Premium
Comparison of the anticoagulant effect of a direct thrombin inhibitor and a low molecular weight heparin in an acquired antithrombin deficiency in children with acute lymphoblastic leukaemia treated with l ‐asparaginase: an in vitro study
Author(s) -
Kuhle Stefan,
Lau Alice,
Bajzar Laszlo,
Vegh Patsy,
Halton Jacqueline,
Cherrick Irene,
Anderson Ron,
Desai Sunil,
McCusker Patricia,
Wu John,
Abshire Thomas,
Mahoney Donald,
Mitchell Lesley
Publication year - 2006
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2006.06209.x
Subject(s) - antithrombin , heparin , anticoagulant , thrombin , low molecular weight heparin , medicine , direct thrombin inhibitor , pharmacology , immunology , cancer research , platelet , warfarin , dabigatran , atrial fibrillation
Summary Thrombosis occurs in 37% of children with acute lymphoblastic leukaemia (ALL) and is related to an l ‐asparaginase‐induced acquired antithrombin (AT) deficiency. The incidence dictates the need for anticoagulant prophylaxis. Direct thrombin inhibitors (DTI) are independent of AT for effect and may thus have advantages in this population. The objective of this study was to determine the interaction of an AT deficiency with the anticoagulant effects of a DTI and a low molecular weight heparin (LMWH). Plasma samples from children with ALL were pooled (mean AT 0·53 U/ml). LMWH 0·3 and 0·7 U/ml or melagatran 0·3 and 0·5 μ mol/l were added to the pools, then divided and AT was added back to one aliquot. In additional experiments, AT was added to AT immuno‐depleted plasma. Endogenous thrombin generation capacity (ETGC) was assessed by the continuous method. In plasma with LMWH, there was a 66–88% decrease in ETGC in AT‐normalised samples compared with neat. Conversely, no significant difference in ETGC with or without AT added for melagatran was seen. Experiments with AT‐depleted plasma showed no effect of AT level on anticoagulant activity of DTI, but a significant relationship for LMWH. By contrast to LMWH, DTI provides a consistent anticoagulant response independent of AT levels in children with AT deficiency.