tailieunhanh - Chapter 110. Coagulation Disorders (Part 5)

The clinical diagnosis of inhibitor is suspected when patients do not respond to factor replacement at therapeutic doses. Inhibitors increase both morbidity and mortality in hemophilia. Because early detection of an inhibitor is critical to a successful correction of the bleeding or to eradication of the antibody, most hemophilia centers perform annual screening for inhibitors. The laboratory test required to confirm the presence of an inhibitor is an aPTT mixed with normal plasma. In most hemophilia patients, a 1:1 mix with normal plasma completely corrects the aPTT. In inhibitor patients, the aPTT on a 1:1 mix is abnormally prolonged,. | Chapter 110. Coagulation Disorders Part 5 The clinical diagnosis of inhibitor is suspected when patients do not respond to factor replacement at therapeutic doses. Inhibitors increase both morbidity and mortality in hemophilia. Because early detection of an inhibitor is critical to a successful correction of the bleeding or to eradication of the antibody most hemophilia centers perform annual screening for inhibitors. The laboratory test required to confirm the presence of an inhibitor is an aPTT mixed with normal plasma. In most hemophilia patients a 1 1 mix with normal plasma completely corrects the aPTT. In inhibitor patients the aPTT on a 1 1 mix is abnormally prolonged because the inhibitor neutralizes the FVIII clotting activity of the normal plasma. The Bethesda assay uses a similar principle and defines the specificity of the inhibitor and its titer. The results are expressed in Bethesda units BU in which 1 BU is the amount of antibody that neutralizes 50 of the FVIII or FIX present in normal plasma after 2 h of incubation at 37 C. Clinically inhibitor patients are classified as low responders or high responders which provides guidelines for optimal therapy. Therapy for inhibitor patients has two goals the control of acute bleeding episodes and the eradication of the inhibitor. For the control of bleeding episodes low responders those with titers 5 BU respond well to high doses of human or porcine FVIII 50-100 U kg with minimal or no increase in the inhibitor titers. However high-responder patients those with initial inhibitor titer 10 BU or an anamnestic response in the antibody titer to 10 BU even if low titer initially do not respond to FVIII or FIX concentrates. The control of bleeding episodes in high-responder patients can be achieved by using concentrates enriched for prothrombin FVII FIX FX prothrombin complex concentrates PCCs or activated PCCs and more recently by recombinant activated Factor VII FVIIa Fig. 110-1 . The rates of therapeutic success