Variable serotonin release assay pattern and specificity of PF4-specific antibodies in HIT, and clinical relevance.
antibody
platelet factor 4
platelets
serotonin release assay
thrombocytopenia
thrombosis
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:
11 2022
11 2022
Historique:
revised:
11
08
2022
received:
09
03
2022
accepted:
12
08
2022
pubmed:
17
8
2022
medline:
26
10
2022
entrez:
16
8
2022
Statut:
ppublish
Résumé
The diagnosis of heparin-induced thrombocytopenia (HIT) requires functional assays to demonstrate that platelet factor 4 (PF4)-specific antibodies activate platelets, typically when therapeutic heparin (H) concentrations are tested ("classical" pattern). Some HIT samples also activate platelets without heparin ("atypical" pattern), but with unclear clinical significance. We aimed to assess whether platelet activation pattern and some characteristics of PF4-specific antibodies were associated with the severity of HIT. Serotonin release assay (SRA) pattern of 81 HIT patients were analyzed and compared with their clinical and biological data, including levels of anti-PF4/H immunoglobulin G (IgG) and anti-PF4 IgG in 47 of them. Higher anti-PF4/H IgG titers were measured in patients with an "atypical" SRA (optical density 2.52 vs. 1.94 in those with a "classical" pattern, p < .001). Patients of both groups had similar platelet count (PC) nadir and time to recovery, but those with an "atypical" SRA more frequently developed thrombotic events (69% vs. 34%, p = .037). Significant levels of anti-PF4 IgG were detected in both groups (38% and 61%, respectively). Whatever the SRA pattern, a lower PC nadir (35 vs. 53 G/L, p = .006) and a longer PC recovery time (6 vs. 3 days, p = .015) were evidenced in patients with anti-PF4 antibodies, compared with those with anti-PF4/H IgG only. An atypical SRA pattern with elevated anti-PF4/H IgG titers seems associated with an increased risk of thrombosis in HIT. IgG antibodies to native PF4 may contribute to more severe and persistent thrombocytopenia, and their detection could be useful in clinical practice.
Sections du résumé
BACKGROUND
The diagnosis of heparin-induced thrombocytopenia (HIT) requires functional assays to demonstrate that platelet factor 4 (PF4)-specific antibodies activate platelets, typically when therapeutic heparin (H) concentrations are tested ("classical" pattern). Some HIT samples also activate platelets without heparin ("atypical" pattern), but with unclear clinical significance.
OBJECTIVES
We aimed to assess whether platelet activation pattern and some characteristics of PF4-specific antibodies were associated with the severity of HIT.
PATIENTS/METHODS
Serotonin release assay (SRA) pattern of 81 HIT patients were analyzed and compared with their clinical and biological data, including levels of anti-PF4/H immunoglobulin G (IgG) and anti-PF4 IgG in 47 of them.
RESULTS
Higher anti-PF4/H IgG titers were measured in patients with an "atypical" SRA (optical density 2.52 vs. 1.94 in those with a "classical" pattern, p < .001). Patients of both groups had similar platelet count (PC) nadir and time to recovery, but those with an "atypical" SRA more frequently developed thrombotic events (69% vs. 34%, p = .037). Significant levels of anti-PF4 IgG were detected in both groups (38% and 61%, respectively). Whatever the SRA pattern, a lower PC nadir (35 vs. 53 G/L, p = .006) and a longer PC recovery time (6 vs. 3 days, p = .015) were evidenced in patients with anti-PF4 antibodies, compared with those with anti-PF4/H IgG only.
CONCLUSIONS
An atypical SRA pattern with elevated anti-PF4/H IgG titers seems associated with an increased risk of thrombosis in HIT. IgG antibodies to native PF4 may contribute to more severe and persistent thrombocytopenia, and their detection could be useful in clinical practice.
Identifiants
pubmed: 35971886
doi: 10.1111/jth.15848
pmc: PMC9826218
pii: S1538-7836(22)18477-1
doi:
Substances chimiques
Anticoagulants
0
Heparin
9005-49-6
Immunoglobulin G
0
Immunologic Factors
0
Platelet Factor 4
37270-94-3
Serotonin
333DO1RDJY
PF4 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2646-2655Informations de copyright
© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.
Références
Semin Thromb Hemost. 2011 Sep;37(6):653-63
pubmed: 22102268
J Thromb Haemost. 2005 Oct;3(10):2168-75
pubmed: 16150048
Br J Haematol. 1997 Nov;99(2):273-80
pubmed: 9375738
Thromb Haemost. 2013 Jun;109(6):1141-7
pubmed: 23636177
J Thromb Haemost. 2017 Nov;15(11):2099-2114
pubmed: 28846826
J Thromb Haemost. 2017 Oct;15(10):2065-2075
pubmed: 28771917
Br J Haematol. 2005 Mar;128(6):837-41
pubmed: 15755289
Chest. 2012 Feb;141(2 Suppl):e495S-e530S
pubmed: 22315270
J Thromb Haemost. 2008 Jan;6(1):197-200
pubmed: 17956599
Blood. 2017 Oct 5;130(14):1679-1682
pubmed: 28830891
Blood. 1986 Jan;67(1):27-30
pubmed: 3940551
Am J Med. 2012 Jan;125(1):44-9
pubmed: 22075045
Thromb Haemost. 2019 Jul;119(7):1138-1146
pubmed: 31129914
J Thromb Haemost. 2004 Dec;2(12):2133-7
pubmed: 15613017
Br J Haematol. 2017 Dec;179(5):811-819
pubmed: 29048130
Blood. 2015 Jan 1;125(1):155-61
pubmed: 25342714
Arterioscler Thromb Vasc Biol. 2021 Jan;41(1):141-152
pubmed: 33267665
Thromb Haemost. 2021 Mar;121(3):322-331
pubmed: 33086397
Thromb Haemost. 2020 Jul;120(7):1096-1107
pubmed: 32572863
Blood. 2006 Mar 15;107(6):2346-53
pubmed: 16304054
Circulation. 1999 May 18;99(19):2530-6
pubmed: 10330384
J Thromb Haemost. 2008 Aug;6(8):1304-12
pubmed: 18489711
J Thromb Haemost. 2022 Nov;20(11):2646-2655
pubmed: 35971886
Br J Haematol. 2000 May;109(2):336-41
pubmed: 10848821
Nat Commun. 2017 May 22;8:14945
pubmed: 28530237
Ann Intern Med. 2001 Oct 2;135(7):502-6
pubmed: 11578153
Thromb Res. 2008;122(2):211-20
pubmed: 18262226