Chapter 110. Coagulation Disorders (Part 1) pot

Chapter 110. Coagulation Disorders (Part 1) Harrison's Internal Medicine > Chapter 110. Coagulation Disorders Coagulation Disorders: Introduction Deficiencies of coagulation factors have been recognized for centuries. Patients with genetic deficiencies of plasma coagulation factors exhibit lifelong recurrent bleeding episodes into joints, muscles, and closed spaces, either spontaneously or following an injury. The most common inherited factor deficiencies are the hemophilias, X-linked diseases caused by deficiency of Factor (F) VIII (hemophilia A) or Factor IX (FIX, hemophilia B). Rare congenital bleeding disorders due to deficiencies of other factors, including FII (prothrombin), FV, FVII, FX, FXI, FXIII, and fibrinogen are usually inherited in an autosomal recessive manner (Table 110-1). Advances in characterization of the molecular bases of clotting factor deficiencies have contributed to a better understanding of the disease phenotypes and may allow more targeted therapeutic approaches through the development of small molecules, recombinant proteins, or cell and gene-based therapies. Table 110- 1 Genetic and Laboratory Characteristics of Inherited Coagulation Disorders Laborator y Abnormality a Clo tting Factor Deficienc y In heritance Pr evalence in General Populati on a PTT T T M inimum Hemosta tic Levels Trea tment P lasma Half- Life Fib rinogen AR 1 in 1,000,000 + 10 0 mg/dL Cryo precipitate 2 –4 d Pro AR 1 + 20 FFP/ 3 thrombin in 2,000,000 –30% PCCs –4 d Fac tor V AR 1 in 1,000,000 + /– /– 15 –20% FFP 3 6 h Fac tor VII AR 1 in 500,000 – 15 –20% FFP/ PCCs 4 –6 h Fac tor VIII X- linked 1 in 5,000 + 30 % FVII I concentrate s 8 –12 h Fac tor IX X- linked 1 in 30,000 + 30 % FIX concentrate s 1 8–24 h Fac AR 1 + 15 FFP/ 4 tor X in 1,000,000 /– /– –20% PCCs 0–60 h Fac tor XI AR 1 in 1,000,000 + 15 –20% FFP 4 0–70 h Fac tor XII AR N D + b b 6 0 h HK AR N D + b b 1 50 h Pre kallikrein AR N D + b b 3 5 h Fac tor XIII AR 1 in 2,000,000 – /– 2– 5% Cryo precipitate 1 1–14 d a Values within normal range (–) or prolonged (+). b No risk for bleeding, treatment is not indicated. Abbreviations: HK, high- molecular weight kininogen; AR, autosomal recessive; aPTT, activated partial thromboplastin time; PT, prothrombin time; TT, thrombin time; ND, not determined; FFP, fresh frozen plasma; PCCs, prothrombin complex concentrates. . Chapter 110. Coagulation Disorders (Part 1) Harrison's Internal Medicine > Chapter 110. Coagulation Disorders Coagulation Disorders: Introduction Deficiencies of coagulation. bleeding disorders due to deficiencies of other factors, including FII (prothrombin), FV, FVII, FX, FXI, FXIII, and fibrinogen are usually inherited in an autosomal recessive manner (Table 110- 1). . recombinant proteins, or cell and gene-based therapies. Table 110- 1 Genetic and Laboratory Characteristics of Inherited Coagulation Disorders Laborator y Abnormality a Clo tting Factor