Factor XIa reacts covalently with Antithrombin III to form the XIa-ATIII binary complex and the XIa-(ATIII)2 ternary complex, as readily followed by SDS-Page.   Relative to the control binary band of 11.7�0.27 units and the tertiary band of 0.65�0.04 units, 1�g Heparin increased the binary complex to 18.6�1.6 (p=0.0008, n=4) and the ternary complex to 3.5�2.9 (p=0.04, n=4).  Protamine Sulfate (1�g), in contrast, reduced the level of binary and ternary complexes to 5.75�1.96 (p=0.00098, n=4) and 0.0�0.0 (p=0.008, n=4), respectively, thereby exhibiting a �procoagulant� effect in this reaction.  Spermine and Spermidine, two basic neural compounds which are not peptides, as is protamine, exhibited comparable activities as Protamine when preincubated  at room temperature with ATIII. At the 0.7�g level of Spermine, the binary and ternary bands were reduced to 6.0�6.5 (p=0.009, n=4), and 0.0�0.008 (p=0.008, n=4), respectively, which are both statistically significant.  At the 0.07�g level of Spermine, the corresponding numbers were 6.5�2.5 (p=0.005, n=4) and 0.0�0.0 (p=0.008, n=4).  When 0.5�g Spermidine replaced the Spermine, the values were 3.1�0.1 (p=0.018, n=4) and 0.0�0.0 (p=0.008, n=4) while at the 0.05�g level, the values were 4.4�8.6 (p=0.013, n=4) and 0.0�0.0 (p=0.008, n=4), respectively.  Here, both Spermine and Spermidine at 2 levels each lower the level of FXIa-ATIII complexes formed, thereby permitting the free FXIa to serve as a catalyst with the consequential procoagulant effect.

Procoagulant role for spermine and spermidine in the FXIa-antithrombin III interaction

247th National Meeting (2014)

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