--- title: Paroxysmal Nocturnal Hemoglobinuria (PNH) url: "https://www.yyhmedical.com/en/guide/blood/disease-paroxysmal-nocturnal-hemoglobinuria" type: MedicalWebPage inLanguage: en-US --- # Paroxysmal Nocturnal Hemoglobinuria (PNH) > Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal disorder of hematopoietic stem cells. It can cause intravascular hemolysis, thrombosis, and varying degrees of bone marrow failure. Some patients develop dark urine, anemia, fatigue, abdominal pain, or blood clots, while others may not have visible hemoglobinuria. ## Overview PNH is an acquired blood disorder caused by a genetic change in a hematopoietic stem cell. Despite the term “nocturnal” in its name, hemolysis does not occur only at night or after sleep. The name reflects early observations of the disease. Hemolysis can occur at any time, and not every patient develops visibly dark urine. The three major clinical problems in PNH are **intravascular hemolysis, thrombosis, and bone marrow failure**. The presentation varies widely. Some patients mainly have hemolysis and anemia, some first present with thrombosis, and others have PNH together with bone marrow failure disorders such as aplastic anemia. ## Causes PNH is associated with an acquired mutation in the **PIGA gene** in a hematopoietic stem cell. PIGA is involved in the production of glycosylphosphatidylinositol (GPI) anchors. When this pathway is disrupted, blood cells lose several GPI-anchored proteins, including the complement-regulating proteins **CD55 and CD59**. Without these protective proteins, red blood cells become unusually vulnerable to complement-mediated destruction, leading to intravascular hemolysis. The reason why some people develop a clinically significant PNH clone after acquiring a PIGA mutation is not fully understood. ## Signs and Symptoms Symptoms of PNH vary considerably, and not everyone develops the classic dark-colored urine. Possible signs and symptoms include: - Fatigue, weakness, pale skin, or shortness of breath from anemia - Red-brown, tea-colored, or very dark urine during significant hemolysis - Jaundice - Abdominal pain - Difficulty swallowing or esophageal spasm - Erectile dysfunction in men - Headache, chest pain, or shortness of breath - Bleeding related to low platelet counts - Increased infection risk when white blood cell counts are low Thrombosis is one of the most serious complications of PNH. Blood clots can occur in common veins as well as unusual sites such as the hepatic, portal, mesenteric, or cerebral veins. Dark urine in PNH is caused by **free hemoglobin being filtered into the urine**, rather than intact destroyed blood cells being excreted. ## Diagnosis Diagnosis of PNH usually combines blood counts, laboratory evidence of hemolysis, and peripheral blood flow cytometry. **Blood Tests** A complete blood count may show anemia, and some patients also have low white blood cell or platelet counts. Laboratory tests for hemolysis may include LDH, bilirubin, reticulocyte count, haptoglobin, and kidney function. **Flow Cytometry** High-sensitivity flow cytometry is the key test used to confirm PNH. Testing usually evaluates GPI-anchored proteins on granulocytes and monocytes and may use **FLAER** together with markers such as CD24, CD14, CD55, and CD59. Modern diagnosis does not rely on red blood cell CD55 and CD59 testing alone, because transfusions and ongoing hemolysis can affect red blood cell results. **Bone Marrow Testing** Bone marrow aspiration or biopsy does not directly diagnose PNH but may be important in patients with pancytopenia or suspected aplastic anemia, myelodysplastic neoplasms, or another bone marrow failure disorder. **Urine Tests** Urinalysis may show hemoglobin in the urine, sometimes without a corresponding increase in intact red blood cells. Older tests such as the Ham test and sucrose lysis test have largely been replaced by high-sensitivity flow cytometry and are no longer the primary diagnostic tests for PNH. ## Treatment **Complement Inhibitors** Complement inhibitors block different parts of the complement system and reduce complement-mediated destruction of red blood cells. C5 inhibitors include **eculizumab and ravulizumab**. Newer treatments target other parts of the complement pathway, including C3 and the alternative complement pathway. The choice of therapy depends on previous treatment, severity of anemia, ongoing hemolysis, and local approval and availability. **Supportive Care** Supportive care may include red blood cell transfusions, folic acid supplementation, and treatment of infections, kidney problems, or other complications. Iron replacement may be appropriate when true iron deficiency is confirmed. Long-term hemoglobin loss in the urine can itself lead to iron deficiency in some patients. Patients with significant bone marrow failure may need additional treatment directed at conditions such as aplastic anemia. **Thrombosis Prevention and Treatment** Patients who develop thrombosis generally need anticoagulation, together with evaluation for initiation or optimization of complement inhibitor therapy. Preventive anticoagulation is not a simple “yes or no” decision and should be individualized based on thrombosis risk, bleeding risk, previous clotting events, disease activity, and complement inhibitor treatment. **Hematopoietic Stem Cell Transplantation** **Allogeneic hematopoietic stem cell transplantation (allo-HSCT)** is the treatment with curative potential because it can replace the abnormal hematopoietic stem cell clone. However, complement inhibitors can now effectively control hemolysis and thrombosis in many patients with classical PNH, so transplantation is not routinely chosen simply because a patient has PNH. It is more often considered in selected patients with severe bone marrow failure, inadequate response to other treatment, or other specific high-risk features. ## Content attribution (YMYL) - Author: - Medically reviewed by: - Last reviewed: - First published: > --- Original (HTML):https://www.yyhmedical.com/en/guide/blood/disease-paroxysmal-nocturnal-hemoglobinuria This is a clean Markdown mirror for large language models; the original page is authoritative.