Skip to main content

Advertisement

SpringerLink
Log in

Platelet abnormalities in nephrotic syndrome

  • Educational Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Nephrotic syndrome (NS) is a common kidney disease associated with a significantly increased risk of thrombotic events. Alterations in plasma levels of pro- and anti-coagulant factors are involved in the pathophysiology of venous thrombosis in NS. However, the fact that the risk of both venous and arterial thrombosis is elevated in NS points to an additional role for blood platelets. Increased platelet counts and platelet hyperactivity have been observed in nephrotic children. Platelet hyperaggregability, increased release of active substances, and elevated surface expression of activation-dependent platelet markers have been documented. The mechanisms underlying those platelet alterations are multifactorial and are probably due to changes in plasma levels of platelet-interfering proteins and lipid changes, as a consequence of nephrosis. The causal relationship between platelet alterations seen in NS and the occurrence of thromboembolic phenomena remains unclear. Moreover, the efficiency of prophylactic treatment using antiplatelet agents for the prevention of thrombotic complications in nephrotic patients is also unknown. Thus, antiplatelet medication is currently not generally recommended for routine prophylactic therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

AA:

Arachidonic acid

AC:

Adenylate cyclase

ACE:

Angiotensin-converting enzyme

ADP:

Adenosine diphosphate

AT:

Angiotensin

ATP:

Adenosine triphosphate

cAMP:

Cyclic adenosine monophosphate

COX:

Cyclooxygenase

DAG:

Diacylglycerol

ELISA:

Enzyme-linked immunosorbent assay

GP:

Glycoprotein

IP3:

Inositol triphosphate

IL-6:

Interleukin-6

IL-7:

Interleukin-7

MDA:

Malondialdehyde

MPV:

Mean platelet volume

NS:

Nephrotic syndrome

NSAID:

Non-steroidal anti-inflammatory drugs

OCS:

Open canalicular system

PACAP:

Pituitary adenylate cyclase-activating polypeptide

PAR:

Protease-activated receptor

PCT:

Plateletcrit

PDGF:

Platelet-derived growth factor

PDW:

Platelet distribution width

PIP2:

Phosphatidylinositol bisphosphate

PKC:

Protein kinase C

PLCβ:

Phospholipase C β

PLT count:

Platelet count

PRP:

Platelet-rich plasma

PS:

Phosphatidylserine

TXA2:

Thromboxane A2

TXB2:

Thromboxane B2

vWF:

von Willebrand factor

References

  1. Kaushansky K (1999) Thrombopoietin and hematopoietic stem cell development. Ann N Y Acad Sci 872:314–319

    Article  CAS  PubMed  Google Scholar 

  2. George JN (2000) Platelets. Lancet 355:1531–1539

    Article  CAS  PubMed  Google Scholar 

  3. Bautista AP, Buckler PW, Towler HM, Dawson AA, Bennett B (1984) Measurement of platelet life-span in normal subjects and patients with myeloproliferative disease with indium oxine labelled platelets. Br J Haematol 58:679–687

    Article  CAS  PubMed  Google Scholar 

  4. Kamath S, Blann AD, Lip GY (2001) Platelet activation: assessment and quantification. Eur Heart J 22:1561–1571

    Article  CAS  PubMed  Google Scholar 

  5. Thon JN, Italiano JE (2012) Platelets: production, morphology and ultrastructure. Handb Exp Pharmacol 210:3–22

    Article  CAS  PubMed  Google Scholar 

  6. Gawaz M, Langer H, May AE (2005) Platelets in inflammation and atherogenesis. J Clin Invest 115:3378–3384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Semple JW, Freedman J (2010) Platelets and innate immunity. Cell Mol Life Sci 67:499–511

    Article  CAS  PubMed  Google Scholar 

  8. Elzey BD, Sprague DL, Ratliff TL (2005) The emerging role of platelets in adaptive immunity. Cell Immunol 238:1–9

    Article  CAS  PubMed  Google Scholar 

  9. Bryckaert M, Rosa JP, Denis CV, Lenting PJ (2015) Of von Willebrand factor and platelets. Cell Mol Life Sci 72:307–326

    Article  CAS  PubMed  Google Scholar 

  10. Choi JL, Li S, Han JY (2014) Platelet function tests: a review of progresses in clinical application. Biomed Res Int 2014:456569

    PubMed  PubMed Central  Google Scholar 

  11. Lentz BR (2003) Exposure of platelet membrane phosphatidylserine regulates blood coagulation. Prog Lipid Res 42:423–438

    Article  CAS  PubMed  Google Scholar 

  12. Skeaff CM, Holub BJ (1985) Altered phospholipid composition of plasma membranes from thrombin-stimulated human platelets. Biochim Biophys Acta 834:164–171

    Article  CAS  PubMed  Google Scholar 

  13. Dale GL (2005) Coated-platelets: an emerging component of the procoagulant response. J Thromb Haemost 3:2185–2192

    Article  CAS  PubMed  Google Scholar 

  14. Stalker TJ, Traxler EA, Wu J, Wannemacher KM, Cermignano SL, Voronov R, Diamond SL, Brass LF (2013) Hierarchical organization in the hemostatic response and its relationship to the platelet-signaling network. Blood 121:1875–1885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wiwanitkit V (2004) Plateletcrit, mean platelet volume, platelet distribution width: its expected values and correlation with parallel red blood cell parameters. Clin Appl Thromb Hemost 10:175–178

    Article  PubMed  Google Scholar 

  16. Cattaneo M, Cerletti C, Harrison P, Hayward CP, Kenny D, Nugent D, Nurden P, Rao AK, Schmaier AH, Watson SP, Lussana F, Pugliano MT, Michelson AD (2013) Recommendations for the Standardization of Light Transmission Aggregometry: A Consensus of the Working Party from the Platelet Physiology Subcommittee of SSC/ISTH. J Thromb Haemost. doi:10.1111/jth.12231

    Google Scholar 

  17. Gresele P, Subcommittee on Platelet Physiology (2015) Diagnosis of inherited platelet function disorders: guidance from the SSC of the ISTH. J Thromb Haemost 13:314–322

    Article  CAS  PubMed  Google Scholar 

  18. Kang M, Wilson L, Kermode JC (2008) Evidence from limited proteolysis of a ristocetin-induced conformational change in human von Willebrand factor that promotes its binding to platelet glycoprotein Ib-IX-V. Blood Cells Mol Dis 40:433–443

    Article  CAS  PubMed  Google Scholar 

  19. Orth SR, Ritz E (1998) The nephrotic syndrome. N Engl J Med 338:1202–1211

    Article  CAS  PubMed  Google Scholar 

  20. Singhal R, Brimble KS (2006) Thromboembolic complications in the nephrotic syndrome: pathophysiology and clinical management. Thromb Res 118:397–407

    Article  CAS  PubMed  Google Scholar 

  21. Mahmoodi BK, ten Kate MK, Waanders F, Veeger NJ, Brouwer JL, Vogt L, Navis G, van der Meer J (2008) High absolute risks and predictors of venous and arterial thromboembolic events in patients with nephrotic syndrome: results from a large retrospective cohort study. Circulation 117:224–230

    Article  PubMed  Google Scholar 

  22. Kerlin BA, Ayoob R, Smoyer WE (2012) Epidemiology and pathophysiology of nephrotic syndrome-associated thromboembolic disease. Clin J Am Soc Nephrol 7:513–520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Walter E, Deppermann D, Andrassy K, Koderisch J (1981) Platelet hyperaggregability as a consequence of the nephrotic syndrome. Thromb Res 23:473–479

    Article  CAS  PubMed  Google Scholar 

  24. Robert A, Olmer M, Sampol J, Gugliotta JE, Casanova P (1987) Clinical correlation between hypercoagulability and thrombo-embolic phenomena. Kidney Int 31:830–835

    Article  CAS  PubMed  Google Scholar 

  25. Machleidt C, Mettang T, Starz E, Weber J, Risler T, Kuhlmann U (1989) Multifactorial genesis of enhanced platelet aggregability in patients with nephrotic syndrome. Kidney Int 36:1119–1124

    Article  CAS  PubMed  Google Scholar 

  26. Bennett A, Cameron JS (1987) Platelet hyperaggregability in the nephrotic syndrome which is not dependent on arachidonic acid metabolism or on plasma albumin concentration. Clin Nephrol 27:182–188

    CAS  PubMed  Google Scholar 

  27. Gao C, Xie R, Yu C, Wang Q, Shi F, Yao C, Xie R, Zhou J, Gilbert GE, Shi J (2012) Procoagulant activity of erythrocytes and platelets through phosphatidylserine exposure and microparticles release in patients with nephrotic syndrome. Thromb Haemost 107:681–689

    Article  CAS  PubMed  Google Scholar 

  28. Andre E, Voisin P, Andre JL, Briquel ME, Stoltz JF, Martinet N, Alexandre P (1994) Hemorheological and hemostatic parameters in children with nephrotic syndrome undergoing steroid therapy. Nephron 68:184–191

    Article  CAS  PubMed  Google Scholar 

  29. Tkaczyk M, Baj Z (2002) Surface markers of platelet function in idiopathic nephrotic syndrome in children. Pediatr Nephrol 17:673–677

    Article  PubMed  Google Scholar 

  30. Wasilewska AM, Zoch-Zwierz WM, Tomaszewska B, Biernacka A (2005) Platelet-derived growth factor and platelet profiles in childhood nephrotic syndrome. Pediatr Nephrol 20:36–41

    Article  PubMed  Google Scholar 

  31. Eneman B, Freson K, van den Heuvel L, van Hoyweghen E, Collard L, Vande Walle J, van Geet C, Levtchenko E (2015) Pituitary adenylate cyclase-activating polypeptide deficiency associated with increased platelet count and aggregability in nephrotic syndrome. J Thromb Haemost 13:755–767

    Article  CAS  PubMed  Google Scholar 

  32. Mittal A, Aggarwal KC, Saluja S, Aggarwal A, Sureka B (2013) Platelet functions and coagulation changes in Indian children with nephrotic syndrome. J Clin Diagn Res 7:1647–1650

    PubMed  PubMed Central  Google Scholar 

  33. Kocyigit I, Yilmaz MI, Simsek Y, Unal A, Sipahioglu MH, Eroglu E, Dede F, Tokgoz B, Oymak O, Utas C (2013) The role of platelet activation in determining response to therapy in patients with primary nephrotic syndrome. Platelets 24:474–479

    Article  CAS  PubMed  Google Scholar 

  34. Remuzzi G, Mecca G, Marchesi D, Livio M, de Gaetano G, Donati MB, Silver MJ (1979) Platelet hyperaggregability and the nephrotic syndrome. Thromb Res 16:345–354

    Article  CAS  PubMed  Google Scholar 

  35. Jackson CA, Greaves M, Patterson AD, Brown CB, Preston FE (1982) Relationship between platelet aggregation, thromboxane synthesis and albumin concentration in nephrotic syndrome. Br J Haematol 52:69–77

    Article  CAS  PubMed  Google Scholar 

  36. Panicucci F, Sagripanti A, Vispi M, Pinori E, Lecchini L, Barsotti G, Giovannetti S (1983) Comprehensive study of haemostasis in nephrotic syndrome. Nephron 33:9–13

    Article  CAS  PubMed  Google Scholar 

  37. Sirolli V, Ballone E, Garofalo D, Merciaro G, Settefrati N, Di Mascio R, Di Gregorio P, Bonomini M (2002) Platelet activation markers in patients with nephrotic syndrome. A comparative study of different platelet function tests. Nephron 91:424–430

    Article  CAS  PubMed  Google Scholar 

  38. Turi S, Bereczki C, Torday C, Havass Z (1994) Laser aggregometer studies, ATP release and thromboxane B2 release and cAMP concentration of the platelets in nephrotic syndrome. Prostaglandins Leukot Essent Fatty Acids 51:69–73

    Article  CAS  PubMed  Google Scholar 

  39. Bang NU, Trygstad W, Schroeder JE, Heidenreich RO, Csiscko BM (1973) Enhanced platelet function in glomerular renal disease. J Lab Clin Med 81:651–660

    CAS  PubMed  Google Scholar 

  40. Stuart MJ, Gerrard JM, White JG (1980) The influence of albumin and calcium on human platelet arachidonic acid metabolism. Blood 55:418–423

    CAS  PubMed  Google Scholar 

  41. Taira K, Okajima C, Yamashita T, Kawahara S, Matsunaga T, Nakajima M, Kamitsuji H (1990) Ristocetin induced platelet aggregation in children with nephrotic syndrome. Nihon Jinzo Gakkai Shi 32:659–666

    CAS  PubMed  Google Scholar 

  42. Adler AJ, Lundin AP, Feinroth MV, Friedman EA, Berlyne GM (1980) Beta-thromboglobulin levels in the nephrotic syndrome. Am J Med 69:551–554

    Article  CAS  PubMed  Google Scholar 

  43. Goubran F, Maklady F (1988) In vivo platelet activity and serum albumin concentration in nephrotic syndrome. Blut 57:15–17

    Article  CAS  PubMed  Google Scholar 

  44. Wasilewska A, Zoch-Zwierz WM, Tomaszewska B, Zelazowska B (2005) Relationship of serum interleukin-7 concentration and the coagulation state in children with nephrotic syndrome. Pediatr Int 47:424–429

    Article  CAS  PubMed  Google Scholar 

  45. Kilis-Pstrusinska K, Medynska A, Wikiera-Magott I, Zwolinska D (2001) Levels of selected soluble adhesion molecules in blood serum of children with chronic glomerulonephritis. Pol Merkur Lekarski 10:247–249

    CAS  PubMed  Google Scholar 

  46. Kobayashi T, Suzuki J, Watanabe M, Suzuki S, Yoshida K, Kume K, Suzuki H (1997) Changes in platelet calcium concentration by thromboxane A2 stimulation in patients with nephrotic syndrome of childhood. Nephron 77:309–314

    Article  CAS  PubMed  Google Scholar 

  47. Schieppati A, Dodesini P, Benigni A, Massazza M, Mecca G, Remuzzi G, Livio M, de Gaetano G, Rossi EC (1984) The metabolism of arachidonic acid by platelets in nephrotic syndrome. Kidney Int 25:671–676

    Article  CAS  PubMed  Google Scholar 

  48. Matzdorff AC, Kuhnel G, Kemkes-Matthes B, Pralle H (1998) Quantitative assessment of platelets, platelet microparticles, and platelet aggregates with flow cytometry. J Lab Clin Med 131:507–517

    Article  CAS  PubMed  Google Scholar 

  49. Pathansali R, Smith N, Bath P (2001) Altered megakaryocyte-platelet haemostatic axis in hypercholesterolaemia. Platelets 12:292–297

    Article  CAS  PubMed  Google Scholar 

  50. Freson K, Peeters K, De Vos R, Wittevrongel C, Thys C, Hoylaerts MF, Vermylen J, Van Geet C (2008) PACAP and its receptor VPAC1 regulate megakaryocyte maturation: therapeutic implications. Blood 111:1885–1893

    Article  CAS  PubMed  Google Scholar 

  51. Yoshida N, Aoki N (1978) Release of arachidonic acid from human platelets. A key role for the potentiation of platelet aggregability in normal subjects as well as in those with nephrotic syndrome. Blood 52:969–977

    CAS  PubMed  Google Scholar 

  52. Kuhlmann U, Steurer J, Rhyner K, von Felten A, Briner J, Siegenthaler W (1981) Platelet aggregation and beta-thromboglobulin levels in nephrotic patients with and without thrombosis. Clin Nephrol 15:229–235

    CAS  PubMed  Google Scholar 

  53. Ueda N (1990) Effect of corticosteroids on some hemostatic parameters in children with minimal change nephrotic syndrome. Nephron 56:374–378

    Article  CAS  PubMed  Google Scholar 

  54. Shattil SJ, Cooper RA (1978) Role of membrane lipid composition, organization, and fluidity in human platelet function. Prog Hemost Thromb 4:59–86

    CAS  PubMed  Google Scholar 

  55. Gerrard JM (1988) Platelet aggregation: cellular regulation and physiologic role. Hosp Pract (Off Ed) 23:89–98, 103–104, 107–108

  56. Akoglu H, Agbaht K, Piskinpasa S, Falay MY, Dede F, Ozet G, Odabas AR (2012) High frequency of aspirin resistance in patients with nephrotic syndrome. Nephrol Dial Transplant 27:1460–1466

    Article  CAS  PubMed  Google Scholar 

  57. Schlegel N (1997) Thromboembolic risks and complications in nephrotic children. Semin Thromb Hemost 23:271–280

    Article  CAS  PubMed  Google Scholar 

  58. Freson K, Hashimoto H, Thys C, Wittevrongel C, Danloy S, Morita Y, Shintani N, Tomiyama Y, Vermylen J, Hoylaerts MF, Baba A, Van Geet C (2004) The pituitary adenylate cyclase-activating polypeptide is a physiological inhibitor of platelet activation. J Clin Invest 113:905–912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kerlin BA, Blatt NB, Fuh B, Zhao S, Lehman A, Blanchong C, Mahan JD, Smoyer WE (2009) Epidemiology and risk factors for thromboembolic complications of childhood nephrotic syndrome: a Midwest Pediatric Nephrology Consortium (MWPNC) study. J Pediatr 155:105–110, 110 e101

    Article  PubMed  PubMed Central  Google Scholar 

  60. Freedman JE (2005) Molecular regulation of platelet-dependent thrombosis. Circulation 112:2725–2734

    Article  PubMed  Google Scholar 

  61. Undas A, Brummel-Ziedins K, Mann KG (2014) Why does aspirin decrease the risk of venous thromboembolism? On old and novel antithrombotic effects of acetyl salicylic acid. J Thromb Haemost 12:1776–1787

    Article  CAS  PubMed  Google Scholar 

  62. Becattini C, Agnelli G (2014) Aspirin for prevention and treatment of venous thromboembolism. Blood Rev 28:103–108

    Article  CAS  PubMed  Google Scholar 

  63. Riedl J, Hell L, Kaider A, Koder S, Marosi C, Zielinski C, Panzer S, Pabinger I, Ay C (2015) Association of platelet activation markers with cancer-associated venous thromboembolism. Platelets 13:1–6

    Google Scholar 

  64. Simanek R, Vormittag R, Ay C, Alguel G, Dunkler D, Schwarzinger I, Steger G, Jaeger U, Zielinski C, Pabinger I (2010) High platelet count associated with venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). J Thromb Haemost 8:114–120

    Article  CAS  PubMed  Google Scholar 

  65. Zakai NA, Wright J, Cushman M (2004) Risk factors for venous thrombosis in medical inpatients: validation of a thrombosis risk score. J Thromb Haemost 2:2156–2161

    Article  CAS  PubMed  Google Scholar 

  66. Kerlin BA, Haworth K, Smoyer WE (2014) Venous thromboembolism in pediatric nephrotic syndrome. Pediatr Nephrol 29:989–997

    Article  PubMed  Google Scholar 

  67. Tuckuviene R, Christensen AL, Helgestad J, Johnsen SP, Kristensen SR (2011) Pediatric venous and arterial noncerebral thromboembolism in Denmark: a nationwide population-based study. J Pediatr 159:663–669

    Article  PubMed  Google Scholar 

  68. Lindemann S, Tolley ND, Dixon DA, McIntyre TM, Prescott SM, Zimmerman GA, Weyrich AS (2001) Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J Cell Biol 154:485–490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Wagner DD, Burger PC (2003) Platelets in inflammation and thrombosis. Arterioscler Thromb Vasc Biol 23:2131–2137

    Article  CAS  PubMed  Google Scholar 

  70. Sowa JM, Crist SA, Ratliff TL, Elzey BD (2009) Platelet influence on T- and B-cell responses. Arch Immunol Ther Exp (Warsz) 57:235–241

    Article  CAS  Google Scholar 

  71. Peerschke EI, Yin W, Ghebrehiwet B (2008) Platelet mediated complement activation. Adv Exp Med Biol 632:81–91

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Barnes JL (1997) Platelets in glomerular disease. Nephron 77:378–393

    Article  CAS  PubMed  Google Scholar 

  73. Zoja C, Remuzzi G (1995) Role of platelets in progressive glomerular diseases. Pediatr Nephrol 9:495–502

    Article  CAS  PubMed  Google Scholar 

  74. Barnes JL (1989) Glomerular localization of platelet secretory proteins in mesangial proliferative lesions induced by habu snake venom. J Histochem Cytochem 37:1075–1082

    Article  CAS  PubMed  Google Scholar 

  75. Barnes J, Camussi G, Tetta C, Venkatachalam MA (1990) Glomerular localization of platelet cationic proteins after immune complex-induced platelet activation. Lab Invest 63:755–761

    CAS  PubMed  Google Scholar 

  76. Rachidi S, Wallace K, Day TA, Alberg AJ, Li Z (2014) Lower circulating platelet count and antiplatelet therapy independently predict better outcomes in patients with head and neck squamous cell carcinoma. J Hematol Oncol 7:65

    Article  PubMed  PubMed Central  Google Scholar 

  77. Scharf RE (2012) Drugs that affect platelet function. Semin Thromb Hemost 38:865–883

    Article  CAS  PubMed  Google Scholar 

  78. Ueda N, Kawaguchi S, Niinomi Y, Nonoda T, Matsumoto J, Ohnishi M, Yasaki T (1987) Effect of corticosteroids on coagulation factors in children with nephrotic syndrome. Pediatr Nephrol 1:286–289

    Article  CAS  PubMed  Google Scholar 

  79. Moraes LA, Paul-Clark MJ, Rickman A, Flower RJ, Goulding NJ, Perretti M (2005) Ligand-specific glucocorticoid receptor activation in human platelets. Blood 106:4167–4175

    Article  CAS  PubMed  Google Scholar 

  80. Liverani E, Banerjee S, Roberts W, Naseem KM, Perretti M (2012) Prednisolone exerts exquisite inhibitory properties on platelet functions. Biochem Pharmacol 83:1364–1373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Sahin G, Akay OM, Bal C, Yalcin AU, Gulbas Z (2011) The effect of calcineurin inhibitors on endothelial and platelet function in renal transplant patients. Clin Nephrol 76:218–225

    CAS  PubMed  Google Scholar 

  82. George JN, Shattil SJ (1991) The clinical importance of acquired abnormalities of platelet function. N Engl J Med 324:27–39

    Article  CAS  PubMed  Google Scholar 

  83. Escolar G, Diaz-Ricart M, Cases A (2005) Uremic platelet dysfunction: past and present. Curr Hematol Rep 4:359–367

    CAS  PubMed  Google Scholar 

  84. Pincus KJ, Hynicka LM (2013) Prophylaxis of thromboembolic events in patients with nephrotic syndrome. Ann Pharmacother 47:725–734

    Article  PubMed  Google Scholar 

  85. Hodson E (2003) The management of idiopathic nephrotic syndrome in children. Paediatr Drugs 5:335–349

    Article  PubMed  Google Scholar 

  86. Patrono C, Pierucci A (1986) Renal effects of nonsteroidal anti-inflammatory drugs in chronic glomerular disease. Am J Med 81:71–83

    Article  CAS  PubMed  Google Scholar 

  87. Dame C, Sutor AH (2005) Primary and secondary thrombocytosis in childhood. Br J Haematol 129:165–177

    Article  CAS  PubMed  Google Scholar 

  88. Simic I, Tabatabaeifar M, Schaefer F (2013) Animal models of nephrotic syndrome. Pediatr Nephrol 28:2079–2088

    Article  PubMed  Google Scholar 

  89. Goubran F, Maklady F, Saad M, el Ashry M (1986) In vivo platelet activity and lipoprotein patterns in coronary artery disease. Wien Klin Wochenschr 98:209–211

    CAS  PubMed  Google Scholar 

  90. Takagawa K, Nakajima M, Taira K, Sakagami Y, Ueda T, Akazawa H, Maruhashi Y, Shimoyama H, Takahashi Y, Fujimura Y, Kamitsuji H, Yoshioka A (2002) Shear stress-induced platelet aggregation in children with minimal change nephrotic syndrome. Nihon Jinzo Gakkai Shi 44:380–388

    PubMed  Google Scholar 

  91. Zwaginga JJ, Koomans HA, Sixma JJ, Rabelink TJ (1994) Thrombus formation and platelet-vessel wall interaction in the nephrotic syndrome under flow conditions. J Clin Invest 93:204–211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Pediatric Nephrology, Department of Pediatrics, University hospital of Leuven, Leuven, Belgium

    Benedicte Eneman & Elena Levtchenko

  2. Laboratory of Pediatric Nephrology, Department of Development & Regeneration, KU Leuven, Leuven, Belgium

    Benedicte Eneman, Elena Levtchenko & Bert van den Heuvel

  3. Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium

    Chris Van Geet & Kathleen Freson

Authors
  1. Benedicte Eneman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elena Levtchenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bert van den Heuvel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chris Van Geet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kathleen Freson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Benedicte Eneman.

Additional information

Answers to multiple-choice questions

1B - 2C - 3B - 4C - 5C

Appendices

Summary points

  1. 1

    As the risk of not only venous but also arterial thrombosis is elevated in nephrotic syndrome, a role for blood platelets is presumed in the pathogenesis.

  2. 2

    Increased platelet count, platelet hyperaggregability, increased release of active substances, and elevated surface expression of activationdependent platelet markers have been documented during relapse of nephrotic syndrome.

  3. 3

    The mechanisms underlying platelet abnormalities are probably due to changes in plasma levels of platelet-interfering proteins and lipids, as a consequence of nephrosis. Currently, antiplatelet medication is not generally recommended for routine prophylactic therapy in nephrotic patients.

Multiple-choice questions (Answers are provided following the reference list)

  1. 1.

    Which statement about platelet activation is true?

    1. A.

      Von Willebrand factor contributes to platelet adhesion via the platelet PAR4 receptor.

    2. B.

      Increased cytosolic calcium concentrations stimulate platelet activation.

    3. C.

      Coagulation factor VIII stimulates secretion of platelet-dense granules.

    4. D.

      Increased cytosolic calcium concentrations prevent degranulation of dense and α-granules.

  2. 2.

    Which of the following agents is not an inducer of platelet aggregation?

    1. A.

      Collagen

    2. B.

      Arachidonic acid

    3. C.

      cAMP

    4. D.

      Thrombin

  3. 3.

    Which of the following mechanisms is not involved in increased platelet activation during idiopathic nephrotic syndrome?

    1. A.

      Elevated plasma levels of platelet-activating substances

    2. B.

      Factor V Leiden thrombophilia

    3. C.

      Decreased plasma levels of platelet inhibitory proteins

    4. D.

      A reduced negative charge of the platelet surface

  4. 4.

    How many days should aspirin be withheld before reliable platelet aggregation tests can be performed?

    1. A.

      At least 5 days, because it causes reversible inhibition of cyclooxygenase-1

    2. B.

      At least 3 days, because it causes reversible inhibition of cyclooxygenase-1

    3. C.

      At least 10 days, because it causes irreversible inhibition of cyclooxygenase-1

    4. D.

      At least 1 day, because it causes irreversible inhibition of cyclooxygenase-1

  5. 5.

    Which of the following methods is the best measurement of platelet function in the clinical laboratory?

    1. A.

      Quantification of platelet microparticles

    2. B.

      Measurement of platelet count and mean platelet volume

    3. C.

      Light transmission aggregometry after induction with an agonist such as ADP, collagen, epinephrine, arachidonic acid or thrombin

    4. D.

      ELISA for soluble platelet activation markers such as β-thromboglobulin and platelet-derived growth factor

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Eneman, B., Levtchenko, E., van den Heuvel, B. et al. Platelet abnormalities in nephrotic syndrome. Pediatr Nephrol 31, 1267–1279 (2016). https://doi.org/10.1007/s00467-015-3173-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-015-3173-8

Keywords

Search

Navigation