Inhibition of plasma kallikrein mitigates experimental hypertension-enhanced cerebral hematoma expansion

SummaryThe activating principle (CPA) of the factor VII activation seen in plasmas of women taking oral contraceptives after overnight incubation of the plasmas at 0° C was investigated. The reaction was dependent on low temperature, and factor XII was indispensable. Concomitant with the activation of factor VII a 10–30 fold increase in TAME esterolytic activity was observed together with a near 100 per cent drop in plasma kininogen concentration. The results indicated that the activation of factor VII is linked to activation of the kallikrein system, and that the activator may be plasma kallikrein.

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Cold Promoted Activation of Factor VII VI. Effect of Inhibitors

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648105 ◽

1973 ◽

Vol 29 (03) ◽

pp. 633-643

Author(s):

H Gjønnæss

Keyword(s):

Soya Bean ◽

Factor Vii ◽

Plasma Kallikrein ◽

Contact Activation ◽

Activation Reaction ◽

Hexadimethrine Bromide ◽

Bean Trypsin Inhibitor ◽

Plasma Arginine ◽

Kallikrein Activity ◽

Effect Of Inhibitors

SummaryThe cold promoted activation of factor VII occurs in parallel with an activation of a plasma arginine esterase, and, on inhibition of the cold activation of factor VII, the esterase activation also decreased. The inhibitor pattern supported our theory that the arginine esterase that is activated in the cold activation of factor VII is plasma kallikrein.The cold activation of factor VII was completely inhibited with soya bean trypsin inhibitor in doses that did not interfere with the contact activation. On the other hand, inhibition of the contact activation with hexadimethrine bromide did not interfere with the cold activation of factor VII except when this was kaolin induced. Contact and cold activation therefore appear to represent two different pathways for the activation of factor VII. The cold activation reaction is probably mediated by the activation of plasma prekallikrein, and inhibition of the plasma kallikrein activity correlates with the inhibition of the cold promoted activation of factor VII.

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Functional Characterization of a Variant Factor XII (F XII Locarno) in a Cross Reacting Material Positive F XII Deficient Plasma

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648416 ◽

1992 ◽

Vol 67 (02) ◽

pp. 219-225 ◽

Cited By ~ 6

Author(s):

Walter A Wuillemin ◽

Miha Furlan ◽

Hans Stricker ◽

Bernhard Lämmle

Keyword(s):

Dextran Sulfate ◽

Functional Characterization ◽

Healthy Woman ◽

Chain Molecule ◽

Plasma Kallikrein ◽

Factor Xii ◽

Single Chain ◽

Sulfate Adsorption ◽

Prolonged Incubation ◽

Functional Studies

SummaryThe plasma of a healthy woman was found to contain half normal factor XII (FXII) antigen level (0.46 U/ml) without any FXII clotting activity (<0.01 U/ml). The variant FXII in this plasma, denoted as FXII Locarno, was partially characterized by immunological and functional studies on the proposita’s plasma. FXII Locarno is a single chain molecule with the same size (M r = 80 kDa) as normal FXII. Isoelectric focusing suggested an excess of negative charge in the variant FXII as compared to normal FXII. In contrast to FXII in normal plasma, FXII Locarno was not proteolytically cleaved upon prolonged incubation of proposita’s plasma with dextran sulfate. Adsorption to kaolin was similar for both, abnormal and normal FXII. Incubation of the proposita’s plasma with dextran sulfate and exogenous plasma kallikrein showed normal cleavage of FXII Locarno outside of the tentative disulfide loop Cys340-Cys467, but only partial cleavage within this disulfide loop. Furthermore, plasma kallikrein-cleaved abnormal FXII showed neither amidolytic activity nor proteolytic activity against factor XI and plasma prekallikrein.These results suggest a structural alteration of FXII Locarno, affecting the plasma kallikrein cleavage site Arg353-Val354 and thus formation of activated FXII (a-FXIIa).

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