A prospective randomized double-blind trial of antithrombin III concentrate in the treatment of multiple-organ dysfunction syndrome during hematopoietic stem cell transplantation

William D. Haire, Elizabeth I. Ruby, Lana C. Stephens, Elizabeth Reed, Stefano R. Tarantolo, Z. Steven Pavletic, Philip J. Bierman, Michael Bishop, Anne Kessinger, Julie Vose, James O. Armitage

Research output: Contribution to journalArticle

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Abstract

Many of the complications of high-dose therapy with hematopoietic stem cells are caused by or lead to the multiple-organ dysfunction syndrome (MODS). In hematopoietic stem cell transplantation (HSCT), acquired antithrombin III (ATIII) deficiency is independently associated with MODS to the exclusion of transplant type, preparative regimen, and bacteremia. In experimental settings, replacement of ATIII can ameliorate the severity of MODS that develops in response to a variety of pathologic stimuli, suggesting that ATIII supplementation might improve the clinical course of MODS in patients undergoing HSCT. We performed a study to determine if ATIII can improve the morbidity of MODS in HSCT. Forty-nine patients undergoing HSCT, who developed pulmonary dysfunction (oxygen saturation of <90%), central nervous system dysfunction (drop of >4 points in the mini-mental status exam), or hepatic dysfunction (bilirubin >34 μmol/L [2.0 mg%], weight gain of >5% over baseline, and abdominal pain, possibly of hepatic origin) with a concomitant ATIII activity of <84% were double-blind randomized to receive ATIII concentrate, 70 units/kg within 24 hours of recognition of initial organ dysfunction followed by 50 units/kg 8, 16, 48, and 72 hours later, or albumin placebo. The group randomized to ATIII had a lower severity-of-illness score (15.7 ± 19.2 vs. 28.6 ± 25.2, p = 0.03), shorter duration of hospitalization (14.9 ± 16.7 vs. 25.7 ± 17.9 days, p = 0.03), and lower hospital charges ($138,700 ± $23,500 vs. $206,400 ± $34,000). ATIII concentrate was associated with improved morbidity of MODS in patients undergoing HSCT when given early in the evolution of the syndrome.

Original languageEnglish (US)
Pages (from-to)142-150
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume4
Issue number3
StatePublished - Jan 1 1998

Fingerprint

Multiple Organ Failure
Antithrombin III
Hematopoietic Stem Cell Transplantation
Therapeutics
Antithrombin III Deficiency
Morbidity
Hospital Charges
Liver
Bacteremia
Hematopoietic Stem Cells
Bilirubin
Abdominal Pain
Weight Gain
Albumins
Hospitalization
Placebos
Oxygen
Transplants
Lung

Keywords

  • Delerium
  • Hepatic veno-occlusive disease
  • Idiopathic pneumonia syndrome
  • Systemic inflammatory response syndrome

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

A prospective randomized double-blind trial of antithrombin III concentrate in the treatment of multiple-organ dysfunction syndrome during hematopoietic stem cell transplantation. / Haire, William D.; Ruby, Elizabeth I.; Stephens, Lana C.; Reed, Elizabeth; Tarantolo, Stefano R.; Pavletic, Z. Steven; Bierman, Philip J.; Bishop, Michael; Kessinger, Anne; Vose, Julie; Armitage, James O.

In: Biology of Blood and Marrow Transplantation, Vol. 4, No. 3, 01.01.1998, p. 142-150.

Research output: Contribution to journalArticle

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abstract = "Many of the complications of high-dose therapy with hematopoietic stem cells are caused by or lead to the multiple-organ dysfunction syndrome (MODS). In hematopoietic stem cell transplantation (HSCT), acquired antithrombin III (ATIII) deficiency is independently associated with MODS to the exclusion of transplant type, preparative regimen, and bacteremia. In experimental settings, replacement of ATIII can ameliorate the severity of MODS that develops in response to a variety of pathologic stimuli, suggesting that ATIII supplementation might improve the clinical course of MODS in patients undergoing HSCT. We performed a study to determine if ATIII can improve the morbidity of MODS in HSCT. Forty-nine patients undergoing HSCT, who developed pulmonary dysfunction (oxygen saturation of <90{\%}), central nervous system dysfunction (drop of >4 points in the mini-mental status exam), or hepatic dysfunction (bilirubin >34 μmol/L [2.0 mg{\%}], weight gain of >5{\%} over baseline, and abdominal pain, possibly of hepatic origin) with a concomitant ATIII activity of <84{\%} were double-blind randomized to receive ATIII concentrate, 70 units/kg within 24 hours of recognition of initial organ dysfunction followed by 50 units/kg 8, 16, 48, and 72 hours later, or albumin placebo. The group randomized to ATIII had a lower severity-of-illness score (15.7 ± 19.2 vs. 28.6 ± 25.2, p = 0.03), shorter duration of hospitalization (14.9 ± 16.7 vs. 25.7 ± 17.9 days, p = 0.03), and lower hospital charges ($138,700 ± $23,500 vs. $206,400 ± $34,000). ATIII concentrate was associated with improved morbidity of MODS in patients undergoing HSCT when given early in the evolution of the syndrome.",
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