MedGen

Hemophilia B is characterized by deficiency in factor IX clotting activity that results in prolonged oozing after injuries, tooth extractions, or surgery, and delayed or recurrent bleeding prior to complete wound healing. The age of diagnosis and frequency of bleeding episodes are related to the level of factor IX clotting activity. In individuals with severe hemophilia B, spontaneous joint or deep-muscle bleeding is the most frequent sign. Individuals with severe hemophilia B are usually diagnosed during the first two years of life; without prophylactic treatment, they may average up to two to five spontaneous bleeding episodes each month. Individuals with moderate hemophilia B seldom have spontaneous bleeding; however, they do have prolonged or delayed oozing after relatively minor trauma and are usually diagnosed before age five to six years; the frequency of bleeding episodes varies from once a month to once a year. Individuals with mild hemophilia B do not have spontaneous bleeding episodes; however, without pre- and postoperative treatment, abnormal bleeding occurs with surgery or tooth extractions; the frequency of bleeding may vary from once a year to once every ten years. Individuals with mild hemophilia B are often not diagnosed until later in life. In any individual with hemophilia B, bleeding episodes may be more frequent in childhood and adolescence than in adulthood. Approximately 30% of heterozygous females have factor IX clotting activity lower than 40% and are at risk for bleeding (even if the affected family member has mild hemophilia B), although symptoms are usually mild. After major trauma or invasive procedures, prolonged or excessive bleeding usually occurs, regardless of severity. [from GeneReviews]

Von Willebrand disease (VWD), a congenital bleeding disorder caused by deficient or defective plasma von Willebrand factor (VWF), may only become apparent on hemostatic challenge, and bleeding history may become more apparent with increasing age. Recent guidelines on VWD have recommended taking a VWF level of 30 or 40 IU/dL as a cutoff for those diagnosed with the disorder. Individuals with VWF levels greater than 30 IU/dL and lower than 50 IU/dL can be described as having a risk factor for bleeding. This change in guidelines significantly alters the proportion of individuals with each disease type. Type 1 VWD (~30% of VWD) typically manifests as mild mucocutaneous bleeding. Type 2 VWD accounts for approximately 60% of VWD. Type 2 subtypes include: Type 2A, which usually manifests as mild-to-moderate mucocutaneous bleeding; Type 2B, which typically manifests as mild-to-moderate mucocutaneous bleeding that can include thrombocytopenia that worsens in certain circumstances; Type 2M, which typically manifests as mild-moderate mucocutaneous bleeding; Type 2N, which can manifest as excessive bleeding with surgery and mimics mild hemophilia A. Type 3 VWD (<10% of VWD) manifests with severe mucocutaneous and musculoskeletal bleeding. [from GeneReviews]

Hereditary factor XII deficiency is clinically asymptomatic but results in prolonged activated partial thromboplastin time (APTT). Typically, homozygous or compound heterozygous carriers exhibit almost no (less than 1%) factor XII activity as compared with normal individuals, whereas heterozygotes display intermediate activity. Most of these individuals also lack immunologically detectable factor XII and are referred to as cross-reacting material (CRM)-negative (summary by Kondo et al., 1999). [from OMIM]

Factor V deficiency is a rare autosomal recessive bleeding disorder with variable phenotypic expression (summary by van Wijk et al., 2001). [from OMIM]

An abnormal prolongation (delay) in the time required by whole blood to produce a visible clot. [from HPO]