Disease Description (Causes and Symptoms)

Cause: A mutation in the PIGA gene in adult (somatic) hematopoietic stem cells leads to deficiency of the GPI (glycosylphosphatidylinositol) anchor. As a result, complement regulatory proteins (such as CD55 and CD59) on the surface of red blood cells are deficient, causing complement-mediated hemolysis.
Key pathophysiology: The absence of CD55/CD59 makes red blood cells vulnerable to complement attack, resulting in chronic/paroxysmal hemolysis. At the same time, a PNH clone may coexist with bone marrow failure (associated with aplastic anemia or MDS), and abnormal platelets and granulocytes also have increased complement sensitivity, raising the risks of thrombosis, infection, and bleeding. Complement activation may increase at night due to respiratory acidosis and other factors, and hemoglobinuria in the morning urine is common.
Major symptoms: Fatigue (anemia), jaundice, amber or reddish-brown urine (especially in the morning), abdominal pain, chest pain, or shortness of breath (in cases of thrombosis), a tendency to bruise or bleed, splenomegaly or hepatomegaly, pallor related to anemia, and recurrent infections (when accompanied by bone marrow dysfunction).

Treatment Methods

Standard pharmacological treatment
- Complement inhibitors: Eculizumab (anti-C5, Soliris), ravulizumab (longer-acting) — most effective for preventing severe hemolysis and thrombosis and improving survival.
- Supportive treatment: Transfusions (washed red blood cells when necessary), iron and folate supplementation (to replace losses due to hemolysis), and short-term corticosteroids (limited use during the acute phase of severe hemolysis).
Thrombosis management
- If thrombosis occurs, anticoagulation (consideration of indefinite anticoagulation depending on body weight and condition) — a history of thrombosis has a major impact on prognosis.
Definitive treatment
- Allogeneic hematopoietic stem cell transplantation (HSCT): May be the only curative treatment for severe aplastic anemia or treatment-refractory or progressive disease.
Other
- If accompanied by bone marrow dysfunction, immunosuppressive therapy (e.g., antithymocyte globulin + CsA) may be considered.
Lifestyle and management
- Meningococcal (Neisseria meningitidis) vaccination, including restricted vaccines, is recommended before and during treatment with complement inhibitors; prophylactic antibiotics may be used when necessary.
- Treatment plans need to be adjusted in cases of pregnancy, surgery, or infection.
Caution: Long-term corticosteroids are not recommended (because of adverse effects). Complement inhibitors such as eculizumab increase susceptibility to infections, particularly meningococcal infection.

Items and materials to bring
- A list of medications currently being taken (including prescription drugs, over-the-counter drugs, and supplements)
- Previous test results: recent CBC, LDH, bilirubin, reticulocytes (RET), serum creatinine, urinalysis (hemoglobinuria), previous flow cytometry (CD55/CD59/FLAER) results, and records of previous thrombosis and imaging
- Symptom records: changes in urine color (time of day), episodes of fatigue, shortness of breath, abdominal pain, or severe pain, bleeding (bruising or gum bleeding), and frequency of infections
- Lifestyle changes such as surgery, vaccination, or pregnancy plans
Summary that is useful to submit to the doctor during the outpatient visit
- Recent transfusion history (date and amount), whether anticoagulants were previously used, and any history of immunosuppressant use or transplantation
Tests that may be requested
- Recent CBC, LDH, total and indirect bilirubin, reticulocytes, iron and ferritin, creatinine, urine Hb, blood-type crossmatching (if a transfusion is planned), and flow cytometry (including FLAER)

"What are the major side effects of this medication (e.g., eculizumab), and how should the risk of infection be managed?"
"How high is my risk of thrombosis? Do I need anticoagulant treatment?"
"What is the prognosis (medium- and long-term survival and the likelihood of complications)?"
"What precautions should I take regarding lifestyle activities such as exercise, travel, and pregnancy planning?"

"Which vaccinations (such as meningococcal and hepatitis B vaccines) are needed before starting eculizumab (or ravulizumab), and how long should I wait after vaccination?"
"How does the size of my PNH clone (or my flow cytometry results) affect treatment decisions, such as complement inhibitors, anticoagulation, or transplantation? If the clone percentage is small, can I be monitored without treatment?"