PubMed · 8042579
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
C F Arkin. 1994. Coagulation screening tests.. https://doi.org/10.1093/ajcp%2F102.2.150
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
A heparin cofactor II (HCII) mutant with an Arg substituted for Leu444 at the P1 position (L444R-rHCII) was previously found to have altered proteinase specificity (Derechin, V. M., Blinder, M. A., and Tollefsen, D. M. (1990) J. Biol. Chem. 265, 5623-5628). The present study characterizes the effect of glycosaminoglycans on the substrate versus inhibitor activity of L444R-rHCII. Heparin increased the stoichiometry of inhibition of L444R-rHCII with alpha-thrombin (compared with minus glycosaminoglycan) but decreased it with R93A,R97A,R101A-thrombin, a mutant thrombin that does not bind glycosaminoglycans. Dermatan sulfate decreased the stoichiometry of inhibition of L444R-rHCII with both proteinases. SDS-polyacrylamide gel electrophoresis showed no proteolysis of L444R-rHCII when incubated with R93A,R97A,R101A-thrombin in the absence or the presence of glycosaminoglycan or with alpha-thrombin and dermatan sulfate. In contrast, greater than 75% of the L444R-rHCII was converted to a lower molecular weight form when incubated with alpha-thrombin/heparin. A time course of alpha-thrombin inhibition by L444R-rHCII/heparin showed a rapid but transient inhibition with approximately 80% of the alpha-thrombin activity being regained after 6 h of incubation. In contrast, all other combinations of inhibitor, proteinase, and glycosaminoglycan resulted in complete and sustained inhibition of the proteinase. Heparin fragments of 8-20 polysaccharides in length rapidly accelerated L444R-rHCII inhibition of both alpha-thrombin and R93A,R97A,R101A-thrombin. After extended incubations, R93A,R97A,R101A-thrombin was completely inhibited by L444R-rHCII with all the heparin fragments, but approximately 30-50% of alpha-thrombin activity remained with fragments long enough to bridge HCII-thrombin. These results collectively indicate that ternary complex formation, mediated by heparin, increases L444R-rHCII inactivation by alpha-thrombin.
Heparin-associated thrombocytopenia and thrombosis (Type II HAT), the "white clot syndrome," has not been previously reported as a cause for fulminant hepatic failure after liver transplantation. Thrombocytopenia and the use of heparin are common events in the newly transplanted patient. A man who was transplanted for sclerosing cholangitis, and re-exposed to heparin, is described with thrombocytopenia, thrombosis of all hepatic vessels, and heparin antibodies. Type II HAT is an immune phenomenon that can apparently occur despite T-cell-directed immunosuppression. Suspicion is a key element in establishing diagnosis. We no longer use heparin routinely in liver transplant cases.
OBJECTIVE: To determine a rational approach to heparin dosing for thromboembolism prophylaxis. DESIGN: Literature review. RESULTS: Three commonly used heparin dosing regimens were identified: (1) standard low-dose heparin (5000 U administered subcutaneously 2-3 times per day); (2) adjusted-dose heparin (adequate to elevate the activated partial thromboplastin time to 5 seconds above the upper limit of normal); and (3) low-molecular-weight heparin (30 mg subcutaneously twice daily without monitoring). CONCLUSIONS: Adjusted-dose heparin thromboembolism prophylaxis is both the safest and most reliable method currently available.