The coagulopathy and thrombotic risk associated with L-asparaginase treatment in adults with acute lymphoblastic leukaemia

E Truelove; A K Fielding; B J Hunt

doi:10.1038/leu.2012.290

The coagulopathy and thrombotic risk associated with L-asparaginase treatment in adults with acute lymphoblastic leukaemia

E Truelove, A K Fielding, B J Hunt

Research output: Contribution to journal › Review article › peer-review

Abstract

The dramatic improvements seen in the outcome of paediatric patients with acute lymphoblastic leukaemia (ALL) have led to increasing incorporation of L-asparaginase (L-Asp) in adult treatment protocols. However, its use is associated with a disruption in the physiological balance between haemostatic and anticoagulant pathways, with the predominant clinical manifestation being thrombosis. Although L-Asp therapy is known to be associated with an acquired deficiency of antithrombin (AT), the concurrent depletion of fibrinogen and other haemostatic proteins means that the precise mechanism of thrombosis remains to be defined. In vitro coagulation assays are often prolonged but thrombosis rather than haemorrhage is the primary concern. Management of thrombotic events in these patients is based around agents that rely on AT for their anticoagulant effect, even though it is usually depleted. There is currently only limited evidence supporting the use of AT concentrates in either primary prevention or management following an established event. Evidence-based guidelines for prevention and management strategies are lacking.

Original language	English
Pages (from-to)	553-9
Number of pages	7
Journal	Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Volume	27
Issue number	3
DOIs	https://doi.org/10.1038/leu.2012.290
Publication status	Published - Mar 2013

Keywords

Adult
Antineoplastic Agents/adverse effects
Asparaginase/adverse effects
Blood Coagulation Disorders/chemically induced
Humans
Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications
Risk Factors
Thrombosis/chemically induced

Access to Document

10.1038/leu.2012.290

Cite this

@article{810319cbab1646c8902aeb8443378ffa,

title = "The coagulopathy and thrombotic risk associated with L-asparaginase treatment in adults with acute lymphoblastic leukaemia",

abstract = "The dramatic improvements seen in the outcome of paediatric patients with acute lymphoblastic leukaemia (ALL) have led to increasing incorporation of L-asparaginase (L-Asp) in adult treatment protocols. However, its use is associated with a disruption in the physiological balance between haemostatic and anticoagulant pathways, with the predominant clinical manifestation being thrombosis. Although L-Asp therapy is known to be associated with an acquired deficiency of antithrombin (AT), the concurrent depletion of fibrinogen and other haemostatic proteins means that the precise mechanism of thrombosis remains to be defined. In vitro coagulation assays are often prolonged but thrombosis rather than haemorrhage is the primary concern. Management of thrombotic events in these patients is based around agents that rely on AT for their anticoagulant effect, even though it is usually depleted. There is currently only limited evidence supporting the use of AT concentrates in either primary prevention or management following an established event. Evidence-based guidelines for prevention and management strategies are lacking.",

keywords = "Adult, Antineoplastic Agents/adverse effects, Asparaginase/adverse effects, Blood Coagulation Disorders/chemically induced, Humans, Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications, Risk Factors, Thrombosis/chemically induced",

author = "E Truelove and Fielding, {A K} and Hunt, {B J}",

year = "2013",

month = mar,

doi = "10.1038/leu.2012.290",

language = "English",

volume = "27",

pages = "553--9",

journal = "Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K",

issn = "1476-5551",

number = "3",

}

The coagulopathy and thrombotic risk associated with L-asparaginase treatment in adults with acute lymphoblastic leukaemia. / Truelove, E; Fielding, A K; Hunt, B J.
In: Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K, Vol. 27, No. 3, 03.2013, p. 553-9.

Research output: Contribution to journal › Review article › peer-review

TY - JOUR

T1 - The coagulopathy and thrombotic risk associated with L-asparaginase treatment in adults with acute lymphoblastic leukaemia

AU - Truelove, E

AU - Fielding, A K

AU - Hunt, B J

PY - 2013/3

Y1 - 2013/3

N2 - The dramatic improvements seen in the outcome of paediatric patients with acute lymphoblastic leukaemia (ALL) have led to increasing incorporation of L-asparaginase (L-Asp) in adult treatment protocols. However, its use is associated with a disruption in the physiological balance between haemostatic and anticoagulant pathways, with the predominant clinical manifestation being thrombosis. Although L-Asp therapy is known to be associated with an acquired deficiency of antithrombin (AT), the concurrent depletion of fibrinogen and other haemostatic proteins means that the precise mechanism of thrombosis remains to be defined. In vitro coagulation assays are often prolonged but thrombosis rather than haemorrhage is the primary concern. Management of thrombotic events in these patients is based around agents that rely on AT for their anticoagulant effect, even though it is usually depleted. There is currently only limited evidence supporting the use of AT concentrates in either primary prevention or management following an established event. Evidence-based guidelines for prevention and management strategies are lacking.

AB - The dramatic improvements seen in the outcome of paediatric patients with acute lymphoblastic leukaemia (ALL) have led to increasing incorporation of L-asparaginase (L-Asp) in adult treatment protocols. However, its use is associated with a disruption in the physiological balance between haemostatic and anticoagulant pathways, with the predominant clinical manifestation being thrombosis. Although L-Asp therapy is known to be associated with an acquired deficiency of antithrombin (AT), the concurrent depletion of fibrinogen and other haemostatic proteins means that the precise mechanism of thrombosis remains to be defined. In vitro coagulation assays are often prolonged but thrombosis rather than haemorrhage is the primary concern. Management of thrombotic events in these patients is based around agents that rely on AT for their anticoagulant effect, even though it is usually depleted. There is currently only limited evidence supporting the use of AT concentrates in either primary prevention or management following an established event. Evidence-based guidelines for prevention and management strategies are lacking.

KW - Adult

KW - Antineoplastic Agents/adverse effects

KW - Asparaginase/adverse effects

KW - Blood Coagulation Disorders/chemically induced

KW - Humans

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications

KW - Risk Factors

KW - Thrombosis/chemically induced

U2 - 10.1038/leu.2012.290

DO - 10.1038/leu.2012.290

M3 - Review article

C2 - 23099335

SN - 1476-5551

VL - 27

SP - 553

EP - 559

JO - Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K

JF - Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K

IS - 3

ER -