What question did this study set out to answer?

October 1, 1996Arteriosclerosis Thrombosis and Vascular Biology

Sustained Inhibition of Whole-Blood Clot Procoagulant Activity by Inhibition of Thrombus-Associated Factor Xa

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Why the study?

Does inhibition of factor Xa compared to thrombin inhibition reduce thrombus-associated procoagulant activity in ex vivo human clots and arterial thrombi?

Population

Clots prepared ex vivo from human whole blood and pathological arterial thrombi from patients

Comparison

Preincubation with factor Xa inhibitors for 2… vs Preincubation in plasma without inhibitors, or…

Design

Preclinical

Follow-up

7 minutes

Authors

CMClark R. McKenzieMercy Clinic Neurology DADana R. AbendscheinPulse Biosciences (United States)PEPaul R. EisenbergVienna University of Economics and Business

Discussion

Member takes

Implication

Factor Xa inhibition may durably suppress thrombus procoagulant activity unlike thrombin inhibition; hypothesis-generating for recurrent thrombosis mechanisms.

Key Points

To determine whether inhibiting factor Xa results in more sustained attenuation of thrombus-associated procoagulant activity compared with direct or indirect thrombin inhibition.
Ex vivo human whole-blood clots and patient arterial thrombi were preincubated for 2 hours with control plasma, heparin (0.5–1 U/mL), hirudin (0.5–1 µmol/L), tick anticoagulant peptide (TAP, 5–10 µmol/L), tissue factor pathway inhibitor (TFPI, 0.15–3 µmol/L), or hirudin plus TAP.
Clots were washed in phosphate-buffered saline to remove free drug, placed into nonanticoagulated whole blood, and assessed for procoagulant activity via fibrinopeptide A (FPA) generation over 7 minutes.
Clots preincubated without inhibitors caused marked whole-blood coagulation activation compared to blood without clots (FPA: 1522 ± 568 ng/mL vs 117 ± 170 ng/mL, P < .01), which was not attenuated by preincubation with heparin or hirudin.
Preincubation with factor Xa inhibitors significantly reduced subsequent FPA generation in whole blood (TAP: 551 ± 316 ng/mL; TFPI: 508 ± 208 ng/mL; both P < .01 vs no inhibitor), with matching sustained suppression seen in pathological arterial thrombi.

Structured PICO

Does inhibition of factor Xa compared to thrombin inhibition reduce thrombus-associated procoagulant activity in ex vivo human clots and arterial thrombi?

Population

Clots prepared ex vivo from human whole blood and pathological arterial thrombi from patients

Intervention

Preincubation with factor Xa inhibitors (tick anticoagulant peptide [TAP] 5 to 10 mumol/L or tissue factor pathway inhibitor [TFPI] 0.15 to 3 mumol/L) for 2 hours

Comparator

Preincubation in plasma without inhibitors, or with thrombin inhibitors (heparin 0.5 to 1 U/mL or hirudin 0.5 to 1 mumol/L)

Outcome

Increases in the concentration of fibrinopeptide A (FPA) over 7 minutes after addition to nonanticoagulated whole bloodsurrogate

Inhibition of factor Xa, but not thrombin, results in sustained attenuation of thrombus-associated procoagulant activity, suggesting uninhibited Xa may account for recurrent thrombosis after discontinuation of thrombin inhibitors.

Cite This Study

McKenzie et al. (1996) studied this question.

synapsesocial.com/papers/6a74544873ed22dccea7fe33 https://doi.org/10.1161/01.atv.16.10.1285

Topics

Anticoagulation in AF

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Implication

Factor Xa inhibition may durably suppress thrombus procoagulant activity unlike thrombin inhibition; hypothesis-generating for recurrent thrombosis mechanisms.

Sustained Inhibition of Whole-Blood Clot Procoagulant Activity by Inhibition of Thrombus-Associated Factor Xa

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Sustained Inhibition of Whole-Blood Clot Procoagulant Activity by Inhibition of Thrombus-Associated Factor Xa

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Topics

Also Consider