Association of Anti–Factor Xa–Guided Dosing of Enoxaparin With Venous Thromboembolism After Trauma

Karcutskie, Charles A.; Dharmaraja, Arjuna; Patel, Jaimin; Eidelson, Sarah A.; Padiadpu, Anish B.; Martin, Arch G.; Lama, Gabriel; Lineen, Edward B.; Namias, Nicholas; Schulman, Carl I.; Proctor, Kenneth G.

doi:10.1001/jamasurg.2017.3787

Cited by 56 publications

(73 citation statements)

References 34 publications

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“…Moreover, in a study examining the potential antithrombotic benefit of HCQ in patients with anti‐phospholipid syndrome, patients treated with HCQ in addition to standard oral anticoagulant therapy had no increased bleeding events . The trauma literature demonstrates persistently elevated VTE rates despite the use of gold standard therapy via low‐molecular‐weight heparins, suggesting that perhaps targeting the coagulation cascade alone is insufficient in this high‐risk patient population . The addition of platelet inhibition for DVT prophylaxis in trauma has been advocated by some but remains controversial .…”

Section: Discussionmentioning

confidence: 99%

“…56,57 The trauma literature demonstrates persistently elevated VTE rates despite the use of gold standard therapy via low-molecular-weight heparins, suggesting that perhaps targeting the coagulation cascade alone is insufficient in this high-risk patient population. 3,4,[58][59][60][61] The addition of platelet inhibition for DVT prophylaxis in trauma has been advocated by some but remains controversial. [61][62][63] Whether HCQ represents a potential VTE thromboprophylaxis strategy in addition to current standard of care warrants further clinical investigation.…”

Section: Discussionmentioning

confidence: 99%

“…3,4,[58][59][60][61] The addition of platelet inhibition for DVT prophylaxis in trauma has been advocated by some but remains controversial. [61][62][63] Whether HCQ represents a potential VTE thromboprophylaxis strategy in addition to current standard of care warrants further clinical investigation. Importantly, however, HCQ is known to impact numerous cell types and cellular pathways in addition to platelets.…”

Section: Discussionmentioning

confidence: 99%

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Platelet‐derived extracellular vesicles released after trauma promote hemostasis and contribute to DVT in mice

Dyer

Alexander

Hassoune

et al. 2019

Journal of Thrombosis and Haemostasis

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Background Traumatic injury can lead to dysregulation of the normal clotting system, resulting in hemorrhagic and thrombotic complications. Platelet activation is robust following traumatic injury and one process of platelet activation is to release of extracellular vesicles (PEV) that carry heterogenous cargo loads and surface ligands. Objectives We sought to investigate and characterize the release and function of PEVs generated following traumatic injury. Methods PEV content and quantity in circulation following trauma in humans and mice was measured using flow cytometry, size exclusion chromatography, and nanoparticle tracking analysis. PEVs were isolated from circulation and the effects on thrombin generation, bleeding time, hemorrhage control, and thrombus formation were determined. Finally, the effect of hydroxychloroquine (HCQ) on PEV release and thrombosis were examined. Results Human and murine trauma results in a significant release of PEVs into circulation compared with healthy controls. These PEVs result in abundant thrombin generation, increased platelet aggregation, decreased bleeding times, and decreased hemorrhage in uncontrolled bleeding. Conversely, PEVs contributed to enhanced venous thrombus formation and were recruited to the developing thrombus site. Interestingly, HCQ treatment resulted in decreased platelet aggregation, decreased PEV release, and reduced deep vein thrombosis burden in mice. Conclusions These data demonstrate that trauma results in significant release of PEVs which are both pro‐hemostatic and pro‐thrombotic. The effects of PEVs can be mitigated by treatment with HCQ, suggesting the potential use as a form of deep vein thrombosis prophylaxis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Platelet‐derived extracellular vesicles released after trauma promote hemostasis and contribute to DVT in mice

Dyer

Alexander

Hassoune

et al. 2019

Journal of Thrombosis and Haemostasis

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“…However, the clinical implications of such findings are uncertain. A large retrospective study in trauma patients from North America demonstrated no reduction in VTE with twice daily fractionated heparin dosed to achieve peak anti-Xa levels of 0.2-0.4 IU/ml [18] . In comparison, several other studies in trauma patients, including one prospective cohort study, have demonstrated that prophylactic anti-Xa activity can be achieved by up-titrating doses and that these adjustments were associated with a reduction in DVT [13,15,16] .…”

Section: Relationship With Previous Studiesmentioning

confidence: 99%

“…Moreover, higher empirical dosing (e.g. 30 mg SC enoxaparin BD) may still provide inadequate chemoprophylaxis in many patients, as evidenced by low anti-Xa activity and the development of VTE [12][13][14][15]17,18] .…”

Section: Introductionmentioning

confidence: 99%

The ATLANTIC study: Anti-Xa level assessment in trauma intensive care

Rakhra

Martin

Fitzgerald

et al. 2020

Injury

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A Personalized Approach to Prevention of Venous Thromboembolism

2022

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We read with great interest the article by Vincent et al. 1 We commend the authors for their innovative methodology with longitudinal approach to demonstrate acquired antithrombin deficiency in injury and poor responsiveness to enoxaparin and its association with venous thromboembolism (VTE). This article 1 adds to recent literature that recognizes key pitfalls in a universal approach to prevention of trauma-related VTE in contrast to a personalized approach to identify anticoagulant resistance and/or nonresponsiveness to optimize therapy. 2,3 The authors demonstrate a statistically discernable association of low antithrombin activity within the first 72 hours of hospitalization in patients with VTE, consistent with prior literature. 2 However, they extend prior findings by exploring a longitudinal trend wherein patients with VTE fail to exhibit antithrombin rebound after initial decline compared with the nonevent group. Even more interesting are the crude values of late antithrombin activity in the VTE group, ranging from 97% to 99% on days 6 to 8. This challenges the established hematologic definition of antithrombin deficiency as less than 80% and highlights the inherent prothrombotic propensity in this critically ill population. 4 The authors also coupled these antithrombin data with a temporal delay in patients with VTE achieving the first therapeutic anti-factor Xa (anti-FXa) level (0.2 IU/mL or greater).

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Association of Anti–Factor Xa–Guided Dosing of Enoxaparin With Venous Thromboembolism After Trauma

Abstract: Rates of VTE were not reduced with anti-Xa-guided dosing, and almost half of the patients never reached prophylactic anti-Xa levels; achieving those levels did not decrease VTE rates. Thus, other targets, such as platelets, may be necessary to optimize thromboprophylaxis after trauma.

Cited by 56 publications

References 34 publications

Platelet‐derived extracellular vesicles released after trauma promote hemostasis and contribute to DVT in mice

Platelet‐derived extracellular vesicles released after trauma promote hemostasis and contribute to DVT in mice

The ATLANTIC study: Anti-Xa level assessment in trauma intensive care

A Personalized Approach to Prevention of Venous Thromboembolism

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