Clinical and laboratory diagnosis of heparin-induced thrombocytopenia: An integrated approach

Seminars in Thrombosis and Hemostasis

Volumn 40, Issue 1, 2014, Pages 106-114

  Cuker, Adam ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

diagnosis; heparin induced thrombocytopenia; HIT

Indexed keywords

4TS SCORE; ARTICLE; BAYES THEOREM; CLINICAL DECISION MAKING; CLINICAL EVALUATION; CLINICAL FEATURE; ENZYME LINKED IMMUNOSORBENT ASSAY; HEPARIN INDUCED THROMBOCYTOPENIA; HIT EXPERT PROBABILITY SCORE; HUMAN; IMMUNOASSAY; LABORATORY DIAGNOSIS; LILLO-LE LOUET SCORE; PREDICTIVE VALUE; PRIORITY JOURNAL; SCORING SYSTEM; SENSITIVITY AND SPECIFICITY; THROMBOCYTE ACTIVATION; TURNAROUND TIME;

ANTICOAGULANTS; ENZYME-LINKED IMMUNOSORBENT ASSAY; FEMALE; HEPARIN; HUMANS; MALE; PLATELET FACTOR 4; THROMBOCYTOPENIA;

EID: 84893091406     PISSN: 00946176     EISSN: 10989064     Source Type: Journal    
DOI: 10.1055/s-0033-1363461     Document Type: Article

References (77)

1. Amiral J., Bridey F., Dreyfus M., et al. Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia. Thromb Haemost: 1992; 68 1 95 96
2. Rauova L., Poncz M., McKenzie S. E., et al. Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopenia. Blood: 2005; 105 1 131 138 (Pubitemid 40053074)
3. Cines D. B., Tomaski A., Tannenbaum S. Immune endothelial-cell injury in heparin-associated thrombocytopenia. N Engl J Med: 1987; 316 10 581 589 (Pubitemid 17024480)
4. Kasthuri R. S., Glover S. L., Jonas W., et al. PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI. Blood: 2012; 119 22 5285 5293
5. Linkins L. A., Dans A. L., Moores L. K., et al. Treatment and prevention of heparin-induced thrombocytopenia: antithrombotic therapy and prevention of thrombosis. 9th ed. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest: 2012; 141 e495S e530S
6. Cuker A., Cines D. B. How I treat heparin-induced thrombocytopenia. Blood: 2012; 119 10 2209 2218
7. Cuker A. Current and emerging therapeutics for heparin-induced thrombocytopenia. Semin Thromb Hemost: 2012; 38 1 31 37
8. Greinacher A., Eichler P., Lubenow N., Kwasny H., Luz M. Heparin-induced thrombocytopenia with thromboembolic complications: meta-analysis of 2 prospective trials to assess the value of parenteral treatment with lepirudin and its therapeutic aPTT range. Blood: 2000; 96 3 846 851 (Pubitemid 30616845)
9. Warkentin T. E., Kelton J. G. A 14-year study of heparin-induced thrombocytopenia. Am J Med: 1996; 101 5 502 507 (Pubitemid 126335970)
10. Wallis D. E., Workman D. L., Lewis B. E., Steen L., Pifarre R., Moran J. F. Failure of early heparin cessation as treatment for heparin-induced thrombocytopenia. Am J Med: 1999; 106 6 629 635 (Pubitemid 29279299)
11. Cuker A. Heparin-induced thrombocytopenia (HIT) in 2011: an epidemic of overdiagnosis. Thromb Haemost: 2011; 106 6 993 994
12. Lewis B. E., Wallis D. E., Hursting M. J., Levine R. L., Leya F. Effects of argatroban therapy, demographic variables, and platelet count on thrombotic risks in heparin-induced thrombocytopenia. Chest: 2006; 129 6 1407 1416 (Pubitemid 43894967)
13. Lubenow N., Eichler P., Lietz T., Greinacher A.; Hit Investigators Group. Lepirudin in patients with heparin-induced thrombocytopenia - results of the third prospective study (HAT-3) and a combined analysis of HAT-1, HAT-2, and HAT-3. J Thromb Haemost: 2005; 3 11 2428 2436 (Pubitemid 41727158)
14. Magnani H. N., Gallus A. Heparin-induced thrombocytopenia (HIT). A report of 1,478 clinical outcomes of patients treated with danaparoid (Orgaran) from 1982 to mid-2004. Thromb Haemost: 2006; 95 6 967 981 (Pubitemid 43933754)
15. Warkentin T. E., Greinacher A., Gruel Y., Aster R. H., Chong B. H.; Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Laboratory testing for heparin-induced thrombocytopenia: A conceptual framework and. implications for diagnosis. J Thromb Haemost: 2011; 9 2498 2500
16. Oliveira G. B., Crespo E. M., Becker R. C., et al. Complications After Thrombocytopenia Caused by Heparin (CATCH) Registry Investigators. Incidence and prognostic significance of thrombocytopenia in patients treated with prolonged heparin therapy. Arch Intern Med: 2008; 168 1 94 102
17. Girolami B., Prandoni P., Stefani P. M., et al. The incidence of heparin-induced thrombocytopenia in hospitalized medical patients treated with subcutaneous unfractionated heparin: a prospective cohort study. Blood: 2003; 101 8 2955 2959 (Pubitemid 36857979)
18. Büller H. R., Davidson B. L., Decousus H., et al. Matisse Investigators. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med: 2003; 349 18 1695 1702 (Pubitemid 37315006)
19. Morris T. A., Castrejon S., Devendra G., Gamst A. C. No difference in risk for thrombocytopenia during treatment of pulmonary embolism and deep venous thrombosis with either low-molecular-weight heparin or unfractionated heparin: a metaanalysis. Chest: 2007; 132 4 1131 1139 (Pubitemid 47620984)
20. Prandoni P., Siragusa S., Girolami B., Fabris F.; BELZONI Investigators Group. The incidence of heparin-induced thrombocytopenia in medical patients treated with low-molecular-weight heparin: a prospective cohort study. Blood: 2005; 106 9 3049 3054 (Pubitemid 41565898)
21. Hui P., Cook D. J., Lim W., Fraser G. A., Arnold D. M. The frequency and clinical significance of thrombocytopenia complicating critical illness: a systematic review. Chest: 2011; 139 2 271 278
22. Crowther M. A., Cook D. J., Meade M. O., et al. Thrombocytopenia in medical-surgical critically ill patients: prevalence, incidence, and risk factors. J Crit Care: 2005; 20 4 348 353 (Pubitemid 41727593)
23. Cook D., Meade M., Guyatt G., et al. PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med: 2011; 364 14 1305 1314
24. Crowther M. A., Cook D. J., Albert M., et al. Canadian Critical Care Trials Group. The 4Ts scoring system for heparin-induced thrombocytopenia in medical-surgical intensive care unit patients. J Crit Care: 2010; 25 2 287 293
25. Verma A. K., Levine M., Shalansky S. J., Carter C. J., Kelton J. G. Frequency of heparin-induced thrombocytopenia in critical care patients. Pharmacotherapy: 2003; 23 6 745 753 (Pubitemid 36629079)
26. Cuker A. Heparin-induced thrombocytopenia: present and future. J Thromb Thrombolysis: 2011; 31 3 353 366
27. Warkentin T. E., Heddle N. M. Laboratory diagnosis of immune heparin-induced thrombocytopenia. Curr Hematol Rep: 2003; 2 2 148 157
28. Lo G. K., Juhl D., Warkentin T. E., Sigouin C. S., 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 4 759 765
29. Cuker A., Gimotty P. A., Crowther M. A., Warkentin T. E. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood: 2012; 120 20 4160 4167
30. Cuker A., Arepally G., Crowther M. A., et al. The HIT Expert Probability (HEP) Score: a novel pre-test probability model for heparin-induced thrombocytopenia based on broad expert opinion. J Thromb Haemost: 2010; 8 12 2642 2650
31. Strutt J. K., Mackey J. E., Johnson S. M., Sylvia L. M. Assessment of the 4Ts pretest clinical scoring system as a predictor of heparin-induced thrombocytopenia. Pharmacotherapy: 2011; 31 2 138 145
32. Nagler M., Fabbro T., Wuillemin W. A. Prospective evaluation of the interobserver reliability of the 4Ts score in patients with suspected heparin-induced thrombocytopenia. J Thromb Haemost: 2012; 10 1 151 152
33. Uaprasert N., Chanswangphuwana C., Akkawat B., Rojnuckarin P. Comparison of diagnostic performance of the heparin-induced thrombocytopenia expert probability and the 4Ts score in screening for heparin-induced thrombocytopenia. Blood Coagul Fibrinolysis: 2013; 24 3 261 268
34. Farahani N., Kitahara S., Tcherniantchouk O. Prospective comparison of the HIT expert probability (HEP) score versus the Warkentin 4T's score in a quaternary care center. [abstract] J Thromb Haemost: 2013; 11 (s2): 936
35. Lillo-Le Louët A., Boutouyrie P., Alhenc-Gelas M., et al. Diagnostic score for heparin-induced thrombocytopenia after cardiopulmonary bypass. J Thromb Haemost: 2004; 2 11 1882 1888 (Pubitemid 40192738)
36. Messmore H. L., Fabbrini N., Bird M. L., et al. Simple scoring system for early management of heparin-induced thrombocytopenia. Clin Appl Thromb Hemost: 2011; 17 2 197 201
37. Piednoir P., Allou N., Provenchère S., et al. Heparin-induced thrombocytopenia after cardiac surgery: an observational study of 1,722 patients. J Cardiothorac Vasc Anesth: 2012; 26 4 585 590
38. Bakchoul T., Giptner A., Najaoui A., Bein G., Santoso S., Sachs U. J. Prospective evaluation of PF4/heparin immunoassays for the diagnosis of heparin-induced thrombocytopenia. J Thromb Haemost: 2009; 7 8 1260 1265
39. Lo G. K., Sigouin C. S., Warkentin T. E. What is the potential for overdiagnosis of heparin-induced thrombocytopenia? Am J Hematol: 2007; 82 12 1037 1043 (Pubitemid 350209843)
40. Greinacher A., Juhl D., Strobel U., et al. Heparin-induced thrombocytopenia: a prospective study on the incidence, platelet-activating capacity and clinical significance of antiplatelet factor 4/heparin antibodies of the IgG, IgM, and IgA classes. J Thromb Haemost: 2007; 5 8 1666 1673 (Pubitemid 47091409)
41. Juhl D., Eichler P., Lubenow N., Strobel U., Wessel A., Greinacher A. Incidence and clinical significance of anti-PF4/heparin antibodies of the IgG, IgM, and IgA class in 755 consecutive patient samples referred for diagnostic testing for heparin-induced thrombocytopenia. Eur J Haematol: 2006; 76 5 420 426
42. Zwicker J. I., Uhl L., Huang W. Y., Shaz B. H., Bauer K. A. Thrombosis and ELISA optical density values in hospitalized patients with heparin-induced thrombocytopenia. J Thromb Haemost: 2004; 2 12 2133 2137 (Pubitemid 40185772)
43. Warkentin T. E., Sheppard J. I., Moore J. C., Sigouin C. S., Kelton J. G. Quantitative interpretation of optical density measurements using PF4-dependent enzyme-immunoassays. J Thromb Haemost: 2008; 6 8 1304 1312 (Pubitemid 352016309)
44. Raschke R. A., Curry S. C., Warkentin T. E., Gerkin R. D. Improving clinical interpretation of the anti-platelet factor 4/heparin enzyme-linked immunosorbent assay for the diagnosis of heparin-induced thrombocytopenia through the use of receiver operating characteristic analysis, stratum-specific likelihood ratios, and bayes theorem. Chest: 2013; 144 4 1269 1275
45. Cuker A., Ortel T. L. ASH evidence-based guidelines: is the IgG-specific anti-PF4/heparin ELISA superior to the polyspecific ELISA in the laboratory diagnosis of HIT? Hematology (Am Soc Hematol Educ Program): 2009; ••• 250 252
46. Whitlatch N. L., Kong D. F., Metjian A. D., Arepally G. M., Ortel T. L. Validation of the high-dose heparin confirmatory step for the diagnosis of heparin-induced thrombocytopenia. Blood: 2010; 116 10 1761 1766
47. Warkentin T. E., Sheppard J. I. No significant improvement in diagnostic specificity of an anti-PF4/polyanion immunoassay with use of high heparin confirmatory procedure. J Thromb Haemost: 2006; 4 1 281 282
48. Selleng S., Schreier N., Wollert H. G., Greinacher A. The diagnostic value of the anti-PF4/heparin immunoassay high-dose heparin confirmatory test in cardiac surgery patients. Anesth Analg: 2011; 112 4 774 776
49. Sachais B. S., Litvinov R. I., Yarovoi S. V., et al. Dynamic antibody-binding properties in the pathogenesis of HIT. Blood: 2012; 120 5 1137 1142
50. Cuker A., Rux A. H., Hinds J. L., et al. Novel diagnostic assays for heparin-induced thrombocytopenia. Blood: 2013; 121 18 3727 3732
51. Sachs U. J., von Hesberg J., Santoso S., Bein G., Bakchoul T. Evaluation of a new nanoparticle-based lateral-flow immunoassay for the exclusion of heparin-induced thrombocytopenia (HIT). Thromb Haemost: 2011; 106 6 1197 1202
52. Meyer O., Salama A., Pittet N., Schwind P. Rapid detection of heparin-induced platelet antibodies with particle gel immunoassay (ID-HPF4). Lancet: 1999; 354 9189 1525 1526 (Pubitemid 29502110)
53. Bakchoul T., Giptner A., Najaoui A., Bein G., Santoso S., Sachs U. JH. Prospective evaluation of PF4/heparin immunoassays for the diagnosis of heparin-induced thrombocytopenia. J Thromb Haemost: 2009; 7 8 1260 1265
54. Davidson S. J., Ortel T. L., Smith L. J. Performance of a new, rapid, automated immunoassay for the detection of anti-platelet factor 4/heparin complex antibodies. Blood Coagul Fibrinolysis: 2011; 22 4 340 344
55. Althaus K., Hron G., Strobel U., et al. Evaluation of automated immunoassays in the diagnosis of heparin induced thrombocytopenia. Thromb Res: 2013; 131 3 e85 e90
56. Legnani C., Cini M., Pili C., Boggian O., Frascaro M., Palareti G. Evaluation of a new automated panel of assays for the detection of anti-PF4/heparin antibodies in patients suspected of having heparin-induced thrombocytopenia. Thromb Haemost: 2010; 104 2 402 409
57. Van Hoecke F., Devreese K. Evaluation of two new automated chemiluminescent assays (HemosIL® AcuStar HIT-IgG and HemosIL® AcuStar HIT-Ab) for the detection of heparin-induced antibodies in the diagnosis of heparin-induced thrombocytopenia. Int J Lab Hematol: 2012; 34 4 410 416
58. Warkentin T. E., Greinacher A. Laboratory testing for heparin-induced thrombocytopenia. In: Warkentin T. E., Greinacher A., eds. Heparin-Induced Thrombocytopenia. Boca Raton Informa: 2013; 272 314
59. Warkentin T. E., Sheppard J. I., Raschke R. A., Greinacher A. Performance characteristics of a rapid assay for anti-PF4/heparin antibodies: the particle immunofiltration assay. J Thromb Haemost: 2007; 5 11 2308 2310 (Pubitemid 47617888)
60. Sheridan D., Carter C., Kelton J. G. A diagnostic test for heparin-induced thrombocytopenia. Blood: 1986; 67 1 27 30 (Pubitemid 16167006)
61. Greinacher A., Michels I., Kiefel V., Mueller-Eckhardt C. A rapid and sensitive test for diagnosing heparin-associated thrombocytopenia. Thromb Haemost: 1991; 66 6 734 736
62. Stewart M. W., Etches W. S., Boshkov L. K., Gordon P. A. Heparin-induced thrombocytopenia: an improved method of detection based on lumi-aggregometry. Br J Haematol: 1995; 91 1 173 177
63. Lee D. H., Warkentin T. E., Denomme G. A., Hayward C. PM, Kelton J. G. A diagnostic test for heparin-induced thrombocytopenia: detection of platelet microparticles using flow cytometry. Br J Haematol: 1996; 95 4 724 731 (Pubitemid 26423379)
64. Nazi I., Arnold D. M., Smith J. W., et al. FcγRIIa proteolysis as a diagnostic biomarker for heparin-induced thrombocytopenia. J Thromb Haemost: 2013; 11 6 1146 1153
65. Chong B. H., Burgess J., Ismail F. The clinical usefulness of the platelet aggregation test for the diagnosis of heparin-induced thrombocytopenia. Thromb Haemost: 1993; 69 4 344 350 (Pubitemid 23103121)
66. Cines D. B., Kaywin P., Bina M., Tomaski A., Schreiber A. D. Heparin-associated thrombocytopenia. N Engl J Med: 1980; 303 14 788 795 (Pubitemid 10002378)
67. Tomer A. A sensitive and specific functional flow cytometric assay for the diagnosis of heparin-induced thrombocytopenia. Br J Haematol: 1997; 98 3 648 656 (Pubitemid 27386546)
68. Gobbi G., Mirandola P., Tazzari P. L., et al. Flow cytometry detection of serotonin content and release in resting and activated platelets. Br J Haematol: 2003; 121 6 892 896 (Pubitemid 36760308)
69. Vitale M., Tazzari P., Ricci F., et al. Comparison between different laboratory tests for the detection and prevention of heparin-induced thrombocytopenia. Cytometry: 2001; 46 5 290 295 (Pubitemid 33055230)
70. Mullier F., Bailly N., Cornet Y., et al. Contribution of platelet microparticles generation assay to the diagnosis of type II heparin-induced thrombocytopenia. Thromb Haemost: 2010; 103 6 1277 1281
71. Favaloro E. J., Bernal-Hoyos E., Exner T., Koutts J. Heparin-induced thrombocytopenia: laboratory investigation and confirmation of diagnosis. Pathology: 1992; 24 3 177 183
72. Greinacher A., Amiral J., Dummel V., Vissac A., Kiefel V., Mueller-Eckhardt C. Laboratory diagnosis of heparin-associated thrombocytopenia and comparison of platelet aggregation test, heparin-induced platelet activation test, and platelet factor 4/heparin enzyme-linked immunosorbent assay. Transfusion: 1994; 34 5 381 385 (Pubitemid 24172372)
73. Morel-Kopp M. C., Tan C. W., Brighton T. A., et al. ASTH Clinical Trials Group. Validation of whole blood impedance aggregometry as a new diagnostic tool for HIT: results of a large Australian study. Thromb Haemost: 2012; 107 3 575 583
74. Prechel M., Walenga J. M. Heparin-induced thrombocytopenia: an update. Semin Thromb Hemost: 2012; 38 5 483 496
75. Price E. A., Hayward C. P., Moffat K. A., Moore J. C., Warkentin T. E., Zehnder J. L. Laboratory testing for heparin-induced thrombocytopenia is inconsistent in North America: a survey of North American specialized coagulation laboratories. Thromb Haemost: 2007; 98 6 1357 1361 (Pubitemid 350239110)
76. Sachais B. S., Rux A. H., Cines D. B., et al. Rational design and characterization of platelet factor 4 antagonists for the study of heparin-induced thrombocytopenia. Blood: 2012; 119 25 5955 5962
77. Tan C. W., Ward C. M., Morel-Kopp M. C. Evaluating heparin-induced thrombocytopenia: the old and the new. Semin Thromb Hemost: 2012; 38 2 135 143