What does this research mean for the field?

The antithrombotic effect of selective factor Xa inhibition is limited compared to agents that inhibit thrombin generation or inactivate thrombin, such as standard heparin and dermatan sulfate. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To determine the relative importance of thrombin inhibition versus factor Xa inhibition in mediating the in vivo antithrombotic efficacy of heparin and related sulfated polysaccharides.

January 1, 1985Blood

The relative importance of thrombin inhibition and factor Xa inhibition to the antithrombotic effects of heparin

Q: What is the clinical evidence from this study?

Study design: Other. Population: Thrombosis. Intervention: Standard heparin, octasaccharide heparin fraction, and dermatan sulfate. Primary outcome: Inhibition of thrombus formation.

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Key result

Standard heparin and dermatan sulfate inhibit thrombus formation by ~90%, outperforming anti-Xa-only octasaccharide.

Why the study?

Does thrombin inhibition or factor Xa inhibition provide better antithrombotic effects in a rabbit thrombosis model?

Population

Rabbits in a Wessler-type thrombosis model

Design

Preclinical

Authors

MBMR BuchananMcMaster University Medical Centre BBB Boneu FOF Ofosu

Discussion

Member takes

Implication

Thrombin inhibition outperforms isolated factor Xa inhibition in rabbit thrombosis; leaves open relevance to human antithrombotic strategies.

Key Points

To determine the relative importance of thrombin inhibition versus factor Xa inhibition in mediating the in vivo antithrombotic efficacy of heparin and related sulfated polysaccharides.
Evaluated standard heparin, an anti-factor Xa octasaccharide fraction, and dermatan sulfate in a rabbit Wessler-type jugular venous thrombosis model using 125I-fibrinogen incorporation.
Assessed ex vivo thrombin clotting time (TCT) for antithrombin activity and chromogenic assays for anti-factor Xa activity.
Measured plasma thrombin generation inhibition and factor Xa inactivation enhancement across all three compounds.
Standard heparin at 10 anti-factor Xa U/kg inhibited thrombus formation by 90%, lengthened TCT by 2 seconds, and achieved anti-factor Xa levels of 0.32 U/mL, while dermatan sulfate (500 µg/kg) inhibited thrombus formation by 95% without altering TCT.
The octasaccharide fraction at 10 anti-factor Xa U/kg achieved anti-factor Xa levels of 0.28 U/mL without altering TCT, but inhibited thrombus formation by only 41%, with higher doses producing no additional antithrombotic effect despite increased anti-factor Xa levels.

Structured PICO

Does thrombin inhibition or factor Xa inhibition provide better antithrombotic effects in a rabbit thrombosis model?

Population

In vivo rabbit model of tissue thromboplastin-induced thrombosis.

Intervention

Standard heparin (10 anti-factor Xa U/kg), octasaccharide heparin fraction (10 anti-factor Xa U/kg), and dermatan sulfate (500 micrograms/kg)

Outcome

Inhibition of thrombus formation (measured as incorporation of 125I-fibrinogen into tissue thromboplastin-induced thrombi)surrogate

In a rabbit model, antithrombotic effects achieved by inhibiting factor Xa alone are limited compared to those achieved by agents capable of inhibiting thrombin generation or activity.

Cite This Study

Buchanan et al. (1985) studied Thrombosis. Standard heparin, octasaccharide heparin fraction, and dermatan sulfate was evaluated on Inhibition of thrombus formation. Standard heparin and dermatan sulfate inhibited thrombus formation by 90% and 95%, respectively, while an octasaccharide fraction with only anti-factor Xa activity inhibited it by only 41%.

synapsesocial.com/papers/6aa61159d3d41ccc68922a98 https://doi.org/10.1182/blood.v65.1.198.bloodjournal651198

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Implication

Thrombin inhibition outperforms isolated factor Xa inhibition in rabbit thrombosis; leaves open relevance to human antithrombotic strategies.

The relative importance of thrombin inhibition and factor Xa inhibition to the antithrombotic effects of heparin

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

The relative importance of thrombin inhibition and factor Xa inhibition to the antithrombotic effects of heparin

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider