Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019087 (hemorrhagic diathesis)
 678 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The history of the antithrombotic agents--aspirin, heparin, warfarin, and the thrombolytics--is a rich and lively odyssey of serendipity, perseverance, vision, and conflict involving a number of striking personalities. The history of aspirin spans ages and continents from Hippocrates' analgesic for women in labor to the rediscovery of the white willow bark by English country scholar Reverend Edward Stone. Bayer chemist Felix Hoffmann reinvented aspirin for his ailing father; suburban physician L.L. Craven pioneered the prophylactic antithrombotic uses of aspirin; and Sir John Vane elucidated aspirin's mechanism of action as the inhibition of prostaglandin synthetase. Heparin was discovered by McLean, working as a medical student in 1915 in search of a pure procoagulant in dog liver. His original impure material differed somewhat from today's heparin, but purified heparin was rapidly accepted for a myriad of clinical uses; to this day, diverse new properties of this complex glycosaminoglycan continue to be elucidated. The oral anticoagulants emerged from veterinary research in the 1920s on a hemorrhagic disorder afflicting cattle that consumed spoiled sweet clover hay. Several chance encounters led Karl Link and his University of Wisconsin team to the identification of dicumarol as the offending agent in 1939 and its widespread therapeutic use by Wright and others in the 1940s. Link later developed warfarin as a rodenticide, but its use in humans soon followed in the 1950s. Vitamin K was discovered in the 1930s; its involvement in the mechanism of the anticoagulant agents was not delineated until the 1970s. The intrinsic ability of clotted blood to liquify and the fibrinolytic properties of normal urine were noted in the 1800s. Tillett and Sherry's group stumbled on the fibrinolytic properties of streptokinase in the 1930s and pioneered the therapeutic use of streptokinase in the 1940s and of urokinase in the 1960s. Several teams found tissue-type plasminogen activator in various body sites beginning in the 1940s, leading to its cloning and widespread use in the 1980s; anisoylated plasminogen-streptokinase activator complex is an example of rational drug design. The discoverers of these diverse agents have not only provided physicians with a potent armamentarium of antithrombotic drugs but also helped elucidate much basic science and vividly demonstrated the merits of perseverance, independent thought, and adherance to the scientific method.
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PMID:History of drugs for thrombotic disease. Discovery, development, and directions for the future. 828 78

A 69-year-old man, with hepatits C virus-related liver cirrhosis and hemophilia B, developed massive ascites and watery diarrhea after endoscopic injection sclerotherapy for esophageal varices. A multi detector row computed tomography revealed a superior mesenteric venous thrombus without bowel infarction. It was assumed that the thrombus was caused by transient congestion of the portal system after retrograde propagation of the sclerosant agent, in a condition where anticoagulation proteins, such as proteins C and S, had decreased. Because long systemic thrombolytic therapy was hazardous for the patient with hemorrhagic diathesis due to impaired coagulation, a direct thrombolysis was performed with urokinase followed by aspiration thrombectomy, with cannulation of the portal venous system using a transjugular intrahepatic approach. The patient had no complications in this procedure and subsequently diarrhea and refractory ascites were resolved. Direct thrombectomy via the transjugular intrahepatic route may be a useful therapy for mesenteric venous thrombus in the cirrhotic patient.
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PMID:Superior mesenteric venous thrombosis treated by direct aspiration thrombectomy. 1861 68