PNH
MCID: PRX003
MIFTS: 63

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Categories: Blood diseases, Genetic diseases, Immune diseases, Metabolic diseases, Nephrological diseases, Rare diseases
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Aliases & Classifications for Paroxysmal Nocturnal Hemoglobinuria

MalaCards integrated aliases for Paroxysmal Nocturnal Hemoglobinuria:

Name: Paroxysmal Nocturnal Hemoglobinuria 11 19 42 58 75 28 5 14 36 71
Marchiafava-Micheli Disease 19 58 33
Pnh 19 42 58
Marchiafava-Micheli Syndrome 42 33
Hemoglobinuria, Paroxysmal 42 43
Nocturnal Paroxysmal Haemoglobinaemia 33
Paroxysmal Hemoglobinuria Nocturnal 53
Nocturnal Paroxysmal Haematuria 33
Nocturnal Haemoglobinuria 33

Characteristics:


Prevelance:

1-9/1000000 (United Kingdom) 1-9/100000 (United Kingdom, Europe) 58

Age Of Onset:

All ages 58

Classifications:

Orphanet: 58  
Inborn errors of metabolism
Rare haematological diseases


Summaries for Paroxysmal Nocturnal Hemoglobinuria

MedlinePlus Genetics: 42 Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired (not inherited) disorder that leads to the premature death and impaired production of blood cells. The disorder affects red blood cells (erythrocytes), which carry oxygen; white blood cells (leukocytes), which protect the body from infections; and platelets (thrombocytes), which are involved in blood clotting. PNH can occur at any age, although it is most often diagnosed in young adulthood.People with PNH have sudden, recurring episodes of symptoms (paroxysmal symptoms), which may be triggered by stresses on the body, such as infections or physical exertion. During these episodes, red blood cells are broken down earlier than they should be (hemolysis). Affected individuals may pass dark-colored urine because of the presence of hemoglobin, the oxygen-carrying protein in blood. The abnormal presence of hemoglobin in the urine is called hemoglobinuria. In many, but not all cases, hemoglobinuria is most noticeable early in the morning, upon passing urine that has accumulated in the bladder during the night (nocturnal).The premature breakdown of red blood cells results in a shortage of these cells in the blood (hemolytic anemia), which can cause signs and symptoms such as fatigue, weakness, abnormally pale skin (pallor), shortness of breath, and an increased heart rate (tachycardia). People with PNH may also be prone to infections because of a shortage of white blood cells (leukopenia).Abnormal platelets associated with PNH can cause problems in the blood clotting process. As a result, people with this disorder may experience abnormal blood clotting (thrombosis), especially in large abdominal veins; or, less often, episodes of severe bleeding (hemorrhage).Individuals with PNH are at increased risk of developing cancer in blood-forming cells (leukemia). In some cases, people who have or have been treated for another blood disease called aplastic anemia may develop PNH. In a small number of affected individuals, the signs and symptoms of PNH disappear on their own.A very rare form of PNH involves abnormal inflammation in addition to the typical features described above. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). In people with this rare form of PNH, the immune response is turned on (activated) abnormally and can cause recurrent aseptic meningitis (which is inflammation of the membranes surrounding the brain and spinal cord that is not related to infection); a red, itchy rash (known as hives or urticaria); joint pain (arthralgia); or inflammatory bowel disease. The inflammatory disorders usually begin earlier than the blood cell problems.

MalaCards based summary: Paroxysmal Nocturnal Hemoglobinuria, also known as marchiafava-micheli disease, is related to hemolytic anemia and budd-chiari syndrome. An important gene associated with Paroxysmal Nocturnal Hemoglobinuria is PIGA (Phosphatidylinositol Glycan Anchor Biosynthesis Class A), and among its related pathways/superpathways are Innate Immune System and Response to elevated platelet cytosolic Ca2+. The drugs Miconazole and Clotrimazole have been mentioned in the context of this disorder. Affiliated tissues include bone marrow, spinal cord and bone, and related phenotypes are abnormal erythrocyte enzyme level and hemolytic anemia

GARD: 19 Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder that leads to the premature death and impaired production of blood cells. It can occur at any age, but is usually diagnosed in young adulthood. People with PNH have recurring episodes of symptoms due to hemolysis, which may be triggered by stresses on the body such as infections or physical exertion. This results in a deficiency of various types of blood cells and can cause signs and symptoms such as fatigue, weakness, abnormally pale skin (pallor), shortness of breath, and an increased heart rate. People with PNH may also be prone to infections and abnormal blood clotting (thrombosis) or hemorrhage, and are at increased risk of developing leukemia. It is caused by acquired, rather than inherited, genetic changes in the PIGA gene; the condition is not passed down to children of affected individuals.

Disease Ontology: 11 An aquired hemolytic anemia that is characterized by abdominal pain, hematuria, esophageal dysmotility and thrombosis, has material basis in defect in the cell membrane glycosyl phosphatidylinositols that protect red blood cells from the innate complement immune system.

Orphanet: 58 Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder characterized by corpuscular hemolytic anemia, bone marrow failure and frequent thrombotic events.

Wikipedia: 75 Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood... more...

Related Diseases for Paroxysmal Nocturnal Hemoglobinuria

Diseases in the Paroxysmal Nocturnal Hemoglobinuria family:

Paroxysmal Nocturnal Hemoglobinuria 1 Paroxysmal Nocturnal Hemoglobinuria 2

Diseases related to Paroxysmal Nocturnal Hemoglobinuria via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 430)
# Related Disease Score Top Affiliating Genes
1 hemolytic anemia 32.0 PIGT PIGA HP CD59 CD55
2 budd-chiari syndrome 31.8 PIGA CD59 CD55
3 hemoglobinuria 31.7 THPO PLAUR PIGT PIGA HP FCGR3B
4 anemia, autoimmune hemolytic 31.3 HP CD59 CD55
5 pancytopenia 31.2 THPO HP FLT3 CSF3 CSF2 CD55
6 aplastic anemia 31.2 THPO PIGA FLT3 CSF3R CSF3 CSF2
7 deficiency anemia 31.1 THPO HP FLT3 CSF3R CSF3 CSF2
8 hemolytic uremic syndrome, atypical 1 31.0 PIGA HP CD59 CD55
9 multiple congenital anomalies-hypotonia-seizures syndrome 2 30.9 PIGT PIGA CD59
10 hypersplenism 30.9 THPO CSF3 CSF2
11 myelodysplastic syndrome 30.9 THPO PIGA FLT3 FCGR3B CSF3R CSF3
12 myelofibrosis 30.8 THPO FLT3 CSF3R CSF3
13 acute leukemia 30.8 THPO FLT3 CSF3R CSF3 CSF2
14 myeloproliferative neoplasm 30.7 THPO FLT3 CSF3R CSF3 CSF2
15 thrombocytopenia 30.7 THPO RECK HP FLT3 CSF3 CSF2
16 leukemia, acute myeloid 30.7 THPO FLT3 FCGR3B CSF3R CSF3 CSF2
17 granulocytopenia 30.6 CSF3 CSF2
18 evans' syndrome 30.6 THPO HP
19 neutropenia 30.5 THPO FLT3 FCGR3B CSF3R CSF3 CSF2
20 congenital dyserythropoietic anemia 30.5 CD59 CD58 CD55
21 membranous nephropathy 30.4 PLAU HP CD59
22 splenic sequestration 30.4 THPO HP
23 severe covid-19 30.4 FCGR3B CSF3 CSF2
24 leukemia, acute lymphoblastic 30.3 THPO FLT3 CSF3R CSF3 CSF2
25 essential thrombocythemia 30.3 THPO FLT3 CSF3R CSF3 CD14
26 myeloid leukemia 30.3 FLT3 CSF3R CSF3 CSF2
27 cyclic neutropenia 30.3 CSF3R CSF3 CSF2
28 thrombocytosis 30.3 THPO CSF3 CSF2
29 acute megakaryocytic leukemia 30.1 THPO FLT3 CSF2
30 myelodysplastic/myeloproliferative neoplasm 30.1 FLT3 CSF3R CSF2
31 chronic myelomonocytic leukemia 30.0 FLT3 CSF3R CSF3 CSF2
32 hematologic cancer 29.9 THPO FLT3 CSF3 CSF2
33 leukemia, chronic myeloid 29.8 THPO FLT3 FCGR3B CSF3R CSF3 CSF2
34 bacterial infectious disease 29.7 FCGR3B CSF3 CSF2 CD14
35 malaria 29.7 PLAUR HP FCGR3B CSF3 CSF2 CD59
36 leukemia, chronic lymphocytic 29.7 THPO FLT3 FCGR3B CSF3R CSF3 CSF2
37 acute promyelocytic leukemia 29.7 PLAUR FLT3 CSF3R CSF3 CSF2 CD14
38 paroxysmal nocturnal hemoglobinuria 1 12.0
39 paroxysmal nocturnal hemoglobinuria 2 11.8
40 pulmonary fibrosis and/or bone marrow failure, telomere-related, 2 11.3
41 periventricular nodular heterotopia 11.1
42 thrombophilia due to thrombin defect 11.1
43 thrombosis 11.0
44 thrombophilia 10.8
45 kidney disease 10.8
46 acute kidney failure 10.8
47 graft-versus-host disease 10.8
48 iron metabolism disease 10.7
49 acute myeloid leukemia with recurrent genetic anomaly 10.7
50 chronic graft versus host disease 10.7

Graphical network of the top 20 diseases related to Paroxysmal Nocturnal Hemoglobinuria:



Diseases related to Paroxysmal Nocturnal Hemoglobinuria

Symptoms & Phenotypes for Paroxysmal Nocturnal Hemoglobinuria

Human phenotypes related to Paroxysmal Nocturnal Hemoglobinuria:

30 58 (show all 45)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormal erythrocyte enzyme level 30 Obligate (100%) HP:0030272
2 hemolytic anemia 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001878
3 hemoglobinuria 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0003641
4 asthenia 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0025406
5 dyspnea 58 30 Frequent (33%) Frequent (79-30%)
HP:0002094
6 chest pain 58 30 Frequent (33%) Frequent (79-30%)
HP:0100749
7 headache 58 30 Frequent (33%) Frequent (79-30%)
HP:0002315
8 reticulocytosis 58 30 Frequent (33%) Frequent (79-30%)
HP:0001923
9 chronic kidney disease 58 30 Frequent (33%) Frequent (79-30%)
HP:0012622
10 deep venous thrombosis 58 30 Frequent (33%) Frequent (79-30%)
HP:0002625
11 decreased serum iron 58 30 Frequent (33%) Frequent (79-30%)
HP:0040303
12 unconjugated hyperbilirubinemia 58 30 Frequent (33%) Frequent (79-30%)
HP:0008282
13 thromboembolism 58 30 Frequent (33%) Frequent (79-30%)
HP:0001907
14 episodic abdominal pain 58 30 Frequent (33%) Frequent (79-30%)
HP:0002574
15 increased blood urea nitrogen 58 30 Frequent (33%) Frequent (79-30%)
HP:0003138
16 conjunctival icterus 58 30 Frequent (33%) Frequent (79-30%)
HP:0032106
17 reduced haptoglobin level 58 30 Frequent (33%) Frequent (79-30%)
HP:0020181
18 hemosiderinuria 58 30 Frequent (33%) Frequent (79-30%)
HP:0012543
19 increased circulating lactate dehydrogenase concentration 30 Frequent (33%) HP:0025435
20 hypertension 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000822
21 proteinuria 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000093
22 myocardial infarction 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001658
23 thrombocytopenia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001873
24 jaundice 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000952
25 stroke 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001297
26 pulmonary embolism 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002204
27 arterial thrombosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0004420
28 lethargy 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001254
29 impotence 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000802
30 pancytopenia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001876
31 leukopenia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001882
32 acute kidney injury 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001919
33 budd-chiari syndrome 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002639
34 odynophagia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0032043
35 mesenteric venous thrombosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0030248
36 erythroid hyperplasia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0012132
37 dysphagia 58 30 Very rare (1%) Very rare (<4-1%)
HP:0002015
38 renal fanconi syndrome 58 30 Very rare (1%) Very rare (<4-1%)
HP:0001994
39 glycosuria 58 30 Very rare (1%) Very rare (<4-1%)
HP:0003076
40 esophageal spasms 58 30 Very rare (1%) Very rare (<4-1%)
HP:0025271
41 renal insufficiency 58 Occasional (29-5%)
42 anemia 58 Very frequent (99-80%)
43 venous thrombosis 58 Frequent (79-30%)
44 increased lactate dehydrogenase activity 58 Frequent (79-30%)
45 abnormal erythrocyte enzyme activity 58 Obligate (100%)

GenomeRNAi Phenotypes related to Paroxysmal Nocturnal Hemoglobinuria according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 no effect GR00402-S-1 10.2 BST1 CD14 CD55 CD58 CD59 CEACAM8
2 no effect GR00402-S-2 10.2 CD14 CD55 CD58 CD59 CEACAM8 CSF2
3 Reduced mammosphere formation GR00396-S 9.56 BST1 CD59 CSF3 CSF3R PIGA PLAUR

MGI Mouse Phenotypes related to Paroxysmal Nocturnal Hemoglobinuria:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 immune system MP:0005387 10.16 BST1 CD14 CD55 CD59 CSF2 CSF3
2 cellular MP:0005384 10.06 CD59 CSF2 CSF3R FLT3 GFRA1 HP
3 hematopoietic system MP:0005397 9.83 BST1 CD14 CD55 CD59 CSF2 CSF3
4 skeleton MP:0005390 9.81 CD14 CD59 CSF2 FCGR3B FLT3 PIGA
5 mortality/aging MP:0010768 9.47 CD14 CD55 CD59 CEACAM8 CSF2 CSF3R

Drugs & Therapeutics for Paroxysmal Nocturnal Hemoglobinuria

Drugs for Paroxysmal Nocturnal Hemoglobinuria (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 88)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Miconazole Approved, Investigational, Vet_approved Phase 4 22916-47-8 4189
2
Clotrimazole Approved, Vet_approved Phase 4 23593-75-1 2812
3
Warfarin Approved Phase 4 81-81-2, 129-06-6 54678486
4
Sirolimus Approved, Investigational Phase 4 53123-88-9 5284616 6436030
5
Ravulizumab Approved, Investigational Phase 4 1803171-55-2
6 Antifungal Agents Phase 4
7 Anticoagulants Phase 4
8 Pharmaceutical Solutions Phase 4
9 Immunosuppressive Agents Phase 4
10 Immunologic Factors Phase 4
11
Eculizumab Approved, Investigational Phase 3 219685-50-4
12
Temazepam Approved, Investigational Phase 3 846-50-4 5391
13
Thiotepa Approved, Investigational Phase 3 52-24-4 5453
14
Rituximab Approved Phase 3 174722-31-7
15
Protein C Approved Phase 3
16
Methotrexate Approved Phase 3 1959-05-2, 59-05-2 4112 126941
17
Iodine Approved, Investigational Phase 3 7553-56-2 807
18 Antirheumatic Agents Phase 3
19 Cyclosporins Phase 3
20 Antibodies, Monoclonal Phase 3
21 Alkylating Agents Phase 3
22 Antineoplastic Agents, Alkylating Phase 3
23 Antilymphocyte Serum Phase 3
24
Muromonab-CD3 Phase 3
25 Complement System Proteins Phase 3
26 Chrysarobin Phase 3
27 Immunoglobulins Phase 3
28 Antibodies Phase 3
29
Levamisole Approved, Investigational, Vet_approved, Withdrawn Phase 2 14769-73-4 26879
30
Prednisone Approved, Vet_approved Phase 2 53-03-2 5865
31
Lenograstim Approved, Investigational Phase 2 135968-09-1
32
Mycophenolic acid Approved, Investigational Phase 2 24280-93-1 446541
33
Melphalan Approved Phase 2 148-82-3 4053 460612
34
Mechlorethamine Approved, Investigational Phase 2 51-75-2 4033
35
Benzocaine Approved, Investigational Phase 2 1994-09-7, 94-09-7 2337
36
Tannic acid Approved Phase 2 1401-55-4 16129878 16129778
37
Prednisolone phosphate Approved, Vet_approved Phase 2 302-25-0
38
Prednisolone acetate Approved, Vet_approved Phase 2 52-21-1
39
Prednisolone Approved, Vet_approved Phase 2 50-24-8 4894 5755
40
Methylprednisolone hemisuccinate Approved Phase 2 2921-57-5 1875
41
Methylprednisolone Approved, Vet_approved Phase 2 83-43-2 4159 6741
42
Alemtuzumab Approved, Investigational Phase 2 216503-57-0
43
Basiliximab Approved, Investigational Phase 2 179045-86-4
44
Coenzyme M Approved, Investigational Phase 2 3375-50-6 598 23662354
45
Busulfan Approved, Investigational Phase 2 55-98-1 2478
46
Levoleucovorin Approved, Experimental, Investigational Phase 2 68538-85-2, 58-05-9, 73951-54-9 149436 6006
47
Tacrolimus Approved, Investigational Phase 2 104987-11-3 6473866 445643
48
Treosulfan Approved, Investigational Phase 2 299-75-2 9296
49
D-Phenylalanine Approved, Experimental, Investigational, Nutraceutical Phase 2 63-91-2, 673-06-3 6140 71567
50
Folic acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037

Interventional clinical trials:

(show top 50) (show all 118)
# Name Status NCT ID Phase Drugs
1 Sirolimus Combined With Low-dose Warfarin for the Treatment of Refractory Classic Paroxysmal Nocturnal Hemoglobinuria ,a Prospective Study Unknown status NCT03866681 Phase 4 sirolimus
2 An Open-Label Multi-Center Study of Eculizumab in Children and Adolescents With a Diagnosis of Paroxysmal Nocturnal Hemoglobinuria Completed NCT00867932 Phase 4 Eculizumab
3 Phase 4, Single-Arm Study of Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab Active, not recruiting NCT04320602 Phase 4
4 An Open-label Extension Study to Evaluate the Long-term Safety, Tolerability, and Efficacy of REGN3918 in Patients With Paroxysmal Nocturnal Hemoglobinuria Completed NCT04162470 Phase 3 REGN3918
5 A Randomized, Double-Blind, Active-Controlled Phase 3 Study Evaluating the Efficacy and Safety of ABP 959 Compared With Eculizumab in Adult Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH) Completed NCT03818607 Phase 3 ABP 959;Eculizumab
6 A Safety and Immunogenicity Study in Long-term Treatment of Eculizumab (JSC "GENERIUM", Russian Federation) in Patients With Paroxysmal Nocturne Hemoglobinuria, Who Have Been Involved Earlier in the Clinical Trials of Eculizumab Completed NCT04679103 Phase 3
7 A Phase 3, Randomized, Open-Label, Active-Controlled Study of ALXN1210 Versus Eculizumab in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab Completed NCT03056040 Phase 3
8 A Phase 3, Randomized, Multicenter, Open-Label, Controlled Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Completed NCT04085601 Phase 3 APL-2
9 A Phase 3, Open-Label Study of ALXN1210 in Children and Adolescents With Paroxysmal Nocturnal Hemoglobinuria (PNH) Completed NCT03406507 Phase 3
10 Investigational Product ; Coversin. Phase III Safety and Efficacy in Three-Part, Two-Arm, Randomised Open Label Evaluation in Patients With Paroxysmal Nocturnal Haemoglobinuria (PNH) Completed NCT03588026 Phase 3 rVA576
11 A Multicenter, Open Label, Randomized, Parallel-group Study of Efficacy and Safety of Eculizumab (JSC GENERIUM, Russia) vs. Soliris® (Alexion Pharma GmbH, Switzerland) in Patients With Paroxysmal Nocturnal Hemoglobinuria Completed NCT04463056 Phase 3
12 Randomized, Open-Label, International, Multi-center, Comparative Study of Efficacy and Safety of BCD-148 (JSC BIOCAD, Russia) and Soliris® in Patients With Paroxysmal Nocturnal Hemoglobinuria Completed NCT04060264 Phase 3
13 A Phase III Randomised, Double-blind, Multicentre Study to Compare the Efficacy, Safety, Pharmacokinetics, and Immunogenicity Between SB12 (Proposed Eculizumab Biosimilar) and Soliris® in Subjects With Paroxysmal Nocturnal Haemoglobinuria Completed NCT04058158 Phase 3 SB12 (proposed eculizumab biosimilar);Soliris (eculizumab)
14 A Phase III, Randomized, Multi-Center, Open-Label, Active-Comparator Controlled Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Completed NCT03500549 Phase 3 Pegcetacoplan;Soliris
15 A Hemoglobin Stabilization and Transfusion Reduction Efficacy and Safety Clinical Investigation, Randomized, Multi-Center, Double-Blind, Placebo-Controlled, Using Eculizumab in Paroxysmal Nocturnal Hemoglobinuria Patients Completed NCT00098280 Phase 3 Eculizumab
16 TRIUMPH: A Hemoglobin Stabilization and Transfusion Reduction Efficacy and Safety Clinical Investigation, Randomized, Multi-Center, Double-Blind, Placebo-Controlled, Using Eculizumab in Paroxysmal Nocturnal Hemoglobinuria Patients Completed NCT00112983 Phase 3
17 Randomized Comparison of Cyclophosphamide Versus Cyclophosphamide Plus Fludarabine In Addition To Anti-Thymocyte Globulin for the Conditioning Therapy in Allogeneic Hematopoietic Cell Transplantation for Bone Marrow Failure Syndrome Completed NCT00774527 Phase 3 Cyclophosphamide-fludarabine-anti thymocyte globulin
18 Hematopoietic Stem Cell Transplantation Using Matched Unrelated Donor Peripheral Blood or Bone Marrow for Patients With Hematologic Malignancies Completed NCT00152139 Phase 3 Chemotherapy and antibodies
19 Randomized, Double-Blind, and Placebo-Controlled Study Using Eculizumab in Transfusion Dependent PNH Patients Completed NCT00122330 Phase 3 eculizumab
20 Haploidentical Stem Cell Transplantation Utilizing Purified CD34+ Hematopoietic Cells for Patients With Hematologic Malignancies Completed NCT00186823 Phase 3 TBI, systemic chemotherapy and antibodies as follows:
21 Open Label Extension Study of Eculizumab in Patients With Transfusion Dependent PNH Completed NCT00122317 Phase 3 eculizumab
22 Safety in Hemolytic PNH Patients Treated With Eculizumab: a Multi-Center Open-Label Research Design Study Completed NCT00122304 Phase 3 eculizumab
23 SHEPHERD: Safety in Hemolytic PNH Patients Treated With Eculizumab: A Multi-Center Open-Label Research Design Completed NCT00130000 Phase 3 Eculizumab
24 An Open Label, Multicenter Roll-over Extension Program (REP) to Characterize the Long-term Safety and Tolerability of Iptacopan (LNP023) in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have Completed PNH Phase 2 and Phase3 Studies With Iptacopan Recruiting NCT04747613 Phase 3 Iptacopan
25 A Randomized, Open-Label, Ravulizumab-Controlled,Non-Inferiority Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Are Complement Inhibitor Treatment-Naive or Have Not Recently Received Complement Inhibitor Therapy Recruiting NCT05133531 Phase 3 Ravulizumab;Pozelimab;Cemdisiran
26 A Randomized, Open-Label, Eculizumab and Ravulizumab Controlled Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Are Currently Treated With Eculizumab or Ravulizumab Recruiting NCT05131204 Phase 3 Cemdisiran;Eculizumab;Pozelimab;Ravulizumab
27 A Phase III, Randomized, Open-Label, Active-Controlled, Multicenter Study Evaluating The Safety, Pharmacokinetics, Pharmacodynamic And Efficacy of Crovalimab Versus Eculizumab In Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors Recruiting NCT04432584 Phase 3 Crovalimab;Eculizumab
28 A Phase III, Multicenter, Single Arm Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibition Active, not recruiting NCT04654468 Phase 3 Crovalimab
29 A Phase 3, Randomized, Parallel-Group, Multicenter, Open-Label, Pharmacokinetic, Noninferiority Study of Ravulizumab Administered Subcutaneously Versus Intravenously in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With Eculizumab Active, not recruiting NCT03748823 Phase 3
30 A Randomized, Multicenter, Active-comparator Controlled, Open-label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily LNP023 in Adult Patients With PNH and Residual Anemia, Despite Treatment With an Intravenous Anti-C5 Antibody. Active, not recruiting NCT04558918 Phase 3 LNP023;Eculizumab;Ravulizumab
31 A Phase III, Randomized, Open-Label, Active-Controlled, Multicenter Study Evaluating The Efficacy And Safety Of Crovalimab Versus Eculizumab In Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors. Active, not recruiting NCT04434092 Phase 3 Crovalimab;Eculizumab
32 A Multicenter, Single-arm, Open-label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily Iptacopan in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy Active, not recruiting NCT04820530 Phase 3 Iptacopan (LNP023)
33 A Phase 3 Study of Danicopan (ALXN2040) as Add-on Therapy to a C5 Inhibitor (Eculizumab or Ravulizumab) in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Have Clinically Evident Extravascular Hemolysis (EVH) Active, not recruiting NCT04469465 Phase 3 Danicopan;Placebo;C5 Inhibitor
34 A Phase 3, Randomized, Open-Label, Active-Controlled Study of ALXN1210 Versus Eculizumab in Complement Inhibitor-Naïve Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Active, not recruiting NCT02946463 Phase 3
35 An Open Label, Non-Randomized, Multi-Center Extension Study to Evaluate the Long-Term Safety and Efficacy of Pegcetacoplan in the Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) Active, not recruiting NCT03531255 Phase 3 Pegcetacoplan
36 A Multicenter, Single Arm, Open-label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily Iptacopan in Adult PNH Patients Who Have Hb≥10 g/dL in Response to Anti-C5 Antibody and Switch to Iptacopan Not yet recruiting NCT05630001 Phase 3 Iptacopan
37 A Long-term Extension (LTE) Study to Characterize the Safety and Efficacy of Danicopan as an Add-on Therapy to a Complement Component 5 Inhibitor (C5i) in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Previously Treated With Danicopan in an Alexion-sponsored Clinical Study Not yet recruiting NCT05389449 Phase 3 Danicopan
38 CONSERVE: rVA576 (Coversin) Long Term Safety and Efficacy Surveillance Study Terminated NCT03829449 Phase 3 rVA576 (Coversin)
39 Phase II Study of the Levamisole Combined With Cyclosporine A in Patients With Classic Paroxysmal Nocturnal Hemoglobinuria Unknown status NCT01642979 Phase 2 Levamisole+cyclosporin A+Glucocorticoids;cyclosporin A+Glucocorticoids;Glucocorticoids
40 Phase II Study of the Levamisole Combined With Cyclosporine A in Patients With Subclinical Paroxysmal Nocturnal Hemoglobinuria and PNH in the Setting of Another Bone Marrow Failure Syndromes(PNH-2013) Unknown status NCT01760096 Phase 2 Levamisole+cyclosporin A+Glucocorticoids;cyclosporin A+Glucocorticoids;Glucocorticoids
41 A Phase 1 Dose-ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of BCX9930 in Healthy Subjects and in Subjects With Paroxysmal Nocturnal Hemoglobinuria Completed NCT04330534 Phase 1, Phase 2 BCX9930;Placebo
42 A Phase 2 Open-Label Proof of Concept Study to Assess the Efficacy, Safety, and Pharmacokinetics of ACH-0144471 in Untreated Patients With Paroxysmal Nocturnal Hemoglobinuria Completed NCT03053102 Phase 2 Danicopan
43 A Multi-center, Randomized, Open-label, Efficacy, Safety, Pharmacokinetics and Pharmacodynamics Study, Assessing Multiple LNP023 Doses in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria and Active Hemolysis Completed NCT03896152 Phase 2 LNP023
44 A Phase 2 Multicenter, Open-Label, Uncontrolled Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of RA101495 in Subjects With Paroxysmal Nocturnal Hemoglobinuria Who Have an Inadequate Response to Eculizumab Completed NCT03030183 Phase 2 Zilucoplan (RA101495)
45 Low-Dose TBI Dose Escalation to Decrease Risks of Progression and Graft Rejection After Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning as Treatment for Untreated Myelodysplastic Syndrome or Myeloproliferative Disorders - A Multi-Center Trial Completed NCT00397813 Phase 2 Cyclosporine;Fludarabine Phosphate;Mycophenolate Mofetil
46 A Phase 2, Open-label, Multiple Ascending Dose Study to Evaluate the Efficacy, Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of ALXN1210 Administered Intravenously to Patients With Paroxysmal Nocturnal Hemoglobinuria Completed NCT02605993 Phase 2
47 Phase 2 Multicenter, Open-Label, Uncontrolled Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of RA101495 in Subjects With Paroxysmal Nocturnal Hemoglobinuria Completed NCT03078582 Phase 2 Zilucoplan (RA101495)
48 HLA-HAPLOIDENTICAL FAMILIAL DONOR HEMATOPOIETIC CELL TRANSPLANTATION AFTER REDUCED INTENSITY CONDITIONING OF BUSULFAN, FLUDARABINE, AND ANTI-THYMOCYTE GLOBULIN FOR PATIENTS WITH BONE MARROW FAILURE SYNDROME - A PHASE 2 STUDY Completed NCT00731328 Phase 2
49 An Open-label Proof of Concept Study to Assess the Efficacy, Safety and Pharmacokinetics of LFG316, an Anti-C5 Monoclonal Antibody in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Completed NCT02534909 Phase 2
50 Phase II Trial of Allogeneic T-Cell Depleted Hematopoietic Stem Cell Transplants From HLA Compatible, Related and Unrelated Donors After a Myeloablative Preparative Regimen With Hyperfractionated TBI, Thiotepa and Fludarabine For Treatment of Adult Patients (>18 Years) With Lymphohematopoietic Disorders Completed NCT00587054 Phase 2 cytoreductive regimen followed by a CD34+E- selected allogeneic stem cell transplant

Search NIH Clinical Center for Paroxysmal Nocturnal Hemoglobinuria

Cell-based therapeutics:


LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database
Read about Paroxysmal Nocturnal Hemoglobinuria cell therapies at LifeMap Discovery.
Stem-cell-based therapeutic approaches for Paroxysmal Nocturnal Hemoglobinuria:
Hemacord, umbilical cord blood-derived hematopoietic progenitor cells for hematopoietic reconstitution
Embryonic/Adult Cultured Cells Related to Paroxysmal Nocturnal Hemoglobinuria:
Umbilical cord blood-derived hematopoietic progenitor cells (HEMACORD) PMIDs: 9828244

Cochrane evidence based reviews: hemoglobinuria, paroxysmal

Genetic Tests for Paroxysmal Nocturnal Hemoglobinuria

Genetic tests related to Paroxysmal Nocturnal Hemoglobinuria:

# Genetic test Affiliating Genes
1 Paroxysmal Nocturnal Hemoglobinuria 28

Anatomical Context for Paroxysmal Nocturnal Hemoglobinuria

Organs/tissues related to Paroxysmal Nocturnal Hemoglobinuria:

MalaCards : Bone Marrow, Spinal Cord, Bone, Heart, Skin, Brain, Kidney

Publications for Paroxysmal Nocturnal Hemoglobinuria

Articles related to Paroxysmal Nocturnal Hemoglobinuria:

(show top 50) (show all 3344)
# Title Authors PMID Year
1
Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals. 53 62 5
10220445 1999
2
New somatic mutation in the PIG-A gene emerges at relapse of paroxysmal nocturnal hemoglobinuria. 53 62 5
9787183 1998
3
Mutations within the Piga gene in patients with paroxysmal nocturnal hemoglobinuria. 53 62 5
8167330 1994
4
Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. 53 62 5
8500164 1993
5
Recurrent PIG-A mutation (IVS5+1G-->A) in a paediatric case of paroxysmal nocturnal haemoglobinuria: detection by the protein truncation test. 62 5
9233558 1997
6
Somatic mutations in paroxysmal nocturnal hemoglobinuria: a blessing in disguise? 62 5
9019395 1997
7
Identification of three novel mutations in the PIG-A gene in paroxysmal nocturnal haemoglobinuria (PNH) patients. 62 5
8557259 1996
8
Genetic defects underlying paroxysmal nocturnal hemoglobinuria that arises out of aplastic anemia. 62 5
8541558 1995
9
Low concentration of serum haptoglobin has impact on understanding complex pathophysiology in patients with acquired bone marrow failure syndromes. 53 62
20376581 2010
10
Phenotypic and functional characterization of a mouse model of targeted Pig-a deletion in hematopoietic cells. 53 62
19679885 2010
11
[Eculizumab in paroxysmal nocturnal hemoglobinuria]. 53 62
20035691 2009
12
Successful liver transplantation for Budd-Chiari syndrome in a patient with paroxysmal nocturnal hemoglobinuria treated with the anti-complement antibody eculizumab. 53 62
19399743 2009
13
Abnormalities in the expression of CD55 and CD59 surface molecules on peripheral blood cells are not specific to paroxysmal nocturnal hemoglobinuria. 53 62
19154662 2009
14
[Density-specific distribution of erythrocytes in different types of anemia]. 53 62
19253711 2009
15
Glycosylphosphatidylinositol-anchored protein deficiency confers resistance to apoptosis in PNH. 53 62
19013003 2009
16
Increased soluble urokinase plasminogen activator receptor (suPAR) is associated with thrombosis and inhibition of plasmin generation in paroxysmal nocturnal hemoglobinuria (PNH) patients. 53 62
18954937 2008
17
The role of oxidative stress in hemolytic anemia. 53 62
18991647 2008
18
[Paroxysmal nocturnal hemoglobinuria]. 53 62
19080854 2008
19
Expansion of donor-derived hematopoietic stem cells with PIGA mutation associated with late graft failure after allogeneic stem cell transplantation. 53 62
18596225 2008
20
Detailed immunophenotypic characterization of different major and minor subsets of peripheral blood cells in patients with paroxysmal nocturnal hemoglobinuria. 53 62
18422849 2008
21
[Immune pathophysiology of refractory anemias]. 53 62
18326316 2008
22
The pathophysiology of disease in patients with paroxysmal nocturnal hemoglobinuria. 53 62
19074066 2008
23
On the origin of multiple mutant clones in paroxysmal nocturnal hemoglobinuria. 53 62
17823237 2007
24
Haptoglobin therapy during pregnancy for paroxysmal nocturnal hemoglobinuria with renal failure. 53 62
17459392 2007
25
Factor H mediated cell surface protection from complement is critical for the survival of PNH erythrocytes. 53 62
17554058 2007
26
Eculizumab: A novel therapy for paroxysmal nocturnal hemoglobinuria. 53 62
17925885 2007
27
The role of complement regulatory proteins (CD55 and CD59) in the pathogenesis of autoimmune hemocytopenias. 53 62
17289551 2007
28
Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH). 53 62
16940417 2006
29
Case report and literature review: transient Inab phenotype and an agglutinating anti-IFC in a patient with a gastrointestinal problem. 53 62
16965581 2006
30
Immune pathogenesis of paroxysmal nocturnal hemoglobinuria. 53 62
16926131 2006
31
PIG-A mutations in paroxysmal nocturnal hemoglobinuria and in normal hematopoiesis. 53 62
16923549 2006
32
Hypomorphic promoter mutation in PIGM causes inherited glycosylphosphatidylinositol deficiency. 53 62
16767100 2006
33
The mutation rate in PIG-A is normal in patients with paroxysmal nocturnal hemoglobinuria (PNH). 53 62
16543465 2006
34
A cohort study of the nature of paroxysmal nocturnal hemoglobinuria clones and PIG-A mutations in patients with aplastic anemia. 53 62
16529603 2006
35
High frequency of several PIG-A mutations in patients with aplastic anemia and myelodysplastic syndrome. 53 62
16467865 2006
36
[Paroxysmal nocturnal hemoglobinuria--consequences of a missing anchor]. 53 62
16450736 2006
37
New insights into paroxysmal nocturnal hemoglobinuria. 53 62
17124035 2006
38
PIG-A mutations in normal hematopoiesis. 53 62
15687243 2005
39
[The response of bone marrow hematopoietic cells to G-CSF in paroxysmal nocturnal hemoglobinuria patients]. 53 62
15949269 2005
40
Mean fluorescence intensity rate is a useful marker in the detection of paroxysmal nocturnal hemoglobinuria clones. 53 62
16176170 2005
41
Transfer of glycosylphosphatidylinositol-anchored proteins to deficient cells after erythrocyte transfusion in paroxysmal nocturnal hemoglobinuria. 53 62
15304386 2004
42
CD157 is an important mediator of neutrophil adhesion and migration. 53 62
15328157 2004
43
Increased resistance of PIG-A- bone marrow progenitors to tumor necrosis factor a and interferon gamma: possible implications for the in vivo dominance of paroxysmal nocturnal hemoglobinuria clones. 53 62
15194531 2004
44
[Expression of three kinds of GPI-anchor proteins in paroxysmal nocturnal hemoglobinuria, aplastic anemia and myelodysplastic syndromes patients and their clinical implications]. 53 62
15182554 2004
45
Expression of CD59 on lymphocyte and the subsets and its potential clinical application for paroxysmal nocturnal hemoglobinuria diagnosis. 53 62
15053802 2004
46
Enhanced cytotoxicity of rituximab following genetic and biochemical disruption of glycosylphosphatidylinositol anchored proteins. 53 62
15160958 2004
47
[Spontaneous recovery from pancytopenia in a young female patient with paroxysmal nocturnal hemoglobinuria(PNH): changes in the GPI-anchor expression on peripheral blood cells]. 53 62
15103939 2004
48
Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. 53 62
14762182 2004
49
G-CSF induced progenitor mobilization in mice with PIGA- blood cells. 53 62
15297852 2004
50
Effect of proinflammatory cytokines on PIGA- hematopoiesis. 53 62
12962722 2003

Variations for Paroxysmal Nocturnal Hemoglobinuria

ClinVar genetic disease variations for Paroxysmal Nocturnal Hemoglobinuria:

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PIGA NM_002641.4(PIGA):c.1355_1356insAATTGAGATGGATGACTCCAGATTCTATCATTGA (p.Asp452delinsGluIleGluMetAspAspSerArgPheTyrHisTer) INSERT Pathogenic
9966 rs786200912 GRCh37: X:15339727-15339728
GRCh38: X:15321605-15321606
2 PIGA NM_002641.4(PIGA):c.1188+1G>A SNV Pathogenic
9965 GRCh37: X:15342786-15342786
GRCh38: X:15324664-15324664
3 PIGA NM_002641.4(PIGA):c.1323_1324del (p.Leu442fs) DEL Pathogenic
9964 rs587776728 GRCh37: X:15339759-15339760
GRCh38: X:15321637-15321638
4 PIGA NM_002641.4(PIGA):c.431del (p.Thr144fs) DEL Pathogenic
9963 rs587776727 GRCh37: X:15349622-15349622
GRCh38: X:15331500-15331500
5 PIGA NM_002641.4(PIGA):c.249_250insGT (p.Thr84fs) INSERT Pathogenic
9962 rs587776726 GRCh37: X:15349803-15349804
GRCh38: X:15331681-15331682
6 PIGA NM_002641.4(PIGA):c.163C>T (p.Gln55Ter) SNV Pathogenic
9961 rs199422233 GRCh37: X:15349890-15349890
GRCh38: X:15331768-15331768
7 PIGA NM_002641.4(PIGA):c.1115del (p.Pro372fs) DEL Pathogenic
9960 rs587776725 GRCh37: X:15342860-15342860
GRCh38: X:15324738-15324738
8 PIGA NM_002641.4(PIGA):c.459_460insA (p.His154fs) INSERT Pathogenic
9959 rs587776724 GRCh37: X:15349593-15349594
GRCh38: X:15331471-15331472
9 PIGA NM_002641.4(PIGA):c.294C>A (p.Tyr98Ter) SNV Pathogenic
9958 rs199422232 GRCh37: X:15349759-15349759
GRCh38: X:15331637-15331637
10 PIGA NM_002641.4(PIGA):c.1188+2del DEL Pathogenic
9957 rs587776723 GRCh37: X:15342785-15342785
GRCh38: X:15324663-15324663

Expression for Paroxysmal Nocturnal Hemoglobinuria

Search GEO for disease gene expression data for Paroxysmal Nocturnal Hemoglobinuria.

Pathways for Paroxysmal Nocturnal Hemoglobinuria

GO Terms for Paroxysmal Nocturnal Hemoglobinuria

Cellular components related to Paroxysmal Nocturnal Hemoglobinuria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 10.25 BST1 CD14 CD55 CD59 CSF2 CSF3
2 cell surface GO:0009986 10.13 PLAUR PLAU CEACAM8 CD59 CD58 CD55
3 secretory granule membrane GO:0030667 9.86 FCGR3B CD58 CD55 CD14
4 protein complex involved in cell-matrix adhesion GO:0098637 9.67 PLAUR PLAU
5 specific granule membrane GO:0035579 9.65 PLAUR PLAU CEACAM8 CD59 BST1
6 obsolete anchored component of external side of plasma membrane GO:0031362 9.4 CD59 CD14
7 obsolete anchored component of membrane GO:0031225 9.28 RECK PLAUR GFRA1 FCGR3B CEACAM8 CD59

Biological processes related to Paroxysmal Nocturnal Hemoglobinuria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to lipopolysaccharide GO:0071222 9.97 THPO CSF3 CSF2 CD14
2 regulation of complement activation GO:0030449 9.62 CD59 CD55
3 regulation of complement-dependent cytotoxicity GO:1903659 9.56 CD59 CD55
4 regulation of fibrinolysis GO:0051917 9.46 PLAUR PLAU
5 urokinase plasminogen activator signaling pathway GO:0038195 9.26 PLAUR PLAU
6 regulation of plasminogen activation GO:0010755 8.92 PLAUR PLAU

Sources for Paroxysmal Nocturnal Hemoglobinuria

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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