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East Texas Bleeding Disorder

Here is a fascinating response to our September 2 solution to the August 10 Minimally Prolonged PT discussion, from Dimitrios Liapis MSc, Vascular Research Private Medical Center, Athens, Greece.

From Mr. Liapis: A very interesting case! Did the patient or members of the immediate family report any bleeding history? Other coagulation tests besides PT? It could be East Texas Bleeding Disorder. This would explain the slight PT prolongation together with the severity of the bleeding and the apparent ineffectiveness of the plasma therapy. If confirmed by TFPI enzyme immunoassay and FV A2440G genotyping, then wouldn’t utilizing a TFPI antibody result in adequate coagulation?

Needless to say, I (Geo) needed help with this information, so I went to frequent contributor and advisor Dave McGlasson, who located Girolami A, Cosi E, Farrare S, Lombardi AM, Girolami B. New clotting disorders that cast new light on blood coagulation and may play a role in clinical practice. J Thromb Thrombolysis 2017;44:71–5. The article reviews four qualitative (type 2) clotting factor abnormalities. Two are gain of function mutations that promote thrombosis: factor VII Padua with markedly elevated factor VII activity, and a group of Arg396 prothrombin mutations rendering thrombin moderately resistant to antithrombin. Two other mutations yield shortened forms of factor V associated with mild bleeding. These are factor V Amsterdam in which 66 amino acids of the B domain are deleted, and factor V East Texas, identified in an East Texas kindred, with a 702 B domain amino acid deletion.

Factor V East Texas (and to a lesser degree, factor V Amsterdam) possesses increased avidity for TFPI that promotes markedly increased TFPI levels that interfere with the extrinsic mechanism, activation of factor VII in the factor VII-tissue factor complex, conferring a slightly prolonged PT and a mild bleeding disorder. Indeed, Bayer is currently developing an anti-TFPI antibody, for hemophilia therapy.

It is not too much of a stretch to imagine that Dr. Laposata has actually encountered a member of the East Texas Bleeding Disorder kindred at his facility in Galveston. Check back here for more discussion of this interesting case.

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