Editing Prothrombin time (section)

==History==
The prothrombin time was developed by [[Armand J. Quick]] and colleagues in 1935,<ref>{{cite journal |vauthors=Quick AJ, Stanley-Brown M, Bancroft FW | title=A study of the coagulation defect in hemophilia and in jaundice | journal=Am J Med Sci | year=1935 | volume=190 | issue=4 | pages=501–510 | doi=10.1097/00000441-193510000-00009}}</ref> and a second method was published by {{ill|Paul Owren|no}},<ref>{{cite journal |vauthors=Owren PA, Aas K |title=The control of dicumarol therapy and the quantitative determination of prothrombin and proconvertin |journal=Scand. J. Clin. Lab. Invest. |volume=3 |issue=3 |pages=201–8 |year=1951 |pmid=14900966 |doi=10.3109/00365515109060600}}</ref> also called the "p and p" or "prothrombin and proconvertin" method. It aided in the identification of the [[anticoagulant]]s [[dicumarol]] and [[warfarin]],<ref>{{cite journal|vauthors=Campbell HA, Smith WK, Roberts WL, Link KP | title=Studies on the hemorrhagic sweet clover disease. II. The bioassay of hemorrhagic concentrates by following the prothrombin level in the plasma of rabbit blood | journal=J Biol Chem | year=1941 | volume=138 | pages=1–20| doi=10.1016/S0021-9258(18)51406-X | doi-access=free }}</ref> and was used subsequently as a measure of activity for warfarin when used therapeutically.

The INR was invented in the early 1980s by Tom Kirkwood working at the UK National Institute for Biological Standards and Control (and subsequently at the UK National Institute for Medical Research) to provide a consistent way of expressing the prothrombin time ratio, which had previously suffered from a large degree of variation between centres using different reagents. The INR was coupled to Dr Kirkwood's simultaneous invention of the International Sensitivity Index (ISI), which provided the means to calibrate different batches of thromboplastins to an international standard.<ref>{{cite journal |author=Kirkwood TB|title=Calibration of reference thromboplastins and standardisation of the prothrombin time ratio |journal=Thrombosis and Haemostasis |volume=49 |issue=3 |pages=238–44 |date=June 1983 |pmid=6879511|doi=10.1055/s-0038-1657371 |s2cid=32051201 }}</ref> The INR became widely accepted worldwide, especially after endorsement by the World Health Organization.<ref>{{cite book | author=Anonymous | chapter=33: Expert Committee on Biological Standardization. Requirements for thromboplastins and plasma used to control oral anticoagulant therapy | title=World Health Organ Tech Rep Ser | year=1983 | pages=81–105}}<!--Not indexed on PubMed--></ref>