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==Historical Perspective== | ==Historical Perspective== | ||
Hemophilia | Hemophilia is considered a very old [[disease]] with its history dating back to the 2nd century AD. The first modern descriptions of the condition appeared during the 19th century. Extensive work has been done over the centuries regarding the classification, [[Heredity|inheritance]] pattern, and treatment of hemophilia. | ||
==Classification== | ==Classification== | ||
Hemophilia may be classified into three | Hemophilia may be classified into three sub-types based on the lack of functional [[Coagulation|clotting factors]]: [[hemophilia A]] , [[hemophilia B]], [[hemophilia C]]. It can also be divided into different categories based on the severity of the condition. Hemophilia can also be [[acquired]] in the setting of [[antibodies]] directed against the [[Coagulation|clotting factors]]. | ||
==Pathophysiology== | ==Pathophysiology== | ||
Hemophilia is a [[Genetic disorder|genetic bleeding disorder]] resulting from the insufficient levels of [[Coagulation|clotting factors]] in the [[Human body|body]]. The [[Coagulation|clotting factors]] irregularity causes a lack of [[Coagulation|clumping of blood]] required to form a [[Thrombus|clot]] to plug a site of a [[wound]]. The [[genes]] involved in the [[pathogenesis]] of hemophilia include the'' F8 ''[[gene]] in [[hemophilia A]], '' F9'' [[gene]] in [[hemophilia B]], and ''F11'' [[gene]] in [[Hemophilia C|C]]. Hemophilia predominantly affects the male population but the sub-type [[hemophilia C]], with an [[Autosome|autosomal]] [[Heredity|inheritance]] pattern, can affect the males as well as females. | |||
==Causes== | ==Causes== | ||
Hemophilia | Hemophilia A, B, and C are caused by [[mutations]] in ''F8'', ''F9'', and ''F11'' [[genes]] respectively. It can also occur as a result of [[Autoantibody|autoantibodies]] directed against the clotting factors. | ||
==Differentiating Hemophilia from other diseases== | ==Differentiating Hemophilia from other diseases== | ||
Hemophilia must be differentiated from other diseases | Hemophilia must be differentiated from other diseases leading to spontaneous [[bleeding]] and [[bleeding]] following [[Injury|injuries]] or [[surgery]] such as [[von Willebrand disease]], [[hepatic failure]], [[thrombocytopenia]], [[vitamin K deficiency]], [[disseminated intravascular coagulation]], [[uremia]], [[congenital afibrinogenemia]], [[factor V]] [[deficiency]], [[factor X]] [[deficiency]] as seen in [[amyloid purpura]], [[glanzmann's thrombasthenia]], [[Bernard-Soulier syndrome]], [[factor XII]] [[deficiency]] and [[C1-inhibitor|C1-inhibitor (C1INH)]] [[deficiency]]. | ||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
The prevalence of hemophilia is estimated to be 20,000 cases annually. The incidence of hemophilia is estimated to be | The [[prevalence]] of hemophilia is estimated to be 20,000 cases in the United States annually. The age-adjusted [[prevalence]] of hemophilia in six US states (Oklahoma, Massachusetts, Colorado, Georgia, Louisiana, and New York) in 1994 was 13.4 cases per 100, 000 males. The [[incidence]] of hemophilia is estimated to be 1 in 5,000 male births for hemophilia A and 1 in 30,000 births for hemophilia B. | ||
==Risk Factors== | ==Risk Factors== | ||
The most potent risk factor in the development of hemophilia is the family history of hemophilia. Other [[Risk factor|risk factors]] include [[Male|male sex]] and [[Cancer|malignancies]]. | |||
==Screening== | ==Screening== | ||
Initial [[Screening (medicine)|screening]] [[blood]] investigations for any [[child]] with suspected [[Coagulopathy|bleeding disorder]] include [[platelet]] count, [[Prothrombin time|prothrombin time (PT)]], [[Activated partial thromboplastin time|activated partial thromboplastin time (aPTT)]], and [[fibrinogen]] [[test]]. [[Chorionic villus sampling]] at 11-14 weeks of [[gestation]] can be performed for the [[Genetics|genetic]] [[diagnosis]] of hemophilia. | |||
==Natural History, Complications and Prognosis== | ==Natural History, Complications and Prognosis== | ||
Hemophilia can present with a [[bleeding]] episode during the [[Infant|neonatal]] period that is difficult to manage or it can present with [[Medical sign|signs]] and [[Symptom|symptoms]] of concealed [[bleeding]] into the [[joint]] or [[Viscus|viscera]]. If left untreated, hemophilia can result in [[Complication (medicine)|complications]] involving multiple [[Organ (anatomy)|organs]] and in severe [[bleeding]] episodes it can result in death. Hemophilia [[Patient|patients]] can lead an active and [[Health|healthy]] [[life]] and [[life expectancy]] depends on the treatment response and the presence of [[Comorbidity|comorbidities]]. [[Complication (medicine)|Complications]] of hemophilia include [[HIV AIDS|AIDS]], [[hepatitis]], [[Vitamin D deficiency]], [[osteoporosis]], and [[Kidney|renal]] [[Pathology|pathologies]]. | |||
==Diagnostic Study of Choice== | |||
[[Coagulation]] tests and [[coagulation]] [[Assay|assays]] are the [[Gold standard (test)|gold standard]] for the [[diagnosis]] of hemophilia. Prolonged [[Activated partial thromboplastin time|activated partial thromboplastin time (aPTT)]], normal [[Prothrombin time|prothrombin time (PT)]], prolonged [[Bleeding time|bleeding time (BT)]], and normal [[fibrinogen]] concentration are [[Diagnosis|diagnostic]] of hemophilia. [[Coagulation]] tests should be followed by measuring the clotting factors level by [[coagulation]] assays. Once the [[coagulation]] discrepancy has been established, individual clotting factor [[assay]] can be performed to determine the [[Deficiency|deficient]]/absent clotting factor. Bethesda assay can be performed in the case of acquired hemophilia to detect and quantify [[antibodies]] directed against [[factor VIII]]. | |||
==History and Symptoms== | ==History and Symptoms== | ||
[[Patient|Patients]] with hemophilia can present with a history of excessive [[bleeding]] after minor [[Injury|injuries]] or spontaneous [[bleeding]]. They can also report [[family history]] of hemophilia. Hemophilia when mild, can be [[asymptomatic]]. Common [[Symptom|symptoms]], when present, include [[epistaxis]], [[Mouth|oral]] [[mucosal bleeding]], [[Arthralgia|joint pain]] and [[Edema|swelling]], [[lethargy]] and [[fatigue]], excessive [[bleeding]] after [[dental]] procedures, prolonged [[bleeding]] after circumcision and [[muscle]] [[hematoma]] after [[vaccination]]. | |||
==Physical Examination== | ==Physical Examination== | ||
Physical examination of patients with hemophilia is usually remarkable | [[Patient|Patients]] with hemophilia usually appear normal. [[Physical examination]] of [[Patient|patients]] with hemophilia is usually remarkable for [[tachycardia]], [[pallor]], [[Bruise|bruising]], [[abdominal pain]] and [[distension]], [[hypotension]], and [[muscle]] or [[joint]] [[Edema|swelling]]. | ||
==Laboratory Findings== | ==Laboratory Findings== | ||
Laboratory findings consistent with the diagnosis of hemophilia include | [[Medical laboratory|Laboratory]] findings consistent with the [[diagnosis]] of hemophilia include normal [[prothrombin time (PT)]], prolonged [[Activated partial thromboplastin time|activated partial thromboplastin time (aPTT)]], prolonged [[Bleeding time|bleeding time (BT)]], and normal [[platelet count]]. | ||
==Electrocardiogram== | |||
There are no ECG findings associated with hemophilia. | |||
==X-ray Findings== | ==X-ray Findings== | ||
An [[X-rays|x-ray]] of the [[Joint|joints]] in the case of [[Hemophilia|hemophilic]] [[arthropathy]] may be helpful in the [[diagnosis]] of hemophilia. Pettersson scoring system, designed in 1980, is widely applied for the [[classification]] of [[Bone|osteo]]-[[Cartilage|chondral]] changes of [[Hemophilia|hemophilic]] [[arthropathy]] in [[Elbow|elbows]], [[Knee|knees]], and [[Ankle|ankles]]. This scoring system is based on typical findings of [[Hemophilia|hemophilic]] [[arthropathy]] on [[Anatomical terms of location|posterior]]-[[Anatomical terms of location|anterior]] and [[lateral]] [[x-rays]]. Arnold-Hilgartner classification is also a [[Radiography|plain radiograph]] grading system for [[Hemophilia|hemophilic]] [[arthropathy]]. | |||
==CT Findings== | ==CT Findings== | ||
[[Computed tomography|CT scan]] may be helpful in the [[diagnosis]] of hemophilia. Findings on [[Computed tomography|CT scan]] suggestive of hemophilia include [[muscle]], [[Cranium|intracranial]], and [[Abdomen|intraabdominal]] [[Hematoma|hematomas]], [[Hemophilia|hemophilic]] [[Tumor|pseudotumor]], [[intracranial hemorrhage]], [[muscle]] [[ossification]], and [[pseudoaneurysm]] following [[Artery|arterial]] [[Physical trauma|trauma]]. | |||
==MRI== | |||
[[Magnetic resonance imaging|MRI]] may be helpful in the [[diagnosis]] of hemophilia. Findings on [[Magnetic resonance imaging|MRI]] suggestive of [[Hemophilia|hemophilic]] [[arthropathy]] include effusion, [[synovial]] [[Hypertrophy (medical)|hypertrophy]], [[Erosion (dental)|erosion]], subchondral [[cyst]], [[cartilage]] loss, osteonecrosis, [[fibrocartilage]] [[Tears|tear]], [[ligament]] [[Tears|tear]], loose body. | |||
==Echocardiography/Ultrasound== | |||
There are no [[echocardiography]] findings associated with hemophilia. [[Ultrasound]] may be helpful in the [[diagnosis]] and follow-up of [[Hemophilia|hemophilic]] [[arthropathy]] and in [[Diagnosis|diagnosing]] massive [[Abdomen|intraabdominal]] [[Bleeding|bleeds]]. Findings on an [[ultrasound]] suggestive of [[Hemophilia|hemophilic]] [[arthropathy]] inlcude [[Soft tissue|soft-tissue]] changes, [[Bone|osteo]]-[[Cartilage|chondral]] changes, [[joint]] effusion, [[synovial]] [[Hypertrophy (medical)|hypertrophy]], [[hemosiderin]], and [[Bone|osteo]]-[[Cartilage|chondral]] abnormalities. | |||
==Other Imaging Findings== | |||
There are no other [[imaging]] findings associated with hemophilia. | |||
==Other Diagnostic Tests== | ==Other Diagnostic Tests== | ||
[[ | There are no other [[Diagnosis|diagnostic]] studies associated with hemophilia. | ||
==Medical Therapy== | ==Medical Therapy== | ||
The mainstay of therapy for hemophilia is blood [[clotting factor]] replacement | The mainstay of therapy for hemophilia is blood [[clotting factor]] replacement. | ||
==References== | ==References== | ||
Revision as of 01:57, 23 January 2019
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Hemophilia Microchapters |
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Hemophilia overview On the Web |
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American Roentgen Ray Society Images of Hemophilia overview |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [2]
Overview
Hemophilia usually is inherited. "Inherited” means that the disorder is passed from parents to children through genes. People born with hemophilia have little or no clotting factor. Clotting factor is a protein needed for normal blood clotting. There are several types of clotting factors. These proteins work with platelets to help the blood clot. Platelets are small blood cell fragments that form in the bone marrow—a sponge-like tissue in the bones. Platelets play a major role in blood clotting. When blood vessels are injured, clotting factors help platelets stick together to plug cuts and breaks on the vessels and stop bleeding. The two main types of hemophilia are hemophilia A and hemophilia B. If you have hemophilia A, you're missing or have low levels of clotting factor VIII (8). About 8 out of 10 people who have hemophilia have type A. If you have hemophilia B, you're missing or have low levels of clotting factor IX (9). Rarely, hemophilia can be acquired. "Acquired” means you aren't born with the disorder, but you develop it during your lifetime. This can happen if your body forms antibodies (proteins) that attack the clotting factors in your bloodstream. The antibodies can prevent the clotting factors from working.[1]
Historical Perspective
Hemophilia is considered a very old disease with its history dating back to the 2nd century AD. The first modern descriptions of the condition appeared during the 19th century. Extensive work has been done over the centuries regarding the classification, inheritance pattern, and treatment of hemophilia.
Classification
Hemophilia may be classified into three sub-types based on the lack of functional clotting factors: hemophilia A , hemophilia B, hemophilia C. It can also be divided into different categories based on the severity of the condition. Hemophilia can also be acquired in the setting of antibodies directed against the clotting factors.
Pathophysiology
Hemophilia is a genetic bleeding disorder resulting from the insufficient levels of clotting factors in the body. The clotting factors irregularity causes a lack of clumping of blood required to form a clot to plug a site of a wound. The genes involved in the pathogenesis of hemophilia include the F8 gene in hemophilia A, F9 gene in hemophilia B, and F11 gene in C. Hemophilia predominantly affects the male population but the sub-type hemophilia C, with an autosomal inheritance pattern, can affect the males as well as females.
Causes
Hemophilia A, B, and C are caused by mutations in F8, F9, and F11 genes respectively. It can also occur as a result of autoantibodies directed against the clotting factors.
Differentiating Hemophilia from other diseases
Hemophilia must be differentiated from other diseases leading to spontaneous bleeding and bleeding following injuries or surgery such as von Willebrand disease, hepatic failure, thrombocytopenia, vitamin K deficiency, disseminated intravascular coagulation, uremia, congenital afibrinogenemia, factor V deficiency, factor X deficiency as seen in amyloid purpura, glanzmann's thrombasthenia, Bernard-Soulier syndrome, factor XII deficiency and C1-inhibitor (C1INH) deficiency.
Epidemiology and Demographics
The prevalence of hemophilia is estimated to be 20,000 cases in the United States annually. The age-adjusted prevalence of hemophilia in six US states (Oklahoma, Massachusetts, Colorado, Georgia, Louisiana, and New York) in 1994 was 13.4 cases per 100, 000 males. The incidence of hemophilia is estimated to be 1 in 5,000 male births for hemophilia A and 1 in 30,000 births for hemophilia B.
Risk Factors
The most potent risk factor in the development of hemophilia is the family history of hemophilia. Other risk factors include male sex and malignancies.
Screening
Initial screening blood investigations for any child with suspected bleeding disorder include platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen test. Chorionic villus sampling at 11-14 weeks of gestation can be performed for the genetic diagnosis of hemophilia.
Natural History, Complications and Prognosis
Hemophilia can present with a bleeding episode during the neonatal period that is difficult to manage or it can present with signs and symptoms of concealed bleeding into the joint or viscera. If left untreated, hemophilia can result in complications involving multiple organs and in severe bleeding episodes it can result in death. Hemophilia patients can lead an active and healthy life and life expectancy depends on the treatment response and the presence of comorbidities. Complications of hemophilia include AIDS, hepatitis, Vitamin D deficiency, osteoporosis, and renal pathologies.
Diagnostic Study of Choice
Coagulation tests and coagulation assays are the gold standard for the diagnosis of hemophilia. Prolonged activated partial thromboplastin time (aPTT), normal prothrombin time (PT), prolonged bleeding time (BT), and normal fibrinogen concentration are diagnostic of hemophilia. Coagulation tests should be followed by measuring the clotting factors level by coagulation assays. Once the coagulation discrepancy has been established, individual clotting factor assay can be performed to determine the deficient/absent clotting factor. Bethesda assay can be performed in the case of acquired hemophilia to detect and quantify antibodies directed against factor VIII.
History and Symptoms
Patients with hemophilia can present with a history of excessive bleeding after minor injuries or spontaneous bleeding. They can also report family history of hemophilia. Hemophilia when mild, can be asymptomatic. Common symptoms, when present, include epistaxis, oral mucosal bleeding, joint pain and swelling, lethargy and fatigue, excessive bleeding after dental procedures, prolonged bleeding after circumcision and muscle hematoma after vaccination.
Physical Examination
Patients with hemophilia usually appear normal. Physical examination of patients with hemophilia is usually remarkable for tachycardia, pallor, bruising, abdominal pain and distension, hypotension, and muscle or joint swelling.
Laboratory Findings
Laboratory findings consistent with the diagnosis of hemophilia include normal prothrombin time (PT), prolonged activated partial thromboplastin time (aPTT), prolonged bleeding time (BT), and normal platelet count.
Electrocardiogram
There are no ECG findings associated with hemophilia.
X-ray Findings
An x-ray of the joints in the case of hemophilic arthropathy may be helpful in the diagnosis of hemophilia. Pettersson scoring system, designed in 1980, is widely applied for the classification of osteo-chondral changes of hemophilic arthropathy in elbows, knees, and ankles. This scoring system is based on typical findings of hemophilic arthropathy on posterior-anterior and lateral x-rays. Arnold-Hilgartner classification is also a plain radiograph grading system for hemophilic arthropathy.
CT Findings
CT scan may be helpful in the diagnosis of hemophilia. Findings on CT scan suggestive of hemophilia include muscle, intracranial, and intraabdominal hematomas, hemophilic pseudotumor, intracranial hemorrhage, muscle ossification, and pseudoaneurysm following arterial trauma.
MRI
MRI may be helpful in the diagnosis of hemophilia. Findings on MRI suggestive of hemophilic arthropathy include effusion, synovial hypertrophy, erosion, subchondral cyst, cartilage loss, osteonecrosis, fibrocartilage tear, ligament tear, loose body.
Echocardiography/Ultrasound
There are no echocardiography findings associated with hemophilia. Ultrasound may be helpful in the diagnosis and follow-up of hemophilic arthropathy and in diagnosing massive intraabdominal bleeds. Findings on an ultrasound suggestive of hemophilic arthropathy inlcude soft-tissue changes, osteo-chondral changes, joint effusion, synovial hypertrophy, hemosiderin, and osteo-chondral abnormalities.
Other Imaging Findings
There are no other imaging findings associated with hemophilia.
Other Diagnostic Tests
There are no other diagnostic studies associated with hemophilia.
Medical Therapy
The mainstay of therapy for hemophilia is blood clotting factor replacement.