ABSTRACT
The purpose of this essay is to recall the actions taken globally to improve the viral safety of coagulation factor concentrates, mainly in the years 1985-1990, at a time of confusing and often contradictory information on bloodborne viral infections in multitransfused patients with hemophilia (PWHs). I shall first recall the problem of the transmission and control of the hepatitis viruses, and then that of HIV: not only for temporal reasons, but also because understanding the progress of knowledge on hepatitis and the poor success of the early measures taken to tackle this problem in PWHs is essential to understand how the problem of HIV transmission was ultimately dealt with successfully.
Subject(s)
Blood Coagulation Factors/history , Coagulants/history , Drug Contamination , HIV Infections/history , Hemophilia A/history , Hepatitis, Viral, Human/history , Patient Safety/history , Blood Coagulation Factors/adverse effects , Coagulants/adverse effects , Drug Contamination/prevention & control , HIV Infections/blood , HIV Infections/transmission , Hemophilia A/blood , Hemophilia A/drug therapy , Hepatitis, Viral, Human/blood , Hepatitis, Viral, Human/transmission , History, 20th Century , Humans , Recombinant Proteins/history , Risk Assessment , Risk FactorsSubject(s)
Academies and Institutes/history , Biochemistry/history , Blood Coagulation Disorders, Inherited/diagnosis , Inventions/history , Blood Coagulation Disorders, Inherited/history , Blood Coagulation Factors/history , Blood Coagulation Factors/metabolism , Blood Coagulation Factors/ultrastructure , History, 20th Century , History, 21st Century , Humans , Ukraine , WorkforceABSTRACT
The proverb that probably best exemplifies my career in research is attributable to Yogi Berra (http://www.yogiberra.com/), ie, "when you come to a fork in the road ... take it." My career is a consequence of chance interactions with great mentors and talented students and the opportunities provided by a succession of ground-breaking improvements in technology.
Subject(s)
Biomedical Research/history , Blood Coagulation Factors/history , Blood Coagulation , Hematology/history , Thrombin/history , Animals , Blood Coagulation Factors/chemistry , Blood Coagulation Factors/metabolism , History, 20th Century , History, 21st Century , Humans , Mentors , Protein Conformation , Structure-Activity Relationship , Thrombin/chemistry , Thrombin/metabolismSubject(s)
Biomedical Research/history , Blood Coagulation Factors/history , Endothelial Cells , Hematology/history , Receptors, Cell Surface/history , Animals , Blood Coagulation , Blood Coagulation Factors/chemistry , Blood Coagulation Factors/metabolism , Endothelial Cells/metabolism , History, 20th Century , History, 21st Century , Humans , Models, Molecular , Protein Conformation , Receptors, Cell Surface/chemistry , Receptors, Cell Surface/metabolism , Signal Transduction , Thrombosis/history , Thrombosis/metabolismSubject(s)
Biomedical Research/history , Hemostasis , Thrombosis , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/therapy , Blood Coagulation Factors/history , Blood Coagulation Factors/physiology , Blood Platelet Disorders/diagnosis , Blood Platelet Disorders/etiology , Blood Platelet Disorders/therapy , History, 20th Century , History, 21st Century , HumansSubject(s)
Blood Coagulation Factors/adverse effects , Coagulants/adverse effects , Drug Contamination , HIV Infections/etiology , Hemophilia A/drug therapy , Blood Coagulation Factors/history , Centers for Disease Control and Prevention, U.S./history , Coagulants/history , Guideline Adherence , HIV Infections/history , Hemophilia A/history , History, 20th Century , Humans , Practice Guidelines as Topic , United StatesABSTRACT
Clinical observations have added to the understanding of basic mechanisms of blood coagulation and its alterations in certain hemorrhagic and thrombotic states. Much clinical evidence exists for concluding that the exposure of blood to tissue factor (thromboplastin) on tissue cells represents the key event initiating fibrin clot formation after tissue injury. This then results in the formation of activated factor VII (VIIa)-tissue factor complexes, which must activate both factor X and factor IX for normal hemostasis. I describe the possible clinical consequences of an aberrant function of the natural anticoagulants regulating blood coagulation--antithrombin, protein C, and tissue factor pathway inhibitor. Understanding the physiologic function of tissue factor pathway inhibitor can illuminate why hemophilic patients bleed, but many other questions remain. I briefly review the four causes for acquired disorders of the blood coagulation reactions--vitamin K deficiency, hepatocellular disease, antibodies to clotting factors, and disseminated intravascular coagulation--but limit my comments to the mechanisms that trigger the formation of antibodies to clotting factors and how these antibodies can deplete the blood of clotting factor activities. Finally, heparin is able to potentiate tissue factor pathway inhibitor function, which is a possible reason why the use of heparin but not warfarin can prevent the numerous thrombotic episodes of the Trousseau's syndrome.
