Tissue Factor Pathway Inhibitor Levels During Veno-Arterial Extracorporeal Membrane Oxygenation in Adults

Abstract

Tissue factor pathway inhibitor (TFPI) has multiple anticoagulant properties. To our knowledge, no studies have measured TFPI levels in adult veno-arterial (VA) extracorporeal membrane oxygenation patients. We hypothesized that adult VA ECMO patients would have increased TFPI levels and slowed tissue factor triggered thrombin generation. Twenty VA ECMO patients had TFPI levels and thrombin generation lag time measured on ECMO day 1 or 2, day 3, and day 5. TFPI levels and thrombin generation lag time were compared against healthy control plasma samples. Mean TFPI levels were significantly higher in ECMO patients on ECMO day 1 or 2 = 81,877 ± 19,481 pg/mL, day 3 = 73,907 ± 26,690 pg/mL, and day 5 = 77,812 ± 23,484 pg/mL compared with control plasma = 38,958 ± 9,225 pg/mL (P < 0.001 for all comparisons). Median thrombin generation lag time was significantly longer in ECMO patients on ECMO day 1 or 2 = 10.0 minutes [7.5, 13.8], day 3 = 9.0 minutes [6.8, 12.1], and day 5 = 10.7 minutes [8.3, 15.2] compared with control plasma = 3.6 minutes [2.9, 4.2] (P < 0.001 for all comparisons). TFPI is increased in VA ECMO patients and tissue factor triggered thrombin generation is slowed. Increased TFPI levels could contribute to the multifactorial coagulopathy that occurs during ECMO.

In Vitro Comparison of Recombinant and Plasma-Derived von Willebrand Factor Concentrate for Treatment of Acquired von Willebrand Syndrome in Adult Extracorporeal Membrane Oxygenation Patients

“…In baseline untreated samples, median RIPA was 1 ohm (0-7) in VA ECMO patients and 2 ohms (1-16) in VV ECMO patients (P = .16). In samples treated with low-dose recombinant vWF, median RIPA was 5 ohms (1-9) in VA ECMO patients and 6 ohms (5)(6)(7)(8)(9)(10)(11)(12)(13)(14) in VV ECMO patients (P = .18), and in samples treated with high-dose recombinant vWF, median RIPA was 7 ohms (4-11) in VA ECMO patients and 10…”

“…All patients, except 1, had peripheral cannulation. The median day of blood sampling was ECMO day 7 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), median pump speed was 3258 (2901-3556) revolutions per minute, and median ECMO circuit blood flow was 4.1 liters per minute (3.5-5). Mean platelet count was 134 ± 83 10 9 /L.…”

“…[1][2][3][4] The pathophysiology of ECMO-induced coagulopathy is complex with multiple factors contributing, including loss of large von Willebrand Factor (vWF) multimers, thrombocytopenia, increased tissue factor pathway inhibitor levels, and platelet surface glycoprotein (GP)1bα shedding. [5][6][7][8] Adult ECMO patients almost universally develop acquired von Willebrand syndrome due to loss of large vWF multimers. 5,9,10 In a study by Kalbhenn et al, 5 acquired von Willebrand syndrome occurred within the first 6 hours of ECMO initiation in all patients (N = 59) and returned to normal within 24 hours of ECMO decannulation.…”

Suppression of Fibrinolysis and Hypercoagulability, Severity of Hypoxemia, and Mortality in COVID-19 Patients: A Retrospective Cohort Study

“…44 The tissue factor pathway inhibitor levels observed in our cohort’s ECMO patients are also higher than the tissue factor pathway inhibitor levels reported in the non–COVID-19 ECMO cohort by Mazzeffi et al . 48 (Supplemental Digital Content 2 table S2, http://links.lww.com/ALN/C850). This difference is likely due to widespread endotheliopathy associated with severe COVID-19 and tissue factor pathway inhibitor’s primary location on the endothelial surface and indicates the compounding coagulopathic insults of ECMO and SARS-CoV-2 infection.…”

Coagulation and Transfusion Updates From 2021

“…70 In a study of 20 patients on VA ECMO, the authors found that TFPI levels were increased approximately 2-fold compared to control plasma. 71 Increased TFPI levels correlated with increased TF-triggered lag time on a calibrated automated thrombin generation assay. 71 These findings suggested that patients on ECMO who receive systemic heparinization may have slowed TF-triggered thrombin generation; in part, because of elevated TFPI levels.…”