Skip to main content

Advertisement

SpringerLink
Log in

Venous thromboembolism in pediatric nephrotic syndrome

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

Abstract

Childhood nephrotic syndrome (NS) is one of the most common pediatric kidney diseases, with an incidence of 2–7 per 100,000. Venous thromboembolism (VTE) is associated with significant morbidity and mortality, and occurs in ∼3 % of children with NS, though incidence approaches 25 % in high-risk groups. VTE etiology is multifactorial, with disease-associated coagulopathy thought to be a significant contributor. Other risks include age, disease severity, and treatment-related hazards, such as the presence of central venous catheters. Non-pharmacologic preventive measures such as ambulation and compression stockings are recommended for patients with identified VTE risks. Central venous catheters should be avoided whenever possible. Symptoms of VTE include venous catheter dysfunction, unilateral extremity symptoms, respiratory compromise, flank pain, and gross hematuria. When VTE is suspected, confirmatory imaging studies should be obtained, followed by appropriate laboratory evaluation and treatment. Therapeutic goals include limiting thrombus growth, extension, and embolization by early institution of anticoagulant therapy. Anticoagulation is recommended for a minimum of 3 months, but should be continued until NS remission is achieved. Further studies are necessary to identify VTE-risk biomarkers and optimal therapeutic regimens. Observational cohort studies are needed to identify VTE-risk groups who may benefit from thromboprophylaxis and to define disease-specific treatment algorithms.

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

References

  1. Eddy AA, Symons JM (2003) Nephrotic syndrome in childhood. Lancet 362:629–639

    Article  PubMed  Google Scholar 

  2. Valentini RP, Smoyer WE (2006) Nephrotic syndrome. In: Kher KK, Schnaper HW, Makker SP (eds) Clinical pediatric nephrology. Informa Healthcare, Abingdon, Oxon, pp 155–194

    Google Scholar 

  3. Setty BA, O’Brien SH, Kerlin BA (2012) Pediatric venous thromboembolism in the United States: a tertiary care complication of chronic diseases. Pediatr Blood Cancer 59:258–264

    Google Scholar 

  4. Zaffanello M, Franchini M (2007) Thromboembolism in childhood nephrotic syndrome: a rare but serious complication. Hematology 12:69–73

    Article  PubMed  Google Scholar 

  5. Citak A, Emre S, Sairin A, Bilge I, Nayir A (2000) Hemostatic problems and thromboembolic complications in nephrotic children. Pediatr Nephrol 14:138–142

    Article  PubMed  CAS  Google Scholar 

  6. Egli F, Elmiger P, Stalder G (1973) Thromboembolism in the nephrotic syndrome. Pediatr Res 8:903(Abstr)

    Google Scholar 

  7. Hamed RM, Shomaf M (2001) Congenital nephrotic syndrome: a clinico-pathologic study of thirty children. J Nephrol 14:104–109

    PubMed  CAS  Google Scholar 

  8. Hoyer PF, Gonda S, Barthels M, Krohn HP, Brodehl J (1986) Thromboembolic complications in children with nephrotic syndrome. Risk and incidence. Acta Paediatr Scand 75:804–810

    Article  PubMed  CAS  Google Scholar 

  9. 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 Central  PubMed  Google Scholar 

  10. Lilova MI, Velkovski IG, Topalov IB (2000) Thromboembolic complications in children with nephrotic syndrome in Bulgaria (1974–1996). Pediatr Nephrol 15:74–78

    Article  PubMed  CAS  Google Scholar 

  11. Mahan JD, Mauer SM, Sibley RK, Vernier RL (1984) Congenital nephrotic syndrome: evolution of medical management and results of renal transplantation. J Pediatrs 105:549–557

    Article  CAS  Google Scholar 

  12. Mehls O, Andrassy K, Koderisch J, Herzog U, Ritz E (1987) Hemostasis and thromboembolism in children with nephrotic syndrome: differences from adults. J Pediatr 110:862–867

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  14. Tsau YK, Chen CH, Tsai WS, Sheu JN (1991) Complications of nephrotic syndrome in children. J Formos Med Assoc 90:555–559

    PubMed  CAS  Google Scholar 

  15. Zhang LJ, Wang ZJ, Zhou CS, Lu L, Luo S, Lu GM (2012) Evaluation of pulmonary embolism in pediatric patients with nephrotic syndrome with dual energy CT pulmonary angiography. Academ Radiol 19:341–348

    Article  Google Scholar 

  16. Raffini L, Yuan-Shung H, Witmer C, Feudtner C (2009) A dramatic increase in venous thromboembolism in U.S. Children’s Hospitals from 2001 to 2007. Pediatrics 124:1001–1008

    Article  PubMed  Google Scholar 

  17. Vu LT, Nobuhara KK, Lee H, Farmer DL (2008) Determination of risk factors for deep venous thrombosis in hospitalized children. J Pediatr Surg 43:1095–1099

    Article  PubMed  Google Scholar 

  18. 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  PubMed Central  PubMed  CAS  Google Scholar 

  19. Cueto SM, Cavanaugh SH, Benenson RS, Redclift MS (2001) Computed tomography scan versus ventilation-perfusion lung scan in the detection of pulmonary embolism. J Emerg Med 21:155–164

    Article  PubMed  CAS  Google Scholar 

  20. Kuhle S, Spavor M, Massicotte P, Halton J, Cherrick I, Dix D, Mahoney D, Bauman M, Desai S, Mitchell LG (2008) Prevalence of post-thrombotic syndrome following asymptomatic thrombosis in survivors of acute lymphoblastic leukemia. J Thromb Haemost 6:589–594

    Article  PubMed  CAS  Google Scholar 

  21. Kerlin BA (2012) Current and future management of pediatric venous thromboembolism. Am J Hematol 87(Suppl 1):S68–74

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  22. Boulet SL, Amendah D, Grosse SD, Hooper WC (2012) Health care expenditures associated with venous thromboembolism among children. Thromb Res 129:583–587

    Article  PubMed  CAS  Google Scholar 

  23. Price VE, Chan AK (2008) Venous thrombosis in children. Expert Rev Cardiovasc Ther 6:411–418

    Article  PubMed  Google Scholar 

  24. Kuhle S, Koloshuk B, Marzinotto V, Bauman M, Massicotte P, Andrew M, Chan A, Abdolell M, Mitchell L (2003) A cross-sectional study evaluating post-thrombotic syndrome in children. Thromb Res 111:227–233

    Article  PubMed  CAS  Google Scholar 

  25. Fabri D, Belangero VM, Annichino-Bizzacchi JM, Arruda VR (1998) Inherited risk factors for thrombophilia in children with nephrotic syndrome. Eur J Pediatr 157:939–942

    Article  PubMed  CAS  Google Scholar 

  26. Garbrecht F, Gardner S, Johnson V, Grabowski E (1991) Deep venous thrombosis in a child with nephrotic syndrome associated with a circulating anticoagulant and acquired protein S deficiency. Am J Pediatr Hematol Oncoly 13:330–333

    Article  CAS  Google Scholar 

  27. Male C, Lechner K, Eichinger S, Kyrle PA, Kapiotis S, Wank H, Kaider A, Pabinger I (1999) Clinical significance of lupus anticoagulants in children. J Pediatr 134:199–205

    Article  PubMed  CAS  Google Scholar 

  28. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, PG DEG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306

    Google Scholar 

  29. Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, Brey R, Derksen R, Harris EN, Hughes GR, Triplett DA, Khamashta MA (1999) International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 42:1309–1311

    Article  PubMed  CAS  Google Scholar 

  30. Chan AK, Deveber G, Monagle P, Brooker LA, Massicotte PM (2003) Venous thrombosis in children. J Thromb Haemost 1:1443–1455

    Article  PubMed  CAS  Google Scholar 

  31. Journeycake JM, Buchanan GR (2003) Thrombotic complications of central venous catheters in children. Current Opin Hematol 10:369–374

    Article  Google Scholar 

  32. van Ommen CH, Peters M (2003) Venous thromboembolic disease in childhood. Semin Thromb Hemost 29:391–404

    Article  PubMed  Google Scholar 

  33. Linnemann B, Lindhoff-Last E (2012) Risk factors, management and primary prevention of thrombotic complications related to the use of central venous catheters. VASA Zeitschrift fur Gefasskrankheiten 41:319–332

    Article  PubMed  Google Scholar 

  34. Loscalzo J (2013) Venous thrombosis in the nephrotic syndrome. New Engl J Med 368:956–958

    Article  PubMed  CAS  Google Scholar 

  35. 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 Haemosts 107:681–689

    Article  CAS  Google Scholar 

  36. Dogra GK, Herrmann S, Irish AB, Thomas MA, Watts GF (2002) Insulin resistance, dyslipidaemia, inflammation and endothelial function in nephrotic syndrome. Nephrol Dial Transplant 17:2220–2225

    Article  PubMed  CAS  Google Scholar 

  37. Dogra GK, Watts GF, Herrmann S, Thomas MA, Irish AB (2002) Statin therapy improves brachial artery endothelial function in nephrotic syndrome. Kidney Int 62:550–557

    Article  PubMed  CAS  Google Scholar 

  38. Andrew M, David M, Adams M, Ali K, Anderson R, Barnard D, Bernstein M, Brisson L, Cairney B, DeSai D, Grant R, Israles S, Jardine L, Luke B, Massicotte P, Silva M (1994) Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood 83:1251–1257

    PubMed  CAS  Google Scholar 

  39. Monagle P, Adams M, Mahoney M, Ali K, Barnard D, Bernstein M, Brisson L, David M, Desai S, Scully MF, Halton J, Israels S, Jardine L, Leaker M, McCusker P, Silva M, Wu J, Anderson R, Andrew M, Massicotte MP (2000) Outcome of pediatric thromboembolic disease: a report from the Canadian Childhood Thrombophilia Registry. Pediatr Res 47:763–766

    Article  PubMed  CAS  Google Scholar 

  40. 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 

  41. Htike N, Superdock K, Thiruveedi S, Surkis W, Teehan G (2012) Evaluating proteinuria and nephrotic syndrome in patients with venous thromboembolism. Am J Med Sci 343:124–126

    Article  PubMed  Google Scholar 

  42. Kato S, Chernyavsky S, Tokita JE, Shimada YJ, Homel P, Rosen H, Winchester JF (2010) Relationship between proteinuria and venous thromboembolism. J Thromb Thrombolysis 30:281–285

    Article  PubMed  Google Scholar 

  43. Mahmoodi BK, Gansevoort RT, Veeger NJ, Matthews AG, Navis G, Hillege HL, van der Meer J (2009) Microalbuminuria and risk of venous thromboembolism. JAMA 301:1790–1797

    Article  PubMed  CAS  Google Scholar 

  44. Lionaki S, Derebail VK, Hogan SL, Barbour S, Lee T, Hladunewich M, Greenwald A, Hu Y, Jennette CE, Jennette JC, Falk RJ, Cattran DC, Nachman PH, Reich HN (2012) Venous thromboembolism in patients with membranous nephropathy. Clin J Am Soc Nephrol 7:43–51

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  45. 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  PubMed  CAS  Google Scholar 

  46. Andrew M, Brooker LA (1996) Hemostatic complications in renal disorders of the young. Pediatr Nephrol 10:88–99

    Article  PubMed  CAS  Google Scholar 

  47. Goldenberg NA, Bernard TJ (2008) Venous thromboembolism in children. Pediatr Clin North Am 55:305–322, vii

    Article  PubMed  Google Scholar 

  48. Manco-Johnson MJ (2006) How I treat venous thrombosis in children. Blood 107:21–29

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  49. Monagle P, Chan AK, Goldenberg NA, Ichord RN, Journeycake JM, Nowak-Gottl U, Vesely SK, American College of Chest P (2012) Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141:e737S–e801S

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  50. Raffini L, Thornburg C (2009) Testing children for inherited thrombophilia: more questions than answers. Br J Haematol 147:277–288

    Article  PubMed  CAS  Google Scholar 

  51. Glassock RJ (2007) Prophylactic anticoagulation in nephrotic syndrome: a clinical conundrum. J Am Soc Nephrol 18:2221–2225

    Article  PubMed  Google Scholar 

  52. Gargah T, Abidi K, Nourchene K, Zarrouk C, Lakhoua MR (2012) Thromboembolic complications of childhood nephrotic syndrome. Tunis Med 90:161–165

    PubMed  Google Scholar 

  53. Raffini L, Trimarchi T, Beliveau J, Davis D (2011) Thromboprophylaxis in a pediatric hospital: a patient-safety and quality-improvement initiative. Pediatrics 127:e1326–1332

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  56. Rabelink TJ, Zwaginga JJ, Koomans HA, Sixma JJ (1994) Thrombosis and hemostasis in renal disease. Kidney Int 46:287–296

    Article  PubMed  CAS  Google Scholar 

  57. Konkle BA, Bauer KA, Weinstein R, Greist A, Holmes HE, Bonfiglio J (2003) Use of recombinant human antithrombin in patients with congenital antithrombin deficiency undergoing surgical procedures. Transfusion 43:390–394

    Article  PubMed  CAS  Google Scholar 

  58. Galanaud JP, Kahn SR (2013) The post-thrombotic syndrome: a 2012 therapeutic update. Curr Treat Options Cardovasc Med 15:153–163

    Article  Google Scholar 

  59. Biss TT, Kahr WH, Brandao LR, Chan AK, Thomas KE, Williams S (2009) The use of elastic compression stockings for post-thrombotic syndrome in a child. Pediatric Blood Cancer 53:462–463

    Article  PubMed  Google Scholar 

  60. Mackman N (2012) New insights into the mechanisms of venous thrombosis. J Clin Invest 122:2331–2336

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  61. Mahan JD, Smoyer WE (2009) The need for a children’s oncology group-oriented approach to advance the care of children with idiopathic nephrotic syndrome. Clin J Am Soc Nephrol 4:1549–1550

    Article  PubMed  Google Scholar 

  62. D'Agostino RB Jr (2007) Propensity scores in cardiovascular research. Circulation 115:2340–2343

    Article  PubMed  Google Scholar 

  63. Winkelmayer WC, Kurth T (2004) Propensity scores: help or hype? Nephrol Dial Transplant 19:1671–1673

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA

    Bryce A. Kerlin & William E. Smoyer

  2. Center for Clinical and Translational Research, The Research Institute at Nationwide Children’s, 700 Children’s Dr., W325, Columbus, OH, 43205-2696, USA

    Bryce A. Kerlin & William E. Smoyer

  3. Division of Hematology/Oncology/Bone Marrow Transplantation, Nationwide Children’s Hospital, Columbus, OH, USA

    Bryce A. Kerlin & Kellie Haworth

  4. Division of Nephrology, Nationwide Children’s Hospital, Columbus, OH, USA

    William E. Smoyer

Authors
  1. Bryce A. Kerlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kellie Haworth
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William E. Smoyer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bryce A. Kerlin.

Additional information

Questions (answers are provided following the reference list)

1. Overall, childhood VTE is associated with what increase in likelihood of in-hospital death?

a. 6 %

b. 6-fold (RR = 6)

c. 60 %

d. 16 %

e. 60-fold (RR = 60)

2. Approximately what percentage of pediatric VTE patients develop recurrent VTE?

a. 3 %

b. 52 %

c. 12 %

d. 71 %

e. 32 %

3. What is the strongest risk factor for pediatric VTE?

a. Presence of infection

b. Immobilization

c. Presence of anti-phospholipid antibodies

d. Heritable thrombophilia

e. Presence of a central venous catheter

4. For children with NS, the majority of clinically apparent VTE develop within how long after diagnosis?

a. 1 month

b. 6 months

c. 9 months

d. 3 months

e. 12 months

5. Antithrombin supplementation may become necessary with the use of which anticoagulants?

a. Warfarin

b. Vitamin K antagonists

c. Tissue-type plasminogen activator

d. Heparin

e. Aspirin

Answers:

1. B

2. C

3. E

4. D

5. D

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kerlin, B.A., Haworth, K. & Smoyer, W.E. Venous thromboembolism in pediatric nephrotic syndrome. Pediatr Nephrol 29, 989–997 (2014). https://doi.org/10.1007/s00467-013-2525-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-013-2525-5

Keywords

Search

Navigation