Bovine thrombin-induced inhibitor of factor V and bleeding risk in postoperative neurosurgical patients

Report of three cases

Restricted access

✓ Three patients are reported who developed topical bovine thrombin-induced antibodies to clotting factor V following neurosurgical procedures. In each patient the coagulopathy occurred within 8 to 13 days following exposure to topical bovine thrombin at surgery. Two of the three had previously been exposed to bovine thrombin during cardiothoracic surgery. The three patients were identified by detection of a prolonged prothrombin time, ranging from 20.5 to 39.8 seconds. The patient with the highest factor V level (0.12 U/ml) experienced gastrointestinal bleeding, which ceased when the factor V level increased to more than 0.20 U/ml. One patient required a ventriculostomy. In that case the prothrombin time and factor V level failed to improve following administration of vitamin K, 10 units of fresh frozen plasma, and platelet transfusions; the factor V level temporarily increased from 0.03 to 0.32 U/ml following a 2-day course of intravenous gamma globulin (1 gm/kg/day). Plasmapheresis has also been reported to be of transient benefit in the treatment of this coagulopathy.

In most patients the factor V level rises and the prothrombin time improves toward normal within 3 to 6 weeks following surgical exposure. The individuals identified likely represent only a fraction of the patients who develop the coagulopathy. The latter either do not bleed or are not sufficiently challenged in the postoperative period for the bleeding risk to be tested. It is concluded that bovine thrombin-induced coagulopathy may occur following surgical exposure to topical bovine thrombin and may result in both postoperative morbidity and mortality in a subset of patients.

Article Information

Address reprint requests to: Joel A. Spero, M.D., Allegheny General Hospital, 320 East North Avenue, Pittsburgh, Pennsylvania 15212.

© AANS, except where prohibited by US copyright law.

Headings

References

  • 1.

    Cmolik BLSpero JAMagovern GJet al: Redo cardiac surgery: late bleeding complications from topical thrombin induced factor V deficiency. J Thorac Cardiovasc Surg 105:2222281993Cmolik BL Spero JA Magovern GJ et al: Redo cardiac surgery: late bleeding complications from topical thrombin induced factor V deficiency. J Thorac Cardiovasc Surg 105:222–228 1993

    • Search Google Scholar
    • Export Citation
  • 2.

    Diez-Martin JSikkink RABlackburn MNet al: Acquired inhibitor of bovine thrombin. Blood 66 (Suppl 1):3201985 (Abstract)Diez-Martin J Sikkink RA Blackburn MN et al: Acquired inhibitor of bovine thrombin. Blood 66 (Suppl 1):320 1985 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 3.

    Diez-Martin JSikkink RAGilchrist GSet al: Development of anti-bovine thrombin antibodies following neurosurgical procedures. Br J Haematol 74:3693701990Diez-Martin J Sikkink RA Gilchrist GS et al: Development of anti-bovine thrombin antibodies following neurosurgical procedures. Br J Haematol 74:369–370 1990

    • Search Google Scholar
    • Export Citation
  • 4.

    Feinstein DI: Acquired inhibitors of factor V. Thromb Haemost 39:6636741978Feinstein DI: Acquired inhibitors of factor V. Thromb Haemost 39:663–674 1978

    • Search Google Scholar
    • Export Citation
  • 5.

    Flaherty MJHenderson RWener MH: Iatrogenic immunization with bovine thrombin: a mechanism for prolonged thrombin times after surgery. Ann Intern Med 111:6316341989Flaherty MJ Henderson R Wener MH: Iatrogenic immunization with bovine thrombin: a mechanism for prolonged thrombin times after surgery. Ann Intern Med 111:631–634 1989

    • Search Google Scholar
    • Export Citation
  • 6.

    Nichols WLDaniels TMFisher PKet al: Inhibitors of coagulation factor V and thrombin associated with surgical use of topical bovine thrombin or fibrin “glue.” Blood 78 (Suppl 1):631991 (Abstract)Nichols WL Daniels TM Fisher PK et al: Inhibitors of coagulation factor V and thrombin associated with surgical use of topical bovine thrombin or fibrin “glue.” Blood 78 (Suppl 1):63 1991 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 7.

    Rapaport SIZivelin AMinow RAet al: Clinical significance of antibodies to bovine and human thrombin and factor V after surgical use of bovine thrombin. Am J Clin Pathol 97:84911992Rapaport SI Zivelin A Minow RA et al: Clinical significance of antibodies to bovine and human thrombin and factor V after surgical use of bovine thrombin. Am J Clin Pathol 97:84–91 1992

    • Search Google Scholar
    • Export Citation
  • 8.

    Spero JATriplett DACmolik BLet al: A family of clotting factor inhibitors primarily involving FV and FXI occurring after cardiovascular and neurosurgical procedures. Blood 78 (Suppl 1):631991 (Abstract)Spero JA Triplett DA Cmolik BL et al: A family of clotting factor inhibitors primarily involving FV and FXI occurring after cardiovascular and neurosurgical procedures. Blood 78 (Suppl 1):63 1991 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 9.

    Stricker RBLane PKLeffert JDet al: Development of antithrombin antibodies following surgery in patients with prosthetic cardiac valves. Blood 72:137513801988Stricker RB Lane PK Leffert JD et al: Development of antithrombin antibodies following surgery in patients with prosthetic cardiac valves. Blood 72:1375–1380 1988

    • Search Google Scholar
    • Export Citation
  • 10.

    Sultan YKazatchkine MDNydegger Uet al: Intravenous immunoglobulin in the treatment of spontaneously acquired factor VIII: C inhibitors. Am J Med 91 (Suppl 5A):35391991Sultan Y Kazatchkine MD Nydegger U et al: Intravenous immunoglobulin in the treatment of spontaneously acquired factor VIII: C inhibitors. Am J Med 91 (Suppl 5A):35–39 1991

    • Search Google Scholar
    • Export Citation
  • 11.

    Tsang PWKNaiman SC: Development of antibodies to bovine thrombin and to other coagulation factors in three patients after cardiac surgery. Blood 78 (Suppl 1):651991 (Abstract)Tsang PWK Naiman SC: Development of antibodies to bovine thrombin and to other coagulation factors in three patients after cardiac surgery. Blood 78 (Suppl 1):65 1991 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 12.

    Zehnder JLLeung LLK: Development of antibodies to thrombin and factor V with recurrent bleeding in a patient exposed to topical bovine thrombin. Blood 76:201120161990Zehnder JL Leung LLK: Development of antibodies to thrombin and factor V with recurrent bleeding in a patient exposed to topical bovine thrombin. Blood 76:2011–2016 1990

    • Search Google Scholar
    • Export Citation

TrendMD

Cited By

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 69 69 5
Full Text Views 142 142 0
PDF Downloads 114 114 0
EPUB Downloads 0 0 0

PubMed

Google Scholar