hematology and oncology
Coagulation Disorders Caused by Circulating Anticoagulants
Factor VIII and Factor IX Inhibitors
Isoantibodies to factor VIII develop in about 30% of patients with severe Hemophilia as a complication of repeated exposure to normal factor VIII molecules during Similarly, patients with severe Hemophilia can develop isoantibodies to Plasma containing a factor VIII antibody has a prolonged PTT that does not correct when normal plasma or another source of factor VIII is added in a 1:1 mixture to the patient’s plasma. Testing is done immediately after mixture and again after incubation. Similar testing is done forfactor IXantibody. 1.Iorio A, Fischer K, Makris M. Large scale studies assessing anti-factor VIII antibody development in previously untreated haemophilia A: what has been learned, what to believe and how to learn more.Br J Haematol2017;178(1):20-31. doi:10.1111/bjh.14610 2.Puetz J, Soucie JM, Kempton CL, Monahan PE; Hemophilia Treatment Center Network (HTCN) Investigators. Prevalent inhibitors in haemophilia B subjects enrolled in the Universal Data Collection database.Haemophilia2014;20(1):25-31. doi:10.1111/hae.12229 In patients without hemophilia,cyclophosphamide, corticosteroids, orrituximabare used to eliminate inhibitors In patients with hemophilia, immune tolerance induction with long-term high-dose factor replacement is used to eliminate inhibitors In patients without hemophilia who develop factor inhibitors, therapy withcyclophosphamide, corticosteroids, orrituximab(monoclonal antibody to CD20 on lymphocytes) is used to suppress autoantibody production. In some patients, the autoantibodies may disappear spontaneously. In patients with hemophilia A, factor VIII inhibitors are eliminated with immune tolerance induction using high-dose factor VIII replacement. Some protocols include immunosupression in patients with refractory disease. can cause Anaphylaxis and inhibitors. ( Treatment references ). Emicizumabis a recombinant humanized bispecific monoclonal antibody that binds to bothfactor IXandfactor X, links them into a factor Xase-like active complex that obviates the need for factor VIII.Emicizumabcan be used to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A with factor VIII inhibitors. antibodies ( Treatment references ). Also in clinical trials is a B-domain depleted form of recombinant porcine factor VIII ( Treatment references ) that has reduced cross-reactivity with anti-human antibody inhibitors of factor VIII. 1.Kruse-Jarres R, Kempton CL, Baudo F, et al. Acquired hemophilia A: Updated review of evidence and treatment guidance.Am J Hematol2017;92(7):695-705. doi:10.1002/ajh.24777 2.Sehgal A, Barros S, Ivanciu L, et al: An RNAi therapeutic targeting antithrombin to rebalance the coagulation system and promote hemostasis in hemophilia.Nat Med21:492–497, 2015. 3.Chowdary P, Lethagen S, Friedrich U, et al: Safety and pharmacokinetics of anti-TFPI antibody (concizumab) in healthy volunteers and patients with hemophilia: A randomized first human dose trial.J Thromb Haemost13:743–754, 2015. 4.Kempton CL, Abshire TC, Deveras RA, et al: Pharmacokinetics and safety of OBI-1, a recombinant B domain-deleted porcine factor VIII in subjects with hemophilia A.Haemophilia18:798–804, 2012. 