Elevated levels of tissue factor pathway inhibitor in patients with mild to moderate bleeding tendency
Autor: | Dino Mehic, Matthias Haimel, Stefanie Hofer, Helmuth Haslacher, Alexander Tolios, Cihan Ay, Johanna Gebhart, Judit Rejtö, Willem H. Ouwehand, Kate Downes, Ingrid Pabinger |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Lipoproteins 030204 cardiovascular system & hematology Hemorrhagic Disorders Gastroenterology Thrombosis and Hemostasis 03 medical and health sciences 0302 clinical medicine Tissue factor pathway inhibitor Interquartile range Internal medicine medicine Humans Platelet biology business.industry Factor V Hematology Odds ratio Blood Coagulation Disorders Confidence interval 030104 developmental biology Coagulation Cohort biology.protein business |
Zdroj: | Blood Adv |
ISSN: | 2473-9537 2473-9529 |
Popis: | High levels of tissue factor pathway inhibitor (TFPI), caused by a longer TFPIα half-life after binding to a factor V splice variant and variants in the F5 gene, were recently identified in 2 families with an as-yet-unexplained bleeding tendency. This study aimed to investigate free TFPIα in a well-characterized cohort of 620 patients with mild to moderate bleeding tendencies and its association to genetic alterations in the F5 gene. TFPIα levels were higher in patients with bleeding compared with healthy controls (median [interquartile range], 8.2 [5.5-11.7] vs 7.8 [4.3-11.1]; P = .026). A higher proportion of patients had free TFPIα levels more than or equal to the 95th percentile compared with healthy controls (odds ratio [OR] [95% confidence interval (CI)], 2.82 [0.98-8.13]). This was pronounced in the subgroup of patients in whom no bleeding disorder could be identified (bleeding of unknown cause [BUC; n = 420]; OR [95% CI], 3.03 [1.02-8.98]) and in platelet function defects (PFDs) (n = 121; OR [95% CI], 3.47 [1.09-11.08]). An increase in free TFPIα was associated with a mild delay in thrombin generation (prolonged lag time and time to peak), but not with alterations in routinely used global clotting tests. We could neither identify new or known genetic variations in the F5 gene that are associated with free TFPIα levels, nor an influence of the single-nucleotide variant rs10800453 on free TFPIα levels in our patient cohort. An imbalance of natural coagulation inhibitors such as TFPIα could be an underlying cause or contributor for unexplained bleeding, which is most probably multifactorial in a majority of patients. |
Databáze: | OpenAIRE |
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