title: Thrombin generation assay identifies individual variability in responses to low molecular weight heparin in pregnancy: implications for anticoagulant monitoring.
abstract: Low molecular weight heparin (LMWH) given to inhibit coagulation and reduce the risk of thrombosis, is typically monitored by anti-Xa assay. However, anti-Xa levels may not necessarily provide an accurate measure of coagulation inhibition. Moreover, pregnancy is associated with hypercoagulability, which may compromise the efficacy of LMWH. We looked at the association between anti-Xa levels and parameters of thrombin generation assay [TGA; area under the curve (AUC), peak height (PH) and time to peak (ttP)] using samples from 41 pregnant women receiving LMWH and 40 normal pregnant women controls. TGA results confirmed the physiological hypercoagulability of normal pregnancy (mean normalised values: AUC 119%; PH 157%; ttP 72%). Although anti-Xa measures correlated with all three TGA parameters, this group correlation masked significant inter-individual variability, demonstrated by the R(2) value or coefficient of determination. Anti-Xa levels contributed to 74% of variation in AUC values, 63% of variation in PH values and only 53% of variation in ttP values. The remainder reflects the contribution of patients' intrinsic coagulation status. Hence, some patients with 'safe' anti-Xa levels may potentially be under-anticoagulated, particularly in pregnancy. Measuring coagulability directly with TGA may lower the risk of adverse events due to under-anticoagulation in selected patients.
authors.affiliation: Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London, UK.
authors.forename: Pratima
authors.initials: P
authors.lastname: Chowdary
authors.forename: Despoina
authors.initials: D
authors.lastname: Adamidou
authors.forename: Anne
authors.initials: A
authors.lastname: Riddell
authors.forename: Saman
authors.initials: S
authors.lastname: Aghighi
authors.forename: Anja
authors.initials: A
authors.lastname: Griffioen
authors.forename: Paul
authors.initials: P
authors.lastname: Priest
authors.forename: Lida
authors.initials: L
authors.lastname: Moghadam
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kelaher
authors.forename: Farah Y
authors.initials: FY
authors.lastname: Huq
authors.forename: Rezan A
authors.initials: RA
authors.lastname: Kadir
authors.forename: Edward G
authors.initials: EG
authors.lastname: Tuddenham
authors.forename: Alex
authors.initials: A
authors.lastname: Gatt
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics; D065427:Factor Xa Inhibitors / Q000097:blood*; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D008991:Monitoring, Physiologic; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood / Q000188:drug therapy; D012189:Retrospective Studies; D013918:Thrombin Time / Q000379:methods; D019851:Thrombophilia / Q000097:blood / Q000188:drug therapy
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight
keywords: anti-Xa assay; heart valves; heparins; pregnancy; thrombin generation assay