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Haematological Disease
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
As for haemophilia A, the APTT is typically prolonged but it is factor IX that is deficient whereas factor VIII levels are normal. Management is the same as for haemophilia A, but therapy is IV factor IX concentrate. Gene therapy has also recently proven highly effective in haemophilia B.
Congenital and acquired disorders of coagulation
Published in Jennifer Duguid, Lawrence Tim Goodnough, Michael J. Desmond, Transfusion Medicine in Practice, 2020
Jeanne M Lusher, Roshni Kulkarni
Haemophilia B is less common than haemophilia A, accounting for 15–20% of cases of haemophilia. It is clinically indistinguishable from haemophilia A, and many of the principles of treatment are the same for both disorders. However, there are a few significant differences.26 FIX is a much smaller molecule than is FVIII and distributes extravascularly; thus, dosage calcuation is different. For FIX, 1 IU/kg will result in an increase in circulating FIX of 1%. The half-life of FIX (approximately 18 hours) is longer than that of FVIII. The incidence of FIX inhibitors is 1–2%, which is considerably less than in haemophilia A. Approximately 40% of patients who develop FIX inihibitors also have allergic reactions (often severe) to any FIX-containing material. In haemophilia B patients who develop inhibitors, response to 1TI regimens is approximately 50%, which is considerably less than the 80–85% response rate to ITI seen in haemophilia A. Desmopressin is not a treatment option for haemophilia B, since it increases FVIII and von Willebrand factor, but not FIX.
Hereditary Causes for Plasma Clotting Bleeding
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
The clinical manifestations of hemophilia B or factor IX deficiency are identical to those of factor VIII:C deficiency, except that the abnormality is in the factor IX gene and plasma protein. This form, too, is sex-linked and shows a correlation between factor IX:C levels and clinical expression (1,2). Laboratory diagnosis is based on finding a prolonged PTT and decreased factor IX:C level. Factor VIII:C and the von Willebrand factor are normal. The other vitamin K-dependent factors are normal as well.
Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: research priorities to transform the care of people with hemophilia
Published in Expert Review of Hematology, 2023
Duc Q. Tran, Craig C. Benson, Judith A. Boice, Meera Chitlur, Amy L. Dunn, Miguel A. Escobar, Kalpna Gupta, Jill M. Johnsen, James Jorgenson, Scott D. Martin, Suzanne Martin, Shannon L. Meeks, Alfredo A. Narvaez, Doris V. Quon, Mark T. Reding, Ulrike M. Reiss, Brittany Savage, Kim Schafer, Bruno Steiner, Courtney Thornburg, Lena M. Volland, Annette von Drygalski
The Diagnostics subgroup formulated 13 top priorities as research initiatives to be accomplished, rather than questions (Table 4). Six scored above the high priority threshold, three of which seek to exploit advances in imaging technology encompassing POC MSKUS, including PWH self-imaging, and novel MRI sequences for hemosiderin quantification to assess iron clearance. The other three propose rapid and reliable tests for bleed detection and the accurate prediction of bleeding phenotypes. Research priorities of lesser importance were lab tests to universally assess hemostatic potential and measure the risk of bleeding, the relationship between clotting factor levels and bleed propensity, the impact of routine clinical and imaging assessments on outcomes, the occurrence of anti-drug antibodies to non-factor replacement therapies, companion tests, and the impact of differential tissue distribution of FIX products in hemophilia B.
Hemophilia A gene therapy: current and next-generation approaches
Published in Expert Opinion on Biological Therapy, 2022
Steven W. Pipe, Gil Gonen-Yaacovi, Oscar G. Segurado
Hemophilia is classified as a group of X-linked inherited hemorrhagic disorders resulting from the absence of or defects in critical factors in the coagulation cascade [1]. Patients with hemophilia exhibit compromised thrombin generation and fibrin clot formation, which leads to bleeding episodes, most commonly into the joints (hemarthrosis). The 2 main types of hemophilia (A and B) relate to deficiency or dysfunction of the specific clotting factors VIII or IX, respectively, with the severity depending on the level of clotting factor activity. Hemophilia affects mainly males, and hemophilia A accounts for the large majority of cases (~80%), affecting approximately 1 of every 5000 live-born males. Hemophilia B is 5 times less common than hemophilia A, having an incidence of approximately 1 in 30,000 births [2,3]. Over a million people around the world are estimated to have hemophilia, including more than 30,000 in the United States (US) [4]. The prevalence is higher among Whites than Blacks or Hispanics [5].
Challenges and opportunities when transitioning from in vivo gene replacement to in vivo CRISPR/Cas9 therapies – a spotlight on hemophilia
Published in Expert Opinion on Biological Therapy, 2022
Oscar G Segurado, Ruhong Jiang, Steven W Pipe
Inherited monogenic diseases are the main targets for gene replacement therapies, as the mutations which cause the condition are located on a single gene [1]. A representative example is hemophilia, a rare inherited hemorrhagic disorder characterized by spontaneous bleeding caused by defects in vital coagulation factors. Both Hemophilia A (HemA) and Hemophilia B (HemB) are X-linked recessive disorders that primarily affect males and are caused by defects in clotting factor VIII (FVIII) and clotting factor IX (FIX), respectively. The severity of the bleeding phenotype is related to the residual factor activity levels and categorized as severe (<1% activity), moderate (1–5%) and mild (6–40%). Bleeding episodes characteristically occur in joints (hemarthroses) but may also be present in muscles, soft tissues, and intracranially. Hemophilia patients are also at a greater risk of severe bleeding following trauma or surgery. Repeated hemarthroses leads to progressive osteochondral degeneration and eventually contractures, fixed deformity of joints and reduced quality of life [2]. Accordingly, the standard of care is to reduce bleeding through prophylactic strategies.