Heparin complexation

Schlessinger, J. et al., Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization, Mol. Cell., 6, 743-750, 2000. 

A modified technique consisting of an electric field applied perpendicular to a flowing buffer solution and using chromatography paper as support(cross-electrophoresis) has been exploited to study the reaction of neomycin with heparin 9 184. Evidence for the formation of a neomycin-heparin complex was obtained by this means. 

Heparin Complex polysaccharide used as a drug to prevent blood clotting. 

A substrate recognition site that also functions as the binding site for the AT-heparin complex-AT complex (exosite I) and... 

One of the samples which contained 5 mg. of covalently bonded heparinized beads had only 41 minutes clotting time which is very much shorter than the other sample, but still longer than the ionically bonded heparin complex beads. This shortened clotting time was attributed to an air bubble which was trapped by a mechanical error while the technician was adding the blood into the tube dropwise. The technician predicted a priori that this particular sample would have a low value for clotting time. 

The use of heparinized catheters for in vivo erythrocyte labelling with " Tc-pyrophosphate occasionally produces adverse reports, such as diminution of cardiac activity and increase of renal activity due to the formation of a technetium-heparin complex which localizes avidly in the kidneys. A few cases reported the possibility of reaction of radiopharmaceuticals with the components of a syringe or needle. 

One of the laboratory tests used in the identification of patients with heparin-induced thrombocytopenia, employs a micro-ELISA plate coated with purified PF4-heparin complex. Upon incubation of patient s plasma, if antibody is present, it binds to the PF4-heparin complex. The bound antibody is detected with goat antihuman antibody coupled to peroxidase, followed by incubation with substrates o-phenylenediamine/H202 (Chapter 8). 

The second type of heparin-induced thrombocytopenia is severe and may be associated with a platelet count below 100,000/mm and thrombosis. ° ° The platelet count generally begins to decline 5 to 10 days after the start of heparin therapy (sooner in patients previously treated with heparin). Thrombocytopenia and thrombosis may develop with low-dose heparin, heparin-coated catheters, or even heparin flushes. Historically, the reaction was thought to be mediated by the formation of antibodies to the platelet-heparin complex. However, evidence suggests a complex interaction between heparin, platelet factor 4 (PF4), platelet membrane Fc receptors, and possibly heparin-like molecules on the surface of endothehal cells (Fig. 102-6). Circulating heparin reacts with PF4 to produce a... 

Diminished cardiac activity and increased renal activity has been observed when a heparinized catheter was used for in vivo red cell labeling with pyrophosphate. This was interpreted as formation of a Tc-heparin complex that localizes avidly in the kidneys (Hegge et al. 1978). Injection of Sn-pyrophosphate and " Tc-pertechnetate through a heparin lock should be avoided. 

Heparinoids and mucopolysaccharides react with, and modify, many of the plasma proteins. Heparin combines with fibrinogen, globulins and albumin. As judged by electrophoresis and various types of analysis and staining, the particular plasma protein components with which heparin combines are dependent upon the concentration of protein, concentration of heparin, pH value, and salts present. This explains the somewhat contradictory statements in literature about combinations of heparin with plasma proteins. The combination may result in change of solubility of the protein and reverse protein tests . Heparin can modify the murexide reaction for calcium in serum by affecting the calcium-protein-heparin complex. Many heparinoids... 

Snellman, Sylven and Julen isolated the heparin polypeptide and showed that this material is a potent antithrombin on thrombin with purified fibrinogen, suggesting that heparin in the mast cells is in the active anticoagulant form. Electrophoresis shows that this native heparin forms a complex compound with thrombin and also with a lipoprotein molecule. They conclude the whole heparin complex is produced in the intergranular cytoplasm of the tissue mast cells. 

Careful examination of the possible fates of the bound heparin and the bound inactive complex suggests hypothetical mechanisms which, if effective, could limit the utility of heparinized materials (Table I). For example, either the surface may become saturated with a heparin complex that can no longer accelerate the inactivation of thrombin, or consumption of antithrombin, prothrombin, or other clotting factors may result, leaving the blood systematically hypocoagulable. 

The thrombin-heparin complex was also injected onto both the PAOM and PSSO supports, to investigate Th/Hep/resin interactions. The chromatographic profiles on each of the solid phases were almost identical as shown in Figure 4B. To identify the components in each peak, the enzyme and heparin were chromatograghed separately but under the same experimental conditions (Figures 1 and 3). The first peak was thus attributed to free-heparin molecules and the second, eluted at a higher ionic strength, to the enzyme alone. In contrast to the Th-AT III complex, the Th-Hep complex was dissociated by both solid phases. 

Lietha D, Chirgadze DY, Mulloy B, Blundell TL, Gherardi E. Crystal structures of NKl-heparin complexes reveal the basis for NKl activity and enable engineering of potent agonists of the MET receptor. Embo J 2001 20 5543-5555. 

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