Kronik böbrek yetmezliği olan pediatrik hastalarda trombosit fonksiyonlarının değerlendirilmesi

Yıl 2019, Cilt: 17 Sayı: 2, 220 - 231, 02.08.2019

Funda Tayfun Küpesiz Canan Vergin Mustafa Bak

Öz

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

Öz

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.

Anahtar Kelimeler

chronic renal failure, platelet function

Kaynakça

• 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.