Decreased sialic acid content of plasma von Willebrand factor in precapillary pulmonary hypertension

pulmonary hypertension, defective von Willebrand factor protein (vWF) lacki ng large multimers is present in circulation. This is associated with evide nce of chronic endogenous platelet activation. Since asialo vWF has been sh own to promote platelet activation and aggregation, we decided to investiga te possible changes in the sialic acid content of plasma VWF in patients wi th precapillary pulmonary hypertension. vWF-associated sialic acid was meas ured indirectly as a wheat germ agglutinin-reactive substance (WGA-RS, West ern blotting), and directly, as a thiobarbituric acid-reactive substance (T BA-RS, spectrophotometric reading). In the sixteen patients we studied (age s 8-45 yr), circulating vWF concentration was 2.18 times normal (p <0.001). However, patient vWF subunit contained 19% (WGA-RS) to 24% (TBA-RS) less s ialic acid than the normal protein (p <0.05 for both determinations). In fi ve patients, vWF-associated sialic acid was below 50% normal. We conclude t hat circulating vWF is hyposialylated in precapillary pulmonary hypertensio n and speculate that this might influence its interaction with platelets in vivo in these patients.