Skip to main content
Log in

Heparin-induced thrombocytopenia in paediatrics: clinical characteristics, therapy and outcomes

  • Neonatal and Pediatric Intensive Care
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Objective: Reports on heparin-induced thrombocytopenia (HIT) in paediatrics are confined to isolated case reports. The objective was to systematically combine the published data. Design and setting: Cases were identified by MEDLINE search and review of bibliographies. Patients: We included subjects reported with HIT, collecting patient demographics, clinical and laboratory characteristics, therapeutic regimens and outcomes. Measurements and results: Reports on 70 patients were retrieved. In a majority of children, HIT occurred during hospitalisation in a paediatric ICU. In most patients, the typical onset pattern was reported, although rapid-onset-pattern HIT occurred in some. The median platelet-count nadir was 54×109/l; 11% of reported patients had nadirs in the normal range. Clinical symptoms included isolated thrombocytopenia and solitary or combined venous, arterial and intracardiac thromboembolism, sometimes catheter-related. Pulmonary embolism and major bleeding were rarely described. Confirmatory functional or antigenic testing of HIT antibodies showed a similar cumulative sensitivity of about 88%. An unfavourable outcome (death/limb amputation) was reported in 42.1% of patients without therapy and in 18% of patients treated with danaparoid, lepirudin, or argatroban. Conclusions: HIT in children mainly occurs in paediatric intensive care with diagnostic features and outcomes similar to those seen in adults. HIT cannot be ruled out based on normal platelet counts or occurrence after fewer than 5 days of heparin exposure. Children should be presumed to suffer from HIT based on clinical grounds and treated accordingly (immediate heparin withdrawal and alternative anticoagulation). Alternative anticoagulation with danaparoid, lepirudin and argatroban appears to improve outcomes.

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

Access this article

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

Instant access to the full article PDF.

Fig 1
Fig 2
Fig 3
Fig 4

Similar content being viewed by others

References

  1. Warkentin TE (2003) Heparin-induced thrombocytopenia: pathogenesis and management. Br J Haematol 121:535–555

    Article  CAS  PubMed  Google Scholar 

  2. Chong BH (2003) Heparin-induced thrombocytopenia. J Thromb Haemost 1:1471–1478

    Google Scholar 

  3. Warkentin TE (2001) Clinical picture of heparin-induced thrombocytopenia. In: Warkentin TE, Greinacher A (eds) Heparin-induced thrombocytopenia, 2nd edn. Dekker, New York, pp 43–86

  4. Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, Kelton JG (1995) Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 332:1330–1335

    CAS  PubMed  Google Scholar 

  5. Warkentin TE, Kelton JG (2001) Temporal aspects of heparin-induced thrombocytopenia. N Engl J Med 344:1286–1292

    CAS  Google Scholar 

  6. Risch L, Pihan H, Zeller C, Huber AR (2000) ET gets HIT—thrombocytotic heparin-induced thrombocytopenia (HIT) in a patient with essential thrombocythemia (ET). Blood Coagul Fibrinolysis 11:663–667

    Article  CAS  PubMed  Google Scholar 

  7. Warkentin TE, Greinacher A (2001) Laboratory testing for heparin-induced thrombocytopenia. In: Warkentin TE, Greinacher A (eds) Heparin-induced thrombocytopenia, 2nd edn. Dekker, New York, pp 231–270

  8. Warkentin TE, Heddle NM (2003) Laboratory diagnosis of immune heparin-induced thrombocytopenia. Curr Hematol Rep 2:148–157

    PubMed  Google Scholar 

  9. Risch L, Bertschmann W, Heijnen IA, Huber AR (2003). A differentiated approach to assess the diagnostic usefulness of a rapid-particle-gel immunoassay for the detection of antibodies against heparin-platelet factor 4 in cardiac surgery patients. Blood Coagul Fibrinolysis 14:99–106

    Article  CAS  PubMed  Google Scholar 

  10. Dager WE, White RH (2003) Pharmacotherapy of heparin-induced thrombocytopenia. Expert Opin Pharmacother 4:919–940

    Article  CAS  PubMed  Google Scholar 

  11. Greinacher A, Warkentin TE (2001) Treatment of heparin-induced thrombocytopenia: an overview. In: Warkentin TE, Greinacher A (eds) Heparin-induced thrombocytopenia, 2nd edn. Dekker, New York, pp 291–322

  12. Lee DH, Warkentin TE (2001) Frequency of heparin-induced thrombocytopenia. In: Warkentin TE, Greinacher A (eds) Heparin-induced thrombocytopenia, 2nd edn. Dekker, New York, pp 87–121

  13. Spadone D, Clark F, James E (1992) Heparin-induced thrombocytopenia in the newborn. J Vasc Surg 15:306–311

    Article  CAS  PubMed  Google Scholar 

  14. Schmugge M, Risch L, Huber AR, Benn A, Fischer JE (2002) Heparin-induced thrombocytopenia-associated thrombosis in pediatric intensive care patients. Pediatrics 109:e10

    PubMed  Google Scholar 

  15. Newall F, Barnes C, Ignjatovic V, Monagle P (2003) Heparin-induced thrombocytopenia. J Paediatr Child Health 39:289–292

    Article  CAS  PubMed  Google Scholar 

  16. Severin T, Sutor AH (2001) Heparin-induced thrombocytopenia in pediatrics. Semin Thromb Hemost 27:293–299

    Article  CAS  PubMed  Google Scholar 

  17. Laster J, Cikrit D, Walker N, Silver D (1987) The heparin-induced thrombocytopenia syndrome: an update. Surgery 102:763–770

    CAS  PubMed  Google Scholar 

  18. Oriot D, Wolf M, Wood C (1990) Thrombopénie sévère induite par l’heparine chez un nourrisson porteur d’une myocardite aiguë. Arch Fr Pediatr 47:357–359

    CAS  PubMed  Google Scholar 

  19. Potter C, Gill JC, Scott JP, McFarland JG (1992) Heparin-induced thrombocytopenia in a child. J Pediatr 121:135–138

    CAS  PubMed  Google Scholar 

  20. Muntean W, Finding K, Gamillscheg A, Zenz W (1992) Multiple thromboses and coumarin-induced skin necrosis in a young child with antiphospholipid antibodies. Thromb Haemorrh Disorders 5(2):43–45

    Google Scholar 

  21. Murdoch IA, Beatty RM, Silver DM (1993) Heparin induced thrombocytopenia in children. Acta Paediatr 82:495–497

    CAS  PubMed  Google Scholar 

  22. Klement D, Ramnos S, von Kries R, Kirschke W, Kniemeyer HW, Greinacher A (1996) Heparin as a cause of thrombus progression. Heparin-induced thrombocytopenia is an important differential diagnosis in pediatric patients even with normal platelet counts. Eur J Pediatr 155:11–14

    CAS  PubMed  Google Scholar 

  23. Wilhelm MJ, Schmid C, Kececioglu D (1996) Cardiopulmonary bypass in patients with heparin induced thrombocytopenia using Organonon 10172. Ann Thorac Surg 61:920–924

    Article  CAS  PubMed  Google Scholar 

  24. Butler TJ, Sodoma LJ, Doski JJ, Cheu HW, Berg ST, Stokes GN, Lancaster KJ (1997) Heparin-associated thrombocytopenia and thrombocytopenia and thrombosis as the cause of a fatal thrombus on extracorporeal membrane oxygenation. J Pediatr Surg 32:768–771

    CAS  PubMed  Google Scholar 

  25. Schiffmann H, Unterhalt M, Harms K, Figulla HR, Volpel H, Greinacher A (1997) Erfolgreiche Behandlung einer Heparin-induzierten Thrombozytopenie Typ II im Kindesalter mit rekombinantem Hirudin. Monatsschr Kinderheilkd 145:606–612

    Article  Google Scholar 

  26. Nowak-Gottl U, Schneppenheim R, Vielhaber H (1997) APC resistance in childhood thromboembolism: diagnosis and clinical aspects. Semin Thromb Hemost 23:253–258

    CAS  PubMed  Google Scholar 

  27. Sauer M, Gruhn B, Fuchs D, Altermann W, Zintl F (1998) Heparin-induzierte Thrombozytopenie Typ II im Rahmen einer Hochdosis-Chemotherapie mit anschliessender Stammzellrescue. Klin Padiatr 210:102–103

    CAS  PubMed  Google Scholar 

  28. Saxon B, Black M, Edgell D, Noel D, Leaker M (1999). Pediatric heparin-induced thrombocytopenia: management with danaparoid. Ann Thorac Surg 68:1076–1078

    Article  CAS  PubMed  Google Scholar 

  29. Tomer A, Masalunga C, Abshire T (1999) Determination of Heparin-induced thrombocytopenia: a rapid flow cytometric assay for direct demonstration of antibody-mediated platelet activation. Am J Hematol 61:53–61

    Article  CAS  PubMed  Google Scholar 

  30. Ranze O, Ranze P, Magnani HN, Greinacher A (1999) Heparin-induced thrombocytopenia in paediatric patients—a review of the literature and a new case treated with danaparoid sodium. Eur J Pediatr 158:S130–133

    PubMed  Google Scholar 

  31. Bocquet R, Blanot S, Dautzenberg MD, Pierre-Kahn A, Carli P (1999) Syndrome des anticorps antiphospholipides en neurochirurgie pédiatrique: un problème d’hémostase. Ann Fr Anesth Reanim 18:991–995

    Article  CAS  PubMed  Google Scholar 

  32. Weigel B, Lasky A, Krishnamurti L (1999) Danaparoid (Orgaran) anticoagulation of pediatric patients with heparin-induced thrombocytopenia (HIT). J Pediatr Hematol Oncol 21:327

    Article  Google Scholar 

  33. Greinacher A, Janssens U, Berg G, Böck M, Kwasny H, Kemkes-Matthes B, Eichler P, Völper H, Pötzsch B, Luz M (1999) Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia. Circulation 100:587–593

    CAS  PubMed  Google Scholar 

  34. Neuhaus T, Goetschel P, Schmugge M, Leumann E (2000) Heparin-induced thrombocytopenia type II on hemodialysis: switch to danaparoid. Pediatr Nephrol 14:713–716

    CAS  PubMed  Google Scholar 

  35. Ranze O, Rakow A, Ranze P, Eichler P, Greinacher A, Fusch C (2001) Low-dose danaparoid sodium catheter flushes in an intensive care infant suffering from heparin-induced thrombocytopenia. Pediatr Crit Care Med 2:175–177

    Article  PubMed  Google Scholar 

  36. Zöhrer B, Zenz W, Rettenbacher A, Covi P, Kurnik K, Kroll H, Grubbauer HM, Muntean W (2001) Danaparoid sodium (Orgaran) in four children with heparin induced thrombocytopenia type II. Acta Paediatr 2001; 90:765–771

    Google Scholar 

  37. Girisch M, Buheitel G, Ries M, Klinge J (2001) Safe and effective use of danaparoid during cardiac catheterization in a 14-month-old boy with tetralogy of Fallot and heparin-induced thrombocytopenia. Ann Hematol [Suppl1] 80:A20

  38. Deitcher SR, Topoulos AP, Bartholomew JR, Kichuk-Chrisant MR (2002) Lepirudin anticoagulation for heparin-induced thrombocytopenia. J Pediatr 140:264–266

    Article  PubMed  Google Scholar 

  39. Boshkov LK, Thomas G, Kirby A, Shen I, Swanson V, Burch G, Ungerleider R (2002) Pharmacokinetics of argatroban in a 6-month-old congenital cardiac patient with previously diagnosed heparin-induced thrombocytopenia. Blood 100:269a

    Google Scholar 

  40. Severin T, Zieger B, Sutor AH (2002) Anticoagulation with recombinant hirudin and danaparoid sodium in pediatric patients. Semin Thromb Hemost 28:447–454

    Article  CAS  PubMed  Google Scholar 

  41. Porcelli R, Moskowitz BC, Cetta F, Graham LC, Godwin JE, Eidem BW, Prechel MM, Walenga JM (2003) Heparin-induced thrombocytopenia with associated thrombosis in children after the Fontan operation. Report of two cases. Tex Heart Inst J 30:58–61

    PubMed  Google Scholar 

  42. Gatti L, Carnelli V, Rusoni R, Moia M (2003) Heparin-induced thrombocytopenia and warfarin-induced skin necrosis in a child with severe protein C deficiency: successful treatment with dermatan sulfate and protein C concentrate. J Thromb Haemost 1:1387–1388

    Article  Google Scholar 

  43. Nguyen TN, Gal P, Ransom JL, Carlos R (2003) Lepirudin use in a neonate with heparin-induced thrombocytopenia. Ann Pharmacother 37:229–233

    Article  PubMed  Google Scholar 

  44. Greinacher A (2001) Recombinant hirudin for the treatment of heparin-induced thrombocytopenia. In: Warkentin TE, Greinacher A (eds) Heparin-induced thrombocytopenia, 2nd edn. Dekker, New York, pp 349–380

  45. Chong BH, Magnani HN (2001) Danaparoid for the treatment of heparin-induced thrombocytopenia. In: Warkentin TE, Greinacher A (eds) Heparin-induced thrombocytopenia, 2nd edn. Dekker, New York, pp 323–347

  46. Lewis BE, Hursting MJ (2001) Argatroban therapy in heparin-induced thrombocytopenia. In: Warkentin TE, Greinacher A (eds) Heparin-induced thrombocytopenia, 2nd edn. Dekker, New York, pp 381–407

  47. Almeida JI, Coats R, Liem TK, Silver D (1998) Reduced morbidity and mortality rates of the heparin-induced thrombocytopenia syndrome. J Vasc Surg 27:309-316.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  49. Swan SK, Hursting MJ (2000) The pharmacokinetics and pharmacodynamics of argatroban: effects of age, gender, and hepatic or renal dysfunction. Pharmacotherapy 20:318–329

    CAS  PubMed  Google Scholar 

  50. Kawada T, Kitagawa H, Hoson M, Okada Y, Shiomura J (2000) Clinical application of argatroban as an alternative anticoagulant for extracorporeal circulation. Hematol Oncol Clin North Am 14:445–457

    CAS  PubMed  Google Scholar 

  51. Taliani MR, Agnelli G, Nenci G, Gianese F (1999) Dermatan sulphate in patients with heparin-induced thrombocytopenia. Br J Haematol 104:87–89

    Article  CAS  PubMed  Google Scholar 

  52. Albisetti M, Andrew M (2002) Low-molecular-weight heparin in children. Eur J Pediatr 161:71–77

    Article  CAS  PubMed  Google Scholar 

  53. Hong AP, Cook DJ, Sigouin CS, Warkentin TE (2003) Central venous catheters and upper-extremity deep-venous thrombosis complicating immune heparin-induced thrombocytopenia. Blood 101:3049–3051

    Article  CAS  PubMed  Google Scholar 

  54. Risch L, Fischer JE, Schmugge M, Huber AR (2003) Association of anti-heparin platelet factor 4 antibody levels and thrombosis in pediatric intensive care patients without thrombocytopenia. Blood Coagul Fibrinolysis 14:113–116

    Article  CAS  PubMed  Google Scholar 

  55. Warkentin TE, Kelton JG (1996) A 14-year study of heparin-induced thrombocytopenia. Am J Med 101:502–507

    Article  CAS  PubMed  Google Scholar 

  56. Nand S Wong W, Yuen B, Yetter A, Schmulnach E, Fisher SG (1997) Heparin-induced thrombocytopenia with thrombosis: incidence, analysis of risk factors, and clinical outcomes in 108 consecutive patients treated at a single institution. Am J Hematol 56:12–16

    Article  CAS  PubMed  Google Scholar 

  57. Wallis DE, Workman DL, Lewis BE, Stehen L, Pifarre R, Moran JF (1999) Failure of early heparin cessation as treatment of heparin-induced thrombocytopenia. Am J Med 106:629–635

    Article  CAS  PubMed  Google Scholar 

  58. Silver D, Kapsch DN, Tsoi EK (1983) Heparin-induced thrombocytopenia, thrombosis, and hemorrhage. Ann Surg 198:301–306.

    CAS  PubMed  Google Scholar 

  59. Eichler P, Raschke R, Lubenow N, Meyer O, Schwind P, Greinacher A (2002) The new ID-heparin/PF4 antibody test for rapid detection of heparin-induced antibodies in comparison with functional and antigenic assays. Br J Haematol 116:887–891

    Article  CAS  PubMed  Google Scholar 

  60. Fischer JF, Bachmann LM, Jaeschke R (2003) A reader’s guide to the interpretation of diagnostic test properties: clinical example of sepsis. Intensive Care Med 29:1043–1051

    Article  PubMed  Google Scholar 

  61. Warkentin TE (2002) Platelet count monitoring and laboratory testing for heparin-induced thrombocytopenia. Recommendations of the College of American pathologists. Arch Pathol Lab Med 126:1415–1423

    PubMed  Google Scholar 

  62. Warkentin TE, Aird WC, Rand JH (2003) Platelet-endothelial interactions: sepsis, HIT, and antiphospholipid syndrome. Hematology (Am Soc Hematol Educ Program) 497–519

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andreas R. Huber.

Electronic Supplementary Material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Risch, L., Fischer, J.E., Herklotz, R. et al. Heparin-induced thrombocytopenia in paediatrics: clinical characteristics, therapy and outcomes. Intensive Care Med 30, 1615–1624 (2004). https://doi.org/10.1007/s00134-004-2315-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-004-2315-4

Keywords

Navigation