Heparan sulfates from arteries and veins differ in their antithrombin-mediated anticoagulant activity

Abstract

The patient was then discharged in a stable condition. Because he moved to another city a few weeks after hospital discharge, a repeat TG assay was not possible. A telephone interview conducted 6 months later revealed that he did not experience any clinically obvious clotting abnormality again. In our patient, treatment with IVIG led to a normalization of hemostasis as confirmed by the TG assay, the disappearance of FV inhibitor, and the rise in FV activity. IVIG was given on the basis of its reported efficacy in patients with acquired hemo-philia A. However, a spontaneous recovery cannot be ruled out with certainty. The amount of thrombin generated, the lag phase and the time to thrombin peak are influenced by FV, as FV is part of every step in the process of TG [4]. Platelet FV rather than plasma FV plays a significant role in the amplification phase of coagulation. FV inhibitor leads to an impaired initiation phase, and this in turn results in impaired platelet activation. On the other hand, FV on the surface of activated platelets becomes neutraliszed by FV inhibitor, which leads to a reduction in prothrombinase activity and thrombin burst. The amount of FV needed to produce an adequate thrombin burst is still unclear. In our patient, minimal changes in FV activity from 7.4% to 8.6% led to a considerable increase in thrombin formation. Higher concentrations of FV did not result in any further increase in ETP, but did result in further reductions in the lag phase and the time to peak. Al Dieri et al. [5] observed no severe impairment in ETP at FV levels of 2% in patients with congenital FV deficiency. However, they used much higher TF concentrations (15 pM) in their assay. Therefore, their data are hardly comparable to ours. Furthermore , a measurable amount of the coagulation factor in the presence of an acquired autologous inhibitor may not necessarily correlate with its hemostatic function. Studies in patients with acquired autoantibody hemophilia A have shown that the inactivation has a type II pattern, with some residual FVIII activity being identifiable even after incubation at high concentrations of antibody. The presence of the inhibitor rather than the measurable coagulation factor activity is thus important in assessing the hemostatic state. In conclusion, the TG assay could be useful for monitoring hemostatic changes in patients with FV deficiency due to an inhibitor. However, there are issues of standardization to be dealt with. Clinical correlation with TG cutoff values is also lacking. These issues have to be addressed before the assay can be used in clinical routine practice. Disclosure of Conflict of Interests The authors state that they have no conflict of interest. References 1 Favaloro EJ, Posen J, Ramakrishna R, Soltani S, McRae S, Just S, Aboud M, Low J, Gemmell R, Kershaw G, Coleman R, Dean M. Factor V inhibitors: rare or not so uncommon? A multi-laboratory investigation Blood Coagul Fibrinolysis 2004; 15: 637-47. 2 Streiff MB, Ness PM. Acquired FV inhibitors: a needless iatrogenic compl...

Exploiting enzyme specificities in digestions of chondroitin sulfates A and C: Production of well-defined hexasaccharides

“…Complexes involving glycosaminoglycans (GAGs) of the extracellular matrix and various proteins are important in regulating cell-cell interactions and cell-signaling events (Lindahl and Hook 1978;Handel et al 2005;Raman et al 2005;Sasisekharan et al 2006;Imberty et al 2007;Gandhi and Mancera 2008). Those interactions have innumerable physiological consequences including organogenesis/growth control (Cohn et al 1976;Beaulieu et al 1991), cell adhesion (de Aguiar et al 2005), coagulation/thrombosis (De Mattos et al 2008;He et al 2008), regeneration/wound healing (Gorio et al 1997;Cattaruzza and Perris 2005), tumorigenesis/metastasis (Cattaruzza and Perris 2005;Muramatsu and Muramatsu 2008), morphogenesis (Thesleff et al 1988;Domowicz et al 2000), inflammation (Kaplan et al 2002;Handel et al 2005;Koninger et al 2006;Doodes et al 2009) and neural development/regeneration (Perris et al 1996;Pettway et al 1996;Inatani et al 2001;Tully et al 2004). They also play an important role in infection by pathogens (vanPutten et al 1997) and in mediation of prion internalization (Warner et al 2002;Ben-Zaken et al 2003;Horonchik et al 2005).…”

Characterization of Glycosaminoglycans by15N NMR Spectroscopy and in Vivo Isotopic Labeling

“…These glycans are commonly attached to a membrane protein core to form the cell surface proteoglycans found virtually in all mammalian cells 4. As a part of the ECM they influence numerous physiological processes, including organogenesis/growth control,5, 6 cell adhesion,7 angiogenesis,8 wound healing,9, 10 tumorigenesis,10, 11 morphogenesis,12, 13 inflammation,14–16 haemostasis,17, 18 and neural development/regeneration 19–22. GAGs also participate as receptors of various pathogens during the process of infection,23 and they have found applications in the treatment of diseases,24–26 for example, in the use of heparins for the treatment of acute coronary conditions 27–30.…”

Multitasking Human Lectin Galectin-3 Interacts with Sulfated Glycosaminoglycans and Chondroitin Sulfate Proteoglycans

“…Binding of a variety of GAG binding proteins (GAGBPs) to free GAGs or to the covalently linked GAGs of proteoglycans is essential for many cellular events, 1,2,5−9 including metastasis, 3,10 morphogenesis, 11 neural development/regeneration, 12,13 organogenesis, 14 wound healing, 10,15 inflammation, 16−18 pathogen invasion, 19 cell adhesion, 20 and coagulation. 21 Growth factors, cytokines, morphogens, ECM proteins, nuclear proteins, and pathogen surface proteins are among the most notable GAGBPs.…”