Dino Mehic, MD from the Medical University of Vienna speaks about Elevated levels of tissue factor pathway inhibitor in patients with mild to moderate bleeding tendency.
Link to Abstract:
Points to Remember -
* TFPI levels are higher in patients with minor bleeding disorders, especially those that have BUC or PFDs.
* There were no genetic changes in the F5 gene that were related to increased TFPI levels.
High levels of tissue factor pathway inhibitor (TFPI) were recently discovered in two families with an unknown bleeding propensity, due to a longer TFPI half-life after binding to a factor V splice variant and variations in the F5 gene. The aim of this research was to look at the relationship between free TFPI and genetic alterations in the F5 gene in a well-characterized population of 620 patients with mild to moderate bleeding tendencies. Patients with leakage have higher TFPI values than stable controls (median [interquartile range], 8.2 [5.5-11.7] vs 7.8 [4.3-11.1]; P =.026). In comparison to stable samples, a higher percentage of patients had free TFPI ratios greater than or equal to the 95th percentile (odds ratio [OR] [95 percent confidence interval (CI)], 2.82 [0.98-8.13]). This was particularly noticeable in patients with no documented bleeding condition (bleeding of uncertain origin [BUC; n = 420]; OR [95 percent CI], 3.03 [1.02-8.98]) and platelet function defects (PFDs) (n = 121; OR [95 percent CI], 3.47 [1.09-11.08]). A rise in free TFPI was linked to a slight thrombin generation delay (longer lag time and time to peak), but not to changes in commonly used global clotting tests. In our patient cohort, we were unable to find any new or established genetic variants in the F5 gene that are linked to free TFPI levels, nor any effect of the single-nucleotide variant rs10800453 on free TFPI levels. Unexpected bleeding, which is more often multifactorial in the majority of patients, maybe caused or contributed by an excess of natural coagulation inhibitors such as TFPI.