Funda TAYFUN KÜPESİZ, Canan VERGİN, Mustafa BAK

Kronik böbrek yetmezliği olan pediatrik hastalarda trombosit fonksiyonlarının değerlendirilmesi

GİRİŞ ve AMAÇ: Kronik böbrek yetmezliği olan hastalarda üreminin ciddiyeti ve süresine bağlı olarak kanamaya yatkınlık görülebilir. Günümüzde etkin diyaliz işlemleri ile trombosit fonksiyon bozukluğu yapan üremik toksinlerin uzaklaştırılması kanama bozukluklarının kısmen düzeltilmesi sağlamıştır. Bu çalışmada kronik böbrek yetmezliği hastalarında kanama bulgularını, trombosit fonksiyon bozukluğunun varlığını ve bunu etkileyen faktörleri değerlendirmeyi amaçladık. YÖNTEM ve GEREÇLER: Dr. Behçet Uz Çocuk Hastalıkları ve Çocuk Cerrahisi Eğitim ve Araştırma Hastanesi Nefroloji Kliniğinde KBY olarak takip edilen hastalar prospektif olarak değerlendirildi. Çalışma grubu 57 hasta ve 31 sağlıklı kontrol grubundan oluştu. Trombosit yüzeyi fibrinojen (GP IIb-IIa) ve von Willebrand Faktör (vWF) reseptörleri (GP Ib-IX) akım sitometri ile ölçüldü. İn vitro kanama zamanı ise trombosit fonksiyon ölçüm (PFA 100) yöntemi ile ölçüldü. BULGULAR: PFA 100 analizi sonucunda; hemodiyaliz hastalarında ortanca kollojen/epinefrin, kollojen/ADP kapanma zamanı periton diyalizi ve kontrol grubu hastalarına göre istatistiksel olarak anlamlı yüksek bulundu (p=0,000, p=0,000); ancak bu değerler hemodiyaliz işleminden sonra normal düzeylere döndü (p= 0,018, p= 0,028). Periton diyalizi hastalarının in vitro kanama zamanı normal aralıktaydı. Periton diyalizi in vitro kanama zamanını hemodiyalize göre daha iyi düzeltiyordu. Akım sitometri ile yapılan analizlerde; diyaliz yapılan hastalardaki GP Ib (CD42b mAb) düzeylerinin kontrol grubuna göre anlamlı olarak yüksek olduğu görüldü (p= 0,037). Hemodiyaliz yapılan hastalarda ise fibrinojen reseptör (GPIIb) düzeyi hemodiyaliz sonrası anlamlı düzeyde azalıyordu (p=0,018). TARTIŞMA ve SONUÇ: Üremik hastalarda trombosit fonksiyon bozukluğuna bağlı primer hemostazı değerlendirebilmek için PFA 100 yöntemi akım sitometriye göre daha kolay uygulanabilen ve ulaşılabilen bir test olarak kanama riski olan hastaların ilk değerlendirmesinde yol gösterici olabilir.

Anahtar Kelimeler:

kronik böbrek yetmezliği, diyaliz, trombosit fonksiyonu

Evaluation of platelet functions in pediatric patients with chronic renal failure

INTRODUCTION: Patients with chronic renal failure may tend to bleed in relation to the severity and duration of uremia. Currently, effective dialysis procedures and the removal of uremic toxins that cause platelet dysfunction partially alleviate bleeding disorders. In this study, our aim was to evaluate bleeding, platelet dysfunction, and factors that were effective on platelet dysfunction in patients with chronic renal failure. METHODS: This study was a prospective evaluation of patients who were followed by the Nephrology Clinic of Behçet Uz Children's Diseases and Pediatric Surgery Training and Research Hospital with a diagnosis of chronic renal failure. The study group consisted of 57 patients and 31 healthy controls. Platelet surface fibrinogen (GP IIb-IIa) and von Willebrand Factor (vWF) receptors (GP Ib-IX) were measured by flow cytometry. In vitro bleeding time was measured by the platelet function analyzer method (PFA 100). RESULTS: PFA 100 analysis showed that median closure time was significantly higher among hemodialysis patients in terms of collagen/epinephrine, collagen/ADP comparisons (p = 0.000, p = 0.000); however, these values returned to normal after hemodialysis (p = 0.018, p = 0.028). The in vitro bleeding time of patients undergoing peritoneal dialysis was found to be in the normal range. The in vitro bleeding time improvements were better in peritoneal dialysis compared to hemodialysis. Analysis with flow cytometry showed that; GP Ib (CD42b mAb) levels in dialysis patients were significantly higher than control group and predialysis patients (p = 0.037). The fibrinogen receptor (GPIIb) level decreased significantly in hemodialysis patients,after hemodialysis (p = 0.018). DISCUSSION AND CONCLUSION: The PFA 100 method, which is easier than the flow cytometry method for the evaluation of primary hemostasis due to platelet dysfunction in uremic patients, may prove to be an ideal method for the general evaluation of primary hemostasis in the event of bleeding in uremic patients.

Keywords:

chronic renal failure, platelet function,

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1. Gangji AS, Sohal AS, Treleaven D, Crowther MA. Bleeding in patients with renal insufficiency: a practical guide to clinical management. Thromb Res 2006;118(3):423-8.
2. Mohapatra A, Valson AT, Gopal B, Singh S, Nair SC, Viswabandya A, et al. Hemostatic Abnormalities in Severe Renal Failure: Do They Bark or Bite? Indian J Nephrol 2018;28(2):135-42.
3. Mekawy MA, Habashy DM, Abd El-Mohsen WA. Effect of hemodialysis on platelet function in end-stage renal disease Egyptian patients using in vitro closure time test (PFA-100 analyzer). Platelets 2015;26(5):443-7.
4. Bilgin AU, Karadogan I, Artac M, Kizilors A, Bligin R, Undar L. Hemodialysis shortens long in vitro closure times as measured by the PFA-100. Med Sci Monit 2007;13(3):CR141-5.
5. Rios DR, Carvalho M, Lwaleed BA, Simoes e Silva AC, Borges KB, Dusse LM. Hemostatic changes in patients with end stage renal disease undergoing hemodialysis. Clin Chim Acta 2010;411(3-4):135-9.
6. Boccardo P, Remuzzi G, Galbusera M. Platelet dysfunction in renal failure. Semin Thromb Hemost 2004;30(5):579-89.
7. Soyoral YU, Demir C, Begenik H, Esen R, Kucukoglu ME, Aldemir MN, et al. Skin bleeding time for the evaluation of uremic platelet dysfunction and effect of dialysis. Clin Appl Thromb Hemost 2012;18(2):185-8.
8. Zupan IP, Sabovic M, Salobir B, Ponikvar JB, Cernelc P. Utility of in vitro closure time test for evaluating platelet-related primary hemostasis in dialysis patients. Am J Kidney Dis 2003;42(4):746-51.
9. Gawaz MP, Dobos G, Spath M, Schollmeyer P, Gurland HJ, Mujais SK. Impaired function of platelet membrane glycoprotein IIb-IIIa in end-stage renal disease. J Am Soc Nephrol 1994;5(1):36-46.
10. Liani M, Salvati F, Golato M, Tresca E. Platelet glycoproteins GPIb and GPIIb/IIIa abnormalities in uremia. Nephron 1996;72(4):716.
11. Sohal AS, Gangji AS, Crowther MA, Treleaven D. Uremic bleeding: pathophysiology and clinical risk factors. Thromb Res 2006;118(3):417-22.
12. Sreedhara R, Itagaki I, Hakim RM. Uremic patients have decreased shear-induced platelet aggregation mediated by decreased availability of glycoprotein IIb-IIIa receptors. Am J Kidney Dis 1996;27(3):355-64.
13. Thekkedath UR, Chirananthavat T, Leypoldt JK, Cheung AK, Mohammad SF. Elevated fibrinogen fragment levels in uremic plasma inhibit platelet function and expression of glycoprotein IIb-IIIa. Am J Hematol 2006;81(12):915-26.
14. Kozek-Langenecker SA, Masaki T, Mohammad H, Green W, Mohammad SF, Cheung AK. Fibrinogen fragments and platelet dysfunction in uremia. Kidney Int 1999;56(1):299-305.
15. Escolar G, Diaz-Ricart M, Cases A. Uremic platelet dysfunction: past and present. Curr Hematol Rep 2005;4(5):359-67.
16. Kaw D, Malhotra D. Platelet dysfunction and end-stage renal disease. Semin Dial 2006;19(4):317-22.
17. Rodeghiero F, Tosetto A, Abshire T, Arnold DM, Coller B, James P, et al. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost 2010;8(9):2063-5.
18. Zeck J, Schallheim J, Lew SQ, DePalma L. Whole blood platelet aggregation and release reaction testing in uremic patients. Biomed Res Int 2013;2013:486290.
19. Zupan IP, Sabovic M, Salobir B, Ponikvar JB, Cernelc P, Lavre J, et al. The study of anaemia-related haemostasis impairment in haemodialysis patients by in vitro closure time test. Thromb Haemost 2005;93(2):375-9.
20. Sreedhara R, Itagaki I, Lynn B, Hakim RM. Defective platelet aggregation in uremia is transiently worsened by hemodialysis. Am J Kidney Dis 1995;25(4):555-63.
21. Benigni A, Boccardo P, Galbusera M, Monteagudo J, De Marco L, Remuzzi G, et al. Reversible activation defect of the platelet glycoprotein IIb-IIIa complex in patients with uremia. Am J Kidney Dis 1993;22(5):668-76.
22. Salvati F, Liani M. Role of platelet surface receptor abnormalities in the bleeding and thrombotic diathesis of uremic patients on hemodialysis and peritoneal dialysis. Int J Artif Organs 2001;24(3):131-5.
23. Shaydakov ME, Blebea J. Thromboelastography (TEG). StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019.