• Fathelrahman M Hassan Department of Clinical Laboratory Science, College of Applied Medical Science, Immam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.


Objective: The objective of this study was to determine the fibrinolytic alteration associated with daily administration of sildenafil.

Methods: A total of 12 adult male rabbits without mortality rate had been fed standard and subdivided into four groups; their average weight was 1.5, 2.5, 1.9, and 2 kg randomly selected during the period of March 2012–July 2013. Depending on weight, the control groups (2.25 mg/1.5 kg day) and sildenafil groups (3 mg/2 kg/day, 2.85 mg/1.9 kg/day, and 1.7 mg/2.5 kg/day) were injected by normal saline and sildenafil concentration, respectively to create four groups, every group was composed of three rabbits; saline rabbit (control group, n=3) and sildenafil rabbits (sildenafil group, n=9). All rabbit's plasma samples have been investigated for prothrombin time, activated partial thromboplastin time, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), prothrombin fragment 1+2, tissues plasminogen activator (tPA), plasmin antiplasmin (PAP), plasminogen, and D-dimer after 24 h of administration.

Results: The PAP level was significantly (p<0.05) decreased following sildenafil injection. Sildenafil-injected (3 mg/ml) rabbits had decreased the means of PAI-1 and mean tPA, as early as 1-day post-injection, with a considerable lower PAP first determined 3 days after injection that continued into each rabbit 2 and 3.

Conclusion: Better strategies are to initiate and manipulate this drug ought to reduce the chance of each thrombosis and hemorrhage, at the same time as minimizing the need for laboratory monitoring with the aid of the use of PAI-1, tPA, and PAP checks.

Keywords: Fibrinolytic, Alteration, Administration, Sildenafil.


1. Sastry B, Narasimhan C, Reddy N, Anand B, Prakash G, Raju PR, et al. A study of clinical efficacy of sildenafil in patients with primary pulmonary hypertension. Indian Heart J 2002;54:410-4.
2. Sastry B, Narasimhan C, Reddy NK, Raju BS. Clinical efficacy of sildenafil in primary pulmonary hypertension: A randomized, placebo-controlled, double-blind, crossover study. J Am Coll Cardiol 2004;43:1149-53.
3. Chen YJ, Traverse JH, Hou M, Li Y, Du R, Bache RJ. Effect of PDE5 inhibition on coronary hemodynamics in pacing-induced heart failure. Am J Physiol Heart Circ Physiol 2003;284:H1513-20.
4. Fischer T, Erbel R, Treese N. Current status of phosphodiesterase inhibitors in the treatment of congestive heart failure. Drugs 1992;44:928-45.
5. Ulusoy MG, Uysal A, Koãer U, Karaaslan Ã, Cuzdan SS, Ayyldz A, et al. Improved flap viability with site-specific delivery of sildenafil citrate using fibrin glue. Ann Plastic Surg 2005;55:292.
6. Sarifakioglu N, Gokrem S, Ates L, Akbuga UB, Aslan G. The influence of sildenafil on random skin flap survival in rats: An experimental study. Br J Plast Surg 2004;57:769-72.
7. Li Z, Xi X, Gu M, Feil R, Ye RD, Eigenthaler M, et al. A stimulatory role for cGMP-dependent protein kinase in platelet activation. Cell 2003;112:77-86.
8. Gore J, Silver R. Oral sildenafil for the treatment of Raynaud’s phenomenon and digital ulcers secondary to systemic sclerosis. Ann Rheum Dis 2005;64:1387.
9. Ambach A, Seo W, Bonnekoh B, Gollnick H. Lowdose combination therapy of severe digital ulcers in diffuse progressive systemic sclerosis with the endothelin-1 receptor antagonist bosentan and the phosphodiesterase V inhibitor sildenafil. J Dtsch Dermatol Ges 2009;7:888-91.
10. Chung L. Therapeutic options for digital ulcers in patients with systemic sclerosis. J Dtsch Dermatol Ges 2007;5:460-5.
11. Moinzadeh P, Hunzelmann N, Krieg T. Combination therapy with an endothelin-1 receptor antagonist (bosentan) and a phosphodiesterase V inhibitor (sildenafil) for the management of severe digital ulcerations in systemic sclerosis. J Am Acad Dermatol 2011;65:102-4.
12. Austin MJ, McDougall NI, Wendon JA, Sizer E, Knisely AS, Rela M, et al. Safety and efficacy of combined use of sildenafil, bosentan, and iloprost before and after liver transplantation in severe portopulmonary hypertension. Liver Transpl 2008;14:287-91.
13. Catapano-Minotti G, Corsonello A, Guadalupi G, Spani R, Antonelli-Incalzi R. Treatment of severe pulmonary hypertension secondary to scleroderma: A three-drug approach. Intern Med 2008;47:511.
14. Konstantinos G, Petros P. Phosphodiesterase-5 inhibitors: Future perspectives. Curr Pharm Design 2009;15:3540-51.
15. Wells PS, Anderson DR, Bormanis J, Guy F, Mitchell M, Gray L, et al. Application of a diagnostic clinical model for the management of hospitalized patients with suspected deep-vein thrombosis. Thromb Haemost 1999;81:493-7.
16. Nurnberg HG, Hensley PL, Lauriello J, Parker LM, Keith SJ. Sildenafil for women patients with antidepressant-induced sexual dysfunction. Psychiatr Serv 1999;50:1076-8.
17. Wells PS, Anderson DR, Bormanis J, Guy F, Mitchell M, Lewandowski B. SimpliRED D-dimer can reduce the diagnostic tests in suspected deep vein thrombosis. Lancet 1998;351:1405-6.
18. Heijboer H, Büller HR, Lensing AW, Turpie AG, Colly LP, ten Cate JW. A comparison of real-time compression ultrasonography with impedance plethysmography for the diagnosis of deep-vein thrombosis in symptomatic outpatients. N Engl J Med 1993;329:1365-9.
19. Lennox AF, Delis KT, Serunkuma S, Zarka ZA, Daskalopoulou SE, Nicolaides AN. Combination of a clinical risk assessment score and rapid whole blood D-dimer testing in the diagnosis of deep vein thrombosis in symptomatic patients. J Vasc Surg 1999;30:794-803.
20. Kearon C, Ginsberg JS, Douketis J, Crowther M, Brill-Edwards P, Weitz JI, et al. Management of suspected deep venous thrombosis in outpatients by using clinical assessment and D-dimer testing. Ann Intern Med 2001;135:108-11.
21. Ahmed HA, Nadan A, Mohammed MA. Evaluation of chemopreventiv response of pentoxiphylline and sildenfil in colorectal carcinoma experimentally indued in rats: Comparative study with 5-Fluorouracil. Int J Pharm Pharm Sci 2015;7:217-22.
22. Wells PS, Anderson DR, Bormanis J, Guy F, Mitchell M, Gray L, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 1997;350:1795-8.
23. Kovacs MJ, MacKinnon KM, Anderson D, O’Rourke K, Keeney M, Kearon C, et al. A comparison of three rapid D-dimer methods for the diagnosis of venous thromboembolism. Br J Haematol 2001;115:140-4.
24. Nurnberg HG, Hensley PL, Heiman JR, Croft HA, Debattista C, Paine S. Sildenafil treatment of women with antidepressant-associated sexual dysfunction. JAMA 2008;300:395-404.
25. Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG, et al. VTE impact assessment group in Europe (VITAE). Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost 2007;98:756-64.
26. Eguchi Y, Takahari Y, Higashijima N, Ishizuka N, Tamura N, Kawamura Y, et al. Nicorandil attenuates FeCl-induced thrombus formation through the inhibition of reactive oxygen species production. Circ J 2009;73:554-61.
27. Miyhir KP, Kiranjk C, Anta AM. Role of nitric oxide(NO) in capsaicin mediated anti-platelet activity in In vitro, In vivo, Ex-vivo nodel of platelet agreggation assay and artterial thrombosis in rat: Potential therapeutic target? Int J Pharm Pharm Sci 2018;10:44-8.
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How to Cite
Hassan, F. M. “THE FIBRINOLYTIC ALTERATION ASSOCIATED WITH DAILY ADMINISTRATION OF SILDENAFIL”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 11, no. 8, Aug. 2018, pp. 107-9, doi:10.22159/ajpcr.2018.v11i8.23144.
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