Pegasparaginase treatment alters thrombin generation by modulating the protein C and S system in acute lymphoblastic leukaemia/lymphoma

Jack H. Staddon; Kristi J. Smock; Joshua D. Schiffman; Mark N. Fluchel; Michael E. Engel; Andrew S. Weyrich; Robert A. Campbell

doi:10.1097/MBC.0000000000000356

Pegasparaginase treatment alters thrombin generation by modulating the protein C and S system in acute lymphoblastic leukaemia/lymphoma

Jack H. Staddon
, Kristi J. Smock
, Joshua D. Schiffman
, Mark N. Fluchel
, Michael E. Engel
, Andrew S. Weyrich
, Robert A. Campbell

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Paediatric patients with acute lymphoblastic leukaemia/lymphoma treated with pegasparaginase are at an increased risk of thrombosis. We evaluated changes in thrombin generation in the presence and absence of thrombomodulin using paired plasma samples collected from paediatric patients treated with pegasparaginase. Postpegasparaginase samples were significantly less sensitive to reductions in thrombin generation in the presence of thrombomodulin compared with prepegasparaginase, suggesting reduced protein C and S activity. This corresponded to a significant decrease in protein C and protein S antigen. Alterations in the protein C and S pathway may contribute to the increased risk of thrombosis in patients treated with pegasparaginase.

Original language	English
Pages (from-to)	840-843
Number of pages	4
Journal	Blood Coagulation and Fibrinolysis
Volume	26
Issue number	7
DOIs	https://doi.org/10.1097/MBC.0000000000000356
State	Published - Jan 1 2015

Keywords

acute lymphoblastic leukaemia
pegasparaginase
protein C and S
thrombin generation
thrombomodulin

Access to Document

10.1097/MBC.0000000000000356

Cite this

@article{477b3a3c0fe343ee87833a168757cf5a,

title = "Pegasparaginase treatment alters thrombin generation by modulating the protein C and S system in acute lymphoblastic leukaemia/lymphoma",

abstract = "Paediatric patients with acute lymphoblastic leukaemia/lymphoma treated with pegasparaginase are at an increased risk of thrombosis. We evaluated changes in thrombin generation in the presence and absence of thrombomodulin using paired plasma samples collected from paediatric patients treated with pegasparaginase. Postpegasparaginase samples were significantly less sensitive to reductions in thrombin generation in the presence of thrombomodulin compared with prepegasparaginase, suggesting reduced protein C and S activity. This corresponded to a significant decrease in protein C and protein S antigen. Alterations in the protein C and S pathway may contribute to the increased risk of thrombosis in patients treated with pegasparaginase.",

keywords = "acute lymphoblastic leukaemia, pegasparaginase, protein C and S, thrombin generation, thrombomodulin",

author = "Staddon, \{Jack H.\} and Smock, \{Kristi J.\} and Schiffman, \{Joshua D.\} and Fluchel, \{Mark N.\} and Engel, \{Michael E.\} and Weyrich, \{Andrew S.\} and Campbell, \{Robert A.\}",

year = "2015",

month = jan,

day = "1",

doi = "10.1097/MBC.0000000000000356",

language = "English",

volume = "26",

pages = "840--843",

journal = "Blood Coagulation and Fibrinolysis",

issn = "0957-5235",

number = "7",

}

TY - JOUR

T1 - Pegasparaginase treatment alters thrombin generation by modulating the protein C and S system in acute lymphoblastic leukaemia/lymphoma

AU - Staddon, Jack H.

AU - Smock, Kristi J.

AU - Schiffman, Joshua D.

AU - Fluchel, Mark N.

AU - Engel, Michael E.

AU - Weyrich, Andrew S.

AU - Campbell, Robert A.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Paediatric patients with acute lymphoblastic leukaemia/lymphoma treated with pegasparaginase are at an increased risk of thrombosis. We evaluated changes in thrombin generation in the presence and absence of thrombomodulin using paired plasma samples collected from paediatric patients treated with pegasparaginase. Postpegasparaginase samples were significantly less sensitive to reductions in thrombin generation in the presence of thrombomodulin compared with prepegasparaginase, suggesting reduced protein C and S activity. This corresponded to a significant decrease in protein C and protein S antigen. Alterations in the protein C and S pathway may contribute to the increased risk of thrombosis in patients treated with pegasparaginase.

AB - Paediatric patients with acute lymphoblastic leukaemia/lymphoma treated with pegasparaginase are at an increased risk of thrombosis. We evaluated changes in thrombin generation in the presence and absence of thrombomodulin using paired plasma samples collected from paediatric patients treated with pegasparaginase. Postpegasparaginase samples were significantly less sensitive to reductions in thrombin generation in the presence of thrombomodulin compared with prepegasparaginase, suggesting reduced protein C and S activity. This corresponded to a significant decrease in protein C and protein S antigen. Alterations in the protein C and S pathway may contribute to the increased risk of thrombosis in patients treated with pegasparaginase.

KW - acute lymphoblastic leukaemia

KW - pegasparaginase

KW - protein C and S

KW - thrombin generation

KW - thrombomodulin

UR - https://www.scopus.com/pages/publications/84960080140

U2 - 10.1097/MBC.0000000000000356

DO - 10.1097/MBC.0000000000000356

M3 - Article

C2 - 26196196

AN - SCOPUS:84960080140

SN - 0957-5235

VL - 26

SP - 840

EP - 843

JO - Blood Coagulation and Fibrinolysis

JF - Blood Coagulation and Fibrinolysis

IS - 7

ER -

Pegasparaginase treatment alters thrombin generation by modulating the protein C and S system in acute lymphoblastic leukaemia/lymphoma

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this