Antithrombin III (ATIII) Replacement Therapy in Patients with Sepsis And/or Postsurgical Complications: a Controlled Double-blind, Randomized, Multicenter Study

Overview

Journal Intensive Care Med

Specialty Critical Care

Date 1998 Jun 3

PMID 9609411

Citations 43

Authors

F Baudo

T M Caimi

F de Cataldo

A Ravizza

S Arlati

G Casella

D Carugo

G Palareti

C Legnani

L Ridolfi

R Rossi

A DAngelo

L Crippa

D Giudici

G GALLIOLI

A Wolfler

G Calori

Affiliations

Soon will be listed here.

Abstract

Background: ATIII is decreased in sepsis and/or shock and its baseline value correlates with mortality. The efficacy of ATIII therapy on mortality was assessed in a selected group of patients admitted to the intensive care unit (ICU) in a double-blind, randomized, multicenter study.

Methods: 120 patients admitted to the ICU with an ATIII concentration < 70% were randomized to receive ATIII (total dose 24000 units) or placebo treatment for 5 days; 56 patients had septic shock.

Results: ATIII concentrations in the treated group remained constant throughout the treatment period (range 97-102%). The Kaplan-Meier analysis showed no difference in overall survival between the two groups: 50 and 46% for ATIII and placebo, respectively. Septic shock and hemodynamic support were unbalanced in the two groups at admission. Therefore the Cox analysis was carried out after adjusting for these two variables. Treatment with ATIII decreases the risk of death with an odds ratio (OR) of 0.56. Of the covariates analyzed, septic shock and the baseline multiple organ failure score were negatively associated with survival and plasma activity level was positively associated with survival with an OR of 0.97 for each 1% increase in the ATIII plasma concentration at baseline.

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

Citing Articles

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2024.

Shime N, Nakada T, Yatabe T, Yamakawa K, Aoki Y, Inoue S Acute Med Surg. 2025; 12(1):e70037.

PMID: 39996161 PMC: 11848044. DOI: 10.1002/ams2.70037.

The transition of the criteria for disseminated intravascular coagulation and the targeted patients in randomized controlled trials over the decades: a scoping review.

Matsuoka T, Yamakawa K, Umemura Y, Homma K, Iba T, Sasaki J Thromb J. 2024; 22(1):112.

PMID: 39716150 PMC: 11665092. DOI: 10.1186/s12959-024-00681-w.

Clinical practice guidelines for management of disseminated intravascular coagulation in Japan 2024. Part 1: sepsis.

Yamakawa K, Okamoto K, Seki Y, Ikezoe T, Ito T, Iba T Int J Hematol. 2024; .

PMID: 39676120 DOI: 10.1007/s12185-024-03896-9.

Anticoagulation management during veno-venous ECMO support because of ARDS: Single-center experience.

Kuzmin B, Wacker M, Ponomarenko J, Movsisyan A, Praetsch F, Marsch G Heliyon. 2024; 10(22):e40417.

PMID: 39634389 PMC: 11616490. DOI: 10.1016/j.heliyon.2024.e40417.

Efficacy of antithrombin administration for patients with sepsis: A systematic review, meta-analysis, and meta-regression.

Tsuchida T, Makino Y, Wada T, Ushio N, Totoki T, Fujie N Acute Med Surg. 2024; 11(1):e950.

PMID: 38638892 PMC: 11024450. DOI: 10.1002/ams2.950.

References

Blauhut B, NECEK S, VINAZZER H, Bergmann H . Substitution therapy with an antithrombin III concentrate in shock and DIC. Thromb Res. 1982; 27(3):271-8. DOI: 10.1016/0049-3848(82)90074-3. View

Eisele B, Lamy M, Thijs L, Keinecke H, Schuster H, Matthias F . Antithrombin III in patients with severe sepsis. A randomized, placebo-controlled, double-blind multicenter trial plus a meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis. Intensive Care Med. 1998; 24(7):663-72. DOI: 10.1007/s001340050642. View

Dickneite G, Paques E . Reduction of mortality with antithrombin III in septicemic rats: a study of Klebsiella pneumoniae induced sepsis. Thromb Haemost. 1993; 69(2):98-102. View

Hesselvik J, Blomback M, Brodin B, Maller R . Coagulation, fibrinolysis, and kallikrein systems in sepsis: relation to outcome. Crit Care Med. 1989; 17(8):724-33. DOI: 10.1097/00003246-198908000-00002. View

Le Gall J, Loirat P, Alperovitch A, Glaser P, Granthil C, Mathieu D . A simplified acute physiology score for ICU patients. Crit Care Med. 1984; 12(11):975-7. DOI: 10.1097/00003246-198411000-00012. View

Fourrier F, Chopin C, Goudemand J, Hendrycx S, Caron C, Rime A . Septic shock, multiple organ failure, and disseminated intravascular coagulation. Compared patterns of antithrombin III, protein C, and protein S deficiencies. Chest. 1992; 101(3):816-23. DOI: 10.1378/chest.101.3.816. View

Buller H, Ten Cate J . Acquired antithrombin III deficiency: laboratory diagnosis, incidence, clinical implications, and treatment with antithrombin III concentrate. Am J Med. 1989; 87(3B):44S-48S. DOI: 10.1016/0002-9343(89)80531-5. View

Kessler C, Tang Z, Jacobs H, Szymanski L . The suprapharmacologic dosing of antithrombin concentrate for Staphylococcus aureus-induced disseminated intravascular coagulation in guinea pigs: substantial reduction in mortality and morbidity. Blood. 1997; 89(12):4393-401. View

Knaus W, Draper E, Wagner D, Zimmerman J . APACHE II: a severity of disease classification system. Crit Care Med. 1985; 13(10):818-29. View

10.

Mesters R, Mannucci P, Coppola R, Keller T, Ostermann H, Kienast J . Factor VIIa and antithrombin III activity during severe sepsis and septic shock in neutropenic patients. Blood. 1996; 88(3):881-6. View

11.

Jochum M . Influence of high-dose antithrombin concentrate therapy on the release of cellular proteinases, cytokines, and soluble adhesion molecules in acute inflammation. Semin Hematol. 1995; 32(4 Suppl 2):19-32. View

12.

Blauhut B, Kramar H, VINAZZER H, Bergmann H . Substitution of antithrombin III in shock and DIC: a randomized study. Thromb Res. 1985; 39(1):81-9. DOI: 10.1016/0049-3848(85)90123-9. View

13.

Lechner K, Kyrle P . Antithrombin III concentrates--are they clinically useful?. Thromb Haemost. 1995; 73(3):340-8. View

14.

Lammle B, Tran T, Ritz R, DUCKERT F . Plasma prekallikrein, factor XII, antithrombin III, C1(-)-inhibitor and alpha 2-macroglobulin in critically ill patients with suspected disseminated intravascular coagulation (DIC). Am J Clin Pathol. 1984; 82(4):396-404. DOI: 10.1093/ajcp/82.4.396. View

15.

Salvo I, de Cian W, Musicco M, Langer M, Piadena R, Wolfler A . The Italian SEPSIS study: preliminary results on the incidence and evolution of SIRS, sepsis, severe sepsis and septic shock. Intensive Care Med. 1995; 21 Suppl 2:S244-9. DOI: 10.1007/BF01740762. View

16.

Goris R, te Boekhorst T, Nuytinck J, Gimbrere J . Multiple-organ failure. Generalized autodestructive inflammation?. Arch Surg. 1985; 120(10):1109-15. DOI: 10.1001/archsurg.1985.01390340007001. View

17.

VINAZZER H . Therapeutic use of antithrombin III in shock and disseminated intravascular coagulation. Semin Thromb Hemost. 1989; 15(3):347-52. DOI: 10.1055/s-2007-1002727. View

18.

Hesselvik J, Malm J, Dahlback B, Blomback M . Protein C, protein S and C4b-binding protein in severe infection and septic shock. Thromb Haemost. 1991; 65(2):126-9. View

19.

Sandset P, Roise O, Aasen A, Abildgaard U . Extrinsic pathway inhibitor in postoperative/posttraumatic septicemia: increased levels in fatal cases. Haemostasis. 1989; 19(4):189-95. DOI: 10.1159/000215916. View

20.

Fourrier F, Chopin C, Huart J, Runge I, Caron C, Goudemand J . Double-blind, placebo-controlled trial of antithrombin III concentrates in septic shock with disseminated intravascular coagulation. Chest. 1993; 104(3):882-8. DOI: 10.1378/chest.104.3.882. View