Potential role of interleukin-1 as the trigger for diffuse intravascular coagulation in acute nonlymphoblastic leukemia

Federico Cozzolino, Maria Torcia, Anna Miliani, Anna M. Carossino, Rosanna Giordani, Sandro Cinotti, Erminio Filimberti, Riccardo Saccardi, Pierantonio Bernabei, Giovanni Guidi, Renato Di Guglielmo, Vito Pistoia, Manlio Ferrarini, Peter P. Nawroth, David Stern

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Abstract

Abnormalities of coagulation are common in patients with acute nonlymphoblastic leukemia, although the mechanisms involved are unclear, except in a few cases. To investigate the pathogenesis of this coagulopathy, suspensions of purified leukemic cells were prepared and tested for procoagulant activity. Neither the leukemic cells nor their supernatants directly accelerated the clotting of plasma. Since the leukemic cells did not possess direct procoagulant activity, their ability or inability to elaborate a mediator of cellular coagulant properties, interleukin-1, was studied. Leukemic cells from patients with coagulopathy elaborated interleukin-1, and addition of phytohemagglutinin increased interleukin-1 release. In contrast, no interleukin-1 was released, before or after stimulation with phytohemagglutinin, from leukemic cells from patients without coagulopathy. Leukemic cells from another group of patients with abnormalities of coagulation released interleukin-1 only after phytohemagglutinin treatment. In terms of the coagulation mechanism, interleukin-1 containing supematants from leukemic cell cultures induced the procoagulant receptor tissue factor, a co-factor in the initiation of coagulation, on the endothelial cell surface. There was coordinate suppression of the anticoagulant endothelial cell receptor thrombomodulin, a co-factor for the antithrombotic protein C pathway. Antibody to interleukin-1 prevented these changes in cellular coagulant properties. Taken together, these changes result in a shift in the balance of endothelial cell coagulant properties to an activated state in which mechanisms promoting procoagulant reactions on the vessel surface predominate. Synthesis and release of the mediator interleukin-1 by leukemic cells thus defines a new mechanism through which malignant cells can potentially activate the coagulation mechanism.

Original languageEnglish (US)
Pages (from-to)240-250
Number of pages11
JournalThe American journal of medicine
Volume84
Issue number2
DOIs
StatePublished - Jan 1 1988
Externally publishedYes

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Interleukin-1
Acute Myeloid Leukemia
Coagulants
Phytohemagglutinins
Endothelial Cells
Thrombomodulin
Peptide Initiation Factors
Thromboplastin
Protein C
Anticoagulants
Suspensions
Cell Culture Techniques
Antibodies

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Potential role of interleukin-1 as the trigger for diffuse intravascular coagulation in acute nonlymphoblastic leukemia. / Cozzolino, Federico; Torcia, Maria; Miliani, Anna; Carossino, Anna M.; Giordani, Rosanna; Cinotti, Sandro; Filimberti, Erminio; Saccardi, Riccardo; Bernabei, Pierantonio; Guidi, Giovanni; Di Guglielmo, Renato; Pistoia, Vito; Ferrarini, Manlio; Nawroth, Peter P.; Stern, David.

In: The American journal of medicine, Vol. 84, No. 2, 01.01.1988, p. 240-250.

Research output: Contribution to journalArticle

Cozzolino, F, Torcia, M, Miliani, A, Carossino, AM, Giordani, R, Cinotti, S, Filimberti, E, Saccardi, R, Bernabei, P, Guidi, G, Di Guglielmo, R, Pistoia, V, Ferrarini, M, Nawroth, PP & Stern, D 1988, 'Potential role of interleukin-1 as the trigger for diffuse intravascular coagulation in acute nonlymphoblastic leukemia', The American journal of medicine, vol. 84, no. 2, pp. 240-250. https://doi.org/10.1016/0002-9343(88)90420-2
Cozzolino, Federico ; Torcia, Maria ; Miliani, Anna ; Carossino, Anna M. ; Giordani, Rosanna ; Cinotti, Sandro ; Filimberti, Erminio ; Saccardi, Riccardo ; Bernabei, Pierantonio ; Guidi, Giovanni ; Di Guglielmo, Renato ; Pistoia, Vito ; Ferrarini, Manlio ; Nawroth, Peter P. ; Stern, David. / Potential role of interleukin-1 as the trigger for diffuse intravascular coagulation in acute nonlymphoblastic leukemia. In: The American journal of medicine. 1988 ; Vol. 84, No. 2. pp. 240-250.
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abstract = "Abnormalities of coagulation are common in patients with acute nonlymphoblastic leukemia, although the mechanisms involved are unclear, except in a few cases. To investigate the pathogenesis of this coagulopathy, suspensions of purified leukemic cells were prepared and tested for procoagulant activity. Neither the leukemic cells nor their supernatants directly accelerated the clotting of plasma. Since the leukemic cells did not possess direct procoagulant activity, their ability or inability to elaborate a mediator of cellular coagulant properties, interleukin-1, was studied. Leukemic cells from patients with coagulopathy elaborated interleukin-1, and addition of phytohemagglutinin increased interleukin-1 release. In contrast, no interleukin-1 was released, before or after stimulation with phytohemagglutinin, from leukemic cells from patients without coagulopathy. Leukemic cells from another group of patients with abnormalities of coagulation released interleukin-1 only after phytohemagglutinin treatment. In terms of the coagulation mechanism, interleukin-1 containing supematants from leukemic cell cultures induced the procoagulant receptor tissue factor, a co-factor in the initiation of coagulation, on the endothelial cell surface. There was coordinate suppression of the anticoagulant endothelial cell receptor thrombomodulin, a co-factor for the antithrombotic protein C pathway. Antibody to interleukin-1 prevented these changes in cellular coagulant properties. Taken together, these changes result in a shift in the balance of endothelial cell coagulant properties to an activated state in which mechanisms promoting procoagulant reactions on the vessel surface predominate. Synthesis and release of the mediator interleukin-1 by leukemic cells thus defines a new mechanism through which malignant cells can potentially activate the coagulation mechanism.",
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AU - Torcia, Maria

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AU - Giordani, Rosanna

AU - Cinotti, Sandro

AU - Filimberti, Erminio

AU - Saccardi, Riccardo

AU - Bernabei, Pierantonio

AU - Guidi, Giovanni

AU - Di Guglielmo, Renato

AU - Pistoia, Vito

AU - Ferrarini, Manlio

AU - Nawroth, Peter P.

AU - Stern, David

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N2 - Abnormalities of coagulation are common in patients with acute nonlymphoblastic leukemia, although the mechanisms involved are unclear, except in a few cases. To investigate the pathogenesis of this coagulopathy, suspensions of purified leukemic cells were prepared and tested for procoagulant activity. Neither the leukemic cells nor their supernatants directly accelerated the clotting of plasma. Since the leukemic cells did not possess direct procoagulant activity, their ability or inability to elaborate a mediator of cellular coagulant properties, interleukin-1, was studied. Leukemic cells from patients with coagulopathy elaborated interleukin-1, and addition of phytohemagglutinin increased interleukin-1 release. In contrast, no interleukin-1 was released, before or after stimulation with phytohemagglutinin, from leukemic cells from patients without coagulopathy. Leukemic cells from another group of patients with abnormalities of coagulation released interleukin-1 only after phytohemagglutinin treatment. In terms of the coagulation mechanism, interleukin-1 containing supematants from leukemic cell cultures induced the procoagulant receptor tissue factor, a co-factor in the initiation of coagulation, on the endothelial cell surface. There was coordinate suppression of the anticoagulant endothelial cell receptor thrombomodulin, a co-factor for the antithrombotic protein C pathway. Antibody to interleukin-1 prevented these changes in cellular coagulant properties. Taken together, these changes result in a shift in the balance of endothelial cell coagulant properties to an activated state in which mechanisms promoting procoagulant reactions on the vessel surface predominate. Synthesis and release of the mediator interleukin-1 by leukemic cells thus defines a new mechanism through which malignant cells can potentially activate the coagulation mechanism.

AB - Abnormalities of coagulation are common in patients with acute nonlymphoblastic leukemia, although the mechanisms involved are unclear, except in a few cases. To investigate the pathogenesis of this coagulopathy, suspensions of purified leukemic cells were prepared and tested for procoagulant activity. Neither the leukemic cells nor their supernatants directly accelerated the clotting of plasma. Since the leukemic cells did not possess direct procoagulant activity, their ability or inability to elaborate a mediator of cellular coagulant properties, interleukin-1, was studied. Leukemic cells from patients with coagulopathy elaborated interleukin-1, and addition of phytohemagglutinin increased interleukin-1 release. In contrast, no interleukin-1 was released, before or after stimulation with phytohemagglutinin, from leukemic cells from patients without coagulopathy. Leukemic cells from another group of patients with abnormalities of coagulation released interleukin-1 only after phytohemagglutinin treatment. In terms of the coagulation mechanism, interleukin-1 containing supematants from leukemic cell cultures induced the procoagulant receptor tissue factor, a co-factor in the initiation of coagulation, on the endothelial cell surface. There was coordinate suppression of the anticoagulant endothelial cell receptor thrombomodulin, a co-factor for the antithrombotic protein C pathway. Antibody to interleukin-1 prevented these changes in cellular coagulant properties. Taken together, these changes result in a shift in the balance of endothelial cell coagulant properties to an activated state in which mechanisms promoting procoagulant reactions on the vessel surface predominate. Synthesis and release of the mediator interleukin-1 by leukemic cells thus defines a new mechanism through which malignant cells can potentially activate the coagulation mechanism.

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