Download PDF
Thromb Haemost 2002; 88(05): 768-772
DOI: 10.1055/s-0037-1613300
Review Article
Schattauer GmbH

The In Vitro Analysis of the Coagulation Mechanism of Activated Factor VII Using Thrombelastogram

Chiharu Kawaguchi
1   Division of Neonatal Intensive Care, Nara Medical University Hospital, Kashihara, Nara, Japan
,
Yukihiro Takahashi
1   Division of Neonatal Intensive Care, Nara Medical University Hospital, Kashihara, Nara, Japan
,
Yae Hanesaka
1   Division of Neonatal Intensive Care, Nara Medical University Hospital, Kashihara, Nara, Japan
,
Akira Yoshioka
1   Division of Neonatal Intensive Care, Nara Medical University Hospital, Kashihara, Nara, Japan
› Author Affiliations
Further Information

Publication History

Received 04 March 2002

Accepted after resubmission 02 July 2002

Publication Date:
08 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

We investigated the effects of addition of recombinant activated coagulation factor VII (rFVIIa) to coagulation factor-deficient plasma and whole blood, using thrombelastograms (TEGs). The addition of rFVIIa to factor II-or X-deficient plasma did not correct hemostatic parameters, whereas it produced partial responses in factor V-, VIII-or IX-deficient plasma and good responses in factor VII-, XI-or XII-deficient plasma. Furthermore, the addition of rFVIIa and platelets (30-100 X 103/µl) to platelet-poor plasma produced marked corrections, producing TEGs similar to those of platelet-rich plasma. These results indicate that factors II and X are essential for the hemostatic effects of rFVIIa, and that factors V and VIII promote these effects. We believe that TEGs are, at present, one of the most useful tools for evaluating in vitro hemostatic effects of rFVIIa.

Keywords

Recombinant activated factor VII - thrombelastogram
 

  • References

  • 1 Hedner U, Glazer S. Management of hemophilia patients with inhibitors. Hematol Oncol Clin North Am 1992; 06: 1035-46.
    PubMedGoogle Scholar
  • 2 Robers HR. Clinical experience with activated factor VII. Focus on safety aspects. Blood Coagul Fibrinolysis 1998; 09: 115-8.
    PubMedGoogle Scholar
  • 3 Negrier C, Hay CRM. The treatment of bleeding in hemophilic patients with inhibitors with recombinant factor VIIa. Semin Thromb Hemost 2000; 26: 407-12.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Kristensen J, Killander A, Hippe E, Helleberg C, Ellegard J, Holm M, Kutti J, Mellqvist UH, Johansson JE, Glazer S, Hedner U. Clinical experience with recombinant factor VIIa in patients with thrombocytopenia. Haemostasis 1996; 26: 159-64.
    PubMedGoogle Scholar
  • 5 Tengborn L, Petruson B. A patient with Glanzmann thrombasthenia and epistaxis successfully treated with recombinant factor VIIa. Thromb Haemost 1996; 75: 981-2.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Peters M, Heijboer H. Treatment of a patient with Bernard-Soulier syndrome and recurrent nosebleeds with recombinant factor VIIa. Thromb Haemost 1998; 80: 352 (Abstract).
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Friederich PW, Geerdink MG, Spataro M, Messelink EJ, Henny CP, Buller HR, Levi M. The effect of the administration of recombinant activated factor VII (NovoSeven) on perioperative blood loss in patients undergoing transabdominal retropubic prostatectomy: the PROSE study. Blood Coagul Fibrinolysis 2000; 11: 129-32.
    CrossrefPubMedGoogle Scholar
  • 8 Fukui H, Fujimura Y, Takahashi Y, Mikami S, Yoshioka A. Laboratory evidence of DIC under FEIBA treatment of a hemophilia patient with intracranial bleeding and high titre factor VIII inhibitor. Thromb Res 1981; 22: 177-84.
    CrossrefPubMedGoogle Scholar
  • 9 Turecek PL, Gritsch H, Richter G, Váradi K, Schwarz HP. Activated prothrombin complex concentrates: A concept for the mechanism of action. Thromb Haemost. 2001 Suppl, Abstract no: OC1772.
    PubMedGoogle Scholar
  • 10 Hoffman M, Monroe DM. The action of high-dose factor VIIa (FVIIa) in a cell-based model of hemostasis. Semin Hematol 2001; 38: 6-9.
    PubMedGoogle Scholar
  • 11 Hedner U. Dosing and monitoring NovoSevenR treatment. Haemostasis 1996; 26: 102-8.
    PubMedGoogle Scholar
  • 12 Lusher JM, Ingerslev J, Roberts HR, Hedner U. Clinical experience with recombinant factor VIIa. Blood Coagul Fibrinolysis 1998; 09: 119-28.
    CrossrefPubMedGoogle Scholar
  • 13 Yoshioka A, Nishio K, Shima M. Thrombelastogram as a hemostatic monitor during recombinant factor VIIa treatment in haemophilia A patients with inhibitor to factor VIII. Haemostasis 1996; 26: 139-42.
    PubMedGoogle Scholar
  • 14 Sims PJ, Wiedmer T, Esmon CT, Weiss HJ, Shattil SJ. Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. J Biol Chem 1989; 264: 17049-57.
    PubMedGoogle Scholar
  • 15 Gilbert GE, Sims PJ, Wiedmer T, Furie B, Furie BC, Shattil SJ. Platelet-derived microparticles express high affinity receptors for factor VIII. J Biol Chem 1991; 266: 17261-8.
    PubMedGoogle Scholar
  • 16 Comfurius P, Senden JMG, Tilly RHJ, Schroit AJ, Bevers EM, Zwaal RFA. Loss of membrane phospholipid asymmetry in platelets and red cells may be associated with calcium induced shedding of plasma membrane and inhibition of aminophospholipid translocase. Biochim Biophys Acta 1990; 1026: 153-60.
    CrossrefPubMedGoogle Scholar
  • 17 Østerud B, Rapaport SI. Activation of 125I-factor IX and 125I-factor X: effect of tissue factor and factor VII, factor Xa and thrombin. Scand J Haematol 1980; 24: 213-26.
    PubMedGoogle Scholar
  • 18 Vant Veer C, Mann K. The regulation of the factor VII-dependent coagulation pathway: rationale for the effectiveness of recombinant factor VIIa in refractory bleeding disorders. Semin Thromb Hemost 2000; 26: 367-72.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Monroe DM, Hoffman M, Allen GA, Roberts HR. The factor VII-platelet interplay: Effectiveness of recombinant factor VIIa in the treatment of bleeding in severe thrombocytopathia. Semin Thromb Hemost 2000; 26: 373-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Monroe DM, Hoffman M, Olliver JA, Roberts HR. Platelet activity of highdose factor VIIa is independent of tissue factor. Br J Haematol 1997; 99: 542-7.
    CrossrefPubMedGoogle Scholar