The effects of glycosaminoglycans on coagulation: a thromboelastographic study.

Endogenous heparinoids impair coagulation, evidenced by thrombelastography in cirrhotic patients with bacterial infection, but it is not clear which glycosaminoglycans can be detected by native and heparinase-modified thrombelastography. To assess the effects of different glycosaminoglycans on thrombelastography parameters and the reversibility of these effects by heparinase-I-modified thrombelastography. Twenty volunteers were enrolled. Solutions of heparan sulphate, dermatan sulphate, and chondroitin-4-sulphate were prepared at 'equivalent' concentrations, based on the composition and anticoagulant activity of danaparoid. Serial dilutions of each glycosaminoglycan were prepared to achieve 1.0, 0.5, 0.1, and 0.05 U/ml. Native and heparinase-modified thrombelastography, anti-activated factor X activity and heparin cofactor II activity were evaluated at each concentration. A statistically significant heparin-like effect was seen with 1 and 0.5 U/ml heparan sulphate, and 1 and 0.5 U/ml dermatan sulphate, which was completely reversed by heparinase-modified thrombelastography. Anti-activated factor X activity was significantly increased in samples containing heparan and dermatan sulphates. The heparin cofactor II activity decreased with 1.0 and 0.5 U/ml dermatan sulphate and chondroitin-4-sulphate, but not with heparan sulphate. Heparan and dermatan sulphates affect haemostasis when added to whole blood in vitro, detectable by native thrombelastography and completely reversed by heparinase-I-modified thrombelastography. They may therefore be responsible for the heparin-like effect seen by thrombelastography in patients with cirrhosis and bacterial infection.

Consider 'hyperviscosity syndrome' in unexplained breathlessness.

A 58-year-old man presenting with increasing shortness of breath over several months is reported here. All investigations were repeatedly normal until he suddenly and rapidly deteriorated, warranting admission, and a diagnosis was made of early multiple myeloma associated with the hyperviscosity syndrome. The plasma viscosity was extremely high compared to the low concentration of paraprotein present, and the possible mechanisms are discussed. Although uncommon, the hyperviscosity syndrome is an important cause of dyspnoea which is readily reversible, and should be considered when investigations of cardiac and pulmonary function are normal.

Endogenous heparin-like activity detected by anti-Xa assay in infected cirrhotic and non-cirrhotic patients.

BACKGROUND: Bacterial infections have been proposed as a trigger for portal hypertensive bleeding in cirrhotic patients. Endogenous low molecular weight heparinoids have been previously detected in vitro by heparinase-modified thromboelastography, but it is not known what type of heparinoids they are. The aim of this study was to assay anti-Xa concentrations to detect heparin activity in infected cirrhotics in vivo. METHODS: We evaluated 30 cirrhotic patients (15 with bacterial infection, 15 not infected) and 9 non-cirrhotic patients with bacterial infection. The anti-Xa assay was performed at the start of infection in all patients and after resolution of infection in 8 cirrhotics (5 to 10 days after starting antibiotics); thromboelastography (native and heparinase I-modified TEG) was performed in a subgroup of 11 cirrhotic patients with infection, 8 cirrhotics without infection and 8 non-cirrhotics with infection. RESULTS: Anti-Xa activity was detected in 9 of the 15 infected cirrhotics (60%) and only in 1 of 15 non-infected cirrhotics (6.7%) (P < 0.01). In the infected cirrhotic patients, a heparinase effect was shown in the heparinase I-modified TEG: k time (P < 0.01), alpha-angle (P < 0.01) and r time (P = 0.05), with no effect in the non-infected cirrhotics. Four of 9 (44%) infected non-cirrhotics were positive with the anti-Xa assay. CONCLUSION: In cirrhotic patients, bacterial infections modify haemostasis by producing endogenous heparin-like substances which can inhibit the activated clotting factor X (factor Xa). In infected non-cirrhotics, anti-Xa activity can also be found.