SerpinB2 deficiency in mice reduces bleeding times via dysregulated platelet activation

Wayne A. Schroder, Thuy T. Le, Joy Gardner, Robert K. Andrews, Elizabeth E. Gardiner, Leonie Callaway, Andreas Suhrbier

Research output: Contribution to journalArticleResearchpeer-review

Abstract

SerpinB2, also known as plasminogen activation inhibitor type 2 (PAI-2), is classically viewed as an inhibitor of fibrinolysis. However, we show herein a distinct, hitherto unrecognized role for SerpinB2 in hemostasis. Mice deficient in SerpinB2 expression and mice with an active site mutation in SerpinB2, both showed significant reductions in tail bleeding times. This hemostatic phenotype was associated with platelets, with SerpinB2 and SerpinB2-urokinase complexes clearly present in platelet fractions, and immunohistochemistry of blood clots suggesting SerpinB2 is associated with platelet aggregates. Thromboelastography illustrated faster onset of clot formation in blood from SerpinB2 deficient mice, whereas clotting of platelet-free plasma was unaffected. The results appear consistent with the low circulating SerpinB2 levels and hypercoagulation seen during pre-eclampsia; however, SerpinB2 was not detected in human platelets.

Original languageEnglish
Pages (from-to)658-663
Number of pages6
JournalPlatelets
Volume30
Issue number5
DOIs
Publication statusPublished - 4 Jul 2019

Keywords

  • Bleeding times
  • PAI-2
  • plasminogen activation inhibitor type 2
  • platelet
  • SerpinB2
  • urokinase

Cite this

Schroder, W. A., Le, T. T., Gardner, J., Andrews, R. K., Gardiner, E. E., Callaway, L., & Suhrbier, A. (2019). SerpinB2 deficiency in mice reduces bleeding times via dysregulated platelet activation. Platelets, 30(5), 658-663. https://doi.org/10.1080/09537104.2018.1535702
Schroder, Wayne A. ; Le, Thuy T. ; Gardner, Joy ; Andrews, Robert K. ; Gardiner, Elizabeth E. ; Callaway, Leonie ; Suhrbier, Andreas. / SerpinB2 deficiency in mice reduces bleeding times via dysregulated platelet activation. In: Platelets. 2019 ; Vol. 30, No. 5. pp. 658-663.
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abstract = "SerpinB2, also known as plasminogen activation inhibitor type 2 (PAI-2), is classically viewed as an inhibitor of fibrinolysis. However, we show herein a distinct, hitherto unrecognized role for SerpinB2 in hemostasis. Mice deficient in SerpinB2 expression and mice with an active site mutation in SerpinB2, both showed significant reductions in tail bleeding times. This hemostatic phenotype was associated with platelets, with SerpinB2 and SerpinB2-urokinase complexes clearly present in platelet fractions, and immunohistochemistry of blood clots suggesting SerpinB2 is associated with platelet aggregates. Thromboelastography illustrated faster onset of clot formation in blood from SerpinB2 deficient mice, whereas clotting of platelet-free plasma was unaffected. The results appear consistent with the low circulating SerpinB2 levels and hypercoagulation seen during pre-eclampsia; however, SerpinB2 was not detected in human platelets.",
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Schroder, WA, Le, TT, Gardner, J, Andrews, RK, Gardiner, EE, Callaway, L & Suhrbier, A 2019, 'SerpinB2 deficiency in mice reduces bleeding times via dysregulated platelet activation' Platelets, vol. 30, no. 5, pp. 658-663. https://doi.org/10.1080/09537104.2018.1535702

SerpinB2 deficiency in mice reduces bleeding times via dysregulated platelet activation. / Schroder, Wayne A.; Le, Thuy T.; Gardner, Joy; Andrews, Robert K.; Gardiner, Elizabeth E.; Callaway, Leonie; Suhrbier, Andreas.

In: Platelets, Vol. 30, No. 5, 04.07.2019, p. 658-663.

Research output: Contribution to journalArticleResearchpeer-review

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