Anticoagulation with Recombinant Hirudin and Danaparoid Sodium in Pediatric Patients

Thomas Severin; Barbara Zieger; Anton H. Sutor

doi:10.1055/s-2002-35285

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2002; 28(5): 447-454
DOI: 10.1055/s-2002-35285

Anticoagulation with Recombinant Hirudin and Danaparoid Sodium in Pediatric Patients

Thomas Severin, Barbara Zieger, Anton H. Sutor

Department of Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg, Germany

Abstract

ABSTRACT

Patients receiving heparin are at risk of developing heparin-induced thrombocytopenia (HIT). Whereas in HIT I only reversible mild thrombocytopenia occurs within the first days of heparin treatment, HIT II may lead to potentially life-threatening thromboembolic events. Pediatric patients suffering from HIT II have been reported in a study on newborns and in a few reports on children and adolescents. However, thrombotic complications can be as severe in children as they are in adults. In the case of HIT II, the withdrawal of heparin is required and alternative anticoagulation should be started. In contrast to numerous investigations in adult patients, including prospective studies, experience with alternative anticoagulants in pediatric patients is limited. The available data were analyzed according to HIT II complications, alternative anticoagulation, and clinical outcome. In conclusion, HIT II represents a potentially dangerous complication of heparin therapy in pediatric patients also. Alternative anticoagulation applied in pediatric patients mainly included danaparoid sodium and recombinant hirudin. In most patients treated with these anticoagulants, effective anticoagulation and clinical improvement were observed. Because of limited experience, more data are required for optimal management of HIT II in young patients.

KEYWORDS

Heparin-induced thrombocytopenia - HIT - anticoagulation - children - thrombosis

Full Text

References

REFERENCES

1 Andrew M, Michelson A D, Bovill E. Guidelines for antithrombotic therapy in pediatric patients. J Pediatr . 1998; 132 575-588
2 Sutor A H. Thrombosis in Childhood. New York: Schattauer 1997
3 Streif W, Mitchell L G, Andrew M. Antithrombotic therapy in children. Curr Opin Pediatr . 1999; 11 56-64
4 Monagle P, Michelson A D, Bovill E, Andrew M. Antithrombotic therapy in children. Chest . 2001; 119(Suppl 1) 344S-370S
5 Sutor A H, Massicotte P, Leaker M, Andrew M. Heparin therapy in pediatric patients. Semin Thromb Hemost . 1997; 23 303-319
6 Fareed J, Hoppensteadt D A, Bick R L. An update on heparins at the beginning of the new millennium. Semin Thromb Hemost . 2000; 26(Suppl 1) 5-21
7 Massicotte M P. Low-molecular-weight heparin therapy in children. J Pediatr Hematol Oncol . 2001; 23 189-194
8 Greinacher A. Heparin-induced thrombocytopenia-pathogenesis and treatment [in German]. Hämostaseologie . 1999; 19 1-12
9 Greinacher A. Treatment of heparin-induced thrombocytopenia. Thromb Haemost . 1999; 82 457-467
10 Visentin G P. Heparin-induced thrombocytopenia: molecular pathogenesis. Thromb Haemost . 1999; 82 448-456
11 Warkentin T E, Chong B H, Greinacher A. Heparin-induced thrombocytopenia: towards consensus. Thromb Haemost . 1998; 79 1-7
12 Fabris F, Ahmad S, Cella G. Pathophysiology of heparin-induced thrombocytopenia. Arch Pathol Lab Med . 2000; 124 1657-1666
13 Warkentin T E, Soutar R L, Panju A, Ginsberg J S. Acute systemic reactions to intravenous bolus heparin therapy: characterization and relationship to heparin-induced thrombocytopenia (Abst). Blood . 1992; 80 160a
14 Ali O. Images in heparin-induced thrombocytopenia. J Thromb Thrombolysis . 2000; 10 S27-S33
15 Warkentin T E. Heparin-induced skin lesions. Br J Haematol . 1996; 92 494-497
16 Hartman A R, Hood R M, Anagnostopoulus C E. Phenomenon of heparin-induced thrombocytopenia associated with skin necrosis. J Vasc Surg . 1988; 7 781-784
17 Warkentin T E, Hirte H W, Anderson D R. Transient global amnesia associated with acute heparin-induced thrombocytopenia. Am J Med . 1994; 97 489-491
18 Kadidal V V, Mayo D J, Horne M K. Heparin-induced thrombocytopenia (HIT) due to heparin flushes: a report of three cases. J Intern Med . 1999; 246 325-329
19 Walenga J M, Lewis B E, Bakhos M. Anticoagulant management of patients with heparin-induced thrombocytopenia. Turk J Haematol . 2000; 17(Suppl) 68-77
20 Magnani H N. Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with Orgaran. Thromb Haemost . 1993; 70 554-561
21 Chong B H, Magnani H N. Danaparoid for the treatment of heparin-induced thrombocytopenia. In: Warkentin TE, Greinacher A, eds. Heparin-Induced Thrombocytopenia New York: Dekker 2001: 323-347
22 Greinacher A. Recombinant hirudin for further anticoagulation in heparin-induced thrombocytopenia [in German]. Hämostaseologie . 1999; 19 19-29
23 Greinacher A, Völpel H, Janssens U. Recombinant hirudin (lepirudin) provides safe and effective anticoagulation in patients with heparin-induced thrombocytopenia. Circulation . 1999; 99 73-80
24 Greinacher A, Janssens U, Berg G, for the Heparin-Associated Thrombocytopenia (HAT) Study investigators. Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia. Circulation . 1999; 100 587-593
25 Spadone D, Clark F, James E. Heparin-induced thrombocytopenia in the newborn. J Vasc Surg . 1992; 15 306-311
26 Laster J, Cikrit D, Walker N. The heparin-induced thrombocytopenia syndrome: an update. Surgery . 1987; 102 763-770
27 Boon D MS, Michiels J J, Stibbe J, van Vliet H D M H, Kappers-Klunne M C. Heparin-induced thrombocytopenia and antithrombotic therapy. Lancet . 1994; 344 1296
28 Butler T J, Sodoma L J, Doski J J. Heparin-associated thrombocytopenia and thrombosis as the cause of a fatal thrombus on extracorporeal membrane oxygenation. J Pediatr Surg . 1997; 32 768-771
29 Ranze O, Ranze P, Magnani H N, Greinacher A. Heparin-induced thrombocytopenia in paediatric patients-a review of the literature and a new case treated with danaparoid sodium. Eur J Pediatr . 1999; 158(Suppl 3) 130-133
30 Murdoch I A, Beattie R M, Silver D M. Heparin-induced thrombocytopenia in children. Acta Paediatr . 1993; 82 495-497
31 Oriot D, Wolf M, Wood C. Severe thrombocytopenia induced by heparin in an infant with acute myocarditis. Arch Fr Pediatr . 1990; 47 357-359
32 Saxon B R, Black M D, Edgell D, Noel D, Leaker M T. Pediatric heparin-induced thrombocytopenia: management with danaparoid (Orgaran). Ann Thorac Surg . 1999; 68 1076-1078
33 Zöhrer B, Zenz W, Rettenbacher A. Danaparoid sodium (Orgaran) in four children with heparin-induced thrombocytopenia type II. Acta Paediatr . 2001; 90 765-771
34 Neuhaus T J, Goetschel P, Schmugge M, Leumann E. Heparin-induced thrombocytopenia type II on hemodialysis: switch to danaparoid. Pediatr Nephrol . 2000; 14 713-716
35 Schiffmann H, Unterhalt M, Harms K. Successful treatment of heparin-induced thrombocytopenia type II in childhood with recombinant hirudin [in German]. Monatsschr Kinderheilkd . 1997; 145 606-612
36 Potter C, Gill J C, Scott J P, McFarland J G. Heparin-induced thrombocytopenia in a child. J Pediatr . 1992; 121 135-138
37 Bocquet R, Blanot S, Dautzenberg M D. Antiphospholipid antibody syndrome in pediatric neurosurgery: a hemostasis problem. Ann Fr Anesth Reanim . 1999; 18 991-995
38 Wilhelm M J, Schmid C, Kececioglu D. Cardiopulmonary bypass in patients with heparin-induced thrombocytopenia using Org 10172. Ann Thorac Surg . 1996; 61 920-924
39 Severin T, Ensenauer R, Wiedensohler A. HIT type II without thrombocytopenia in a 15-year-old boy with protein S deficiency and recurrent deep vein thrombosis. Proceedings of the 30th Hemophilia Symposium; 1999; Hamburg, Germany. New York: Springer-Verlag 2000: 114-116
40 Klement D, Rammos S, von Kries R. Heparin as a cause of thrombus progression. Eur J Pediatr . 1996; 155 11-14
41 Sauer M, Gruhn B, Fuchs D, Altermann W, Zintl F. Heparin-induced thrombocytopenia type II during high-dose-chemotherapy with stem cell rescue [in German]. Klein Pädiatr . 1998; 210 102-105
42 Severin T, Sutor A H. Heparin-induced thrombocytopenia in pediatrics. Semin Thromb Hemost . 2001; 27 293-299
43 Weigel B, Lasky A, Krishnamurti L. Danaparoid (Orgaran) anticoagulation of pediatric patients with heparin-induced thrombocytopenia (HIT) (Abst). J Pediatr Hematol Oncol . 1999; 21 327
44 Girisch M, Buheitel G, Ries M, Klinge J. 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 . 2001; 80(Suppl 1) A20
45 Greinacher A, Warkentin T E. Treatment of heparin-induced thrombocytopenia: an overview. In: Warkentin TE, Greinacher A, eds. Heparin-Induced Thrombocytopenia New York: Dekker 2001: 291-322
46 Product Information: Orgaran Thiemann GmbH, Waltrop, Germany .
47 Roth B, Johnen M, Busch P. Use of a new heparinoid for anticoagulation during hemodialysis in a child with intracranial hemorrhage [in German]. Nieren-u. Hochdruckkrankheiten . 1985; 14 62-64
48 Lubenow N, Greinacher A. Management of patients with heparin-induced thrombocytopenia: focus on recombinant hirudin. J Thromb Thrombolysis . 2000; 10 47-57
49 Greinacher A, Lubenow N. Recombinant hirudin in clinical practice. Circulation . 2001; 103 1479-1484
50 Product Information: Refludan Aventis, Frankfurt, Germany .
51 Warkentin T E, Levine M N, Hirsh J. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med . 1995; 332 1330-1335