Investigation of patients with unclassified bleeding disorder and abnormal thrombin generation for physiological coagulation inhibitors reveals multiple abnormalities and a subset of patients with increased tissue factor pathway inhibitor activity.
Journal
International journal of laboratory hematology
ISSN: 1751-553X
Titre abrégé: Int J Lab Hematol
Pays: England
ID NLM: 101300213
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
31
10
2019
revised:
29
11
2019
accepted:
29
12
2019
pubmed:
1
2
2020
medline:
1
1
2021
entrez:
1
2
2020
Statut:
ppublish
Résumé
We have routinely used thrombin generation to investigate patients with unclassified bleeding disorder (UBD). To investigate haemostatic abnormalities in patients with UBD that had abnormal thrombin generation on at least one occasion. Investigation of 13 known UBD patients with thrombin generation and detailed haemostatic testing was undertaken including TFPI assays but also thrombomodulin and fibrinogen-γ. 12 females and 1 male were included. No patient had a platelet function disorder or coagulation factor deficiency that explained the bleeding phenotype, though 2 patients had factor deficiencies; a factor X of 0.41 IU/mL and a factor XI of 0.51 IU/mL. ThromboGenomics revealed variants for these factors but no other abnormalities. Patients were included who previously had either prolonged lag time or decreased endogenous thrombin potential (ETP) via high dose tissue factor (5 pmol/L) or low dose tissue factor (1.5 pmol/L) with corn trypsin inhibitor (CTI). Tissue factor pathway inhibitor (TFPI) activity was significantly increased (P < .001; increased in 8 patients) compared with controls and abnormalities in soluble thrombomodulin (2 patients), fibrinogen-γ (1 patient) and tPA (4 patients for each) were seen. Total and free TFPI levels were not increased. Mixing studies of patient plasma with 50:50 normal plasma for thrombin generation via low dose tissue factor failed to correct the ETP consistent with ongoing inhibition. Addition of an anti-TFPI antibody partially corrected thrombin generation to normal levels. TFPI sequencing was unremarkable. TFPI activity may be increased in a subset of UBD patients. Further research studies are warranted in UBD patients for coagulation inhibitor abnormalities.
Substances chimiques
Blood Coagulation Factor Inhibitors
0
Lipoproteins
0
lipoprotein-associated coagulation inhibitor
0
Thrombin
EC 3.4.21.5
Types de publication
Clinical Trial
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
246-255Subventions
Organisme : British Society for Haematology
ID : Early-Stage Research Start-up Grant
Informations de copyright
© 2020 John Wiley & Sons Ltd.
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