Defining heparin resistance: communication from the ISTH SSC Subcommittee of Perioperative and Critical Care Thrombosis and Hemostasis

Levy, Jerrold H.; Sniecinski, Roman M.; Rocca, Bianca; Ghadimi, Kamrouz; Douketis, James; Frere, Corinne; Helms, Julie; Iba, Toshiaki; Koster, Andreas; Lech, Tara K.; Maier, Cheryl L.; Neal, Mathew D.; Scarlestscu, Ecatarina; Spyropoulos, Alex; Steiner, Marie E.; Tafur, Alfonso J.; Tanaka, Kenichi A.; Connors, Jean M.

doi:10.1016/j.jtha.2023.08.013

Cited by 13 publications

(8 citation statements)

References 26 publications

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“…However, it is recognized that antithrombin levels decrease significantly with the severity of sepsis and septic DIC, and adequate antithrombin activity cannot be maintained without supplementation. 36 37 Nearly all studies examining the effect of heparins did not include antithrombin substitution, thereby hindering heparins' ability to demonstrate any anticipated effect. 37 The monitoring of UFH is usually performed by activated partial thromboplastin time or with factor Xa activity assays 38 ; however, such tests were not performed in any of the reported studies.…”

Section: Limitations and Perspectivesmentioning

confidence: 99%

“…36 37 Nearly all studies examining the effect of heparins did not include antithrombin substitution, thereby hindering heparins' ability to demonstrate any anticipated effect. 37 The monitoring of UFH is usually performed by activated partial thromboplastin time or with factor Xa activity assays 38 ; however, such tests were not performed in any of the reported studies.…”

Section: Limitations and Perspectivesmentioning

confidence: 99%

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Heparins May Not Be the Optimal Anticoagulants for Sepsis and Sepsis-Associated Disseminated Intravascular Coagulation

Iba,

Helms,

Totoki

et al. 2024

Semin Thromb Hemost

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Historically, heparin has had the longest historical use as an anticoagulant and continues this day to be the primary therapeutic option for preventing thrombosis and thromboembolism in critically ill hospitalized patients. Heparin is also used to treat sepsis and sepsis-associated disseminated intravascular coagulation (DIC) in various countries. However, the efficacy and safety of heparin for this indication remains controversial, as adequately powered randomized clinical studies have not demonstrated as yet a survival benefit in sepsis and sepsis-associated DIC, despite meta-analyses and propensity analyses reporting improved outcomes without increasing bleeding risk. Further, activated protein C and recombinant thrombomodulin showed greater improvements in outcomes compared with heparin, although these effects were inconclusive. In summary, further research is warranted, despite the ongoing clinical use of heparin for sepsis and sepsis-associated DIC. Based on Japanese guidelines, antithrombin or recombinant thrombomodulin may be a preferable choice if they are accessible.

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Section: Limitations and Perspectivesmentioning

confidence: 99%

Section: Limitations and Perspectivesmentioning

confidence: 99%

Heparins May Not Be the Optimal Anticoagulants for Sepsis and Sepsis-Associated Disseminated Intravascular Coagulation

Iba,

Helms,

Totoki

et al. 2024

Semin Thromb Hemost

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“…However, there is no evidence supporting the numerous definitions found in the literature. 12 Decreased heparin responsiveness may be particularly frequent during ECMO. 2,13 Acquired AT deficiency is often arbitrarily defined as plasma AT levels less than 70 to 80% or U/dl, based on the definition of constitutional deficiency and the normal AT range in plasma (80 to 120% or U/dl).…”

Section: What This Article Tells Us That Is Newmentioning

confidence: 99%

“…However, there is no evidence supporting the numerous definitions found in the literature. 12 Decreased heparin responsiveness may be particularly frequent during ECMO. 2 , 13 …”

mentioning

confidence: 99%

Antithrombin Levels and Heparin Responsiveness during Venoarterial Extracorporeal Membrane Oxygenation: A Prospective Single-center Cohort Study

Mansour,

Berahou,

Odot

et al. 2024

Anesthesiology

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Background Unfractionated heparin, administered during veno-arterial extracorporeal membrane oxygenation to prevent thromboembolic events, largely depend on plasma antithrombin for its antithrombotic effects. Decreased heparin responsiveness seems frequent on extracorporeal membrane oxygenation however its association with acquired antithrombin deficiency is poorly understood. Our objective was to describe longitudinal changes in plasma antithrombin levels during extracorporeal membrane oxygenation support and evaluate the association between antithrombin levels and heparin responsiveness. We hypothesized that extracorporeal membrane oxygenation support would be associated with acquired antithrombin deficiency and related decreased heparin responsiveness. Methods Adults receiving veno-arterial extracorporeal membrane oxygenation were prospectively included. All patients received continuous intravenous unfractionated heparin using a standardized protocol (target anti-Xa 0.3-0.5 IU.mL -1). For each patient, arterial blood was withdrawn into citrate-containing tubes, at 11 time-points (from H0 up to day 7) . Anti-Xa (without dextran or antithrombin added) and antithrombin levels were measured. The primary outcome was antithrombin plasma level. In the absence of consensus, antithrombin deficiency was defined as a time-weighted average of antithrombin ≤70%. Data regarding clinical management and heparin dosage were collected. Results Fifty patients, including 42% post-cardiotomy, were included between April 2020 and May 2021, with a total of 447 samples. Median extracorporeal membrane oxygenation duration was 7 (interquartile range, 4-12) days. Median antithrombin level was 48 (37-60)% at H0. Antithrombin levels significantly increased throughout the follow-up. Time-weighted average of antithrombin levels was 63 (57-73)%, and was ≤70% in 32 (64%) of patients. Overall, 45 (90%) patients had at least one antithrombin value below 70%, and 35 (70%) below 50%. Antithrombin levels were not significantly associated with heparin responsiveness evaluated by anti-Xa assay or heparin dosage. Conclusions Veno-arterial extracorporeal membrane oxygenation support was associated with a moderate acquired antithrombin deficiency, mainly during the first 72 hours, that did not correlate with heparin responsiveness.

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“…Although antithrombin supplementation is commonly used to treat heparin resistance in ECMO patients, determining a critical level for supplementation remains to be determined. 12 Management strategies for anticoagulating adult ECMO patients and optimal management continue to be a work in progress. Some ECMO centers have switched to bivalirudin or argatroban, direct thrombin inhibitors that do not require antithrombin for their anticoagulant effect as first-line anticoagulants.…”

mentioning

confidence: 99%

Antithrombin Deficiency during Venoarterial Extracorporeal Membrane Oxygenation: Extremely Common, but Does It Matter?

Mazzeffi,

Levy

2024

Anesthesiology

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Defining heparin resistance: communication from the ISTH SSC Subcommittee of Perioperative and Critical Care Thrombosis and Hemostasis

Cited by 13 publications

References 26 publications

Heparins May Not Be the Optimal Anticoagulants for Sepsis and Sepsis-Associated Disseminated Intravascular Coagulation

Heparins May Not Be the Optimal Anticoagulants for Sepsis and Sepsis-Associated Disseminated Intravascular Coagulation

Antithrombin Levels and Heparin Responsiveness during Venoarterial Extracorporeal Membrane Oxygenation: A Prospective Single-center Cohort Study

Antithrombin Deficiency during Venoarterial Extracorporeal Membrane Oxygenation: Extremely Common, but Does It Matter?

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