Antiplatelet effects of prostacyclin analogues: Which one to choose in case of thrombosis or bleeding?

Sylwester P. Rogula1, Hubert M. Mutwil1, Aleksandra Gąsecka1, Marcin Kurzyna2, Krzysztof J. Filipiak1
DOI: 10.5603/CJ.a2020.0164
Pubmed: 33200814
Cardiol J 2021;28(6):954-961.

Abstract

Prostacyclin and analogues are successfully used in the treatment of pulmonary arterial hypertension (PAH) due to their vasodilatory effect on pulmonary arteries. Besides vasodilatory effect, prostacyclin analogues inhibit platelets, but their antiplatelet effect is not thoroughly established. The antiplatelet effect of prostacyclin analogues may be beneficial in case of increased risk of thromboembolic events, or undesirable in case of increased risk of bleeding. Since prostacyclin and analogues differ regarding their potency and form of administration, they might also inhibit platelets to a different extent. This review summarizes the recent evidence on the antiplatelet effects of prostacyclin and analogue in the treatment of PAH, this is important to consider when choosing the optimal treatment regimen in tailoring to an individual patients’ needs.

Keywords: prostacyclin analoguespulmonary arterial hypertensionplateletsantiplatelet effectthrombosisbleeding

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References

  1. Von Euler US. Über die Spezifische Blutdrucksenkende Substanz des Menschlichen Prostata- und Samenblasensekretes. Klin Wochenschr. 1935; 14(33): 1182–1183.
    CrossRef
  2. The Nobel Prize. https://www.nobelprize.org/prizes/medicine/1982/press-release/ (Accessed: 7 April 2020).
  3. Woodward DF, Jones RL, Narumiya S. International Union of Basic and Clinical Pharmacology. LXXXIII: classification of prostanoid receptors, updating 15 years of progress. Pharmacol Rev. 2011; 63(3): 471–538.
    CrossRefPubMed
  4. Mubarak KK. A review of prostaglandin analogs in the management of patients with pulmonary arterial hypertension. Respir Med. 2010; 104(1): 9–21.
    CrossRefPubMed
  5. Safdar Z. Treatment of pulmonary arterial hypertension: the role of prostacyclin and prostaglandin analogs. Respir Med. 2011; 105(6): 818–827.
    CrossRefPubMed
  6. Uptravi® Full Prescribing Information. https://www.uptravi.com/assets/pdf/UPTRAVI-full-prescribing-information.pdf (Accessed 7 April 2020).
  7. Heemskerk JWM, Bevers EM, Lindhout T. Platelet activation and blood coagulation. Thromb Haemost. 2002; 88(2): 186–193.
    PubMed
  8. Palta S, Saroa R, Palta A. Overview of the coagulation system. Indian J Anaesth. 2014; 58(5): 515–523.
    CrossRefPubMed
  9. Winter WE, Flax SD, Harris NS. Coagulation testing in the core laboratory. Lab Med. 2017; 48(4): 295–313.
    CrossRefPubMed
  10. Lasne D, Jude B, Susen S. From normal to pathological hemostasis. Can J Anaesth. 2006; 53(6 Suppl): S2–11.
    CrossRefPubMed
  11. Gomberg-Maitland M, Olschewski H. Prostacyclin therapies for the treatment of pulmonary arterial hypertension. Eur Respir J. 2008; 31(4): 891–901.
    CrossRefPubMed
  12. Armstrong RA. Platelet prostanoid receptors. Pharmacol Ther. 1996; 72(3): 171–191.
    CrossRefPubMed
  13. Boie Y, Sawyer N, Slipetz DM, et al. Molecular cloning and characterization of the human prostanoid DP receptor. J Biol Chem. 1995; 270(32): 18910–18916.
    CrossRefPubMed
  14. Deep A, Zoha M, Dutta Kukreja P. Prostacyclin as an anticoagulant for continuous renal replacement therapy in children. Blood Purif. 2017; 43(4): 279–289.
    CrossRefPubMed
  15. Boie Y, Rushmore TH, Darmon-Goodwin A, et al. Cloning and expression of a cDNA for the human prostanoid IP receptor. J Biol Chem. 1994; 269(16): 12173–12178.
    PubMed
  16. Berridge MJ. Inositol trisphosphate and calcium signaling. Nature. 1993; 361(6410): 315–325.
  17. Hirata M, Hayashi Y, Ushikubi F, et al. Cloning and expression of cDNA for a human thromboxane A2 receptor. Nature. 1991; 349(6310): 617–620.
    CrossRefPubMed
  18. Nagy Z, Smolenski A. Cyclic nucleotide-dependent inhibitory signaling interweaves with activating pathways to determine platelet responses. Res Pract Thromb Haemost. 2018; 2(3): 558–571.
    CrossRefPubMed
  19. Chakraborty R, Pydi SP, Gleim S, et al. New insights into structural determinants for prostanoid thromboxane A2 receptor- and prostacyclin receptor-G protein coupling. Mol Cell Biol. 2013; 33(2): 184–193.
    CrossRefPubMed
  20. Kotani M, Tanaka I, Ogawa Y, et al. Structural organization of the human prostaglandin EP3 receptor subtype gene (PTGER3). Genomics. 1997; 40(3): 425–434.
    CrossRefPubMed
  21. Sitbon O, Channick R, Chin K, et al. Selexipag for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2015; 373(26): 2522–2533.
    CrossRef
  22. Abramovitz M, Adam M, Boie Y, et al. The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim Biophys Acta. 2000; 1483(2): 285–293.
    CrossRefPubMed
  23. Kiriyama M, Ushikubi F, Kobayashi T, et al. Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1997; 122(2): 217–224.
    CrossRefPubMed
  24. Kuwano K, Hashino A, Asaki T, et al. 2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug. J Pharmacol Exp Ther. 2007; 322(3): 1181–1188.
    CrossRefPubMed
  25. Whittle BJ, Silverstein AM, Mottola DM, et al. Binding and activity of the prostacyclin receptor (IP) agonists, treprostinil and iloprost, at human prostanoid receptors: treprostinil is a potent DP1 and EP2 agonist. Biochem Pharmacol. 2012; 84(1): 68–75.
    CrossRefPubMed
  26. Gomberg-Maitland M, Tapson VF, Benza RL, et al. Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension. Am J Respir Crit Care Med. 2005; 172(12): 1586–1589.
    CrossRefPubMed
  27. Chin KM, Channick RN, de Lemos JA, et al. Hemodynamics and epoprostenol use are associated with thrombocytopenia in pulmonary arterial hypertension. Chest. 2009; 135(1): 130–136.
    CrossRefPubMed
  28. Hargett C, Ahearn G, Krichman A, et al. Thrombocytopenia associated with chronic intravenous epoprostenol therapy. Chest. 2004; 126(4).
    CrossRef
  29. Ogawa A, Matsubara H, Fujio H, et al. Risk of alveolar hemorrhage in patients with primary pulmonary hypertension--anticoagulation and epoprostenol therapy. Circ J. 2005; 69(2): 216–220.
    CrossRefPubMed
  30. Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996; 334(5): 296–301.
    CrossRefPubMed
  31. Herrero T, Martin E, Poch DS, et al. Anti-coagulation complications in pregnancies with severe pulmonary arterial hypertension. J Matern Fetal Neonatal Med. 2018; 31(9): 1209–1213.
    CrossRefPubMed
  32. Louis L, Bair N, Banjac S, et al. Subdural hematomas in pulmonary arterial hypertension patients treated with prostacyclin analogs [corrected]. Pulm Circ. 2012; 2(4): 518–521.
    CrossRefPubMed
  33. Ascha M, Zhou X, Rao Y, et al. Impact on survival of warfarin in patients with pulmonary arterial hypertension receiving subcutaneous treprostinil. Cardiovasc Ther. 2017; 35(5).
    CrossRefPubMed
  34. Barst RJ, Galie N, Naeije R, et al. Long-term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil. Eur Respir J. 2006; 28(6): 1195–1203.
    CrossRefPubMed
  35. Simonneau G, Barst RJ, Galie N, et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2002; 165(6): 800–804.
    CrossRefPubMed
  36. Mindus S, Pawlowski J, Nisell M, et al. Intra-abdominal bleeding during treprostinil infusion in a patient with pulmonary arterial hypertension. BMJ Case Rep. 2013; 2013.
    CrossRefPubMed
  37. Ferdman DJ, Rosenzweig EB, Zuckerman WA, et al. Subcutaneous treprostinil for pulmonary hypertension in chronic lung disease of infancy. Pediatrics. 2014; 134(1): e274–e278.
    CrossRefPubMed
  38. Sadushi-Kolici R, Jansa P, Kopec G, et al. Subcutaneous treprostinil for the treatment of severe non-operable chronic thromboembolic pulmonary hypertension (CTREPH): a double-blind, phase 3, randomised controlled trial. Lancet Respir Med. 2019; 7(3): 239–248.
    CrossRefPubMed
  39. Kurzyna M, Małaczyńska-Rajpold K, Koteja A, et al. An implantable pump Lenus pro® in the treatment of pulmonary arterial hypertension with intravenous treprostinil. BMC Pulm Med. 2017; 17(1): 162.
    CrossRefPubMed
  40. Bajwa AA, Shujaat A, Patel M, et al. The safety and tolerability of inhaled treprostinil in patients with pulmonary hypertension and chronic obstructive pulmonary disease. Pulm Circ. 2017; 7(1): 82–88.
    CrossRefPubMed
  41. Bettoni L, Geri A, Airò P, et al. Systemic sclerosis therapy with iloprost: a prospective observational study of 30 patients treated for a median of 3 years. Clin Rheumatol. 2002; 21(3): 244–250.
    CrossRefPubMed
  42. de Donato G, Gussoni G, de Donato G, et al. The ILAILL study: iloprost as adjuvant to surgery for acute ischemia of lower limbs: a randomized, placebo-controlled, double-blind study by the italian society for vascular and endovascular surgery. Ann Surg. 2006; 244(2): 185–193.
    CrossRefPubMed
  43. Eifinger F, Sreeram N, Mehler K, et al. Aerosolized iloprost in the treatment of pulmonary hypertension in extremely preterm infants: a pilot study. Klin Padiatr. 2008; 220(2): 66–69.
    CrossRefPubMed
  44. Chen S, Xie S, He W, et al. Beneficial effect of beraprost sodium plus aspirin in the treatment of acute ischemic stroke. Med Sci Monit. 2017; 23: 4401–4407.
    CrossRefPubMed
  45. Kim M, Kim JiU, Kim SoMi, et al. Effectiveness of beraprost sodium in maintaining vascular access patency in patients on hemodialysis. Int Urol Nephrol. 2017; 49(7): 1287–1295.
    CrossRefPubMed
  46. Krause A, Machacek M, Lott D, et al. Population Modeling of Selexipag Pharmacokinetics and Clinical Response Parameters in Patients With Pulmonary Arterial Hypertension. CPT Pharmacometrics Syst Pharmacol. 2017; 6(7): 477–485.
    CrossRefPubMed
  47. Bruderer S, Hurst N, Kaufmann P, et al. Multiple-dose up-titration study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of selexipag, an orally available selective prostacyclin receptor agonist, in healthy subjects. Pharmacology. 2014; 94(3-4): 148–156.
    CrossRefPubMed
  48. Stitham J, Arehart E, Gleim SR, et al. New insights into human prostacyclin receptor structure and function through natural and synthetic mutations of transmembrane charged residues. Br J Pharmacol. 2007; 152(4): 513–522.
    CrossRefPubMed
  49. Wright DH, Metters KM, Abramovitz M, et al. Characterization of the recombinant human prostanoid DP receptor and identification of L-644,698, a novel selective DP agonist. Br J Pharmacol. 1998; 123(7): 1317–1324.
    CrossRefPubMed
  50. Flolan® Full Prescribing Information. https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Flolan/pdf/FLOLAN-PI-PIL.PDF (Accessed 7 April 2020).
  51. Veletri® Full Prescribing Information. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/VELETRI-pi.pdf (Accessed 7 April 2020).
  52. Orenitram® Full Prescribing Information. https://www.orenitram.com/pdf/Orenitram_Full_Prescribing_Information.pdf (Accessed 7 April 2020).
  53. Remodulin® Full Prescribing Information. https://www.remodulin.com/downloads/remodulin-prescribinginformation.pdf (Accessed 7 April 2020).
  54. Tyvaso® Full Prescribing Information. https://www.tyvaso.com/hcp/pdf/Tyvaso-PI.pdf (Accessed 7 April 2020).
  55. Ventavis® Full Prescribing Information. https://www.4ventavis.com/pdf/Ventavis_PI.pdf (Accessed 7 April 2020).
  56. Melian EB1, Goa KL. Beraprost: a review of its pharmacology and therapeutic efficacy in the treatment of peripheral arterial disease and pulmonary arterial hypertension. Drugs. 2002; 62(1): 107–133.
  57. Kingman M, Archer-Chicko C, Bartlett M, et al. Management of prostacyclin side effects in adult patients with pulmonary arterial hypertension. Pulm Circ. 2017; 7(3): 598–608.
    CrossRefPubMed

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