Paroxysmal nocturnal hemoglobinuria overview: Difference between revisions

	Paroxysmal nocturnal hemoglobinuria Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Paroxysmal nocturnal hemoglobinuria from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X Ray
CT
MRI
Echocardiography or Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Paroxysmal nocturnal hemoglobinuria overview On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Paroxysmal nocturnal hemoglobinuria overview All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Paroxysmal nocturnal hemoglobinuria overview
CDC on Paroxysmal nocturnal hemoglobinuria overview
Paroxysmal nocturnal hemoglobinuria overview in the news
Blogs on Paroxysmal nocturnal hemoglobinuria overview
Directions to Hospitals Treating Paroxysmal nocturnal hemoglobinuria
Risk calculators and risk factors for Paroxysmal nocturnal hemoglobinuria overview

VisualWikitext

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

Template:WikiDoc Sources

@@ Line 1: / Line 1: @@
 __NOTOC__
-{{ Paroxysmal nocturnal hemoglobinuria }}
+{{Paroxysmal nocturnal hemoglobinuria}}
+{{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]].
+==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.
+==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|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]].
+==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 myeloid leukemia|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 anchor|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]], [[Pallor|skin pallor]], [[Ecchymoses|skin ecchymoses]]<nowiki/>and [[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.
-{{CMG}}
+===X-ray===
+There are no x-ray findings associated with paroxysmal nocturnal hemoglobinuria.
-==Overview==
+===CT scan===
-'''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]].
+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.
-==References==
-{{Reflist|2}}
+===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:Disease]]
+==References==
-[[Category:Hematology]]
+{{reflist|2}}
-[[Category:Rare diseases]]
-[[Category:Genetic disorders]]
-[[Category:Mature chapter]]
-{{WH}}
+{{WikiDoc Help Menu}}
-{{WS}}
+{{WikiDoc Sources}}
+[[Category: (name of the system)]]