Factor IX inhibitors

Ehrenforth S, Kreuz W, Scharrer I, et al. Incidence of development of factor VIII and factor IX inhibitors in hemophiliacs. Lancet 1992 339(8793) 594-8. 

Ingerslev J. Efficacy and safety of recombinant factor Vila in the prophylaxis of bleeding in various surgical procedures in hemophilic patients with factor VIII and factor IX inhibitors. Semin Thromb Hemost 2000 26(4) 425-32. 

Parqnet A, Laurian Y, Rothschild C, Navarro R, Gnerois C, Gay V, Durin A, Peynet J, Snltan Y. Incidence of factor IX inhibitor development in severe haemophilia B patients treated with only one brand of high pnrity plasma derived factor IX concentrate. Thromb Haemost 1999 82(4) 1247-9. 

Allergic and anaphylactic reactions due to factor IX inhibitor have been described (SEDA-21, 343) (6). Anaphylactic reactions occur particularly in patients with undetectable concentrations of factor IX, because of major disruptions in the factor IX gene (10). In patients with factor IX inhibitor, IgGl subclass antibodies have been found, which may activate complement, resulting in allergic reactions (SEDA-21, 343) (10). However, it has also been suggested that allergic reactions to factor IX products are IgE-mediated. 

In two patients with severe factor IX deficiency and high concentrations of factor IX inhibitors who... 

Warrier I, Ewenstein BM, Koerper MA, et al. Factor IX inhibitors and anaphylaxis in hemophiUa B. J Pediatr Hematol Oncol 1997 19 23-27. 

Hedner U. Treatment of patients with factor Vlll and factor IX inhibitors with special focus on the use of recombinant factor Vila. Thromb Haemost 1999 82 531-539. 

Treatment of Patients with Factor VIII or IX Inhibitors... 

Factor VIII and IX inhibitors are antibodies that develop in 20% and 12% of hemophilia A and hemophilia B patients, respectively, in response to replacement therapy. These antibodies bind to and neutralize the activity of infused factor concentrates. Although the inhibitors do not increase hemorrhage frequency, their existence challenges the treatment of bleeding episodes. Titers of inhibitors are measured and... 

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... 

Factor VIII process, 12 143 Factor IX, 4 86-87 Factor IXa, 4 86-87, 89 Factor IXa inhibitors, 4 103 Factor IX concentrates, properties of, 72 152t... 

Indications Treatment of bleeding episodes in hemophilia A or B patients with inhibitors to factor VIII or factor IX... 

B. Indications and use NovoSeven is indicated for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to factor VIII or factor IX. It should be administered to patients only under the direct supervision of a physician experienced in the treatment of hemophilia. 

Lusher, J. M. (1996). Recombinant factor Vila (NovoSeven) in the treatment of internal bleeding in patients with factor VIII and IX inhibitors. 

Lusher JM. Inhibitor antibodies to factor VIII and factor IX management. Sem Thromb Hemost 2000 26 179-88. 

Tissue factor pathway inhibitor. This limits the action of TF. It also inhibits excessive TF-mediated activation of factor IX and X. 

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). 

Hasegawa DK, Edson JR. Detection of factor VIII and IX inhibitors after first exposure to heat-treated concentrates. Lancet I987 l(8530) 449. 

Barthels M. Chnical efficacy of prothrombin complex concentrates and recombinant factor Vila in the treatment of bleeding episodes in patients with factor VII and IX inhibitors. Thromb Res 1999 95(4 Suppl l) S31-8. 

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). 

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