The Classical Hypothesis of Blood Coagulation

Such protestations availed little. Schmidt's mechanistic conclusions were promulgated as the 'classical theory (more correctly, hypothesis) of blood coagulation' 20 years later (Schmidt 1892). He isolated fibrinogen from plasma by salt precipitation and 'fibrin-ferment' from serum by alcohol precipitation. He also found evidence suggesting the existence of antithrombins. 'Fibrin-ferment' caused the purified fibrinogen to coagulate and had a similar effect on hydrocoele fluid, but it could not be extracted from plasma. Since no 'fibrin-ferment' (later re-named 'thrombin') could be obtained from tissue extracts,8 the most plausible hypothesis seemed to be that it is formed during coagulation from a precursor in the plasma:

Fibrinogen Thrombin > Fibrin

Tissue extracts were presumed to contain a factor or factors that converted the then-hypothetical prothrombin to thrombin; this factor appeared to be alcohol-soluble and resistant to boiling. Not until the years immediately preceding the First World War (see Section 5.3) did further details emerge, but the philosophical orientation of the 'classical hypothesis' was clear from the outset. The mechanistic-materialist perspective was explicit in the account of the thrombin hypothesis by Morawitz (1905). The findings that fibrinogen levels rise after trauma (Foster and Whipple 1922) and platelet levels rise after surgery (Evans 1929), concomitantly with an increased likelihood of DVT, helped to entrench this approach.

Arthus and Pages (1890) discovered that calcium was necessary for coagulation. It was quickly shown that it is not directly involved in fibrinogenesis, but none doubted that it was a cofactor in a biochemical reaction. The test tube-based, biochemical discipline that developed over the ensuing 50 years, and matured into the cascade model after the Second World War, was thus rooted in the mechanistic materialism of 1847. By the time Schmidt's later papers were published, many physiologists had distanced themselves from the extreme 'physicalist' stance of du Bois Reymond and his colleagues (Cranefield 1957). However, the same metaphysic underpinned its successor, biochemistry, which aimed to reduce the phenomena of life to the language of chemistry instead of Newtonian mechanics. Both classical biochemistry and modern biochemically orientated haematology are rooted in du Bois-Reymond's failed metaphysic.

8 In view of this history of discovery, the term 'thrombin' seems misconceived. Notwithstanding the commonly assumed desirability of Greek etymologies, the chemical preparations had been obtained from clots, not thrombi; so should 'thrombin' have been 'clottin'? Quite possibly Schmidt and other mechanists were unaware of the basis of Virchow's careful nomenclature, by then almost four decades old (see Chapter 6).

5.3 Phase 2: 1893-1947

When the word 'haemophilia' was given its first clear clinical definition, Addis (1910) showed that addition of a small amount of normal plasma to haemo-philic blood in vitro corrected its characteristically prolonged clotting time. Haemophilic blood was thus shown not to be deficient in either thrombin or fibrinogen and the hunt was on for the missing plasma component. Although the contemporaneous haematological literature emphasised this concern, it said little or nothing about thrombosis.

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