A bleeding disorder caused by mutations in the F8 gene, which encodes for factor VIII?
Hemophilia A
A bleeding disorder caused by mutations in the F9 gene, which encodes for factor IX?
Hemophilia B
F8 and F9 are inherited in what pattern?
X-linked recessive, only males are affected and females are carriers.
These people frequently present with spontaneous bleeding into joints (hemarthroses) and muscles (hematomas), and experience variable degrees of prolonged or abnormal bleeding.
Hemophiliacs
Screening tests for hemophilia include what?
Prolonged activated partial thromboplastin time with normal prothrombin time, normal bleeding time, and normal fibrinogen levels.
Diagnosis of hemophilia is made by what?
Specific factor assays
Evaluation of a person with newly diagnosed with hemophilia A or B should include what?
Identification of the specific mutation
A personal history of bleeding
Family history of bleeding
A thorough musculoskeletal evaluation
Associated disease screenings
Baseline laboratory tests
What two things are used to treat bleeding episodes and for maintenance therapy?
Factor VIII concentrate and nasal desmopressin
Production of autoantibody that inactivates coagulation factors (VIII or IX) and results in the same clinical bleeding diathesis as occurs in inherited hemophilias.
Acquired hemophilia
A form of von Willebrand's disease that is not inherited but rather develops late in life. It is caused by the development of antibodies that attack and destroy a person's von Willebrand factor. This disease is commonly "acquired" in conjunction with anot
Acquired von Willebrand's disease
A protein that attacks the body's own tissues.
Autoantibody
A group of distinct conditions in which a person's body cannot properly develop a clot, resulting in an increased tendency for bleeding.
Bleeding diathesis.
A person (usually female) who can pass an altered gene to her children, but generally does not express the disease herself.
Carrier
A collection of blood under the skull due to an effusion of blood, usually as a result of trauma.
Cephalohematoma
Any of several proteins that are involved in the blood coagulation process.
Clotting factor
The chemical reaction mediated by coagulation factor proteins that results in a stable fibrin clot.
Coagulation
Mutations that are not inherited, but rather appear first in the affected individual.
De novo mutations
Any spontaneous elimination of part of the normal genetic complement, whether cytogenetically visible (chromosomal deletion) or found by molecular techniques.
Deletion
A synthetic hormone that increases factor VIII levels.
Desmopressin acetate
A condition of altered coagulation that results in consumption of clotting factors and platelets and yields a clinical presentation characterized by both excessive clotting and excessive bleeding.
Disseminated Intravascular Coagulation
A specialized lab test used to determine the level of circulating factor VIII or IX.
Factor assay
Any of several rare disorders characterized by the complete absence or an abnormally low level of clotting factor in the blood.
Factor deficiency
Antibodies that develop in patients in response to factor replacement therapy.
Factor inhibitors
Replacement of a deficient clotting factor from another source (either human derived or recombinant) in an effort to stop or prevent abnormal bleeding.
Factor replacement therapy
Bleeding into joints.
Hemarthroses
Bleeding into soft tissue, such as muscle or visceral organs.
Hematoma
A bleeding disorder in which a specific clotting factor protein-namely, factor VIII or IX- is missing or does not function normally.
Hemophilia
A deficiency or absence of factor VIII; also been called "classic" hemophilia. It is the most common severe bleeding disorder.
Hemophilia A
A deficiency or absence of factor IX; also called "Christmas disease" after the first family that was identified with the condition.
Hemophilia B
A rare variant of hemophilia B inherited in an X-linked pattern.
Hemophilia B Leyden
A deficiency or absence of factor XI; more commonly known as plasma thromboplastin antecedent deficiency.
Hemophilia C
A group of federally funded hospitals that specialize in treating patients with coagulation disorders.
Hemophilia Treatment Centers
The process by which the body stops bleeding.
Hemostasis
Excessive bleeding during the time of menses, in terms of either duration or volume, or both.
Menorrhagia
A categorical term used to describe someone with a factor VIII or IX level ranging between 5% and 25% of normal blood levels.
Mild hemophilia
A mutation in which a base change or substitution results results in a codon that causes insertion of a different amino acid into the growing polypeptide chain, giving rise to an altered protein.
Missense mutation
A categorical term used to describe someone with a factor VIII or IX level ranging between 1%-5% of normal blood levels.
Moderate hemophilia
An affected person as identified in a family pedigree.
Proband
A categorical term used to describe someone with a factor VIII or IX level that is less than 1% of normal blood levels.
Severe hemophilia
Heavy bleeding without history of trauma.
Spontaneous bleeding
A condition in which an abnormally small number of platelets appear in the circulating blood.
Thrombocytopenia
Variation in which the disease symptoms are present.
Variable expressivity
A bleeding disorder in which von Willebrand factor, a blood protein, is either missing or does not function properly. It is the most common congenital bleeding disorder in the US.
Von Willebrand's disease
Recessive inheritance pattern of alleles at loci on the X chromosome that do not undergo crossing over during male meiosis.
X-linked recessive
Hemophilia is a bleeding disorder caused by mutations in the _____ or _____ genes.
F8
F9
Generally, in an X-linked recessive pattern of inheritance, only _____ are affected.
Males
A person with severe hemophilia often presents with ______, ______, and ______.
spontaneous bleeding, hemarthrosis, and cephalohematoma
Screening test results consistent with hemophilia that warrant further evaluation include _____, _____, _____, _____, and _____.
Prolonged APTT
Normal PT
Normal Bleeding Time
Normal Platelet Count
Treatment for severe and moderate hemophilia includes ______.
IV infusion of factor VIII concentrate.
Hemophilia is a bleeding disorder caused by mutations in what genes?
F8 and F9
F8 and F9 code for?
Factor VIII and Factor IX
Factor 8 deficiency?
Hemophilia A
Factor 9 deficiency?
Hemophilia B
Another name for hemophilia B?
Christmas disease
Clinical Findings: spontaneous joint and muscle bleeding; post-trauma and postoperative bleeding.
Severe Hemophilia
Clinical Findings: bleeding in joints and muscles due ot minor trauma; postoperative bleeding.
Moderate Hemophilia
Clinical finding: Postoperative and mild trauma bleeding
Mild hemophilia
F8 and F9 are inherited in what kind of pattern?
X-linked recessive
Are males or females usually affected by hemophilia?
Males
Are Factors 8 and 9 extrinsic or intrinsic?
Extrinsic
Females with only one altered X chromosome are considered?
Carriers
Hemophilia cannot be passed from?
Father to son
Joints most commonly affected by hemophilia?
Knees, ankles, and elbows
Most frequent cause internal bleeding?
GI bleeds
People with moderate hemophilia are usually diagnosed when?
Before age 6
What percent of hemophiliacs do not present with a known family history?
25%
What evaluates intrinsic pathway of coagulation?
APTT
What evaluates extrinsic pathway?
PT
Useful for monitoring Warfarin therapy?
PT (extrinsic)
Decreases in circulating factor VIII and IX may be due to in vivo consumption, such as occurs in?
Disseminated Intravascular Coagulation
Best individual screening test for coagulation disorders?
APTT
Can PT or APTT differentiate between factor deficiencies?
No
What can increase levels of VIII and IX?
Estrogens, oral contraceptives, epinephrine, desmopressin acetate, and vigorous exercise.
Platelet disorders due to quantitative platelet disorders?
Thrombocytopenia
Mutations in mild to moderate hemophilia are usually?
Missense mutations
Patients with hemophilia may be referred to?
Hemophilia treatment centers
Children with hemophilia should be assessed every?
6-12 months
Treatment of bleeding manifestations include?
IV infusions of Factor VIII concentrate within an hour of onset of bleeding
What can be used as mild treatment?
Nasal desmopressin
Two major complications associated with factor replacement therapy?
Transfusion transmitted infection
Development of factor antibodies.
Risk of developing antibodies is greatest when?
During the initial treatment for hemophilia.
Disease with single point mutations in F9 gene?
Hemophilia B Leyden
What causes acquired hemophilia?
Production of autoantibody which inactivates factor VIII or IX. Associated with pregnancy, immune disorders, cancer, and allergic reactions.
Von Willebrand's disease is inherited in what fashion?
Autosomal dominant
Most common inheritable bleeding disorder?
Von Willebrand's
Factor XI deficiency also known as PTA deficiency?
Hemophilia C
Who is more likely to get Hemophilia C?
Ashkenazi Jews
Does Hemophilia C usually require treatment?
No