Factor VIII inhibitors

Proplex T (Factor IX Complex)—used for factor VIII inhibitors, and factor VII or IX deficiency... 

Factor VIII inhibitor dose = 75 factor IX units/kg... 

Dimichele DM. Management of factor VIII inhibitors. Int J Hematol 2006 83 119-25. 

The effectiveness of immunosuppressive drugs in autoimmune disorders varies widely. Nonetheless, with immunosuppressive therapy, remissions can be obtained in many instances of autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, type 1 diabetes, Hashimoto s thyroiditis, and temporal arteritis. Improvement is also often seen in patients with systemic lupus erythematosus, acute glomerulonephritis, acquired factor VIII inhibitors (antibodies), rheumatoid arthritis, inflammatory myopathy, scleroderma, and certain other autoimmune states. 

Kasper CK, Aledort LM, Counts RB, et al. A more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrhag 1975 34 869-872. 

Sultan Y Loyer F In vitro evaluation of factor VI11-bypassing activity of activated prothrombin complex concentrates and factor Vila in the plasma of patients with factor VIII inhibitors thrombin generation test in the presence of collagen-activated platelets. J Lab Clin Med 1993 121 444-452. 

Kopecky, E.M., Greinstetter, S., Pabinger, I., Buchacher, A., Rdmisch, J., and Jungbauer, A. "Effect of oriented or random PEGylation on bioactivity of a factor VIII inhibitor blocking peptide". Biotechnol. Bioeng. 93(4), 647-655 (2006). 

FDA, CBER, Workshop on Factor VIII Inhibitors, 2003. http //www.fda.gov/cber/ minutes/fctrviiill2103t.htm... 

Peerlinck K, Arnout J, Gilles JG, Saint-Remy JM, Vermylen J. A higher than expected incidence of factor VIII inhibitors in multitransfused haemophilia A patients treated with an intermediate purity pasteurized factor VIII concentrate. Thromb Haemost 1993 69 115-18. 

For patients with high titre factor VIII inhibitors, standard factor IX complex products are first-line therapy but activated factor IX complex concentrates may be necessary for continued, more frequent or more severe bleeding. Porcine factor VIII or recombinant human factor Vila may be necessary for major bleeds or elective surgery. 

Coagulation protein concentrates became available in the 1970s, a significant step in the prevention and management of bleeding. The factors that are currently available are factor VII, factor Vila, factor VIII, factor IX, factor XI, and factor XIII. There is also a factor VIII inhibitor bypassing factor, activated prothrombin... 

Patients with bleeding disorders are at risk of developing antibodies against the protein that is absent, present in reduced amounts, or present in an inactive form in their blood. Such coagulation inhibitors make treatment very difficult. Inhibitors of factor VIII are the most common and develop in 5-20% of patients with hemophiha A. Inhibitors of factor IX develop in 1-4% of patients with hemophilia B (3,4). Patients with factor VIII inhibitors present clinically either as high responders who show a strong anamnestic response and a sharp rise in inhibitor concentrations after exposure to factor VIII, or low responders, who show little or no anamnestic response (5). 

A 38-year-old patient with hemophiha A with factor VIII inhibitors was treated with recombinant factor Vila for about 1 month and 18 days after the last infusion developed a distal deep venous thrombosis. Au effect of the factor Vila could not be ruled out, but... 

Smith MP, Ludlam CA, Collins PW, Hay CR, Wilde IT, Grigeri A, Melsen T, Savidge GF. Elective surgery on factor VIII inhibitor patients using continuous infusion of recombinant activated factor VII plasma factor VII activity of 10 lU/ml is associated with an increased incidence of bleeding. Thromb Haemost 2001 86(4) 949-53. 

Santagostino E, Gringeri A, Mannucci PM. Home treatment with recombinant activated factor VII in patients with factor VIII inhibitors the advantages of early intervention. Br J Haematol 1999 104(l) 22-6. 

Antibodies to factor VIII (factor VIII inhibitors)... 

The formation of inhibitors of factor VIII is not restricted to patients with severe hemophiha. There have been two cases of high-titer factor VIII inhibitors in two children with mild hemophiha A one occurred after only minimal exposure to factor VlllrC (33). 

Treatment options for patients with inhibitors are high dosages of clotting factor or recombinant factor Vila for both hemophilia A and B or, in the case of hemophiha A, porcine factor VlllrC or activated prothrombin complex (37). Regular administration of intermediate or low-dose factor Vin concentrates leads to the rapid disappearance of factor VIII inhibitors in some high responders (27) this is thought to be due to the development of immune tolerance. 

This may explain the effectiveness of treating patients with hemophilia who have inhibitors with high doses of factor VIII. Another approach involves the use of prothrombin complex concentrate to treat bleeding episodes in patients with factor VIII inhibitors (38) however, thromboembolic complications related to higher doses of prothrombin complex concentrate have been described, although these are relatively rare (39,40). Thrombotic events are extremely rare when highly purified factor IX is used. Activated prothrombin complex concentrate is also effective in patients with factor VIII inhibitors (41). Serious complications are rare, but disseminated intravascular coagulation has been reported (42). 

Parvovirus B19 transmission occurred in a child who had received vapor heat-treated prothrombin complex concentrate (60° C for 10 hours and 80° C for 1 hour) and in another child who received dry-heated factor VIII concentrate (80° C for 72 hours). Both children had severe hemophiha A and were treated for factor VIII inhibitors (52). 

DehaCroce FJ, Kountakis S, Aguilar EF 3rd. Manifestations of factor VIII inhibitor in the head and neck. Arch Otolaryngol Head Neck Surg 1999 125(11) 1258-61. 

White B, Cotter M, Byrne M, O Shea E, Smith OP. High responding factor VIII inhibitors in mild haemophiha—is there a link with recent changes in clinical practice Haemophilia 2000 6(2) 113-15. 

Yee TT, Lee CA. Is a change of factor VIII product a risk factor for the development of a factor VIII inhibitor Thromb Haemost 1999 81(5) 852. 

Puetz JJ, Bouhasin JD. High-titre factor VIII inhibitor in two children with mild haemophiha A. Haemophiha 2001 7(2) 215-19. 

Abildgaard CF, Penner JA, Watson-Williams EJ. Anti-inhibitor Coagulant Complex (Autoplex) for treatment of factor VIII inhibitors in hemophiha. Blood 1980 56(6) 978-84. 

Rodeghiero F, Castronovo S, Dini E. Disseminated intravascular coagulation after infusion of FEIBA (factor VIII inhibitor bypassing activity) in a patient with acquired haemophiha. Thromb Haemost 1982 48(3) 339-40. 

Roberts HR. The use of agents that by-pass factor VIII inhibitors in patients with haemophiha. Vox Sang 1999 77(Suppl 1) 38-41. 

Ehrlich HJ, Henzl MJ, Gomperts ED. Safety of factor VIII inhibitor bypass activity (FEIBA) 10-year compilation of thrombotic adverse events. Haemophiha 2002 8(2) 83-90. 

There was significant bleeding with hematomas in association with an inhibitor of factor VIII in a 58-year-old man who took interferon alfa for 1 year for chronic myelogenous leukemia (239). The factor VIII inhibitor, which was markedly raised, disappeared within 6 weeks of interferon alfa withdrawal and prednisone treatment. 

Strieker RB, Barlogie B, Kiprov DD. Acquired factor VIII inhibitor associated with chronic interferon-alpha therapy. J Rheumatol 1994 21(2) 350-2. 

English KE, Brien WF, Howson-Jan K, Kovacs MJ. Acquired factor VIII inhibitor in a patient with chronic myelogenous leukemia receiving interferon-alfa therapy. Ann Pharmacother 2000 34(6) 737-9. 

White GC 2nd. Seventeen years experience with Autoplex/ Autoplex T evaluation of inpatients with severe haemophi-ha A and factor VIII inhibitors at a major haemophiUa centre. Haemophilia 2000 6(5) 508-12. 

Gilles J G, Jacquemin M G, Saint-Remy J M (1997). Factor VIII inhibitors. Thromb. Haemost. 78 641-646. 

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