Paroxysmal nocturnal hemoglobinuria overview: Difference between revisions

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Latest revision as of 16:42, 8 November 2018

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Overview

Paroxysmal nocturnal hemoglobinuria is a rare, acquired, potentially life-threatening disease of the blood characterised by hemolytic anemia, thrombosis and red urine due to breakdown of red blood cells. PNH is the only hemolytic anemia caused by an acquired intrinsic defect in the cell membrane.

Historical Perspective

Paroxysmal nocturnal hemoglobinuria was first described by the European physicians in the 19th century. The hypothesis of hemolysis of red blood cells due to the increased plasma acidity in the night time was described by Dr. Strübing in 1815. From 1911 to 1950, more studies were conducted in order to establish the full description of PNH.

Classification

Paroxysmal nocturnal hemoglobinuria may be classified according to the diagnosis results into three subtypes. The subtypes of PNH include classic PNH, secondary PNH, or subclinical PNH.

Pathophysiology

Paroxysmal nocturnal hemoglobinuria is believed to be caused by a genetic mutation and complement mediated hemolysis. A mutation in PIGA gene (Posphatidylinositol Glycan anchor biosynthesis, class A) is considered the main pathogenic factor in development of PNH because PIGA gene is responsible for the GPI anchor synthesis. The PIGA gene mutation is most common a frameshift mutation which results in a misfolded protein product which is nonfunctional proteins and degraded by proteasomes. Other genetic mutation may also cause PNH like TET2, SUZ12, U2AF1, and JAK2. The anemia in PNH is due to complement mediated hemolysis of RBCs which are defective in the CD59//CD55 markers which are important in inactivating the complement system and protecting the RBCs. Paroxysmal nocturnal hemoglobinuria may be associated with aplastic anemia, myelodysplastic syndrome, and acute myelogenous leukemia.

Causes

Common causes of paroxysmal nocturnal hemoglobinuria include a somatic mutation in the PIGA gene. Other causes include mutations in genes of TET2, SUZ12, U2AF1, and JAK2.

Differentiating Paroxysmal Nocturnal Hemoglobinuria from Other Diseases

Paroxysmal nocturnal hemoglobinuria must be differentiated from other causes of anemia which include iron deficiency anemia, thalassemia, anemia of chronic disease, lead poisoning, and blood loss.

Epidemiology and Demographics

The incidence of paroxysmal nocturnal hemoglobinuria is approximately 0.13 per 100,000 individuals worldwide. Paroxysmal nocturnal hemoglobinuria commonly affects adults. However, some cases of PNH in the childhood have been reported.

Risk Factors

There are no established risk factors for paroxysmal nocturnal hemoglobinuria. However, PNH is usually associated with aplastic anemia, myelodysplastic syndrome, and acute myelogenous leukemia.

Screening

According to the American society of hematology, screening for paroxysmal nocturnal hemolglobinuria is recommended among patients with hemoglobinuria, cytopenia, suspected myelodysplasia, negative direct coombs test intravascular hemolytic anemia, refractory anemia, and aplastic anemia with no apparent sign of intravascular hemolysis.

Natural History, Complications, and Prognosis

If left untreated, patients with paroxysmal nocturnal hemoglobinuria may progress to develop thrombosis which is a main cause of death in PNH. Common complications include intracranial thrombosis, splenic vein thrombosis, and portal vein thrombosis. Prognosis of paroxysmal nocturnal hemoglobinuria is good as long as anti-complemant therapy eculizumab is taken regularly.

Diagnosis

Diagnostic Study of Choice

Diagnosis of paroxysmal nocturnal hemoglobinuria has a minimal essential diagnostic criteria. The diagnostic test of choice is flow cytometry. The flow cytometry is used in order to reveal the GPI deficient RBCs.

History and Symptoms

Common symptoms of paroxysmal nocturnal hemoglobinuria include fatigue, dyspnea, headaches, abdominal pain, dysphagia and chest pain. Less common symptoms may include necrotic skin lesions.

Physical Examination

Patients with paroxysmal nocturnal hemoglobinuria usually appear tired. Physical examination of patients with PNH is usually remarkable for fever, skin pallor, skin ecchymosesand skin nodules. Physical examination may show abdominal distension if PNH is associated with budd chiari syndrome.

Laboratory Findings

Laboratory findings consistent with the diagnosis of paroxysmal nocturnal hemoglobinuria include low hemoglobin level, low RBCs count, and negative coombs test. Flow cytometry is the diagnostic test of choice where it shows GPI deficient RBCs.

Electrocardiogram

There are no ECG findings associated with paroxysmal nocturnal hemoglobinuria.

X-ray

There are no x-ray findings associated with paroxysmal nocturnal hemoglobinuria.

CT scan

There are no CT scan findings associated with paroxysmal nocturnal hemoglobinuria. However, a CT scan may be helpful in the diagnosis of complications of PNH, which include intracranial thrombosis, splenic vein thrombosis, and portal vein thrombosis.

MRI

There are no MRI findings associated with PNH. However, MRI may be helpful in the diagnosis of complications of PNH which include intracranial thrombosis, splenic vein thrombosis, and portal vein thrombosis.

Other Imaging Findings

There are no other imaging findings associated with PNH.

Other Diagnostic Studies

There are no other diagnostic studies associated with PNH.

Treatment

Medical Therapy

The mainstay of treatment for paroxysmal nocturnal hemoglobinuria is medical therapy. Treatment includes anticomplement therapy which includes Eculizumab which acts on reducing the hemolysis and possible complications of PNH. Other treatment regimens include hematopoietic cell transplantation and treatment of the anemia.

Surgery

Surgical intervention is not recommended for the management of paroxysmal nocturnal hemoglobinuria.

Primary Prevention

There are no established measures for the primary prevention of paroxysmal nocturnal hemoglobinuria.

Secondary Prevention

There are no established measures for the secondary prevention of paroxysmal nocturnal hemoglobinuria.

References

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@@ Line 1: / Line 1: @@
 __NOTOC__
-{{ Paroxysmal nocturnal hemoglobinuria }}
+{{Paroxysmal nocturnal hemoglobinuria}}
-{{CMG}}
+{{CMG}}; {{AE}} {{AEL}}
 ==Overview==
-'''Paroxysmal nocturnal hemoglobinuria'''  is a rare, acquired, potentially life-threatening disease of the blood characterised by[[hemolytic anemia]], [[thrombosis]] and red [[urine]] due to breakdown of [[red blood cell]]s. [[PNH]] is the only hemolytic anemia caused by an ''acquired'' intrinsic defect in the [[cell membrane]].
+'''Paroxysmal nocturnal hemoglobinuria'''  is a rare, acquired, potentially life-threatening disease of the blood characterised by [[hemolytic anemia]], [[thrombosis]] and red [[urine]] due to breakdown of [[red blood cell]]s. [[PNH]] is the only hemolytic anemia caused by an ''acquired'' intrinsic defect in the [[cell membrane]].
+==Historical Perspective==
+Paroxysmal nocturnal hemoglobinuria was first described by the European physicians in the 19th century. The hypothesis of [[hemolysis]] of [[red blood cells]] due to the increased [[Plasma (blood)|plasma]] acidity in the night time was described by Dr. Strübing in 1815. From 1911 to 1950, more studies were conducted in order to establish the full description of PNH.
-==Historical Perspective==
-*[Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
-*In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
-*In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].
 ==Classification==
-*[Disease name] may be classified according to [classification method] into [number] subtypes/groups:
+Paroxysmal nocturnal hemoglobinuria may be classified according to the diagnosis results into three subtypes. The subtypes of PNH include classic PNH, secondary PNH, or subclinical PNH.
-:*[group1]
-:*[group2]
-:*[group3]
-*Other variants of [disease name] include [disease subtype 1], [disease subtype 2], and [disease subtype 3].
 ==Pathophysiology==
-*The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
+Paroxysmal nocturnal hemoglobinuria is believed to be caused by a [[genetic mutation]] and [[complement]] mediated [[hemolysis]]. A mutation in [[PIGA|PIGA gene]] ([[PIGA|Posphatidylinositol Glycan anchor]] biosynthesis, class A) is considered the main pathogenic factor in development of PNH because PIGA gene is responsible for the [[Glycophosphatidylinositol|GPI anchor]] synthesis. The PIGA gene mutation is most common a [[frameshift mutation]] which results in a misfolded protein product which is nonfunctional proteins and degraded by [[proteasomes]]. Other genetic mutation may also cause PNH like TET2, [[SUZ12]], U2AF1, and [[JAK2]]. The [[anemia]] in PNH is due to complement mediated [[Hemolytic anemia|hemolysis of RBCs]] which are defective in the [[CD59]]/[[Decay accelerating factor|/CD55]] markers which are important in inactivating the [[complement system]] and protecting the [[RBCs]]. Paroxysmal nocturnal hemoglobinuria may be associated with [[aplastic anemia]], [[myelodysplastic syndrome]], and [[acute myelogenous leukemia]].
-*The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
-*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
-*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
 ==Causes==
-* [Disease name] may be caused by either [cause1], [cause2], or [cause3].
+Common causes of paroxysmal nocturnal hemoglobinuria include a somatic mutation in the PIGA gene. Other causes include mutations in genes of TET2, SUZ12, U2AF1, and JAK2.
-* [Disease name] is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
-* There are no established causes for [disease name].
+==Differentiating Paroxysmal Nocturnal Hemoglobinuria from Other Diseases==
+Paroxysmal nocturnal hemoglobinuria must be differentiated from other causes of anemia which include [[iron deficiency anemia]], [[thalassemia]], [[anemia of chronic disease]], [[lead poisoning]], and [[blood loss]].
-==Differentiating [disease name] from other Diseases==
-*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
-:*[Differential dx1]
-:*[Differential dx2]
-:*[Differential dx3]
 ==Epidemiology and Demographics==
-* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
+The incidence of paroxysmal nocturnal hemoglobinuria is approximately 0.13 per 100,000 individuals worldwide. Paroxysmal nocturnal hemoglobinuria commonly affects adults. However, some cases of PNH in the childhood have been reported.
-* In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].
-===Age===
-*Patients of all age groups may develop [disease name].
-*[Disease name] is more commonly observed among patients aged [age range] years old.
-*[Disease name] is more commonly observed among [elderly patients/young patients/children].
-===Gender===
-*[Disease name] affects men and women equally.
-*[Gender 1] are more commonly affected with [disease name] than [gender 2].
-* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.
-===Race===
-*There is no racial predilection for [disease name].
-*[Disease name] usually affects individuals of the [race 1] race.
-*[Race 2] individuals are less likely to develop [disease name].
 ==Risk Factors==
-*Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
+There are no established risk factors for paroxysmal nocturnal hemoglobinuria. However, PNH is usually associated with [[aplastic anemia]], [[myelodysplastic syndrome]], and [[Acute myeloid leukemia|acute myelogenous leukemia]].
-== Natural History, Complications and Prognosis==
+==Screening==
-*The majority of patients with [disease name] remain asymptomatic for [duration/years].
+According to the American society of hematology, screening for paroxysmal nocturnal hemolglobinuria is recommended among patients with hemoglobinuria, cytopenia, suspected myelodysplasia, negative direct coombs test intravascular hemolytic anemia, refractory anemia, and aplastic anemia with no apparent sign of intravascular hemolysis.
-*Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
-*If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
+==Natural History, Complications, and Prognosis==
-*Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
+If left untreated, patients with paroxysmal nocturnal hemoglobinuria may progress to develop [[thrombosis]] which is a main cause of death in PNH. Common complications include intracranial thrombosis, [[splenic vein thrombosis]], and [[portal vein thrombosis]]. Prognosis of paroxysmal nocturnal hemoglobinuria is good as long as anti-complemant therapy [[eculizumab]] is taken regularly.
-*Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with [disease name] is approximately [#%].
 == Diagnosis ==
-===Diagnostic Criteria===
-*The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
-:*[criterion 1]
-:*[criterion 2]
-:*[criterion 3]
-:*[criterion 4]
-=== Symptoms ===
-*[Disease name] is usually asymptomatic.
-*Symptoms of [disease name] may include the following:
-:*[symptom 1]
-:*[symptom 2]
-:*[symptom 3]
-:*[symptom 4]
-:*[symptom 5]
-:*[symptom 6]
-=== Physical Examination ===
-*Patients with [disease name] usually appear [general appearance].
-*Physical examination may be remarkable for:
-:*[finding 1]
-:*[finding 2]
-:*[finding 3]
-:*[finding 4]
-:*[finding 5]
-:*[finding 6]
-=== Laboratory Findings ===
-*There are no specific laboratory findings associated with [disease name].
-*A  [positive/negative] [test name] is diagnostic of [disease name].
+===Diagnostic Study of Choice===
-*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
+Diagnosis of paroxysmal nocturnal hemoglobinuria has a minimal essential diagnostic criteria. The diagnostic test of choice is [[flow cytometry]]. The flow cytometry is used in order to reveal the [[GPI anchor|GPI]] deficient [[RBCs]].
-*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
+===History and Symptoms===
-===Imaging Findings===
+Common symptoms of paroxysmal nocturnal hemoglobinuria include fatigue, [[dyspnea]], [[headaches]], [[abdominal pain]], [[dysphagia]] and [[chest pain]]. Less common symptoms may include necrotic skin lesions.
-*There are no [imaging study] findings associated with [disease name].
+===Physical Examination===
-*[Imaging study 1] is the imaging modality of choice for [disease name].
+Patients with paroxysmal nocturnal hemoglobinuria usually appear tired. Physical examination of patients with PNH is usually remarkable for [[fever]], [[Pallor|skin pallor]], [[Ecchymoses|skin ecchymoses]]<nowiki/>and [[skin nodules]]. Physical examination may show [[abdominal distension]] if PNH is associated with [[budd chiari syndrome]].
-*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
-*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].
+===Laboratory Findings===
+Laboratory findings consistent with the diagnosis of paroxysmal nocturnal hemoglobinuria include low hemoglobin level, low RBCs count, and negative coombs test. Flow cytometry is the diagnostic test of choice where it shows GPI deficient RBCs.
-=== Other Diagnostic Studies ===
-*[Disease name] may also be diagnosed using [diagnostic study name].
+===Electrocardiogram===
-*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].
+There are no ECG findings associated with paroxysmal nocturnal hemoglobinuria.
-== Treatment ==
-=== Medical Therapy ===
-*There is no treatment for [disease name]; the mainstay of therapy is supportive care.
-*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
-*[Medical therapy 1] acts by [mechanism of action 1].
-*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].
-=== Surgery ===
-*Surgery is the mainstay of therapy for [disease name].
-*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
-*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].
-=== Prevention ===
-*There are no primary preventive measures available for [disease name].
-*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
-*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
+===X-ray===
+There are no x-ray findings associated with paroxysmal nocturnal hemoglobinuria.
-==References==
+===CT scan===
-{{Reflist|2}}
+There are no CT scan findings associated with paroxysmal nocturnal hemoglobinuria. However, a CT scan may be helpful in the diagnosis of complications of PNH, which include intracranial thrombosis, splenic vein thrombosis, and portal vein thrombosis.
+===MRI===
+There are no MRI findings associated with PNH. However, MRI may be helpful in the diagnosis of complications of PNH which include  intracranial thrombosis, splenic vein thrombosis, and portal vein thrombosis.
+===Other Imaging Findings===
+There are no other imaging findings associated with PNH.
+===Other Diagnostic Studies===
+There are no other diagnostic studies associated with PNH.
+==Treatment==
+===Medical Therapy===
+The mainstay of treatment for paroxysmal nocturnal hemoglobinuria is medical therapy. Treatment includes anticomplement therapy which includes Eculizumab which acts on reducing the hemolysis and possible complications of PNH. Other treatment regimens include hematopoietic cell transplantation and treatment of the anemia.
+===Surgery===
+Surgical intervention is not recommended for the management of paroxysmal nocturnal hemoglobinuria.
+===Primary Prevention===
+There are no established measures for the primary prevention of paroxysmal nocturnal hemoglobinuria.
+===Secondary Prevention===
+There are no established measures for the secondary prevention of paroxysmal nocturnal hemoglobinuria.
-[[Category:Hematology]]
+==References==
-[[Category:Rheumatology]]
+{{reflist|2}}
-[[Category:Mature chapter]]
-{{WH}}
+{{WikiDoc Help Menu}}
-{{WS}}
+{{WikiDoc Sources}}
+[[Category: (name of the system)]]