Acquired inhibitors.
Factor VIII auto-antibody inhibitors, though rare, may present significant and often life-threatening haemorrhage. These auto-antibodies, arising predominantly in older individuals, occur in association with autoimmune disorders, lymphoproliferative disorders, solid tumours, medications and the postpartum state. Almost half of the patients develop auto-antibodies spontaneously without an underlying medical condition. Factor VIII auto-antibody inhibitors are characterized as polyclonal IgG immunoglobulins directed against the FVIII procoagulant activity. Laboratory diagnosis is made by performing the aPTT clotting time in conjunction with a mixing study, and subsequently with specific factor assays. Auto-antibodies are quantified most commonly utilizing the Bethesda assay. Acquired inhibitors to other coagulation factors, including factors IX, XI, XIII, vWF protein, and the vitamin K-dependent proteins are extremely rare. The principles of therapy are similar to those which apply to the management of factor VIII auto-antibodies. Treatment of patients with acquired factor VIII auto-antibody inhibitors varies depending upon the underlying medical condition, the titre of the inhibitor, and the clinical presentation. Acutely bleeding patients with high-titre auto-antibodies generally respond well with infusions of porcine factor VIII concentrate, PCCs or rFVIIa. Extracorporeal plasmapheresis with exchange will acutely reduce circulating antibodies and can be used in conjunction with factor infusions and/or IgIV. Haemorrhage in a patient with a low titre auto-antibody will usually respond to high doses of human factor VIII concentrate. DDAVP may also increase factor VIII levels in patients with low-titre inhibitors. Long-term reduction of auto-antibodies can be achieved by immuno-suppressive regimens using steroids and/or cytotoxic agents, IgIV and interferon-alpha. The selection of the appropriate treatment depends upon the associated medical condition, likelihood of spontaneous remission, risk of toxicities of therapy and cost. Determining the efficacy and safety of new treatment modalities for factor VIII auto-antibodies and other coagulation factor inhibitors will require multicentre randomized clinical trials.
Cohen
A J
AJ
St. Michael's Medical Center, Newark, NJ 07102, USA.
Kessler
C M
CM
D000328:Adult; D000375:Aging / Q000276:immunology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D001778:Blood Coagulation Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D001779:Blood Coagulation Factors / Q000276:immunology*; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D005169:Factor VIII / Q000276:immunology / Q000627:therapeutic use; D015942:Factor VIIa / Q000627:therapeutic use; D005260:Female; D006467:Hemophilia A / Q000188:drug therapy / Q000191:economics / Q000276:immunology; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D016898:Interferon-alpha / Q000627:therapeutic use; D007518:Isoantibodies / Q000276:immunology*; D008297:Male; D010951:Plasma Exchange; D010956:Plasmapheresis; D011247:Pregnancy; D011516:Prothrombin / Q000627:therapeutic use; D011644:Puerperal Disorders / Q000453:epidemiology / Q000276:immunology; D011994:Recombinant Proteins / Q000627:therapeutic use; D013552:Swine / Q000097:blood
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D001779:Blood Coagulation Factors; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D007518:Isoantibodies; D011994:Recombinant Proteins; D011516:Prothrombin; D005169:Factor VIII; D015942:Factor VIIa; D003894:Deamino Arginine Vasopressin