Coagulation Disorders

Coagulation Disorders

Roxanne Jeen L. Fornolles

Hemophilia

X-linked recessive hemorrhagic disease due to mutations in the F8gene (hemophilia A or classic hemophilia) or F9 gene (hemophilia B)Male subjects are clinically affected; women, who carry a single mutated gene, are generally asymptomatic.The disease phenotype correlates with the residual activity of FVIII or FIX and can be classified as severe (10 BU even if low titer initially, do not respond to FVIII or FIX concentratesThe 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)ComplicationsThe most effective strategy is the immune tolerance induction (ITI) based on daily infusion of missing protein until the inhibitor disappears, typically requiring periods longer than 1 year, with success rates in the range of 60%.The use of anti-CD20 monoclonal antibody (rituximab) combined with FVIII was thought to be effective. Although this therapy may reduce the inhibitor titers, sustained eradication is uncommon and may require two to three infusions weekly of FVIII concentrates.ComplicationsInfectious DiseasesHepatitis C viral (HCV) infection is the major cause of morbidity and the second leading cause of death in hemophilia patients exposed to older clotting factor concentrates. Emerging Clinical Problems in Aging Hemophilia PatientsCancer is a common cause of mortality in aging hemophilia patients as they are at risk for HIV- and HCV-related malignancies. Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer and a common cause of death in HIV-negative patients. Management of Carriers of HemophiliaUsually hemophilia carriers, with factor levels of 50% of normal, have not been considered to be at risk for bleeding. However, a wide range of values (22116%) have been reported due to random inactivation of the X chromosomes (lyonization). Therefore, it is important to measure the factor level of carriers to recognize those at risk of bleeding and to optimize preoperative and postoperative management.Factor XI Deficiencyis a rare bleeding disorder that occurs in the general population at a frequency of one in a million. Normal FXI clotting activity levels range from 70 to 150 U/dL. In heterozygous patients with moderate deficiency, FXI ranges from 20 to 70 U/dL, whereas in homozygous or double heterozygote patients, FXI levels are