The effect of glycosaminoglycans with acetaldehyde on the activation of prothrombin.
Heparin17-19k, (25, 50, and 100 ng), heparin6k (50 and 100 ng), heparin3k (50, 100, and 200 microg), chondroitin sulfates B (dermatan sulfate) (0.25, 0.5, and 1.0 microg), C (1 and 10 microg), and A (1 and 10 microg) each prolong the activated partial thromboplastin time (APTT) when preincubated with prothrombin to a greater extent than when preincubated with Factor II-deficient plasma prior to their mixing and subsequent additions of APTT reagent and Ca2+. In all cases statistical significance (p < or = 0.05) was observed except with the 2 lower levels of heparin3k. These results suggest that the glycosaminoglycans (GAGs) may exert a direct effect upon prothrombin (FII) in their anticoagulant activity. Pre mix tures of [(FII/25 ng H17-19k) + 447 mmol acetaldehyde (AcH)/L] as well as [(AcH/H) + FII] and [(FII/AcH) + H] each exert a synergistic anticoagulant effect upon APTT. At low AcH concentrations (44.7 mmol/L), neither a synergistic nor an additive effect is seen. H6k and H3k, on premixing with 447 mmol AcH/L, exhibit an additive effect on APTT prolongation but no synergism. Similarly, premixtures of CSB/447 mmol AcH/L/FII show a greater anticoagulant effect than do [(CSB/AcH) + FII] or [(FII/AcH) + CSB] premixtures. CSC-AcH and CSA-AcH patterns are analogous to those of CSB (DS). These data suggest the possibility that AcH, the primary product of ethanol metabolism, may serve as a crosslinking adduct with proteins, in this case, prothrombin, as well as GAGs. Thus ternary complexes between the zymogen form of coagulation factors, GAGs, and AcH are possible, further influencing coagulopathy.
Brecher
Arthur S
AS
Department of Chemistry, Bowling Green State University, OH 43403, USA. artbrec@bgnet.bgsu.edu
Adamu
Mohammed T
MT
D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D002809:Chondroitin Sulfates / Q000494:pharmacology; D003871:Dermatan Sulfate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D066298:In Vitro Techniques; D010314:Partial Thromboplastin Time; D011516:Prothrombin / Q000819:agonists*
D000925:Anticoagulants; D006025:Glycosaminoglycans; D006495:Heparin, Low-Molecular-Weight; D003871:Dermatan Sulfate; D011516:Prothrombin; D006493:Heparin; D002809:Chondroitin Sulfates; D000079:Acetaldehyde