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==Differentiating Paroxysmal Nocturnal Hemoglobinuria from Other Diseases==
==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==
==Epidemiology and Demographics==
Line 52: Line 53:
===MRI===
===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.
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===
===Other Imaging Findings===
There are no other imaging findings associated with PNH.  
There are no other imaging findings associated with PNH.  

Revision as of 19:12, 7 November 2018

Paroxysmal nocturnal hemoglobinuria Microchapters

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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

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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

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

Laboratory Findings

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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