title: In vitro evaluation of clot quality and stability in a model of severe thrombocytopenia: effect of fibrinogen, factor XIII and thrombin-activatable fibrinolysis inhibitor.
abstract: BACKGROUND
  The treatment options in severe thrombocytopenia (platelet count ≤20×10(9)/L) are limited. The aim of this study was to investigate ways of improving blood clotting and stability in reconstituted thrombocytopenia.
  
  
  METHODS
  Thrombocytopenia (platelets [16±4]×10(9)/L) was created by differential centrifugation of normal blood followed by reconstitution of whole blood which was subjected to clotting in a rotation thromboelastometer by CaCl2 and tissue factor, and to fibrinolysis by tissue plasminogen activator (tPA). In separate experiments, blood was diluted by 40% with TRIS/saline solution. Blood was treated with fibrinogen (fib), factor XIII (FXIII), and thrombin-activatable fibrinolysis inhibitor (TAFI).
  
  
  RESULTS
  The maximum clot firmness of thrombocytopenic blood was approximately 2-fold less than that of intact blood. Supplementation of blood with fib and FXIII improved clot formation. In the presence of tPA, among fib, FXIII and TAFI, only fib stimulated clot propagation whereas each of these agents increased clot strength. There was a synergistic effect when fib was added together with FXIII or TAFI. Fibrinolysis was inhibited by TAFI and to a greater extent by TAFI + FXIII. Fourty percent dilution of blood reduced clot strength and increased susceptibility to tPA. Clot strength was increased by the treatments in the following order: fib/FXIII/TAFI > fib/TAFI > fib > TAFI > FXIII. In the presence of tPA, TAFI and FXIII lysed the clots significantly more slowly. This effect was stronger when blood was treated with the combination of fib/FXIII/TAFI. Doubling the fib concentration, alone or together with other agents, did not improve clot strength or stability.
  
  
  CONCLUSIONS
  Augmentation of clot formation and anti-fibrinolysis by combining fib, FXIII and TAFI may be beneficial for the treatment of patients with severe thrombocytopenia especially when complicated by haemodilution following introduction of fluids to compensate for massive blood loss.
authors: National Haemophilia Centre, Chaim Sheba Medical Centre, Tel-Hashomer, Israel.
authors: Boris
authors: B
authors: Shenkman
authors: Faculty of Sciences, Holon Institute of Technology, Holon, Israel.
authors: Yulia
authors: Y
authors: Einav
authors: National Haemophilia Centre, Chaim Sheba Medical Centre, Tel-Hashomer, Israel.
authors: Tami
authors: T
authors: Livnat
authors: Department of Pathophysiology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
authors: Ivan
authors: I
authors: Budnik
authors: National Haemophilia Centre, Chaim Sheba Medical Centre, Tel-Hashomer, Israel.
authors: Uriel
authors: U
authors: Martinowitz
mesh_terms: D001777:Blood Coagulation; D025901:Carboxypeptidase B2 / Q000378:metabolism*; D005176:Factor XIII / Q000378:metabolism*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D008297:Male; D008954:Models, Biological; D013916:Thrombelastography / Q000295:instrumentation / Q000379:methods; D013921:Thrombocytopenia / Q000378:metabolism* / Q000628:therapy; D010959:Tissue Plasminogen Activator / Q000378:metabolism
chemical_list: D005340:Fibrinogen; D005176:Factor XIII; D025901:Carboxypeptidase B2; D010959:Tissue Plasminogen Activator