MISHA MAZHAR 2k10-NUST-BS-V&I-54

 Mutations in F8 or F9 genes.  Leads to lack of proteins made by these genes.  F8 responsible for making the blood clotting factor VIII  F9 responsible for making the blood clotting factor IX  Mutations in F8 or F9 genes.  Leads to lack of proteins made by these genes.  F8 responsible for making the blood clotting factor VIII  F9 responsible for making the blood clotting factor IX

 Classic Hemophilia  X linked recessive hereditary disorder that is due to defective or deficient factor VIII  Classic Hemophilia  X linked recessive hereditary disorder that is due to defective or deficient factor VIII  Also known as christmas disease  X linked recessive hereditary disorder that is due to the defective or deficient factor IX  Also known as christmas disease  X linked recessive hereditary disorder that is due to the defective or deficient factor IX

 CBC with platelet count – normal in hemophilia A, B  Prothrombin time (PT)/PTT  PT – normal in hemophilia A, B  PTT – prolonged in moderate and severe hemophilia May not be prolonged in mild cases or in female carriers Prolonged PTT that corrects in a mixing study suggests factor deficiency PTT that does not correct with mixing study suggests an inhibitor Incubated mixing studies are often necessary to identify FVIII inhibitors  Thrombin clotting time and plasma concentration of fibrinogen – normal in hemophilia A and B  CBC with platelet count – normal in hemophilia A, B  Prothrombin time (PT)/PTT  PT – normal in hemophilia A, B  PTT – prolonged in moderate and severe hemophilia May not be prolonged in mild cases or in female carriers Prolonged PTT that corrects in a mixing study suggests factor deficiency PTT that does not correct with mixing study suggests an inhibitor Incubated mixing studies are often necessary to identify FVIII inhibitors  Thrombin clotting time and plasma concentration of fibrinogen – normal in hemophilia A and B

 Frequency and severity of bleeding are related to F VIII levels SeverityF VIII activityClinical manifestations Severe<1%Spontaneous hemorrhage from early infancy Freq sp hemarthrosis Moderate2-5%Hemorrhage sec to trauma or surgery Occ sp hemarthrosis Mild>5%Hemorrhage sec to trauma or surgery Rare sp bleeding

 Bleeding into the joints  The bleeding causes distension of the joint spaces, significant pain, and over time, can be disfiguring.  Clinically:  Aura: tingling warm sensation  Excruciating pain  Generally affects one joint at the time  The knees and ankles are most often affected  If treated early it can subside in 6 to 8 hrs and disappear in 12 to 24 hrs.  Bleeding into the joints  The bleeding causes distension of the joint spaces, significant pain, and over time, can be disfiguring.  Clinically:  Aura: tingling warm sensation  Excruciating pain  Generally affects one joint at the time  The knees and ankles are most often affected  If treated early it can subside in 6 to 8 hrs and disappear in 12 to 24 hrs.

 Bleeding into the muscles may occur with hematoma formation.  Bleeding from the mouth or nosebleeds may occur. Bleeding after dental procedures is common, and oozing of blood from the gums may occur in young children when new teeth are erupting.  Bleeding from the gastrointestinal tract can lead to blood in stool.  Bleeding from the urinary tract can lead to blood in the urine (hematuria).  Intercranial hemorrhage (bleeding into the brain or skull) can lead to symptoms such as nausea, vomiting, and/or lethargy.  Increased bleeding after surgery or trauma is characteristic of hemophilia.  Bleeding into the muscles may occur with hematoma formation.  Bleeding from the mouth or nosebleeds may occur. Bleeding after dental procedures is common, and oozing of blood from the gums may occur in young children when new teeth are erupting.  Bleeding from the gastrointestinal tract can lead to blood in stool.  Bleeding from the urinary tract can lead to blood in the urine (hematuria).  Intercranial hemorrhage (bleeding into the brain or skull) can lead to symptoms such as nausea, vomiting, and/or lethargy.  Increased bleeding after surgery or trauma is characteristic of hemophilia.