A 17 year old black female was referred to me because of repeated hemorrhages during menstrual cycles. The detailed analysis of clotting factors revealed that her fibrinogen did not clot when exposed to thrombin. We did extensive physicochemical and immunological analysis of her fibrinogen but the defect in the fibrinogen molecule could not be determined. Luckily we met Blombäcks from Karolinska Institute who was exceedingly interested in fibrinogen molecule and they had studied many fibrinogens from different species. They had observed that α (A) chain of the fibrinogen molecule was the same in all the species suggesting that this chain may be the most important part of the molecule for its physiological function. We handed Birger Blombäck the purified fibrinogen protein from our patient for analysis. Three weeks later I got a call from Birger that he would like to see me at the airport on a certain day. I arrived there and he showed me the results of analysis. He concluded that there was an amino acid substitute (arginine to serine) in the vicinity of the bond split by thrombin during normal blood coagulation. We were all very happy and excited. The paper was written at the airport, hand carried by Blombäck to the Editor of Nature and the article entitled, Fibrinogen Detroit – a Molecular Defect in the N-terminal Disulphide Knot of Human Fibrinogen, was published in three weeks. This was a great discovery in this field.
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