title: Low plasma heparin cofactor II levels in thalassaemia syndromes are corrected by chronic blood transfusion.
abstract: Low plasma heparin cofactor II (HCII) levels are associated with a thrombotic tendency, and we have previously shown these to be decreased in a variety of haemolytic conditions. The risk of thrombosis is recognized to be increased in both thalassaemia major (TM) and intermedia (TI), although the exact mechanisms are poorly understood. HCII levels have therefore been compared in 20 untransfused patients with TI and 20 regularly transfused TM patients to determine the influence of transfusion on HCII. Additionally, untransfused TI patients have been commenced on regular red cell transfusion and the effects on correction of low HCII levels investigated. HCII levels were significantly lower in the untransfused TI patients (mean 0.56 +/- 0.06 U/ml) compared to TM patients (mean 0.85 +/- 0.1 U/ml; P < 0.001). Levels in TI were significantly less than in healthy age-matched controls (P < 0.001) and correlated with Hb values (r = 0.8), whereas levels in TM were at the lower end of the normal range. ATIII values were within the normal reference range in both TI and TM, and HCII antigen showed a parallel reduction to HCII activity, indicating that reduction in HCII is not a consequence of increased thrombin consumption. Three patients with TI were commenced prospectively on hypertransfusion programmes which resulted in a slow normalization of their levels taking 2-3 months. These findings support a hypothesis that the low HCII levels are related to increased red cell turnover and can be normalized once this turnover has been suppressed by hypertransfusion. The thrombotic risk to patients with low HCII levels in the presence of haemolysis might in principle be decreased by such transfusion regimes.
authors.affiliation: Department of Haematology, University College London Medical School.
authors.forename: A
authors.initials: A
authors.lastname: O'Driscoll
authors.forename: I J
authors.initials: IJ
authors.lastname: Mackie
authors.forename: J B
authors.initials: JB
authors.lastname: Porter
authors.forename: S J
authors.initials: SJ
authors.lastname: Machin
mesh_terms: D000293:Adolescent; D000328:Adult; D000990:Antithrombin III / Q000032:analysis; D001803:Blood Transfusion; D002648:Child; D017707:Erythrocyte Transfusion; D005260:Female; D015844:Heparin Cofactor II / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012016:Reference Values; D017086:beta-Thalassemia / Q000097:blood* / Q000628:therapy
chemical_list: D015844:Heparin Cofactor II; D000990:Antithrombin III