Disease Description (Causes and Symptoms)
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder in which a somatic PIGA gene mutation occurring in hematopoietic stem cells in the bone marrow causes a deficiency of the GPI (glycosylphosphatidylinositol) anchor. As a result, protective proteins on the surface of red blood cells, such as CD55 and CD59, are deficient, leading to complement-mediated hemolysis, mainly intravascular hemolysis. The main symptoms and clinical findings are as follows.
- Hemolytic anemia: fatigue, pallor, jaundice, and mild enlargement of the liver and spleen
- Hemoglobinuria, especially dark-colored urine in the morning, or intermittent hematuria
- Thrombosis: venous thrombosis is common; there is a risk of thrombosis in the liver (central hepatic vein/hepatic vein), portal vein, cerebral veins, and pulmonary embolism
- Bone marrow dysfunction or overlap with aplastic anemia, including decreased white blood cells and platelets
- Increased free hemoglobin in the blood due to intravascular hemolysis → pain caused by nitric oxide depletion, including abdominal pain and chest pain, as well as erectile dysfunction
Treatment Methods
- Complement inhibition therapy
- Eculizumab or ravulizumab: C5 inhibitors and standard treatment for patients with severe hemolysis, recurrent need for transfusions, or a risk of thrombosis. Meningococcal (Neisseria meningitidis) vaccination is required before administration. Although the medication is often administered without delay after vaccination, follow the doctor's instructions regarding vaccination and prophylactic antibiotics.
- Thrombosis management
- If thrombosis occurs, long-term anticoagulation therapy, generally indefinitely, is considered, usually with warfarin or a DOAC. Individual risk assessment is necessary even when an asymptomatic clone is present.
- Transfusion and supportive treatment
- For symptomatic anemia, transfuse washed red blood cells rather than fresh frozen plasma, and assess iron status, as chronic urinary iron deficiency may occur.
- When bone marrow or hematopoietic dysfunction is severe
- Allogeneic hematopoietic stem cell transplantation (HSCT): considered in cases of bone marrow failure or bone marrow abnormalities, or when the condition cannot be controlled with medication.
- Other
- Short-term steroid use, such as when severe hemolysis worsens, may be possible, but long-term administration is not recommended.
- Infection prevention and regular monitoring, including LDH, blood tests, and kidney function.
- Lifestyle management and precautions
- The risk of meningococcal infection increases during complement inhibitor treatment → vaccination is essential, and contact a medical institution immediately if symptoms of infection occur.
- Be cautious about situations that may trigger hemolysis, such as dehydration, infection, surgery, and pregnancy.
- Pregnancy is a high-risk condition requiring management of thrombosis and anemia; specialized prenatal care is necessary.
Checklist Before an Outpatient Visit (Including Example Questions)
Things to prepare/check
- A list of all medications and supplements currently being taken, including anticoagulants and immunosuppressants
- Recent test results, including CBC, LDH, total/indirect bilirubin, serum creatinine, urinalysis, and iron-related tests
- Previous transfusion history, including the number and timing of transfusions
- History of thrombosis, including the location and duration of treatment
- Vaccination records, especially the meningococcal vaccine
- Symptom records: changes in urine color and the time of day, degree of fatigue, episodes of pain, bleeding or bruising, and menstrual changes
- Whether pregnancy is possible or planned, for women
Examples of questions to prepare in advance to ask the doctor during an outpatient visit
- "How should I interpret the recent changes in my LDH and hemoglobin levels?"
- "When should I receive the meningococcal vaccine, what type should I receive, and how long should I wait after vaccination before receiving a complement inhibitor?"
Examples of General Questions to Ask the Doctor
- "What is the main cause of the symptoms I am experiencing, such as fatigue and changes in urine color?"
- "Which medication is more appropriate for my situation, eculizumab or ravulizumab? What are the differences in side effects and dosing intervals?"
- "What are the criteria for assessing whether I have a high risk of thrombosis, and when should anticoagulant treatment be started?"
- "I am planning a pregnancy. How should my treatment plan be adjusted?"
Examples of Disease-Specific Questions
- "What is the size of my PNH clone—the CD55/CD59 or FLAER-negative clone measured by flow cytometry—and how do the criteria for starting treatment, such as elevated LDH, transfusion dependence, and thrombosis risk, apply to me?"
- "I have no history of thrombosis, but my clone is relatively large. Would you recommend preventive anticoagulation, or should I only be monitored?"
(End)