A History of Coagulopathy in Liver Disease: Legends and Myths

Abstract

Cirrhosis and its end-stage complications have been well-known by medical practitioners for many centuries and were frequently described in historical writings and medical literature as far back as Hippocrates in 400 bce. 1 The ancient Greeks believed the liver to be the center of the circulation and the site of blood production, perhaps because of its propensity to bleed when injured in battle or accidents. Indeed, the liver was referred to by Galen 2 as the "blood sac" because of its abundant blood flow, which comes from its almost unique dual blood supply, namely, the hepatic artery and the portal vein (almost because there is also a portal venous system between the pituitary and the hypothalamus 3) (Fig. 1). In 200 ce, Galen wrote of the liver as the fons venarum, the source of the major veins of the body and the sanguifactionis officina or the "factory of the blood," the site of sanguification. 2 In modern times, even after the gross anatomy of the liver was clearly elucidated, poor understanding of liver disease resulted in a diagnosis of cirrhosis Abbreviations: ADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; AHG, antihemophilic globulin; aPTT, activated partial thromboplastin time; AT, antithrombin; C, protein C; FFP, fresh frozen plasma; HMWK,

Elevated factor VIII level: An implication for thrombosis during pregnancy

“…The clotting factors are 12 in number and are sequentially designated from I to XIII based on their chronological discovery with an omission of factor VI [15]. Initially it was believed to be a separate coagulation factor, however, it is presently recognized as being indistinguishable from factor V, hence, instead of renumbering the remaining factors, factor VI was intentionally retained as a temporary marker and a means of remembering the progressive nature of medical knowledge.…”

A History of the Assessment of Liver Performance

“…It was not until the 1950s that the diagnostic value of the serum transaminases (officially referred to as aminotransferases since 1961 70 ) was appreciated in the diagnosis of viral hepatitis 71 . There are many clinical applications for liver‐associated serum biochemical tests that include aminotransferases, bilirubin, alkaline phosphatase, and albumin, 72 which are usually bundled together with the Quick prothrombin time (i.e., the number of seconds that it takes plasma to clot in a test tube)—a major facet of blood coagulation in which the liver has a near monopoly 67 . Such blood test bundles are popularly but, as Gerald Klatskin pointed out in 1948, 73 erroneously denoted as “liver function tests” (LFTs), yet they are widely used essential noninvasive tools of hepatology.…”

“…The early decades of the 20th century witnessed the development of a serum bilirubin test, 64 utilization of Bauer’s 1906 galactose test, 65 hippuric acid synthesis assays 66 based on the research of Armand J. Quick (of Quick Test fame 67 ), and tests based on the disposal by the body of a rainbow of dyes: indigo carmine, Congo red, methylene blue, Evans blue, Rose Bengal, indocyanine green (ICG), and arguably the most popular, the now‐obsolete bromsulphalein (BSP) that is gloriously purple in alkaline solution. The clinical importance of the 1913 van den Bergh reaction for bilirubin estimation in the blood 64 was endorsed by many clinicians 68 .…”

“…71 There are many clinical applications for liver-associated serum biochemical tests that include aminotransferases, bilirubin, alkaline phosphatase, and albumin, 72 which are usually bundled together with the Quick prothrombin time (i.e., the number of seconds that it takes plasma to clot in a test tube)-a major facet of blood coagulation in which the liver has a near monopoly. 67 Such blood test bundles are popularly but, as Gerald Klatskin pointed out in 1948, 73 erroneously denoted as "liver function tests" (LFTs), yet they are widely used essential noninvasive tools of hepatology. It is not commonly known that the term liver function test had been in use since the 1930s 59 at least and included some curious laboratory procedures that are reminiscent of alchemy and witchcraft, in which the flocculation of negatively charged colloids of gold by serum globulin or the precipitation of gammaglobulins from serum by heavy metals, pungent phenols, or mixtures of sheep brain cephalin and cholesterol was relied History of Hepatology Mousa and Kamath review on to distinguish among different etiologies of jaundice and other liver afflictions.…”

Coagulopathy and hemorrhage management in cirrhotic patients

“…Si è potuto osservare come, nonostante i pazienti cirrotici rappresentassero una minima percentuale dei pazienti presi in considerazione nello studio, si trovassero al terzo posto per complicazioni e mortalità (1). essere in una sorta di "ribilanciamento" della funzione emostatica a causa di cambiamenti concomitanti che riguardano le vie sia pro-che anti-emostatiche, come mostrato nella Figura 1 (7,8).…”