Antithrombin III (ATILL) replacement therapy in patients with sepsis and/or postsurgical complications: a controlled double-blind, randomized, multicenter study

Baudo, F.; Caimi, Teresa Maria; Decataldo, Francesco; Ravizza, A.; Arlati, Sergio; Casella, G; Carugo, Dario; Palareti, Gualtiero; Legnani, Cristina; Ridolfi, Lorenza; Rossi, Roberto; D’Angelo, Armando; Crippa, L.; Giudici, D.; Gallioli, G; Wolfler, Andrea; Calori, Giliola

doi:10.1007/s001340050576

Cited by 217 publications

(119 citation statements)

References 23 publications

(28 reference statements)

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“…4,20,21 A theoretical limitation to the use of both UFH and LMWH in critically ill patients is driven by the low levels of antithrombin III that occur in sepsis thus reducing their therapeutic effectiveness, particularly in the case of UFH whose main mechanism of action is the high affinity to and activation of antithrombin III. 22,23 This can contribute to a shorter filter survival even when UFH anticoagulation level seems to be adequate, as indicated by targeted aPTT measurements. 24 Reported advantages of LMWH over other anticoagulants are easier administration (intermittent doses) due to their low affinity to plasma proteins, endothelial cells, and macrophages, larger bioavailability and a more predictable therapeutic effect not requiring laboratory monitoring of their antithrombotic activity.…”

Section: Discussionmentioning

confidence: 99%

Enoxaparin versus unfractioned heparin as anticoagulant for continuous venovenous hemodialysis: a randomized open-label trial

et al. 2010

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Aim: In this study we aimed to compare the efficacy and safety of enoxaparin with unfractioned heparin (UFH) as anticoagulant for continuous venovenous hemodialysis (CVVHD). Methods: An open-label randomized controlled trial was carried out in an intensive care unit (ICU) where 40 patients with acute renal failure (ARF) who needed continuous renal replacement therapy were randomized to receive UFH (n = 21) or enoxaparin (n = 19). Coagulation parameters were evaluated, and antithrombotic activity of UFH was measured by activated partial thromboplastin time (aPTT) and for enoxaparin by anti-factor Xa activity. Primary outcomes were thrombosis of the extracorporeal circuit and bleeding, classified as major or minor. Results: Minor bleeding episodes were observed only in patients anticoagulated with enoxaparin (26 vs. 0%, p = 0.018). Comparing patients with or without bleeding after 24 hours of therapy, the level of anticoagulation tended to be higher (anti-factor Xa: 1.62 vs. 1.13 IU/mL, p = 0.09) and the platelet count to be lower [107 ± 53 vs. 229 ± 84 (×10 3 /μL), p = 0.09] in patients who bled, but without statistical difference. Filter life span of enoxaparin and UFH groups was similar (43 ± 15 vs. 52 ± 18 hr, p = 0.10), as well as the proportion of circuit clotting. Conclusion: Weightunadjusted enoxaparin in patients with ARF in CVVHD was associated with an increased rate of bleeding, a finding that addresses the need to adjust drug dose and to monitor anti-factor Xa activity during dialysis. No benefit to prolong dialysis circuit survival was found with enoxaparin. In patients who do not present contraindication for systemic anticoagulation, UFH remains an effective and low-cost option.

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Section: Discussionmentioning

confidence: 99%

Enoxaparin versus unfractioned heparin as anticoagulant for continuous venovenous hemodialysis: a randomized open-label trial

et al. 2010

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“…However, in sepsis‐induced DIC, a decrease in AT activity is frequently observed27, 28, 29, 30 and is associated with high mortality rates 31, 32. Several RCTs to investigate the effects of high‐dose AT administration in patients with sepsis have been carried out 4, 33, 34, 35, 36. Although some RCTs indicated benefits of high‐dose AT administration in patients with sepsis,33, 34, 35 a large RCT (the KyberSept trial) failed to show any survival benefits 4.…”

Section: Antithrombinmentioning

confidence: 99%

“…Several RCTs to investigate the effects of high‐dose AT administration in patients with sepsis have been carried out 4, 33, 34, 35, 36. Although some RCTs indicated benefits of high‐dose AT administration in patients with sepsis,33, 34, 35 a large RCT (the KyberSept trial) failed to show any survival benefits 4. However, a subgroup analysis of the KyberSept trial indicated that AT administration significantly improved survival rates in patients with sepsis‐induced DIC 9…”

Section: Antithrombinmentioning

confidence: 99%

A summary of the Japan septic disseminated intravascular coagulation study

Hayakawa

Ono

2018

Acute Medicine & Surgery

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Over the past few decades, the large, international, randomized controlled trials of anticoagulant therapies for patients with sepsis have not yielded any improvement in mortality rates. However, in Japan, anticoagulant therapies are administered for sepsis patients with disseminated intravascular coagulation (DIC), but not for sepsis patients without DIC. Furthermore, epidemiological data regarding sepsis in Japan are scarce. Therefore, a nationwide multicenter retrospective observational study, the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study, was undertaken. The JSEPTIC DIC study enrolled 42 intensive care units and included 3,195 patients with sepsis. The results of the JSEPTIC DIC study indicated the following: (i) anticoagulant therapy may be effective in sepsis‐induced DIC patients at high risk for death, (ii) recombinant human soluble thrombomodulin administration and antithrombin supplementation are associated with survival benefits in patients with sepsis‐induced DIC.

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“…60 Small clinical trials suggested improved survival rates in patients receiving rATIII. [61][62][63][64] Eisele et al 62 reported that rATIII therapy was associated with decreased lung dysfunction. However, Waydas et al 63 found no difference in the duration of organ failure.…”

Section: -22mentioning

confidence: 99%

Intracellular and extracellular serpins modulate lung disease

Askew

Silverman

2008

J Perinatol

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An imbalance between peptidases and their inhibitors leads to pulmonary disease. Imbalances occur in the adult and the neonate at risk for a specific set of lung pathologies. Serpins (serine peptidase inhibitors) make up the major source of antipeptidase activity in the lung. The purpose of this review is to describe the serpin mechanism of inhibition, their roles in the normal and pathological lung and their potential as therapeutic agents.

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Antithrombin III (ATILL) replacement therapy in patients with sepsis and/or postsurgical complications: a controlled double-blind, randomized, multicenter study

Abstract: The results of ATIII treatment in this population of patients suggests that replacement therapy reduces mortality in the subgroup of septic shock patients only.

Cited by 217 publications

References 23 publications

Enoxaparin versus unfractioned heparin as anticoagulant for continuous venovenous hemodialysis: a randomized open-label trial

Enoxaparin versus unfractioned heparin as anticoagulant for continuous venovenous hemodialysis: a randomized open-label trial

A summary of the Japan septic disseminated intravascular coagulation study

Intracellular and extracellular serpins modulate lung disease

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