Centenary of Heparin: 1916-2016

1909

Hirudin extracts from medicinal leeches first used for parenteral anticoagulation...
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1911

Eugène Choay founds Laboratories Choay...
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1913

The National Institute of Medical Research is established in London...
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1916

Second-year medical student Jay MacLean, working under the guidance of US physiologist William H. Ho...
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1916

Howell presents, at the 12th International Physiological Congress, further refinements to his earlie...
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1917

MacLean has to leave John Hopkins Medical School, Baltimore, due to a lack of funds...
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1918

Howell and Emmett Holt develop a fat-soluble form and coin the word ‘heparin’ after the Greek ??...
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1918

André and Maurice Choay, both pharmacists, join their father Eugène at Laboratories Choay...
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1922

Howell and Holt present an aqueous extraction protocol for isolating heparin at the annual meeting o...
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1923

Canadian physiologist Charles Best awarded the Nobel prize for his discovery of insulin alongside Fr...
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1924

The compound refined by Howell and colleagues begins to be commercialised, although side effects of ...
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1926

André Choay publishes his medical thesis...
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1928

Best assembles a team of biochemists, physiologists and clinicians, and begins to show interest in t...
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1929

Best becomes Professor and Head of Physiology at the National Institute of Medical Research...
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1929

Swedish scientist Erik Jorpes visits Best in Canada, then returns to the Karolinska Institute in Swe...
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1930

Discovery of Xa factor and first purification tests...
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1931

Howell retires and does not continue research on heparin...
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1932

Pharmaceutical activities at Choay Laboratories are growing; implantation in Auteuil...
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1933

Best and David Scott, assistant director at Connaught Laboratories, publish a series of papers on th...
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1933

Connaught Laboratories develop a first process to extract heparin from bovine liver...
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1934

Complaint about the quality consistency of Connaught’s heparin by Robert Cornish...
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1935

Purified heparin (sulfate glycosaminoglycans) developed...
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1935

In Sweden, Jorpes publishes first conclusion of his research...
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1936

Swedish company Vitrium AB produces parental heparin for human use...
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1937

After several years of using heparin to treat thrombosis in dogs, Connaught Laboratories commence hu...
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1939

First US-approved heparin manufactured using bovine lungs...
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1939

Jay MacLean experiments with heparin and sulfapyridine in treating endocarditis and gangrene...
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1942

Second US-approved heparin manufactured using bovine lungs...
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Post 1942

Both bovine and porcine heparins approved in the US...
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1943

Heparin used to preserve a gangrenous leg from full amputation...
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1945

Howell dies...
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1949

Drs. Peter Moloney and Edith Taylor develop and patent a method to produce large quantities of purif...
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Early 1950s

Connaught Laboratories abandons production of the compound they had pioneered due to economic compet...
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1950s

Heparin established as a therapy for venous and arterial thrombosis...
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1954

Marks, Truscott, and Withycombe publishes a series reports of patients treated with heparin for clot...
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1957

Description by Weisman and Tobin of 10 patients who developed unexpected arterial thrombosis after s...
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1957

MacLean passes away while writing his own version of the events surrounding the discovery of heparin...
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1958

Professor Charles Dubost from Hopital Broussais requests a calcium heparin for open-heart surgery...
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1959

Circulation Magazine publishes MacLean’s unpublished paper about the heparin discovery...
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1959

Choay Laboratories establishes a manufacturing activities setting in Maromme...
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1960

First randomised trial undertaken by Barritt and Jordan with patients with pulmonary embolism, rando...
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1962

US Congress passes Kefauver-Harris amendment, requiring drug manufacturers to prove effectiveness of...
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1962

Claude Raby, previously at Hopital du Val de Grace, joins Choay. Raby refers to himself as a hepa...
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1962

Professor L. Léger (Hopital Cochin) and Edmond Vairel make a comparative study of Ca vs Na...
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1962

Jean Choay decides to put heparin back as an R&D subject at Choay...
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1963

Plaque unveiled at John Hopkins to commemorate Jay MacLean’s ‘major contribution to the discover...
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1965

Calcium heparin introduced...
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1966-1972

Roberts and colleagues have findings similar to that of Weisman and Tobin, leading to speculation th...
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1967

Choay launches Calciparine®...
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1968

Jean Choay, son of Maurice Choay, establishes Choay’s Notre-Dame-de-Bondeville manufacturing site...
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1970

Professor Kakkar writes to Choay, suggesting a study on a prophylactic anti-thrombotic treatment, pr...
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1976

Low-Molecular-Weight-Heparin (LMWH) discovered by Jean Choay...
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1976

Basic biochemistry of heparin’s anticoagulant activity discovered...
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1977

In the aftermath of the ISTH meeting in Philadelphia, Jean Choay decides to lead Choay into developi...
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1978-1980

Professor Jawed Fareed works on pharmacology of LMWH at Loyola University in Chicago and completes t...
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1979

Towne describes white-clot HIT with thrombus: white because made only of fibrin/platelet mesh; its m...
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1980

Nadroparin developed by Choay’s team...
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1980

Kakkar starts the first clinical study using a natural LMWH...
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1981

First article on the heparin structure, Structure-activity relationship in heparin: a synthetic pent...
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1983

Choay obtains both a natural hexasaccharide fraction and the synthesis of a pentasaccharide...
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1985

The first LMWH, nadroparin calcium, launches on the French market  ...
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1986

Fareed shows the synthetic substance to be active on animals...
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1986

Nadroparin commercialised for haemodialysis...
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1987

Nadroparin first marketed for VTE prevention...
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1987

Enoxaparin approved for use in France...
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1990s

DTIs developed (Argatroban / Bivalirudin / Lepirudin / Desirudin)...
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1997-1998

Initial clinical trials of pentasaccharide...
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1997

Nadroparin the first LMWH heparin on the market offering a safety syringe  ...
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1998

Launch of Nadroparin. Nadroparin first marketed once-daily regimen for VTE treatment...
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1999

Phase III clinical trial with pentasaccharide initiated...
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1999

Nadroparin approved in treatment of acute coronary syndromes...
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2000

Factor Xa inhibitors developed (Fondaparinux)...
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2002

Fondaparinux receives first indication in orthopaedic surgery...
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2004

Direct thrombin inhibitors introduced...
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2008

Oral direct factor Xa inhibitors introduced...
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2008

Heparin adulteration crisis due to contaminated raw material processed in China and imported by US c...
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2010-2015

DTI and factor Xa inhibitors (Dabigatran / Rivaroxaban / Apixaban / Edoxaban) marketed...
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2014

Acquisition of Nadroparin and Fondaparinux by Aspen Pharma...
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2016

100 years since the initial discovery that lead to the widespread use of heparin in thrombosis treat...
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