Curriculum Vitae
Ee Thye Yin, PhD
Career:
1959-1963 Kantonspital Zurich, Zurich, Switzerland, Europe
Research Fellow (Swiss Red Cross Blood Bank grant)
1963-1966 University of Washington School of Medicine, Seattle, WA
Research Fellow
1966-1973 Washington University School of Medicine, St. Louis, MO
Research Instructor in Medicine
Research Assistant Professor in Medicine
Research Associate Professor in Medicine,
with joint appointments at
The Jewish Hospital of St. Louis (now Barnes/Jewish)
Associate in Medicine, and
Co-Director, Blood Coagulation Laboratory
1974-present Founded Haemachem, Inc., St. Louis, MO
Heptest Laboratories, Inc., a Texas Corporation (2001)
1974-1978 Sigma Chemicals International, St. Louis, MO
Consultant (established and directed a new blood
coagulation division)
1975-1979 Pharmacia, AB, Uppsala, Sweden, Europe
Research Consultant
Contract research on new anticoagulants for
thromboprophylaxis (a $3 million project)
USA and International Patents assigned to Pharmacia, AB
1996-1997 World Health Organization (Geneva, Switzerland)
Consultant on Heparin Standardization (elected position)
Publications:
Authored and co-authored over 70 scientific publications in peer reviewed scientific and medical journals.
Co-authored chapters:
(1) On the Mechanism of Thrombosis. Wessler, S. and Yin, E.T. in, Progress in Hematology.
Editors, E.R. Brown and C. Moore. Gruen and Stratton (1969)
(2) Inhibitors of Blood Coagulation. Barton, P.G., and Yin, E.T. in Metabolic Inhibitors.
Editors, R.M. Hochster, M. Kates and J.H. Quastel. Academic Press (1973)
(3) Heparin, Heparinoids and Blood Coagulation. Yin, E.T. and Tangen, O. in Heparin Chemistry
and Clinical Usage. Editors, V.V. Kakkar and D.P. Thomas. Academic Press (1976)
(4) Hypercoagulability. Wessler, S. and Yin, E.T., in Metabolic Effects of Gonadal Hormones and
Contraceptive Steroids. Plenum Press (1969)
(5) Heparin Interaction with Activated Factor X and its Inhibitor. Yin, E.T., Eisenkramer, L. and
Butler, J.V. in Heparin. Editors R.A. Bradshaw and S. Wessler. Plenum Press (1976)
Pioneering Work
Since the discovery of heparin by McLean in 1916, the action of heparin as an anticoagulant had been attributed solely to its catalytic effect on the plasma Antithrombin-III's inhibition on the blood clotting enzyme Thrombin (Factor IIa). In 1970 my associate and I discovered that besides thrombin, heparin also has another catalytic effect on Activated Factor X, F.Xa, (1).
Based on this discovery, several events took place that greatly benefited the thrombosis research community. (A) The first quantitative assay for heparin in blood of patients treated with this anticoagulant (2,3) and extended to the current development of Heptest-POC-Hi. (B) We postulated that the major function of heparin is the inhibition of Factor Xa rather than thrombin.
We demonstrated that inhibition of 32 units of Factor Xa (1ug) in the presence of a subliminal amount of heparin could indirectly prevent the generation of 1000ug of the inhibitor. Animal experiments by my group demonstrated in animal studies that Factor Xa on a weight basis is at least 100 times more thrombogenic than thrombin. Based on this finding we hypothesized that to counter act hypercoagulable state in man, one would only need a very small amount of heparin.
Although in the 1970's this was a rather controversial hypothesis, by now the pendulum had swung to our direction. This gave impetus for Prof. Kakkar (Director, Thrombosis Institute in London, UK) to renew assessment on the efficacy of low-dose heparin in prophylaxis in high-risk patients undergoing major surgeries. His multi-center trials led to the current practice of the low-dose heparin regimens for the prevention of post-operative deep vein thrombosis (4-7).
In the meantime, several French and Swedish pharmaceutical companies began developing low molecular weight heparins possessing mainly anti-Factor Xa activity to replace the un-fractionated heparin for the prophylaxis and the treatment of thrombosis. There are currently at least three different successful brands of Factor Xa specific anticoagulants that can be taken either orally or by injection. These companies anticipate the use of such drugs in open-heart surgery. Our Heptest-POC-Hi is very sensitive to these new drugs while the ACT is not.
It is hoped that Heptest-POC-Hi will revolutionize heparin therapy during coronary bypass surgery (CPB), coupled with improved post-operative clinical events, because this test is scientifically sound as proven in the above mentioned Phase I and Phase II clinical trials. Unfortunately with the ACT, clinicians find themselves relying on empirical and "shotgun" methods of therapy.
In an analysis of 200 CPB patients during 10 post-operative days, it was reported (8) that 6% suffered mycardial infarction, 7% pulmonary emboli, 2% mild strokes, 3% phlebitis and 2% required re-operation for bleeding. It is evident that the aim of heparin therapy during CPB should not be only the prevention of thrombus formation in the bypass equipment, but also the maintenance of a normal coagulation status during and in the post-operative period. It is well established that thrombin generation is a continuous process in most bypass patients. Undoubtedly this could be regulated by a more accurate and specific heparin anticoagulant activities monitoring system.
Bibliography:
1. Yin, E.T. and Wessler, S.: Heparin-accelerated inhibition of Factor Xa by its plasma
inhibitor. Biochim. Biophys. Acta 2001:387, (1970).
2. Yin, E.T., Wessler, S. and Butler, J.: Plasma heparin: A unique, practical
submicrogram sensitive assay. J. Lab. Clin. Med. 81:29u, (1973).
3. Yin, E.T.: U.S.A. Patent No. 4,851,336
4. Yin, E.T. and Wessler, S.: Investigation of the apparent thrombogenicity of thrombin.
Thromb. Diath. Haemorrh 20:465, (1968).
5. Yin, E.T., Wessler, S. and Stoll, P.: Biological properties of the naturally occurring
plasma inhibitor to activated Factor X. J. Biol. Chem. 246:3703, (1971).
6. Wessler, S. and Yin, E.T., Theory and Practice of low-dose heparin in surgical patients.
Circulation, Xlvii, (1973).
7. Kakkar, V.V.: Low-dose heparin to low molecular weight heparin prophylaxis:
in pursuit of excellence - a personal perspective. J. Thromb. Haemost. 3:
195-209, (2005).
8. Wisoff, B.G., Hartstein, M.L., Aintablian, A. and Hambry, R.I.: Risk of coronary surgery:
two hundred consecutive patients with no hospital deaths. J. Thoracic and
Cardiovascular Surgery. 69:669 (1976).
