Introduction

Hemolytic anemia is one of the most common reasons a young, otherwise healthy person ends up with unexplained jaundice. It's also why a pregnant woman might suddenly need transfusion, why a child of Mediterranean or African descent needs lifelong follow-up, and why a patient on a new antibiotic might turn yellow within days. Understanding hemolytic anemia means understanding how the body destroys, replaces, and recycles red blood cells when something goes wrong [1].

This guide walks through the mechanisms, the clinical picture, the diagnostic workup, and current treatment, including the gene therapies that have entered clinical practice since 2023.

Normal RBC function and lifespan

Red blood cells (erythrocytes) carry oxygen from the lungs to tissues using hemoglobin, and they shuttle carbon dioxide back. They are made in the bone marrow through a process called erythropoiesis (red blood cell production), enter circulation as immature reticulocytes, and live for about 100 to 120 days. When they age, splenic and hepatic macrophages remove them and recycle the iron and amino acids.

Hemolytic anemia is what happens when this lifespan is cut short. The cells are destroyed faster than the marrow can replace them, even when the marrow is working at full capacity.

Extravascular vs. Intravascular Hemolysis

Where the red blood cells die changes the clinical picture, the lab findings, and the differential diagnosis [4].

Extravascular hemolysis happens outside the bloodstream, mainly inside the spleen. Macrophages spot damaged or antibody-coated red blood cells and engulf them. Because the breakdown happens inside cells, hemoglobin is recycled neatly. This pattern shows raised unconjugated bilirubin, mild splenomegaly, and spherocytes (small, round, dense cells) on a blood smear.

Intravascular hemolysis happens directly inside blood vessels. Cells rupture and spill free hemoglobin into the plasma. The body's clean-up protein, haptoglobin, gets used up quickly. Free hemoglobin spills into the urine (hemoglobinuria, the classic "cola-colored" urine), and over time iron pigment appears in the urine sediment (hemosiderinuria). Schistocytes (fragmented cells) often appear on the smear when the cause is mechanical.

Comparison of Extravascular vs. Intravascular Hemolysis

Classification of Hemolytic Anemia Based on Cause

Hemolytic anemia divides cleanly into hereditary (intrinsic to the red cell) and acquired (an outside force damages a normal cell) [5].

Hereditary hemolytic anemia

Hereditary forms are caused by inherited gene mutations that make red blood cells fragile. The defect can sit in three places.

Membrane defects. Hereditary spherocytosis is the classic example: mutations in membrane-anchoring proteins (ankyrin, spectrin, band 3) make cells sphere-shaped and rigid, so the spleen destroys them early. Hereditary elliptocytosis is usually milder.

Enzyme deficiencies. G6PD deficiency is the most common enzyme defect worldwide. G6PD protects red blood cells from oxidative stress; without it, drugs like primaquine, infections, and even fava beans can trigger sudden hemolysis. Pyruvate kinase (PK) deficiency disrupts red cell energy production, shortening lifespan.

Hemoglobin abnormalities. Sickle cell disease is caused by a single point mutation in the beta-globin gene; under low oxygen, hemoglobin polymerizes and the cell sickles, blocking small vessels. Thalassemia reduces or eliminates production of either alpha or beta globin chains, causing imbalanced hemoglobin and ineffective erythropoiesis.

Acquired hemolytic anemia

Acquired forms develop later in life. The red cell is born normal but something attacks it.

Immune-mediated hemolysis is the largest acquired category. Autoantibodies bind red cells and mark them for destruction. Warm AIHA uses IgG antibodies that bind at body temperature and drive extravascular destruction. Cold agglutinin disease uses IgM antibodies that bind at cooler temperatures, triggering complement and intravascular hemolysis [3,6]. Alloimmune hemolysis happens when foreign antibodies meet incompatible blood, as in a hemolytic transfusion reaction or hemolytic disease of the fetus and newborn (HDFN).

Drug-induced immune hemolytic anemia can be triggered by penicillin, cephalosporins, quinine, and others. Stopping the drug usually stops the hemolysis.

Mechanical fragmentation (microangiopathic hemolytic anemia, or MAHA) occurs when small vessels are blocked by fibrin strands or platelet thrombi, shearing red cells into schistocytes. TTP, HUS, DIC, malignant hypertension, HELLP syndrome of pregnancy, and prosthetic valves all do this.

Paroxysmal nocturnal hemoglobinuria (PNH) is technically acquired but intrinsic: a somatic mutation in the PIGA gene removes the protective GPI anchor on red cells, leaving them vulnerable to complement attack.

Infections like malaria and babesiosis directly invade red cells. Severe sepsis can also cause hemolysis. Toxins (snake venoms, lead, copper in Wilson's disease) damage membranes directly.

Classification of Hemolytic Anemia Based on Etiology

Signs and Symptoms

The symptoms of hemolytic anemia come from three things at once: too little oxygen reaching tissues, too much bilirubin from broken-down hemoglobin, and the body's compensatory response.

The hallmark trio is fatigue, pallor, and jaundice. Patients also report shortness of breath on exertion, rapid heartbeat, and reduced exercise tolerance. When hemolysis is intravascular, urine can turn dark red or brown from free hemoglobin. When extravascular hemolysis is chronic, the spleen enlarges and may cause a dull ache in the upper left abdomen.

Children with chronic hemolytic anemia may show delayed growth, and patients with sickle cell disease often have leg ulcers from microvascular blockage.

Complications

If hemolytic anemia is untreated or severe, several complications follow. Pigment gallstones form because excess bilirubin precipitates in the gallbladder; many patients with chronic hemolysis eventually need cholecystectomy. Iron overload develops in transfusion-dependent patients (especially in thalassemia) and can damage the liver, heart, and pancreas, requiring chelation therapy.

Heart strain from chronic anemia can lead to high-output cardiac failure over years. Splenic rupture is rare but possible when the spleen is massively enlarged. Infection risk rises in three specific situations: functional hyposplenism in sickle cell disease, post-splenectomy state, and immunosuppression from AIHA treatment.

The most dangerous acute complications are TTP (a medical emergency requiring same-day plasma exchange), acute hemolytic transfusion reaction, and severe sickle cell crisis with stroke or acute chest syndrome.

Laboratory Investigations

Workup follows a clear three-step logic: confirm anemia, prove hemolysis is the cause, then find which mechanism is at work [2,4].

Step 1: Confirm anemia and bone marrow response

A complete blood count (CBC) shows low hemoglobin and hematocrit. Mean corpuscular volume (MCV) is often slightly elevated because reticulocytes are larger than mature cells.

The reticulocyte count is the single most informative initial test. A high reticulocyte count means the marrow is responding appropriately to red cell loss. A low count in the face of hemolysis suggests a second problem (such as parvovirus infection causing aplastic crisis in sickle cell disease).

The peripheral blood smear gives morphological clues:

• Spherocytes → hereditary spherocytosis or warm AIHA
• Schistocytes → MAHA (TTP, HUS, DIC, valves)
• Bite cells and blister cells → oxidative damage (G6PD deficiency)
• Sickle cells → sickle cell disease
• Target cells → thalassemia, hemoglobin C disease

In modern practice, peripheral blood smear analysis is increasingly supported by AI-driven digital cell morphology systems. These automated systems flag critical abnormalities like schistocytes and spherocytes with high sensitivity, reducing the human error associated with manual microscopy and accelerating the diagnosis of critical conditions like MAHA [11].

Step 2: Confirm hemolysis with biochemistry

These markers detect the byproducts of red cell destruction.

Step 3: Identify the cause

Once hemolysis is confirmed, targeted tests find the mechanism.

For immune causes. The Direct Antiglobulin Test (DAT, or Coombs test) detects antibodies or complement bound to the patient's red cells. A monospecific DAT (separating IgG from C3) is mandatory in modern AIHA workup [3]. The Indirect Antiglobulin Test (IAT) finds free antibodies in plasma and is used in pre-transfusion crossmatching.

For membrane and enzyme defects. Eosin-5'-maleimide (EMA) flow cytometry has largely replaced the older osmotic fragility test for hereditary spherocytosis. A G6PD enzyme assay confirms G6PD deficiency, but a normal result during an acute crisis can be misleading because the deficient older cells have already been destroyed; repeat testing weeks later is sometimes needed.

For hemoglobinopathies. Hemoglobin electrophoresis or HPLC identifies abnormal hemoglobins (HbS, HbC) and quantifies HbA2 and HbF for thalassemia diagnosis. Rather than relying on a battery of fragile functional enzyme assays, many modern hematology centers now utilize targeted Next-Generation Sequencing (NGS) gene panels as a front-line diagnostic tool. NGS is increasingly deployed immediately after immune and mechanical causes are ruled out to definitively diagnose complex, overlapping, or DAT-negative hereditary hemolytic anemias [12].

For specific syndromes. ADAMTS13 activity assay is essential when TTP is suspected, since severely low activity (<10%) confirms the diagnosis and justifies emergency plasma exchange. Flow cytometry for GPI-anchored proteins (CD55 and CD59) has replaced the old Ham test for diagnosing PNH.

Treatment and Management

Management has three pillars: supportive care that applies to almost every patient, treatments aimed at the specific cause, and modern targeted therapies that change the underlying biology.

General supportive care

Folic acid (typically 5 mg daily) supports the marrow's increased demand during chronic hemolysis and helps prevent megaloblastic crises [1].

Transfusions are used for symptomatic anemia or when hemoglobin drops below 7–8 g/dL in stable patients. In thalassemia, regular transfusions require iron chelation (deferasirox, deferoxamine) to prevent secondary iron overload.

Hydration is critical during intravascular hemolysis to protect kidneys from free hemoglobin damage.

Acquired hemolytic anemia

Management follows current consensus guidance [3,6]:

While corticosteroids and rituximab remain the standard first-line therapies for warm AIHA, the treatment pipeline has matured to address patients who are refractory or suffer from steroid toxicity. Targeted steroid-sparing agents, including SYK inhibitors (e.g., fostamatinib) and FcRn inhibitors (e.g., nipocalimab), are increasingly utilized to manage refractory chronic destruction without the long-term toxicities of immunosuppression [14].

Hereditary hemolytic anemia

Because the defect is genetic, traditional management focuses on prevention and symptom control.

G6PD deficiency. Avoid known triggers: fava beans, naphthalene (mothballs), primaquine, dapsone, nitrofurantoin, rasburicase, and high-dose sulfonamides.

Hereditary spherocytosis. Splenectomy stops extravascular destruction in moderate-to-severe cases. It's typically delayed until after age 6 to reduce the risk of overwhelming post-splenectomy infection (OPSI). Pre-operative vaccination against pneumococcus, meningococcus, and H. influenzae is mandatory.

Sickle cell disease. Hydroxyurea remains the gold standard for raising fetal hemoglobin and reducing vaso-occlusive crises, while L-glutamine and voxelotor address different parts of the disease pathway. Crizanlizumab is no longer recommended; its marketing authorization was revoked in Europe in 2023 following the Phase 3 STAND trial, which failed to demonstrate efficacy in reducing vaso-occlusive crises over placebo [13]. Prophylactic penicillin in young children prevents pneumococcal sepsis.

Thalassemia. Regular transfusions plus iron chelation; HSCT in selected patients.

Recent advances and targeted therapies

The field has moved rapidly toward molecular treatments.

Gene therapy for sickle cell disease (and transfusion-dependent beta-thalassemia). In December 2023 the FDA approved two gene therapies for severe sickle cell disease in patients aged 12 and older: Casgevy (exagamglogene autotemcel), the first-ever CRISPR-Cas9 therapy, which edits the BCL11A gene to reactivate fetal hemoglobin, and Lyfgenia (lovotibeglogene autotemcel), which uses a lentiviral vector to add an anti-sickling globin gene [7]. Both require autologous stem cell collection, conditioning chemotherapy, and reinfusion at specialized centers. They are potentially curative but carry significant cost and procedure-related risks. In real-world application, these therapies require myeloablative conditioning with busulfan to clear the bone marrow prior to reinfusion. This aggressive chemotherapy causes severe acute toxicities and usually results in permanent infertility, necessitating expensive and time-consuming fertility preservation (egg or sperm freezing) before patients can even begin the gene therapy process [15].

Pyruvate kinase activators. Mitapivat is the first oral PK activator. Originally approved for PK deficiency (brand name Pyrukynd), it received FDA approval in December 2025 under the brand name Aqvesme for both transfusion-dependent and non-transfusion-dependent alpha- and beta-thalassemia, based on the ENERGIZE and ENERGIZE-T phase 3 trials [8]. Liver function must be monitored; rare hepatocellular injury has been reported in the first six months of treatment.

Complement inhibitors. The management of PNH has been revolutionized by the arrival of oral complement inhibitors, heavily reducing the burden of frequent infusions. Iptacopan (a Factor B inhibitor) is now approved as a first-in-class oral monotherapy that controls both intravascular and extravascular hemolysis. Danicopan (an oral Factor D inhibitor) is approved as an add-on therapy for patients on intravenous C5 inhibitors (eculizumab or ravulizumab) who continue to experience clinically significant extravascular hemolysis [16,17]. For cold agglutinin disease, sutimlimab remains a targeted option to block the classical complement pathway [9].

Luspatercept improves erythroid maturation and is used in transfusion-dependent beta-thalassemia.

Surgical and interventional options

Allogeneic hematopoietic stem cell transplant (HSCT) remains a curative option for severe sickle cell disease and thalassemia, especially when a matched sibling donor is available. Splenectomy removes the main site of extravascular destruction in selected hereditary spherocytosis or refractory warm AIHA cases. Cholecystectomy is often performed for symptomatic pigment gallstones, sometimes during the same surgery as splenectomy.

Prognosis

Outcomes depend heavily on the cause. Many acquired forms resolve once the trigger is removed. Chronic AIHA, sickle cell disease, and severe thalassemia require lifelong follow-up. With modern treatment, including gene therapy where available, life expectancy and quality of life have improved substantially over the past two decades.

Frequently Asked Questions (FAQs)

What is hemolytic anemia in simple terms?

Hemolytic anemia is a blood disorder where red blood cells are destroyed faster than the bone marrow can replace them. Healthy red blood cells normally live about 120 days. In hemolytic anemia, they break down early, leaving the body short of oxygen-carrying cells. This causes fatigue, pale skin, jaundice (yellow eyes and skin), and sometimes dark urine.

How is hemolytic anemia diagnosed?

Doctors use a three-step approach. A complete blood count and reticulocyte count first confirm anemia and show the marrow's response. Blood markers (high LDH, high unconjugated bilirubin, low haptoglobin) then confirm hemolysis. Specific tests find the cause: a Direct Antiglobulin Test (Coombs test) for autoimmune hemolytic anemia, hemoglobin electrophoresis for sickle cell disease and thalassemia, EMA flow cytometry for hereditary spherocytosis, a G6PD enzyme assay for G6PD deficiency, and ADAMTS13 activity for suspected TTP.

Can hemolytic anemia be cured?

It depends on the cause. Some acquired forms reverse fully when the trigger is removed (a drug, an infection). Hereditary forms were historically managed only symptomatically, but in 2023 the FDA approved two gene therapies, Casgevy and Lyfgenia, that can functionally cure severe sickle cell disease in patients aged 12 and older. Allogeneic stem cell transplant remains another curative option. Many forms, including chronic autoimmune hemolytic anemia, are controlled long-term rather than cured.

What is the difference between intravascular and extravascular hemolysis?

Extravascular hemolysis happens outside blood vessels, mostly inside the spleen, where macrophages remove damaged or antibody-coated cells. It typically shows spherocytes, raised bilirubin, and splenomegaly. Intravascular hemolysis happens directly inside blood vessels; cells burst and release hemoglobin into plasma. It typically shows free hemoglobin in blood and urine, very low haptoglobin, and schistocytes when the cause is mechanical.

Is hemolytic anemia an emergency?

Most cases are chronic and stable, but some are emergencies. TTP requires plasma exchange within hours. Acute hemolytic transfusion reactions need the transfusion stopped immediately and supportive care. A severe sickle cell crisis with stroke, acute chest syndrome, or multi-organ failure is critical. Caregivers should seek urgent medical help for sudden severe weakness, dark "cola-colored" urine, severe jaundice, confusion, or fever in any patient with known hemolytic disease.

What lifestyle changes help with hemolytic anemia?

Specifics depend on the type. Patients with G6PD deficiency must avoid fava beans, mothballs, and trigger drugs (including primaquine and dapsone). Patients with cold agglutinin disease should keep extremities warm. Most patients with chronic hemolysis benefit from daily folic acid. Patients without a spleen need vaccinations against pneumococcus, meningococcus, and Haemophilus influenzae, plus prompt antibiotics for any fever.

How does hemolytic anemia affect pregnancy?

Pregnancy increases demand for red cells and folate, so pre-existing hemolytic anemia often worsens. Risks include severe maternal anemia, fetal growth restriction, and preterm birth. Some immunosuppressive drugs used in AIHA need adjustment for fetal safety. HELLP syndrome, a form of MAHA, is a specific pregnancy-related cause of hemolysis requiring urgent obstetric care.

Is splenomegaly always present in hemolytic anemia?

No. Splenomegaly is classic in extravascular hemolysis (hereditary spherocytosis, warm AIHA) because the spleen is doing the destruction. It's usually absent in pure intravascular hemolysis, where the destruction happens in the bloodstream itself.

Glossary of Related Medical Terms

• Anemia: A condition where the blood has too few red blood cells or not enough hemoglobin to deliver oxygen.
• Bilirubin: A yellow pigment from broken-down hemoglobin; high levels cause jaundice.
• DAT (Direct Antiglobulin Test, Coombs test): Detects antibodies or complement on the surface of red blood cells.
• Erythropoiesis: Production of red blood cells in the bone marrow.
• Extravascular hemolysis: Destruction of red blood cells by macrophages, mostly in the spleen.
• Haptoglobin: A plasma protein that binds free hemoglobin; low levels suggest hemolysis.
• Hemoglobinemia / hemoglobinuria: Free hemoglobin in plasma / urine; markers of intravascular hemolysis.
• Intravascular hemolysis: Destruction of red blood cells inside the blood vessels.
• LDH (lactate dehydrogenase): An intracellular enzyme released when cells break down.
• MAHA (microangiopathic hemolytic anemia): Mechanical fragmentation of red cells in damaged small vessels.
• PNH (paroxysmal nocturnal hemoglobinuria): A rare clonal disorder where red cells are vulnerable to complement attack.
• Reticulocyte: A young red blood cell; a high count signals an active marrow response.
• Schistocytes: Fragmented red cells from mechanical damage.
• Spherocytes: Small, round, dense cells without central pallor; classic for hereditary spherocytosis and warm AIHA.
• Splenomegaly: Enlargement of the spleen.
• TTP (thrombotic thrombocytopenic purpura): A life-threatening MAHA caused by ADAMTS13 deficiency.

Disclaimer: This article is intended for educational and informational purposes only. It is not intended to be a substitute for informed professional medical advice, diagnosis, or treatment. While the information presented here is derived from credible medical sources and is believed to be accurate and up-to-date, it is not guaranteed to be complete or error-free. See additional information.

References

1. Baldwin C, Pandey J, Olarewaju O. Hemolytic Anemia(Archived) [Updated 2023 Jul 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558904/
2. Phillips, J., & Henderson, A. C. (2018). Hemolytic Anemia: Evaluation and Differential Diagnosis. American family physician, 98(6), 354–361.
3. Jäger, U., Barcellini, W., Broome, C. M., Gertz, M. A., Hill, A., Hill, Q. A., Jilma, B., Kuter, D. J., Michel, M., Montillo, M., Röth, A., Zeerleder, S. S., & Berentsen, S. (2020). Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting. Blood reviews, 41, 100648. https://doi.org/10.1016/j.blre.2019.100648
4. Barcellini, W., & Fattizzo, B. (2015). Clinical Applications of Hemolytic Markers in the Differential Diagnosis and Management of Hemolytic Anemia. Disease markers, 2015, 635670. https://doi.org/10.1155/2015/635670
5. Mohandas N. (2018). Inherited hemolytic anemia: a possessive beginner's guide. Hematology. American Society of Hematology. Education Program, 2018(1), 377–381. https://doi.org/10.1182/asheducation-2018.1.377
6. Hill, A., & Hill, Q. A. (2018). Autoimmune hemolytic anemia. Hematology. American Society of Hematology. Education Program, 2018(1), 382–389. https://doi.org/10.1182/asheducation-2018.1.382
7. Frangoul, H., Altshuler, D., Cappellini, M. D., Chen, Y. S., Domm, J., Eustace, B. K., Foell, J., de la Fuente, J., Grupp, S., Handgretinger, R., Ho, T. W., Kattamis, A., Kernytsky, A., Lekstrom-Himes, J., Li, A. M., Locatelli, F., Mapara, M. Y., de Montalembert, M., Rondelli, D., Sharma, A., … Corbacioglu, S. (2021). CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. The New England journal of medicine, 384(3), 252–260. https://doi.org/10.1056/NEJMoa2031054
8. Taher, A. T., Al-Samkari, H., Aydinok, Y., Besser, M., Boscoe, A. N., Dahlin, J. L., De Luna, G., Estepp, J. H., Gheuens, S., Gilroy, K. S., Glenthøj, A., Sim Goh, A., Iyer, V., Kattamis, A., Loggetto, S. R., Morris, S., Musallam, K. M., Osman, K., Ricchi, P., Salido-Fiérrez, E., … ENERGIZE investigators (2025). Mitapivat in adults with non-transfusion-dependent α-thalassaemia or β-thalassaemia (ENERGIZE): a phase 3, international, randomised, double-blind, placebo-controlled trial. Lancet (London, England), 406(10498), 33–42. https://doi.org/10.1016/S0140-6736(25)00635-X
9. Röth, A., Barcellini, W., D'Sa, S., Miyakawa, Y., Broome, C. M., Michel, M., Kuter, D. J., Jilma, B., Tvedt, T. H. A., Fruebis, J., Jiang, X., Lin, S., Reuter, C., Morales-Arias, J., Hobbs, W., & Berentsen, S. (2021). Sutimlimab in Cold Agglutinin Disease. The New England journal of medicine, 384(14), 1323–1334. https://doi.org/10.1056/NEJMoa2027760
10. Hillmen, P., Szer, J., Weitz, I., Röth, A., Höchsmann, B., Panse, J., Usuki, K., Griffin, M., Kiladjian, J. J., de Castro, C., Nishimori, H., Tan, L., Hamdani, M., Deschatelets, P., Francois, C., Grossi, F., Ajayi, T., Risitano, A., & Peffault de Latour, R. (2021). Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. The New England journal of medicine, 384(11), 1028–1037. https://doi.org/10.1056/NEJMoa2029073
11. Xing, Y., Liu, X., Dai, J., Ge, X., Wang, Q., Hu, Z., Wu, Z., Zeng, X., Xu, D., & Qu, C. (2023). Artificial intelligence of digital morphology analyzers improves the efficiency of manual leukocyte differentiation of peripheral blood. BMC medical informatics and decision making, 23(1), 50. https://doi.org/10.1186/s12911-023-02153-z
12. Roy, N. B. A., Da Costa, L., Russo, R., Bianchi, P., Del Mar Mañú-Pereira, M., Fermo, E., Andolfo, I., Clark, B., Proven, M., Sanchez, M., van Wijk, R., van der Zwaag, B., Layton, M., Rees, D., & Iolascon, A. (2022). The Use of Next-generation Sequencing in the Diagnosis of Rare Inherited Anaemias: A Joint BSH/EHA Good Practice Paper. HemaSphere, 6(6), e739. https://doi.org/10.1097/HS9.0000000000000739
13. European Medicines Agency. (2023). Adakveo (crizanlizumab): Revocation of conditional marketing authorisation. EMA/322302/2023.
14. Xiao, Z., & Murakhovskaya, I. (2022). Development of New Drugs for Autoimmune Hemolytic Anemia. Pharmaceutics, 14(5), 1035. https://doi.org/10.3390/pharmaceutics14051035
15. Bedrick, B. S., Kohn, T. P., Pecker, L. H., & Christianson, M. S. (2022). Fertility preservation for pediatric patients with hemoglobinopathies: Multidisciplinary counseling needed to optimize outcomes. Frontiers in endocrinology, 13, 985525. https://doi.org/10.3389/fendo.2022.985525
16. Peffault de Latour, R., Röth, A., Kulasekararaj, A. G., Han, B., Scheinberg, P., Maciejewski, J. P., Ueda, Y., de Castro, C. M., Di Bona, E., Fu, R., Zhang, L., Griffin, M., Langemeijer, S. M. C., Panse, J., Schrezenmeier, H., Barcellini, W., Mauad, V. A. Q., Schafhausen, P., Tavitian, S., Beggiato, E., … Risitano, A. M. (2024). Oral Iptacopan Monotherapy in Paroxysmal Nocturnal Hemoglobinuria. The New England journal of medicine, 390(11), 994–1008. https://doi.org/10.1056/NEJMoa2308695
17. Lee, J. W., Griffin, M., Kim, J. S., Lee Lee, L. W., Piatek, C., Nishimura, J. I., Carrillo Infante, C., Jain, D., Liu, P., Filippov, G., Sicre de Fontbrune, F., Risitano, A., Kulasekararaj, A. G., & ALXN2040-PNH-301 Investigators (2023). Addition of danicopan to ravulizumab or eculizumab in patients with paroxysmal nocturnal haemoglobinuria and clinically significant extravascular haemolysis (ALPHA): a double-blind, randomised, phase 3 trial. The Lancet. Haematology, 10(12), e955–e965. https://doi.org/10.1016/S2352-3026(23)00315-0