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Laboratory Detection of the Antiphospholipid Syndrome via Calibrated Automated Thrombography

(2009) Thrombosis and haemostasis. 101(1). p.185-196
Author
Organization
Abstract
Lupus anticoagulants (LAC) consist of anti phospholipid antibodies, detected via their anti coagulant properties in vitro. Strong LAC relate to thromboembolic events, a hallmark of the anti-phospholipid syndrome. We have analyzed whether detection of this syndrome would benefit from thrombin generation measurements. Therefore, calibrated automated thrombography was done in normal plasma (n=30) and LAC patient plasma (n=48 non-anticoagulated, n=12 on oral anti coagulants), diluted 1: 1 with a normal plasma pool. The anti-beta(2)-glycoprotein I monoclonal antibody 23H9, with known LAC properties, delayed the lag time and reduced the peak height during thrombin generation induction in normal plasma dose-dependently (0-150 mu g/ml). At variance, LAC patient 1: 1 plasma mixtures manifested variable lag time prolongations and/or peak height reductions. Coupling these two most informative thrombin generation parameters in a peak height/lag time ratio,and upon normalization versus the normal plasma pool, this ratio distributed normally and was reduced in the plasma mixtures, for 59/60 known LAC plasmas. The normalized peak height/lag time ratio correlated well with the normalized dilute prothrombin time,diluted Russell's viper venom time and silica clotting time, measured in 1: 1 plasma mixtures (correlation coefficients 0.59-0.72). The anticoagulant effects of activated protein C (0-7.5 nM) or 23H9 (0-150 mu g/ml), spiked in the 1: 1 LAC plasma mixtures were reduced for the majority of patients, compatible with functional competition between patient LAC and activated protein C and LAC and 23H9, respectively. Hence,the normalized thrombin gene ration-derived peak height/lag time ratio identifies LAC in plasma with high sensitivity in a single assay, irrespective of the patient's treatment with oral anticoagulants.
Keywords
ANTICARDIOLIPIN ANTIBODIES, THROMBIN GENERATION, ACQUIRED-RESISTANCE, IGG ANTIBODIES, BETA(2)-GLYCOPROTEIN-I, BETA-2-GLYCOPROTEIN-I, PROTHROMBIN, PLASMA, ACTIVATED PROTEIN-C, LUPUS ANTICOAGULANTS, prothrombin, antibodies, alpha(2)-glycoprotein I, lupus anticoagulants, Thrombosis

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MLA
Devreese, Katrien et al. “Laboratory Detection of the Antiphospholipid Syndrome via Calibrated Automated Thrombography.” Thrombosis and haemostasis 101.1 (2009): 185–196. Print.
APA
Devreese, K., peerlinck, kathelijne, arnout, jef, & hoylaerts, marc. (2009). Laboratory Detection of the Antiphospholipid Syndrome via Calibrated Automated Thrombography. Thrombosis and haemostasis, 101(1), 185–196.
Chicago author-date
Devreese, Katrien, kathelijne peerlinck, jef arnout, and marc hoylaerts. 2009. “Laboratory Detection of the Antiphospholipid Syndrome via Calibrated Automated Thrombography.” Thrombosis and Haemostasis 101 (1): 185–196.
Chicago author-date (all authors)
Devreese, Katrien, kathelijne peerlinck, jef arnout, and marc hoylaerts. 2009. “Laboratory Detection of the Antiphospholipid Syndrome via Calibrated Automated Thrombography.” Thrombosis and Haemostasis 101 (1): 185–196.
Vancouver
1.
Devreese K, peerlinck kathelijne, arnout jef, hoylaerts marc. Laboratory Detection of the Antiphospholipid Syndrome via Calibrated Automated Thrombography. Thrombosis and haemostasis. Stuttgart: Schattauer; 2009;101(1):185–96.
IEEE
[1]
K. Devreese, kathelijne peerlinck, jef arnout, and marc hoylaerts, “Laboratory Detection of the Antiphospholipid Syndrome via Calibrated Automated Thrombography,” Thrombosis and haemostasis, vol. 101, no. 1, pp. 185–196, 2009.
@article{877301,
  abstract     = {Lupus anticoagulants (LAC) consist of anti phospholipid antibodies, detected via their anti coagulant properties in vitro. Strong LAC relate to thromboembolic events, a hallmark of the anti-phospholipid syndrome. We have analyzed whether detection of this syndrome would benefit from thrombin generation measurements. Therefore, calibrated automated thrombography was done in normal plasma (n=30) and LAC patient plasma (n=48 non-anticoagulated, n=12 on oral anti coagulants), diluted 1: 1 with a normal plasma pool. The anti-beta(2)-glycoprotein I monoclonal antibody 23H9, with known LAC properties, delayed the lag time and reduced the peak height during thrombin generation induction in normal plasma dose-dependently (0-150 mu g/ml). At variance, LAC patient 1: 1 plasma mixtures manifested variable lag time prolongations and/or peak height reductions. Coupling these two most informative thrombin generation parameters in a peak height/lag time ratio,and upon normalization versus the normal plasma pool, this ratio distributed normally and was reduced in the plasma mixtures, for 59/60 known LAC plasmas. The normalized peak height/lag time ratio correlated well with the normalized dilute prothrombin time,diluted Russell's viper venom time and silica clotting time, measured in 1: 1 plasma mixtures (correlation coefficients 0.59-0.72). The anticoagulant effects of activated protein C (0-7.5 nM) or 23H9 (0-150 mu g/ml), spiked in the 1: 1 LAC plasma mixtures were reduced for the majority of patients, compatible with functional competition between patient LAC and activated protein C and LAC and 23H9, respectively. Hence,the normalized thrombin gene ration-derived peak height/lag time ratio identifies LAC in plasma with high sensitivity in a single assay, irrespective of the patient's treatment with oral anticoagulants.},
  author       = {Devreese, Katrien and peerlinck, kathelijne and arnout, jef and hoylaerts, marc},
  issn         = {0340-6245},
  journal      = {Thrombosis and haemostasis},
  keywords     = {ANTICARDIOLIPIN ANTIBODIES,THROMBIN GENERATION,ACQUIRED-RESISTANCE,IGG ANTIBODIES,BETA(2)-GLYCOPROTEIN-I,BETA-2-GLYCOPROTEIN-I,PROTHROMBIN,PLASMA,ACTIVATED PROTEIN-C,LUPUS ANTICOAGULANTS,prothrombin,antibodies,alpha(2)-glycoprotein I,lupus anticoagulants,Thrombosis},
  language     = {eng},
  number       = {1},
  pages        = {185--196},
  publisher    = {Schattauer},
  title        = {Laboratory Detection of the Antiphospholipid Syndrome via Calibrated Automated Thrombography},
  url          = {http://dx.doi.org/10.1160/TH08-06-0393},
  volume       = {101},
  year         = {2009},
}

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