Heparin-induced thrombocytopenia: Construction of a pretest diagnostic score derived from the analysis of a prospective multinational database, with internal validation.
heparin
heparin-induced thrombocytopenia
observational study
pre-test score
thrombocytopenia
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
09
04
2021
received:
01
10
2020
accepted:
09
04
2021
pubmed:
20
4
2021
medline:
10
8
2021
entrez:
19
4
2021
Statut:
ppublish
Résumé
Diagnosis of heparin-induced thrombocytopenia (HIT) requires pretest probability assessment and dedicated laboratory assays. To develop a pretest score for HIT. Observational; analysis of prospectively collected data of hospitalized patients suspected with HIT (ClinicalTrials.gov NCT00748839). Thirty-one tertiary hospitals in France, Switzerland, and Belgium. Patients tested for HIT antibodies (2280 evaluable), randomly allocated to derivation and validation cohorts. Independent adjudicators diagnosed HIT based on the prospectively collected data and serotonin release assay results. Heparin-induced thrombocytopenia was diagnosed in 234 (14.7%) and 99 (14.5%) patients in the two cohorts. Eight features were associated with HIT (in brackets, points assigned for score calculation of the score): unfractionated heparin (1); therapeutic-dose heparin (1); cardiopulmonary bypass (cardiac surgery) (2); major trauma (3); 5- to 21-day interval from anticoagulation initiation to suspicion of HIT (4); ≥40% decrease in platelet count over ≤6 days (3); thrombotic event, arterial (3) or venous (3). The C-statistic was 0.79 (95% CI, 0.76-0.82). In the validation cohort, the area under the receiver operating characteristic curve was 0.77 (95% CI, 0.74-0.80). Three groups of scores were defined; HIT prevalence reached almost 30% in the high-probability group. The performance of the score may depend on settings and practices. The objective, easy-to-collect, clinical features of HIT we evidenced were incorporated into a pretest score, which may guide clinical decisions regarding diagnostic testing and anticoagulation.
Sections du résumé
BACKGROUND
Diagnosis of heparin-induced thrombocytopenia (HIT) requires pretest probability assessment and dedicated laboratory assays.
OBJECTIVE
To develop a pretest score for HIT.
DESIGN
Observational; analysis of prospectively collected data of hospitalized patients suspected with HIT (ClinicalTrials.gov NCT00748839).
SETTING
Thirty-one tertiary hospitals in France, Switzerland, and Belgium.
PATIENTS
Patients tested for HIT antibodies (2280 evaluable), randomly allocated to derivation and validation cohorts.
MEASUREMENTS
Independent adjudicators diagnosed HIT based on the prospectively collected data and serotonin release assay results.
RESULTS
Heparin-induced thrombocytopenia was diagnosed in 234 (14.7%) and 99 (14.5%) patients in the two cohorts. Eight features were associated with HIT (in brackets, points assigned for score calculation of the score): unfractionated heparin (1); therapeutic-dose heparin (1); cardiopulmonary bypass (cardiac surgery) (2); major trauma (3); 5- to 21-day interval from anticoagulation initiation to suspicion of HIT (4); ≥40% decrease in platelet count over ≤6 days (3); thrombotic event, arterial (3) or venous (3). The C-statistic was 0.79 (95% CI, 0.76-0.82). In the validation cohort, the area under the receiver operating characteristic curve was 0.77 (95% CI, 0.74-0.80). Three groups of scores were defined; HIT prevalence reached almost 30% in the high-probability group.
LIMITATION
The performance of the score may depend on settings and practices.
CONCLUSION
The objective, easy-to-collect, clinical features of HIT we evidenced were incorporated into a pretest score, which may guide clinical decisions regarding diagnostic testing and anticoagulation.
Identifiants
pubmed: 33872452
doi: 10.1111/jth.15344
pii: S1538-7836(22)01842-6
doi:
Substances chimiques
Anticoagulants
0
Heparin
9005-49-6
Banques de données
ClinicalTrials.gov
['NCT00748839']
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1959-1972Informations de copyright
© 2021 International Society on Thrombosis and Haemostasis.
Références
Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med. 1996;101:502-507.
Wallis DE, Workman DL, Lewis BE, Steen L, Pifarre R, Moran JF. Failure of early heparin cessation as treatment for heparin-induced thrombocytopenia. Am J Med. 1999;106:629-635.
McKenzie SE, Sachais BS. Advances in the pathophysiology and treatment of heparin-induced thrombocytopenia. Curr Opin Hematol. 2014;21:380-387.
Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018;2:3360-3392.
Price EA, Hayward CP, Moffat KA, Moore JC, Warkentin TE, Zehnder JL. Laboratory testing for heparin-induced thrombocytopenia is inconsistent in North America: a survey of North American specialized coagulation laboratories. Thromb Haemost. 2007;98:1357-1361.
Nagler M, Bachmann LM, ten Cate H, ten Cate-Hoek A. Diagnostic value of immunoassays for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood. 2016;127:546-557.
Warkentin TE, Arnold DM, Nazi I, Kelton JG. The platelet serotonin-release assay. Am J Hematol. 2015;90:564-572.
Tardy B, Presles E, Akrour M, de Maistre E, Lecompte T, Tardy-Poncet B. Experts’ opinion or the serotonin release assay as a gold standard for the diagnosis of heparin-induced thrombocytopenia (HIT)? J Thromb Haemost. 2011;9:1667-1669.
Pandya KA, Johnson EG, Davis GA, Padmanabhan A. Serotonin release assay (SRA)-negative HIT, a newly recognized entity: Implications for diagnosis and management. Thromb Res. 2018;172:169-171.
Warkentin TE. Clinical picture of heparin-induced thrombocytopenia. In: Warkentin TE, Greinacher A, eds. Heparin-induced thrombocytopenia, 3rd ed. New York, NY: Marcel Dekker Inc; 2004;53-106.
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;4:759-765.
Lillo-Le Louët A, Boutouyrie P, Alhenc-Gelas M, et al. Diagnostic score for heparin-induced thrombocytopenia after cardiopulmonary bypass. J Thromb Haemost. 2004;2:1882-1888.
Cuker A, Arepally G, Crowther MA, 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;8:2642-2650.
Pouplard C, Guéret P, Fouassier M, et al. Prospective evaluation of the ‘4Ts’ score and particle gel immunoassay specific to heparin/PF4 for the diagnosis of heparin-induced thrombocytopenia. J Thromb Haemost. 2007;5:1373-1379.
Bryant A, Low J, Austin S, Joseph JE. Timely diagnosis and management of heparin-induced thrombocytopenia in a frequent request, low incidence single centre using clinical 4T's score and particle gel immunoassay. Br J Haematol. 2008;143:721-726.
Tawfik NM, Hegazy MA, Hassan EA, Ramadan YK, Nasr AS. Egyptian experience of reliability of 4T's score in diagnosis of heparin induced thrombocytopenia syndrome. Blood Coagul Fibrinolysis. 2011;22:701-705.
Joseph L, Gomes MP, Al Solaiman F, et al. External validation of the HIT expert probability (HEP) score. Thromb Haemost. 2015;113:633-640.
Pishko AM, Fardin S, Lefler DS, et al. Prospective comparison of the HEP score and 4Ts score for the diagnosis of heparin-induced thrombocytopenia. Blood Adv. 2018;2:3155-3162.
Bakchoul T, Giptner A, Najaoui A, Bein G, Santoso S, Sachs UJ. Prospective evaluation of PF4/heparin immunoassays for the diagnosis of heparin-induced thrombocytopenia. J Thromb Haemost. 2009;7:1260-1265.
Nellen V, Sulzer I, Barizzi G, Lämmle B, Alberio L. Rapid exclusion or confirmation of heparin-induced thrombocytopenia: a single-center experience with 1,291 patients. Haematologica. 2012;97:89-97.
Linkins LA, Bates SM, Lee AY, Heddle NM, Wang G, Warkentin TE. Combination of 4Ts score and PF4/H-PaGIA for diagnosis and management of heparin-induced thrombocytopenia: prospective cohort study. Blood. 2015;126:597-603.
Din F, Kovacs MJ, Butler R, Lazo-Langner A. Inter-observer variability in the assessment of the 4TS score for the diagnosis of heparin-induced thrombocytopenia in patients undergoing cardiac surgery. Blood. 2009;114:Abstract 4467.
Nagler M, Fabbro T, Wuillemin WA. Prospective evaluation of the interobserver reliability of the 4Ts score in patients with suspected heparin-induced thrombocytopenia. J Thromb Haemost. 2012;10:151-152.
Strutt JK, Mackey JE, Johnson SM, Sylvia LM. Assessment of the 4Ts pretest clinical scoring system as a predictor of heparin-induced thrombocytopenia. Pharmacotherapy. 2011;31:138-145.
Harbrecht U, Bastians B, Kredteck A, Hanfland P, Klockgether T, Pohl C. Heparin-induced thrombocytopenia in neurologic disease treated with unfractionated heparin. Neurology. 2004;62:657-659.
Smythe MA, Koerber JM, Mattson JC. The incidence of recognized heparin-induced thrombocytopenia in a large, tertiary care teaching hospital. Chest. 2007;131:1644-1649.
Martel L, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin: a meta-analysis. Blood. 2005;106:2710-2715.
Bidet A, Tardy-Poncet B, Desprez D, et al. GEHT-HIT study group. Clinical characteristics and laboratory testing of patients with suspected HIT: a survey on current practice in 11 university hospitals in France. Thromb Res. 2010;125:294-299.
Sheridan D, Carter C, Kelton JG. A diagnostic test for heparin-induced thrombocytopenia. Blood. 1986;67:27-30.
Hendrickson JMT, Geersing GJ, Moons GM, de Groot AH. Diagnostic and prognostic prediction models. J Thromb Haemost. 2013;11:129-141.
Gruel Y, Vayne C, Rollin J, et al. Comparative analysis of a French prospective series of 144 patients with heparin-induced thrombocytopenia (FRIGTIH) and the literature. Thromb Haemost. 2020;120:1096-1107.
Arepally GM. Heparin-induced thrombocytopenia. Blood. 2017;129:2864-2872.
Dhakal B, Kreuziger LB, Rein L, et al. Disease burden, complication rates, and health-care costs of heparin-induced thrombocytopenia in the USA: a population-based study. Lancet Haematol. 2018;5:e220-e231.
Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med. 1995;332:1330-1335.
Lubenow N, Hinz P, Thomaschewski S, et al. The severity of trauma determines the immune response to PF4/heparin and the frequency of heparin-induced thrombocytopenia. Blood. 2010;115:1797-1803.
Gruel Y, Pouplard C, Nguyen P, et al. Biological and clinical features of low-molecular-weight heparin-induced thrombocytopenia. Br J Haematol. 2003;121:786-792.
Warkentin TE. Think of HIT. Hematology Am Soc Hematol Educ Program. 2006;2006(1):408-414.
Pouplard C, May MA, Regina S, Marchand M, Fusciardi J, Gruel Y. Changes in platelet count after cardiac surgery can effectively predict the development of pathogenic heparin-dependent antibodies. Br J Haematol. 2005;128:837-841.
Warkentin TE. HIT as a preventable disease. Blood. 2005;106:2600.
Lefler DS, Cuker A, Linkins LA, Warkentin TE, Pishko AM. Maximum 24-hour platelet count fall: Metric for improving the diagnosis of heparin-induced thrombocytopenia among patients with intermediate probability 4Ts scores. J Thromb Haemost. 2020;18:2018-2024.
Rice L. There is no such thing as a "positive" antibody test: diagnosing heparin-induced thrombocytopenia in 2015. Chest. 2015;148:1-3.
Cuker A, Gimotty PA, Crowther MA, Warkentin TE. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood. 2012;120:4160-4167.
Selleng S, Malowsky B, Strobel U, et al. Early-onset and persisting thrombocytopenia in post-cardiac surgery patients is rarely due to heparin-induced thrombocytopenia, even when antibody tests are positive. J Thromb Haemost. 2010;8:30-36.
Raschke RA, Gallo T, Curry SC, et al. Clinical effectiveness of a Bayesian algorithm for the diagnosis and management of heparin-induced thrombocytopenia. J Thromb Haemost. 2017;15:1640-1645.
Tardy B, Lecompte T, Mullier F, Vayne C, Pouplard C. Detection of platelet-activating antibodies associated with heparin-induced thrombocytopenia. J Clin Med. 2020;9:1226.
Motohashi S, Matsuo T, Inoue H, Kaneko M, Shindo S. Clinical significance of the serotonin release assay and platelet count monitoring after cardiac surgery. Clin Appl Thromb Hemost. 2018;24:944-949.
Moore JC, Arnold DM, Warkentin TE, Warkentin AE, Kelton JG. An algorithm for resolving ‘indeterminate’ test results in the platelet serotonin release assay for investigation of heparin-induced thrombocytopenia. J Thromb Haemost. 2008;6:1595-1597.
East JM, Cserti-Gazdewich CM, Granton JT. Heparin-induced thrombocytopenia in the critically ill patient. Chest. 2018;154:678-690.