Document Type : Original Article
Authors
1 Department of Clinical Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
2 Rajaei Cardiovascular Medical and Research Center, Iran University of Medical Science, Tehran, Iran
3 Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Objective: Thrombocytopenia is a common problem in cardiovascular surgery patients.
However, heparin-induced thrombocytopenia (HIT) is a rare but life-threatening complication
of prophylaxis or treatment with heparin. Prompt management of HIT with an alternative
anticoagulant is necessary due to the extreme risk of thrombotic complications. Therefore,
we evaluated the effects of danaparoid in the treatment of HIT in patients with cardiac
surgery who are at moderate to high risk of HIT.
Methods: A prospective observational study involving 418 postcardiac surgery patients
who received unfractionated heparin and low-molecular weight heparin was conducted
in an educational tertiary cardiac care hospital in Iran. All patients were assessed for HIT
type II based on thrombocytopenia and pretest clinical scoring system, the “4T’s” score. HIT
patients were treated with 1500–2500 units intravenous bolus danaparoid sodium followed
by 200–400 units/h for a mean of 5 days. Successful response to danaparoid therapy, defined
as augmentation in platelet count and improvement of thrombotic events was assessed in
all patients treated with danaparoid.
Findings: According to pretest clinical score (4T’s), the probability of HIT was high in
14 (3.3%) patients and intermediate in three ones (0.7%). 15 patients with HIT were
treated with danaparoid. One death occurred in danaparoid-treated group due to persistent
thrombocytopenia. The rest of patients were treated successfully with danaparoid without
any major thrombotic complication.
Conclusion: According to our data and the previous studies’, HIT can be managed
prosperously with danaparoid in postcardiac surgery patients. However, with the absence of
any increase in platelet count after 3–5 days of danaparoid therapy and/or the occurrence
of a new thrombotic event, danaparoid cross-reactivity with heparin should be suspected.
Keywords
Review of heparin‑induced thrombocytopenia. Circulation
2005;111:2671‑83.
2. Franchini M. Heparin‑induced thrombocytopenia: An update.
Thromb J 2005;3:14.
3. Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS,
Gent M, et al. Heparin‑induced thrombocytopenia in patients
treated with low‑molecular‑weight heparin or unfractionated
heparin. N Engl J Med 1995;332:1330‑5.
4. Warkentin TE, Kelton JG. Temporal aspects of heparin‑induced
thrombocytopenia. N Engl J Med 2001;344:1286‑92.
5. Warkentin TE, Kelton JG. Delayed‑onset heparin‑induced
thrombocytopenia and thrombosis. Ann Intern Med
2001;135:502‑6.
6. Warkentin TE, Greinacher A. Heparin‑induced
thrombocytopenia: Recognition, treatment, and prevention:
The Seventh ACCP Conference on Antithrombotic and
Thrombolytic Therapy. Chest 2004;126:311S‑37.
7. Warkentin TE. Heparin‑induced thrombocytopenia:
Pathogenesis and management. Br J Haematol
2003;121:535‑55.
8. Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P,
Greinacher A. Evaluation of pretest clinical score (4 T’s) for
the diagnosis of heparin‑induced thrombocytopenia in two
clinical settings. J Thromb Haemost 2006;4:759‑65.
9. Warkentin TE, Greinacher A. Heparin‑induced
thrombocytopenia and cardiac surgery. Ann Thorac Surg
2003;76:2121‑31.
10. Lassila R, Antovic JP, Armstrong E, Baghaei F,
Dalsgaard‑Nielsen J, Hillarp A, et al. Practical viewpoints
on the diagnosis and management of heparin‑induced
thrombocytopenia. Semin Thromb Hemost 2011;37:328‑36.
11. Aird WC, Mark EJ. Case records of the Massachusetts
General Hospital. Weekly clinicopathological exercises. Case
15‑200. A 53‑year‑old man with a myocardial infarct and
thromboses after coronary‑artery bypass grafting. N Engl J
Med 2002;346:1562‑70.
12. Walls JT, Curtis JJ, Silver D, Boley TM, Schmaltz RA,
Nawarawong W. Heparin‑induced thrombocytopenia in
open heart surgical patients: Sequelae of late recognition. Ann
Thorac Surg 1992;53:787‑91.
13. Warkentin TE. Clinical picture of heparin‑induced
thrombocytopenia. In: Warkentin TE, Greinacher A, editors.
Heparin Induced Thrombocytopenia. New York: Marcel
Dekker; 2001. p. 43‑86.
14. Hong AP, Cook DJ, Sigouin CS, Warkentin TE. Central
venous catheters and upper‑extremity deep‑vein thrombosis
complicating immune heparin‑induced thrombocytopenia.
Blood 2003;101:3049‑51.
15. Warkentin TE, Greinacher A, Koster A, Lincoff AM, American
College of Chest Physicians. Treatment and prevention
of heparin‑induced thrombocytopenia: American College
of Chest Physicians Evidence‑Based Clinical Practice
Guidelines (8th Edition). Chest 2008;133:340S‑8.
16. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA,
et al. A method for estimating the probability of adverse drug
reactions. Clin Pharmacol Ther 1981;30:239‑45.
17. Ortel TL, Chong BH. New treatment options for heparin‑induced
thrombocytopenia. Semin Hematol 1998;35:26‑34.
18. Chong BH, Gallus AS, Cade JF, Magnani H, Manoharan A,
Oldmeadow M, et al. Prospective randomised open‑label
comparison of danaparoid with dextran 70 in the treatment
of heparin‑induced thrombocytopaenia with thrombosis: A
clinical outcome study. Thromb Haemost 2001;86:1170‑5.
19. GerhardtA, Scharf RE, Zotz RB. Successful use of danaparoid
in two pregnant women with heart valve prosthesis and
heparin‑induced thrombocytopenia Type II (HIT). Clin Appl
Thromb Hemost 2009;15:461‑4.
20. Farner B, Eichler P, Kroll H, Greinacher A. A comparison
of danaparoid and lepirudin in heparin‑induced
thrombocytopenia. Thromb Haemost 2001;85:950‑7.
21. Kodityal S, Manhas AH, Udden M, Rice L. Danaparoid for
heparin‑induced thrombocytopenia: An analysis of treatment
failures. Eur J Haematol 2003;71:109‑13.
22. Warkentin TE. Danaparoid (orgaran) for the treatment of
heparin‑induced thrombocytopenia (HIT) and thrombosis:
Effects on in vivo thrombin and cross‑linked fibrin
generation, and evaluation of the clinical significance of
in vitro cross‑reactivity of danaparoid for HIT‑IgG. Blood
1996;88 Suppl 1:626a. [Abstract].
23. Keng TB, Chong BH. Heparin‑induced thrombocytopenia and thrombosis syndrome: In vivo cross‑reactivity with danaparoid
and successful treatment with r‑Hirudin. Br J Haematol
2001;114:394‑6.
24. Refaai MA, Chuang C, Menegus M, Blumberg N, Francis CW.
Outcomes after platelet transfusion in patients with
heparin‑induced thrombocytopenia. J Thromb Haemost
2010;8:1419‑21.
)