scholarly journals Factor XIII activity mediates red blood cell retention in venous thrombi

2014 ◽  
Vol 124 (8) ◽  
pp. 3590-3600 ◽  
Author(s):  
Maria M. Aleman ◽  
James R. Byrnes ◽  
Jian-Guo Wang ◽  
Reginald Tran ◽  
Wilbur A. Lam ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Factor Xiii ◽  
Cell Retention

Factor XIII and Red Blood Cells in Venous Thrombosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. SCI-14-SCI-14
Author(s):  
Alisa S. Wolberg
Keyword(s):  
Blood Cell ◽  
Venous Thrombosis ◽  
Red Blood Cell ◽  
Factor Xiii ◽  
Conflicts Of Interest ◽  
Thrombus Formation ◽  
Cell Retention ◽  
Fibrin Formation ◽  
Mechanical Disruption ◽  
Fibrin Network

Blood coagulation culminates in the thrombin-mediated conversion of fibrinogen to fibrin and production of a fibrin network that stabilizes the clot. The transglutaminase factor XIII(a) [FXIII(a)] crosslinks fibrin and increases the clot's resistance to fibrinolysis and mechanical disruption. Consequently, fibrin formation and crosslinking are essential for hemostasis. However, the formation of clots with abnormal fibrin network structure and/or stability (resistance to mechanical disruption or pharmacological dissolution) is a risk factor for both arterial and venous thrombosis. Improved understanding of fibrin formation and crosslinking during coagulation is essential for understanding the pathophysiologic mechanisms that promote thrombotic disease. We have shown that elevated levels of fibrinogen accelerate vessel occlusion and enhance thrombus stability in mice, demonstrating etiologic contributions of fibrin(ogen) to thrombosis. Recently, we discovered that FXIIIa transglutaminase activity also mediates venous thrombosis via its ability to promote red blood cell retention during clot contraction in whole blood. Genetic deletion of FXIII or pharmacologic inhibition of FXIIIa activity reduces red blood cell retention in clots and consequently, reduces thrombus size in vitro and in vivo. Furthermore, FXIII zymogen binding to soluble, circulating fibrinogen is necessary for normal FXIII activation and activity. The fibrinogen motif that mediates FXIII binding involves C-terminal residues in the fibrinogen gamma chain (gamma 390-396); mice that express a variant fibrinogen that has mutations within these residues show reduced binding of FXIII zymogen to fibrinogen, and delayed activation of FXIII. In venous thrombosis models, these mice phenocopy FXIII-deficient mice, producing smaller venous thrombi with reduced red blood cell content compared to thrombi from wild-type mice. Intriguingly, these mice do not exhibit bleeding or poor wound healing normally associated with FXIII deficiency. Collectively, these findings provide new insight into the pathophysiology of venous thrombosis, and expose the fibrin(ogen)-FXIII axis as a central determinant of venous thrombus formation and composition. Disclosures No relevant conflicts of interest to declare.

scholarly journals Factor XIII in plasma, but not in platelets, mediates red blood cell retention in clots and venous thrombus size in mice

2018 ◽  
Vol 2 (1) ◽  
pp. 25-35 ◽  
Author(s):  
Sravya Kattula ◽  
James R. Byrnes ◽  
Sara M. Martin ◽  
Lori A. Holle ◽  
Brian C. Cooley ◽  
...  
Keyword(s):  
Blood Cell ◽  
Venous Thrombosis ◽  
Red Blood Cell ◽  
Factor Xiii ◽  
Cell Retention ◽  
Venous Thrombus ◽  
Key Points

Key Points FXIIIplasma, but not FXIIIplt, promotes RBC retention in thrombi and increases thrombus weight. Partial FXIII reduction may reduce venous thrombosis.

Mechanisms for sickle red blood cell retention in choroid

2002 ◽  
Vol 25 (3) ◽  
pp. 163-171 ◽  
Author(s):  
Gerard A. Lutty ◽  
Tsuyoshi Otsuji ◽  
Makoto Taomoto ◽  
Carol Merges ◽  
D. Scott McLeod ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Cell Retention

scholarly journals Glanzmann’s thrombasthenia: Working through cultural barriers

2016 ◽  
Vol 3 (2) ◽  
pp. 78-79
Author(s):  
Colleen Tapia ◽  
Maria Tovar-Herrera
Keyword(s):  
Menstrual Cycle ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Factor Xiii ◽  
Arab American ◽  
Factor Xiii Deficiency ◽  
Glanzmann’S Thrombasthenia ◽  
Glanzmann's Thrombasthenia ◽  
Hormone Control

Abstract Glanzmann’s thrombasthenia is a rare autosomal recessive bleeding syndrome characterised by a lack of platelet aggregation. This case study considers a young woman affected by this disease, integrating the role her culture plays in her medical management. Fatima (patient renamed for the purposes of this case study) is a 16-year-old girl with Glanzmann’s thrombasthenia and heterozygous factor XIII deficiency, complicated by menorrhagia and a history of packed red blood cell (PRBC) transfusion for symptomatic anemia, with subsequent development of red blood cell (RBC) antibodies. Management has included years of working on hormone control, as well as dealing with the side-effects of such treatment, and starting NovoSeven (Novo Nordisk) recombinant factor VII infusions along with factor XIII replacement (Corifact; CSL Behring) via the use of a peripherally inserted central catheter (PICC), following set-backs related to hormone control. Glanzmann’s thrombasthenia had its first true impact on Fatima at the onset of her menstrual cycle, just prior to the start of her teenage years. Her first menstrual cycle resulted in her admission to the intensive care unit (ICU), where emergency measures were required to save her life. When options to help Fatima began to diminish, Corifact was initiated to correct her factor XIII deficiency, thus allowing the cross-linking of fibrin to form a more stable clot. Fatima is Arab American of Palestinian descent. She has undergone HLA testing and evaluation for bone marrow transplant, however no matches have been identified to date. The family has had another child with intention of saving cord blood, but Fatima’s transplant team has determined that better matches are likely to be found in unrelated donors. Pregnancy for Fatima is very high risk and believed to be life-threatening for her, which plays a very significant role in her life as a young Arab American woman.

Activity Staining in Congenital Factor XIII Deficiency

1979 ◽  
Author(s):  
P. Henriksson ◽  
I.M. Nilsson ◽  
P. Stenberg
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Factor Xiii ◽  
Platelet Rich Plasma ◽  
Staining Procedure ◽  
Factor Xiii Deficiency ◽  
Activity Staining ◽  
B Subunit ◽  
Cell Lysate ◽  
Plasma Factor

Recently, Stenberg and Stenflo [Analytical Biochemistry in press 1979) introduced an activity staining procedure for transamidating enzymes (transglutaminases; endo-γ-glutamine: ε-lysine transferases! e.g. Factor XIII). This specific technique combines agarose gel electrophoresis with activity staining based on the enzyme catalyzed incorporation of mono-dansylthiacadaverine into casein. The method permits detection of plasma Factor XIII activity down to 1% of the normal adult standard. The procedure was applied to plasma and red blood cell lysate from two patients with tentative congenital plasma Factor XIII deficiency (based on clot solubility). No activity was found in platelet poor as well as in platelet rich plasma which confirmed the diagnosis. The red blood cell lysate displayed normal transglutaminase activity which means separate genetic determinations of the plasma and red blod cell trans-amidases. By Immunoelectrophoresis, the plasma Factor XIII b-subunit was quantitated to 43 and 44 % of the concentration in normal standard plasma.

scholarly journals Factor XIIIa-dependent retention of red blood cells in clots is mediated by fibrin α-chain crosslinking

Blood ◽  
2015 ◽  
Vol 126 (16) ◽  
pp. 1940-1948 ◽  
Author(s):  
James R. Byrnes ◽  
Cédric Duval ◽  
Yiming Wang ◽  
Caroline E. Hansen ◽  
Byungwook Ahn ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Factor Xiiia ◽  
Cell Retention ◽  
Key Points ◽  
Clot Contraction ◽  
Α Chain ◽  
Contraction Factor

Key Points In the absence of FXIIIa activity, red blood cells are extruded from clots during clot contraction. Factor XIIIa promotes red blood cell retention in contracting clots by crosslinking fibrin α-chains.

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