Acquired factor VIII inhibitors in nonhemophilic patients

D. Söhngen, C. Specker, D. Bach, B. M E Kuntz, M. Burk, C. Aul, G. Kobbe, A. Heyll, K. A. Hollmig, W. Schneider

Research output: Contribution to journalArticle

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Abstract

Antibodies against factor VIII occur in about 15-35% of hemophilia A patients and induce refractoriness to factor VIII substitution. In most cases, these antibodies are of the IgG class. Strategies to avoid or to treat such inhibitors are controversial. In very rare cases, factor VIII inhibitors also develop in nonhemophilic patients. Although there are anecdotal reports that these antibodies may disappear spontaneously without occurrence of bleeding tendencies, in the majority of patients the clinical course is characterized by severe hemorrhages. From 1980 to 1995, we observed ten nonhemophilic patients with acquired factor VIII inhibitors at our hospital. In most cases, a sudden bleeding tendency was observed shortly after an injury or surgery. Coagulation tests showed a prolonged aPTT and a decreased F VIII level. Other deficiencies of blood-clotting factors and acquired or hereditary von Willebrand's disease were excluded. Therapy with F VIII concentrates did not produce the expected increase. Measurement of F VIII inhibitor levels in Bethesda units/ml (BU/ml) revealed maximal values in the range of 2-128 BU/ml. Immunosuppressive therapy with azathioprine or cyclophosphamide in combination with methylprednisolone led to complete disappearance of the inhibitor, normalization of the coagulation tests, and complete remission of the bleeding tendency in seven treated patients within 6 weeks. Although the clinical course is not predictable and inhibitors may disappear spontaneously, combined therapy with methylprednisolone and azathioprine or cyclophosphamide is recommended for patients with bleeding tendency. In pregnancy, therapy should be started only with methylprednisolone; post-partum, azathioprine should be used additionally if methylprednisolone as a single drug does not lead to complete remission. In emergency situations, therapy with high doses of human factor VIII concentrate may be used. When bleeding does not cease, the additional use of activated prothrombin-complex concentrates or porcine factor VIII is indicated. Possible side effects may include hepatitis and short-lived intravascular thrombin production.

Original languageEnglish (US)
Pages (from-to)89-93
Number of pages5
JournalAnnals of Hematology
Volume74
Issue number2
DOIs
StatePublished - 1997

Fingerprint

Factor VIII
Methylprednisolone
Hemorrhage
Azathioprine
Cyclophosphamide
von Willebrand Diseases
Blood Coagulation Factors
Emergency Treatment
Antibodies
Immunoglobulin Isotypes
Hemophilia A
Blood Coagulation
Therapeutics
Immunosuppressive Agents
Thrombin
Hepatitis
Swine
Immunoglobulin G
Pregnancy
Wounds and Injuries

Keywords

  • Bethesda units
  • Factor VIII inhibitor
  • Haemophilia

ASJC Scopus subject areas

  • Hematology

Cite this

Söhngen, D., Specker, C., Bach, D., Kuntz, B. M. E., Burk, M., Aul, C., ... Schneider, W. (1997). Acquired factor VIII inhibitors in nonhemophilic patients. Annals of Hematology, 74(2), 89-93. https://doi.org/10.1007/s002770050263

Acquired factor VIII inhibitors in nonhemophilic patients. / Söhngen, D.; Specker, C.; Bach, D.; Kuntz, B. M E; Burk, M.; Aul, C.; Kobbe, G.; Heyll, A.; Hollmig, K. A.; Schneider, W.

In: Annals of Hematology, Vol. 74, No. 2, 1997, p. 89-93.

Research output: Contribution to journalArticle

Söhngen, D, Specker, C, Bach, D, Kuntz, BME, Burk, M, Aul, C, Kobbe, G, Heyll, A, Hollmig, KA & Schneider, W 1997, 'Acquired factor VIII inhibitors in nonhemophilic patients', Annals of Hematology, vol. 74, no. 2, pp. 89-93. https://doi.org/10.1007/s002770050263
Söhngen D, Specker C, Bach D, Kuntz BME, Burk M, Aul C et al. Acquired factor VIII inhibitors in nonhemophilic patients. Annals of Hematology. 1997;74(2):89-93. https://doi.org/10.1007/s002770050263
Söhngen, D. ; Specker, C. ; Bach, D. ; Kuntz, B. M E ; Burk, M. ; Aul, C. ; Kobbe, G. ; Heyll, A. ; Hollmig, K. A. ; Schneider, W. / Acquired factor VIII inhibitors in nonhemophilic patients. In: Annals of Hematology. 1997 ; Vol. 74, No. 2. pp. 89-93.
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