Studies on the profibrinolytic actions of heparin and its fractions.
Utilizing modified immunochemical methods (ELISA and radioimmunoassay) tissue plasminogen activator, B beta 15-42 RPs and protein C antigen levels were measured in man and a subhuman primate model after subcutaneous and intravenous administration of various low molecular weight heparin fractions. A wide scatter in the data was observed in the t-PA and B beta 15-42 RP levels; however, statistical analysis of the data revealed that certain low molecular weight heparin fractions increased the levels of these endogenous markers of fibrinolysis. No significant alteration in the protein C levels was noted at any time; however, a wide scatter in these data was also evident. The profibrinolytic actions of low molecular weight heparin fractions may be related to the release of t-PA, which is easily measured in plasma. Since it has strong affinity for endogenous sites (thrombus, surface), wide scatter in the data may occur. Physical exercise may also increase the levels. Most of the results reported in our studies represent data on blood samples that were obtained using the simple venipuncture method. We also find that the intravenous administration of the low molecular weight heparin fractions also caused a shortening of the ELT. Since the low molecular weight heparin fractions are heterogeneous in nature, the profibrinolytic actions may be related to one or more of these constituent fragments. Thus, the molecular identity of the profibrinolytic component of low molecular weight fractions remains unknown at this time. Also unknown is if there is a relationship between this effect and anticoagulant activity.
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005164:Factor IX / Q000494:pharmacology; D015949:Factor IXa; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006023:Glycoproteins / Q000097:blood; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D010446:Peptide Fragments; D010960:Plasminogen Activators / Q000097:blood; D011486:Protein C; D012712:Serum Globulins / Q000378:metabolism
D005338:Fibrin Fibrinogen Degradation Products; D006023:Glycoproteins; D010446:Peptide Fragments; D011486:Protein C; D012712:Serum Globulins; C033786:fibrinogen Bbeta (15-42); D005164:Factor IX; D006493:Heparin; D010960:Plasminogen Activators; D015949:Factor IXa