Hemophilia

Diagnosis

The diagnosis of hemophilia is made on the basis of clinical suspicion (usually due to a bleeding event) followed by demonstration of deficient factor levels (< 40%).

History

• Family history Family History Adult Health Maintenance may be present in male ancestors.
• Negative family history Family History Adult Health Maintenance does not exclude the diagnosis.
• Reports of bruising, spontaneous bleeding, or bleeding out of proportion to a given trauma  
• Reports of hemarthrosis, hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma, hematemesis Hematemesis Vomiting of blood that is either fresh bright red, or older ‘coffee-ground’ in character. It generally indicates bleeding of the upper gastrointestinal tract. Mallory-Weiss Syndrome (Mallory-Weiss Tear), etc ETC The electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP). Electron Transport Chain (ETC). 

Physical examination

• Ecchymoses
• Hemarthroses
• Hematomas 

Laboratory evaluation

• CBC:
  • Normal to decreased hemoglobin/ hematocrit Hematocrit The volume of packed red blood cells in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, anemia shows a low value; polycythemia, a high value. Neonatal Polycythemia depending on occult or gross bleeding
  • Normal platelet count 
• Coagulation studies Coagulation studies Coagulation studies are a group of hematologic laboratory studies that reflect the function of blood vessels, platelets, and coagulation factors, which all interact with one another to achieve hemostasis. Coagulation studies are usually ordered to evaluate patients with bleeding or hypercoagulation disorders. Coagulation Studies: 
  • Normal bleeding time Bleeding time Duration of blood flow after skin puncture. This test is used as a measure of capillary and platelet function. Hemostasis
  • Normal PT 
  • Elevated aPTT: intrinsic pathway Intrinsic pathway The intrinsic pathway is mainly responsible for the amplification of factor X activation Hemostasis
  • Low serum levels of factor VIII Factor VIII Factor VIII of blood coagulation. Antihemophilic factor that is part of the factor viii/von Willebrand factor complex. Factor VIII is produced in the liver and acts in the intrinsic pathway of blood coagulation. It serves as a cofactor in factor X activation and this action is markedly enhanced by small amounts of thrombin. Hemostasis, IX, or XI (factor will be < 40% normal range)
  • Check von Willebrand’s factor (VWF) if factor VIII Factor VIII Factor VIII of blood coagulation. Antihemophilic factor that is part of the factor viii/von Willebrand factor complex. Factor VIII is produced in the liver and acts in the intrinsic pathway of blood coagulation. It serves as a cofactor in factor X activation and this action is markedly enhanced by small amounts of thrombin. Hemostasis levels are low to rule out von Willebrand’s disease
• Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies:
  • Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies is not needed to diagnose hemophilia.
  • Generally reserved for female first-degree relatives for the purposes of family planning/ genetic counseling Genetic Counseling An educational process that provides information and advice to individuals or families about a genetic condition that may affect them. The purpose is to help individuals make informed decisions about marriage, reproduction, and other health management issues based on information about the genetic disease, the available diagnostic tests, and management programs. Psychosocial support is usually offered. Myotonic Dystrophies
• Imaging: 
  • CT of brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification: evaluate for intracranial bleeding 
  • CT of abdomen: evaluate for retroperitoneal Retroperitoneal Peritoneum: Anatomy bleeding/ hematoma Hematoma A collection of blood outside the blood vessels. Hematoma can be localized in an organ, space, or tissue. Intussusception
  • Ultrasonography of abdomen: evaluate for retroperitoneal Retroperitoneal Peritoneum: Anatomy bleeding/ hematoma Hematoma A collection of blood outside the blood vessels. Hematoma can be localized in an organ, space, or tissue. Intussusception
  • Ultrasonography of joint: evaluate for joint swelling Swelling Inflammation/hemarthrosis

Differential Diagnosis

• Liver failure Liver failure Severe inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio. Autoimmune Hepatitis: The liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy is the site for synthesis Synthesis Polymerase Chain Reaction (PCR) of coagulation factors Coagulation factors Endogenous substances, usually proteins, that are involved in the blood coagulation process. Hemostasis; thus, a dysfunctional liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy would result in deficiency in the clotting factors. Failure would be diagnosed clinically in the setting of liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease with confirmation of the nature of the bleeding diathesis Bleeding diathesis Wiskott-Aldrich Syndrome via laboratory workup. Treatment is aimed at controlling bleeding, replacing deficient clotting factors, and addressing the underlying cause of liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease. 
• Vitamin K deficiency Vitamin K Deficiency A nutritional condition produced by a deficiency of vitamin K in the diet, characterized by an increased tendency to hemorrhage (hemorrhagic disorders). Such bleeding episodes may be particularly severe in newborn infants. Fat-soluble Vitamins and their Deficiencies: Vitamin K Vitamin K A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: vitamin K 1 (phytomenadione) derived from plants, vitamin K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, vitamin K 3 (menadione). Vitamin k 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin k. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin k. Fat-soluble Vitamins and their Deficiencies is needed for the activation of clotting factors II, VII, IX, and X; thus, a deficiency would lead to inactivation of these factors and present with bleeding complications. Diagnosis is made by laboratory workup demonstrating low vitamin K Vitamin K A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: vitamin K 1 (phytomenadione) derived from plants, vitamin K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, vitamin K 3 (menadione). Vitamin k 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin k. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin k. Fat-soluble Vitamins and their Deficiencies levels and downstream deficiency of associated clotting factors. Treatment is aimed at control of bleeding and correct  vitamin K deficiency Vitamin K Deficiency A nutritional condition produced by a deficiency of vitamin K in the diet, characterized by an increased tendency to hemorrhage (hemorrhagic disorders). Such bleeding episodes may be particularly severe in newborn infants. Fat-soluble Vitamins and their Deficiencies and/or deficient clotting factors.
• Disseminated intravascular coagulation Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation ( DIC DIC Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation): Disseminated intravascular coagulation Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation, an imbalance between native prothrombotic and antithrombotic factors, is a complication of many diseases. An inciting event causes widespread thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus (exhausting available clotting factor reserves) followed by uncontrolled bleeding. It has high morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status and thus requires critical care intervention. Treatment is aimed at control of bleeding, resuscitation Resuscitation The restoration to life or consciousness of one apparently dead. . Neonatal Respiratory Distress Syndrome to maintain hemodynamic stability, and addressing the inciting event.  
• Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of ADAMTS-13, a metalloproteinase that cleaves multimers of von Willebrand factor (VWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Thrombotic Thrombocytopenic Purpura ( TTP TTP Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of adamts-13, a metalloproteinase that cleaves multimers of von Willebrand factor (vWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Thrombotic Thrombocytopenic Purpura): a disorder due to a deficiency in the metalloproteinase responsible for breakdown of VWF, which can be congenital Congenital Chorioretinitis or acquired: Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of ADAMTS-13, a metalloproteinase that cleaves multimers of von Willebrand factor (VWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Thrombotic Thrombocytopenic Purpura falls into the differential diagnosis with idiopathic Idiopathic Dermatomyositis thrombocytopenic purpura ( ITP ITP Immune thrombocytopenic purpura (ITP), formerly known as idiopathic thrombocytopenic purpura, is a condition that develops secondary to immune-mediated destruction of platelets, resulting in thrombocytopenia (platelet count < 100,000/mm³). Immune thrombocytopenic purpura can be either primary or secondary due to drugs or underlying disease. Immune Thrombocytopenic Purpura) and DIC DIC Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation, all presenting with thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia. Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of ADAMTS-13, a metalloproteinase that cleaves multimers of von Willebrand factor (VWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Thrombotic Thrombocytopenic Purpura is more acute than hemophilia and requires urgent plasmapheresis Plasmapheresis Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. Stevens-Johnson Syndrome.
• Henoch–Schönlein purpura: an autoimmune small-vessel vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus: Henoch–Schönlein purpura typically presents as a tetrad of abdominal pain Abdominal Pain Acute Abdomen, hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma, purpuric rash Rash Rocky Mountain Spotted Fever, and hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma. The disorder is diagnosed clinically and managed symptomatically.
• Von Willebrand disease Von Willebrand disease Von Willebrand disease (vWD) is a bleeding disorder characterized by a qualitative or quantitative deficiency of von Willebrand factor (vWF). Von Willebrand factor is a multimeric protein involved in the plate adhesion phase of hemostasis by forming a bridge between platelets and damaged portions of the vessel wall. Von Willebrand Disease: an inherited autosomal bleeding disorder that can present with mild to moderate bleeding at any age: Diagnosis is made by demonstration of VWF deficiency on laboratory analysis. Treatment is with control of bleeding and administration of desmopressin and antifibrinolytic agents.