The assesment of prothrombotic potential using thrombin generation assay in pediatric patients with nephrotic syndrome: preliminary study
Background. Nephrotic syndrome (NS) is a common kidney disease associated with an increased risk of thrombotic events. The aim of this study was to assess the prothrombotic potential of patients with NS using the thrombin generation assay (TGA). Methods. A total of 35 patients with NS, who were followed in the Division of Pediatric Nephrology in Behcet Uz Children’s Hospital, were included in the study. After the patients with Steroid Resistant NS (n:3) were excluded, 32 patients in total were evaluated for TGA. Patients were primarily classified according to their response to corticosteroid therapy. The control group consisted of 34 healthy volunteers with similar gender and age distribution to the patients. Blood urine nitrogen, creatinine, albumin, triglyceride, cholesterol, 24-hour proteinuria, platelets, erythrocyte sedimentation rate, C-reactive protein and thrombin generation values in activation and remission period of NS were compared. Moreover, TGA values of the patients in their remission period were compared with the values of those in the control group. Results. Endogenous thrombin potential (ETP) and peak thrombin levels were significantly higher in the activation period than remission period of NS. Additionally, after the patients achieved remission, their ETP was still higher than the control group. There was a negative correlation between both ETP and peak thrombin levels of patients with serum albumin, whereas a significant positive correlation was detected with platelet levels. Thromboembolic events were not observed in any of the patients during follow-up. Conclusions. Nephrotic syndrome is strongly associated with hypercoagulopathy as assessed by TGA during active NS. The present study reinforces the usefulness of TGA as a marker of hypercoagulability in pediatric patients with NS. Further studies are needed in this regard
___
1. Andolino TP, Reid-Adam J. Nephrotic syndrome. Pediatr Rev 2015; 36: 117-125.2. Kelddal S, Nykjær KM, Gregersen JW, Birn H. Prophylactic anticoagulation in nephrotic syndrome prevents thromboembolic complications. BMC Nephrol 2019; 20: 139.
3. Rankin AJ, McQuarrie EP, Fox JG, Geddes CC, MacKinnon B; Scottish Renal Biopsy Registry. Venous thromboembolism in primary nephrotic syndrome - is the risk high enough to justify prophylactic anticoagulation? Nephron 2017; 135: 39-45.
4. Zhang LJ, Zhang Z, Li SJ, et al. Pulmonary embolism and renal vein thrombosis in patients with nephrotic syndrome: prospective evaluation of prevalence and risk factors with CT. Radiology 2014; 273: 897-906.
5. Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet2003; 362: 629-639.
6. Orth SR, Ritz E. The nephrotic syndrome. N Engl J Med 1998; 338: 1202-1211.
7. Cherng SC, Huang WS, Wang YF, Yang SP, Lin YF. The role of lung scintigraphy in the diagnosis of nephrotic syndrome with pulmonary embolism. Clin Nucl Med 2000; 25: 167-172.
8. Mahan JD, Mauer SM, Sibley RK, Vernier RL. Congenital nephrotic syndrome: evolution of medical management and results of renal transplantation. J Pediatr 1984; 105: 549-557.
9. Kerlin BA, Blatt NB, Fuh B, et al. Epidemiology and risk factors for thromboembolic complications of childhood nephrotic syndrome: a Midwest Pediatric Nephrology Consortium (MWPNC) study. J Pediatr 2009; 155: 105-110.
10. Kerlin BA, Ayoob R, Smoyer WE. Epidemiology and pathophysiology of nephrotic syndrome-associated thromboembolic disease. Clin J Am Soc Nephrol 2012; 7: 513-520.
11. Zhang LJ, Zhang Z, Li SJ, et al. Pulmonary embolism and renal vein thrombosis in patients with nephrotic syndrome: prospective evaluation of prevalence and risk factors with CT. Radiology 2014; 273: 897-906.
12. Kerlin BA, Haworth K, Smoyer WE. Venous thromboembolism in pediatric nephrotic syndrome. Pediatr Nephrol 2014; 29: 989-997.
13. Loscalzo J. Venous thrombosis in the nephrotic syndrome. N Engl J Med 2013; 368: 956-958.
14. Eneman B, Levtchenko E, van den Heuvel B, Van Geet C, Freson K. Platelet abnormalities in nephrotic syndrome. Pediatr Nephrol 2016; 31: 1267-1279.
15. Wang CS , Greenbaum LA. Nephrotic syndrome. Pediatr Clin North Am 2019; 66: 73-85
16. Kerlin BA, Waller AP, Sharma R, Chanley MA, Nieman MT, Smoyer WE. Disease severity correlates with thrombotic capacity in experimental nephrotic syndrome. J Am Soc Nephrol 2015; 26: 3009-3019.
17. Fabri D, Belangero VM, Annichino-Bizzacchi JM, Arruda VR. Inherited risk factors for thrombophilia in children with nephrotic syndrome. Eur J Pediatr 1998; 157: 939-942.
18. Chugh KS, Malik N, Uberoi HS, et al. Renal vein thrombosis in nephrotic syndrome-a prospective study and review. Postgrad Med J 1981; 57: 566-570.
19. Sá H, Freitas L, Mota A, Cunha F, Marques A. Primary antiphospholipid syndrome presented by total infarction of right kidney with nephrotic syndrome. Clin Nephrol 1999; 52: 56-60.
20. Duarte RCF, Ferreira CN, Rios DRA, Reis HJ, Carvalhoa MDG. Thrombin generation assays for global evaluation of the hemostatic system: perspectives and limitations. Rev Bras Hematol Hemoter 2017; 39: 259-265.
21. Tefferi A, Vannucchi AM, Barbui T. Essential thrombocythemia treatment algorithm. Blood Cancer J 2018; 8: 2.
22. Hemker HC, Giesen P, Al Dieri R, et al. Calibrated automated thrombin generation meausurement in clotting plasma. Pathophysiol Haemost Thromb 2003; 33: 4-15.
23. Gerotziafas GT, Depasse F, Busson J, Leflem L, Elalamy I, Samama MM. Towards a standardization of thrombin generation assessment: the influence of tissue factor, platelets and phospholipids concentration on the normal values of Thrombogram- Thrombinoscope assay. Thromb J 2005; 3: 16.
24. Schlegel N. Thromboembolic risks and complications in nephrotic children. Semin Thromb Hemost 1997; 23: 271-280.
25. Citak A, Emre S, Sairin A, Bilge I, Nayir A. Hemostatic problems and thromboembolic complications in nephrotic children. Pediatr Nephrol 2000; 14: 138- 142.
26. Mahmoodi BK, Mulder AB, Waanders F, et al. The impact of antiproteinuric therapy on the prothrombotic state in patients with overt proteinuria. J Thromb Haemost 2011; 9: 2416-2423.
27. Ozkayin N, Mir S, Kavakli K. Hypercoagulability risk factors in children with minimal change disease and the protective role of protein-C activity. Int Urol Nephrol 2004; 36: 599-603.
28. Broder A, Tobin JN, Putterman C. High antiphospholipid antibody levels are associated with statin use and may reflect chronic endothelial damage in non-autoimmune thrombosis: cross- sectional study. J Clin Pathol 2012; 65: 551-556.
29. Ozkaya O, Bek K, Fisgin T, et al. Low protein Z levels in children with nephrotic syndrome. Pediatr Nephrol 2006; 21: 1122-1126.
30. Paraskevas KI, Bessias N, Perdikides TP, Mikhailidis DP. Statins and venous thromboembolism: a novel effect of statins? Curr Med Res Opin 2009; 25: 1807- 1809.
31. Dargaud Y, Luddington R, Gray E, et al. Standardisation of thrombin generation test- which reference plasma for TGT? An international multicentre study. Thromb Res 2010; 125: 353-356.
32. Dargaud Y, Wolberg AS, Luddington R, et al. Evaluation of a standardized protocol for thrombin generation measurement using the calibrated automated thrombogram: an international multicentre study. Thromb Res 2012; 130: 929-934.
33. Kumar S, Chapagain A, Nitsch D, Yaqoob MM. Proteinuria and hypoalbuminemia are risk factors for thromboembolic events in patients with idiopathic membranous nephropathy: an observational study. BMC Nephrol 2012; 13: 107.
34. Resh M, Mahmoodi BK, Navis GJ, Veeger NJ, Lijfering WM. Statin use in patients with nephrotic syndrome is associated with a lower risk of venous thromboembolism. Thromb Res 2011; 127: 395-399.
35. Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet 2003; 362: 629-639.
36. Walter E, Deppermann D, Andrassy K, Koderisch J. Platelet hyperaggregability as a consequence of the nephrotic syndrome. Thromb Res 1981; 23: 473-479.
37. Mahmoodi BK, ten Kate MK, Waanders F, et al. High absolute risks and predictors of venous and arterial thromboembolic events in patients with nephrotic syndrome: results from a large retrospective cohort study. Circulation 2008; 117: 224-230.
38. Dame C, Sutor AH. Primary and secondary thrombocytosis in childhood. Br J Haematol 2005; 129: 165-177.
- ISSN: 0041-4301
- Yayın Aralığı: Yılda 6 Sayı
- Başlangıç: 1958
- Yayıncı: Hacettepe Üniversitesi Çocuk Sağlığı Enstitüsü Müdürlüğü
Sayıdaki Diğer Makaleler
Sinan TÜFEKCİ, Birol ŞAFAK, Burçin NALBANTOĞLU, Nedim SAMANCI, Nuri KİRAZ
The role of plasma exchange in acute liver failure of autoimmune etiology
Selim GÖKÇE, Banu Bal ÇERMİK, Nurettin Onur KUTLU, İlhan OCAK
Zafer Hasan Ali SAK, Şerif KURTULUŞ, Birsen OCAKLI, Zehra Nur TÖREYİN, İbrahim BAYHAN, M. İrfan YEŞİLNACAR, Metin AKGÜN, İlknur ARSLANOĞLU, Peri Meram ARBAK
Assesment of obesogenic factors in school-age children
Pınar YILMAZBAŞ, Gülbin GÖKÇAY
Eren SOYALTIN, Yılmaz AY, Erkin SERDAROĞLU, Raziye Canan VERGİN
Aspirin-induced hepatotoxicity and anemia in children with acute rheumatic fever
Derya ALTAY, Özge PAMUKÇU, Ali BAYKAN, Kazım ÜZÜM, Duran ARSLAN
Ece Mekik AKAR, Zeynep Birsin ÖZÇAKAR, Nilgün ÇAKAR, Saba KİREMİTÇİ, Eda Didem Kurt ŞÜKÜR, Suat FİTÖZ, Fatoş YALÇINKAYA
Kübra Seyhan BIYIK, Cemil ÖZAL, Merve TUNÇDEMİR, Sefa ÜNEŞ, Kıvanç DELİOĞLU, Mintaze Kerem GÜNEL
Demographic, ocular and associated neurological findings in corpus callosum malformations
Pınar Bingöl KIZILTUNÇ, Esra ŞAHLI, Aysun İDİL, Huban ATİLLA
Thrombin generation in children with febrile neutropenia
Ayça Koca YOZGAT, İbrahim EKER, Orhan GÜRSEL, Muhammed Fevzi KILINÇKAYA, Abdurrahman KARA, Neşe YARALI, Namık Yaşar ÖZBEK