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Paroxysmal Nocturnal Haemoglobinuria (PNH)

Last updated 31 May 2026 · Haematology clinical guideline

📋 Key Information Summary

📋
  • Paroxysmal Nocturnal Haemoglobinuria (PNH) is a rare, acquired clonal haematopoietic stem cell disorder characterised by complement-mediated intravascular haemolysis, thrombophilia, and bone marrow failure.
  • Caused by somatic mutations in the PIG-A gene leading to deficiency of GPI-anchored complement regulatory proteins CD55 and CD59 on affected blood cells.
  • Classic triad: episodic intravascular haemolysis (dark urine, fatigue), cytopenias (often overlapping aplastic anaemia), and thrombosis (venous and arterial, including unusual sites such as hepatic veins).
  • Thrombosis is the leading cause of death in untreated PNH and may occur in unusual sites — hepatic vein (Budd–Chiari), cerebral sinuses, mesenteric veins, dermal veins.
  • Flow cytometry detecting CD55 and CD59 deficiency on red cells and granulocytes is the gold-standard diagnostic test; LDH is markedly elevated and the primary monitoring biomarker.
  • Eculizumab (Soliris®) and ravulizumab (Ultomiris®) — terminal complement (C5) inhibitors — are the cornerstone of therapy for classic PNH with haemolysis or thrombosis; PBS Authority Required listing.
  • Eculizumab/ravulizumab carry a significant risk of Neisseria meningitidis infection; meningococcal vaccination is mandatory ≥2 weeks before initiation, with ongoing prophylactic antibiotics.
  • All patients require baseline meningococcal vaccination (ACWY and B strains) and indefinite antibiotic prophylaxis (penicillin V 500 mg BD or alternative) while on C5 inhibitor therapy.
  • Anticoagulation is indicated for thrombotic events but primary thromboprophylaxis decisions are individualised; PNH-directed anticoagulation is not routinely recommended without C5 inhibitor therapy.
  • Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative option, reserved for severe/refractory disease or severe aplastic anaemia component; transplant-related mortality remains significant.
  • Pregnancy in PNH is high-risk (increased thrombosis and haemolysis); eculizumab can be continued in pregnancy and is preferred over ravulizumab due to more extensive safety data.
  • Aboriginal and Torres Strait Islander patients face barriers including remote geographic access, limited specialist haematology services, and need for culturally safe care and regular monitoring pathways.

Introduction & Australian Epidemiology

Paroxysmal Nocturnal Haemoglobinuria (PNH) is a rare, acquired clonal haematopoietic stem cell disorder arising from somatic mutations in the PIG-A gene. These mutations impair biosynthesis of the glycosylphosphatidylinositol (GPI) anchor, rendering blood cells deficient in complement regulatory surface proteins — most critically CD55 (decay-accelerating factor) and CD59 (membrane inhibitor of reactive lysis). The result is complement-mediated intravascular haemolysis, a prothrombotic state, and variable degrees of bone marrow failure.

PNH is exceptionally rare, with an estimated prevalence of approximately 1–1.5 per 100,000 population in developed countries. In Australia, with a population of ~26 million, the total number of diagnosed PNH patients is estimated at 250–400 individuals, though underdiagnosis remains likely. The median age at diagnosis is 30–40 years, with a slight female predominance. PNH is frequently associated with, or evolves from, aplastic anaemia — approximately 30–50% of patients with aplastic anaemia harbour a detectable PNH clone.

The advent of complement-inhibitor therapy — first eculizumab (Soliris®, Alexion) and subsequently ravulizumab (Ultomiris®) — has transformed the natural history of PNH, reducing intravascular haemolysis, thrombotic risk, and transfusion dependence, and markedly improving survival. Access to these therapies in Australia is via the Pharmaceutical Benefits Scheme (PBS) Authority Required programme, managed through specialist haematology centres.

Paroxysmal Nocturnal Haemoglobinuria (PNH) clinical infographic — pathophysiology, clinical clues, diagnosis, imaging, and management
Tap or click image to enlarge — Paroxysmal Nocturnal Haemoglobinuria (PNH): pathophysiology, clinical clues, diagnosis, imaging, and management.
Paroxysmal Nocturnal Haemoglobinuria (PNH) infographic, full size

Pathogenesis — GPI Anchor Deficiency, CD55 & CD59

PNH arises from a somatic mutation in the X-linked PIG-A (phosphatidylinositol glycan class A) gene in a haematopoietic stem cell. Because the mutation is X-linked and males have only one copy, a single hit is sufficient; in females, random X-inactivation means that one hit in the active-X copy produces the phenotype. The mutation impairs the first step of GPI-anchor biosynthesis, preventing attachment of GPI-anchored proteins to the cell surface.

The GPI Anchor and Complement Regulation

The GPI anchor is a glycolipid structure that tethers numerous proteins to the extracellular surface of haematopoietic cells. Of particular relevance to PNH are two complement-regulatory proteins:

  • CD55 (decay-accelerating factor, DAF): Accelerates decay of C3 and C5 convertases (C3bBb and C4b2a), limiting amplification of complement activation on the cell surface.
  • CD59 (membrane inhibitor of reactive lysis, MIRL): Prevents incorporation of C9 into the C5b-9 membrane attack complex (MAC), directly blocking terminal complement-mediated lysis.

In PNH, the clonal expansion of PIG-A-mutated stem cells produces erythrocytes, granulocytes, monocytes, and platelets that lack both CD55 and CD59. This renders them exquisitely sensitive to complement activation. Under physiological conditions — triggered by infection, surgery, stress, or even the acidotic milieu of sleep (historically explaining the "nocturnal" component, though this mechanism is debated) — complement activation proceeds unimpeded, leading to direct intravascular haemolysis via MAC (C5b-9 deposition).

Clonal Dynamics

The PIG-A mutation alone is insufficient to explain the clonal dominance seen in PNH. Additional factors confer a selective growth advantage to the PNH clone, particularly in the setting of immune-mediated bone marrow suppression (overlapping aplastic anaemia). Hypothesised drivers include resistance of GPI-deficient stem cells to T-cell–mediated attack and altered cytokine signalling. Patients with large PNH clones (>50% GPI-deficient granulocytes) are more likely to develop clinically significant haemolysis and thrombosis.

Downstream Pathological Consequences

Mechanism Clinical Consequence
Complement-mediated intravascular haemolysis (C5b-9 MAC) Anaemia, haemoglobinuria, fatigue, dysphagia, erectile dysfunction, abdominal pain
Free haemoglobin scavenges nitric oxide (NO) Pulmonary hypertension, smooth muscle dystonia (dysphagia, abdominal pain, erectile dysfunction)
Platelet activation and NO depletion Venous and arterial thrombosis — hepatic veins, cerebral sinuses, mesenteric, dermal
Chronic haemolysis and iron loss (urinary) Iron deficiency (paradoxically, despite intravascular haemolysis), renal tubular injury
Underlying stem cell failure Cytopenias (aplastic anaemia overlap), risk of MDS/AML transformation

Clinical Features — Haemolysis, Thrombosis & Cytopenias

The clinical presentation of PNH is heterogeneous and often insidious. Many patients present with nonspecific symptoms for months to years before diagnosis. The disease is conventionally classified into three overlapping syndromes:

Haemolytic
Classic PNH
Episodic or chronic intravascular haemolysis: dark urine (haemoglobinuria, classically nocturnal), fatigue, jaundice, iron deficiency. Symptoms worsen with infections, surgery, stress, or menstruation.
LDH markedly elevated, reticulocytosis, low haptoglobin
Thrombotic
Thrombosis-Predominant PNH
Venous thrombosis in unusual sites is the most dangerous complication and leading cause of death. Includes Budd–Chiari syndrome (hepatic vein), cerebral venous sinus thrombosis, mesenteric vein thrombosis, portal vein thrombosis, dermal vein thrombosis, and deep vein thrombosis / pulmonary embolism.
May be the presenting feature; anticoagulation alone is often insufficient without complement inhibition
Cytopenic
Bone Marrow Failure Overlap
Cytopenias from underlying aplastic anaemia or hypoplastic marrow: neutropenia, thrombocytopenia, anaemia beyond haemolysis alone. 30–50% of aplastic anaemia patients harbour a PNH clone.
May require immunosuppressive therapy or HSCT; complement inhibition may not address marrow failure

Other Clinical Features

  • Smooth muscle dystonia: Oesophageal spasm (dysphagia), abdominal colic, erectile dysfunction — driven by NO depletion from free haemoglobin.
  • Pulmonary hypertension: Due to chronic NO scavenging and possible thrombotic microangiopathy in pulmonary vasculature.
  • Renal involvement: Chronic haemoglobinuria causes tubular iron deposition (haemosiderinuria), progressive renal impairment.
  • Iron deficiency: Urinary iron loss through haemoglobinuria can be profound despite haemolytic anaemia — monitor ferritin and transferrin saturation.
  • Severe paroxysms: Triggered by infection, surgery, stress, menstruation — may require transfusion support.
🚨
Thrombosis is the leading cause of death in PNH. Any patient with PNH who develops new symptoms — particularly abdominal pain, headache, limb swelling, or dyspnoea — must be evaluated urgently for thrombosis. Atypical sites (hepatic, cerebral, mesenteric veins) should be actively sought with appropriate imaging.

Investigations — Flow Cytometry & Biomarkers

Diagnosis of PNH requires a high index of clinical suspicion. The diagnostic pathway combines laboratory evidence of intravascular haemolysis with confirmation of GPI-anchor–deficient clones via flow cytometry.

Diagnostic Investigations

Essential
Flow Cytometry for GPI-Anchored Proteins (CD55, CD59)
Gold-standard diagnostic test. Performed on peripheral blood granulocytes and erythrocytes using monoclonal antibodies against CD55 and CD59 (and/or FLAER — fluorescent aerolysin). Detects PNH clones as small as 0.01%. Australian reference laboratories (e.g., Royal Melbourne Hospital, Westmead) offer high-sensitivity FLAER-based assays. MBS item: refer to specialist haematology laboratory.
Essential
Lactate Dehydrogenase (LDH)
Markedly elevated (often >2× ULN) in active haemolysis. Primary biomarker for monitoring disease activity and treatment response on C5 inhibitor therapy. MBS item 66525.
Available
Full Blood Count & Reticulocyte Count
Anaemia with elevated reticulocytes (if marrow reserve adequate); may show pancytopenia if overlapping aplastic anaemia. MBS item 65070.
Available
Serum Haptoglobin
Low or undetectable in intravascular haemolysis. Less specific than LDH but supportive. MBS item 66530.
Available
Direct Antiglobulin Test (DAT / Coombs)
Negative in PNH (complement-mediated, not antibody-mediated). Important to exclude autoimmune haemolytic anaemia.
Available
Iron Studies
Ferritin and transferrin saturation. Iron deficiency is common due to urinary haemoglobin loss and may worsen thrombocytosis. MBS item 66550.
Available
Renal Function (eGFR, Urine Haemosiderin)
Chronic haemoglobinuria causes renal tubular iron deposition; monitor eGFR and urine haemosiderin.
Referral
Thrombophilia Screen
Not routinely indicated (PNH itself is a strong thrombophilic state); performed to exclude concurrent inherited thrombophilia if clinical concern. Coordinate with haematologist.

Imaging for Thrombosis

  • CT pulmonary angiography (CTPA): Suspected pulmonary embolism.
  • Doppler ultrasound: Hepatic vein (Budd–Chiari), portal vein, limb DVT.
  • MRI venography: Cerebral venous sinus thrombosis.
  • CT abdomen with contrast: Mesenteric vein thrombosis, hepatic vein thrombosis.

Management — Eculizumab, Anticoagulation & SCT

Management of PNH has been transformed by complement inhibition. Current Australian practice follows international consensus guidelines (International PNH Interest Group) adapted to the PBS and TGA regulatory framework.

Complement (C5) Inhibitor Therapy — The Cornerstone of Treatment

C5 inhibitors block terminal complement activation, preventing C5b-9 MAC formation and intravascular haemolysis. They are indicated for PNH patients with:

  • Classic haemolytic PNH with elevated LDH (>1.5× ULN) and symptoms
  • Thrombotic events attributable to PNH
  • Transfusion-dependent anaemia with evidence of complement-mediated haemolysis
  • Significant symptoms (fatigue, dysphagia, abdominal pain, erectile dysfunction) affecting quality of life
💊
Eculizumab
Soliris® · Alexion · Anti-C5 monoclonal antibody
Adult dose Induction: 600 mg IV weekly × 4 weeks. Maintenance: 900 mg IV every 2 weeks (± 1 day) indefinitely.
Paediatric dose ≥18 kg: weight-based dosing per SmPC (5–<40 kg: 600 mg induction then 300 mg q2w; ≥40 kg: adult dosing).
Route Intravenous infusion (over 25–45 min depending on dose)
Renal adjustment Not required
Hepatic adjustment Not required
PBS status Authority Required — Specialist Haematologist
Key adverse effects Meningococcal infection (critical risk — see below), headache, nasopharyngitis, back pain, infusion reactions. Breakthrough haemolysis possible at end of dosing interval.
💊
Ravulizumab
Ultomiris® · Alexion · Long-acting anti-C5 monoclonal antibody
Adult dose Weight-based loading then maintenance every 8 weeks: ≥40–<60 kg: 2400 mg load → 3000 mg q8w; ≥60–<100 kg: 2700 mg load → 3300 mg q8w; ≥100 kg: 3000 mg load → 3600 mg q8w. IV infusion.
Paediatric dose ≥18 kg: weight-based per SmPC. Note: limited data in pregnancy — eculizumab preferred.
Route Intravenous infusion (over 25–45 min depending on dose and weight)
Renal adjustment Not required
Hepatic adjustment Not required
PBS status Authority Required — Specialist Haematologist
Key advantage Extended dosing interval (q8w vs q2w for eculizumab), reducing treatment burden. Equivalent efficacy. Patients on stable eculizumab may be switched.
🚨
Mandatory Meningococcal Prophylaxis: All patients commencing eculizumab or ravulizumab MUST receive meningococcal vaccination (MenACWY and MenB) at least 2 weeks prior to first dose. Lifelong antibiotic prophylaxis is required — penicillin V 500 mg PO BD (or alternative if penicillin-allergic: ciprofloxacin 500 mg PO daily, or rifampicin). Educate patients on recognising meningococcal symptoms (fever, rash, headache, neck stiffness) — present to ED immediately. Annual influenza vaccination recommended.

Anticoagulation

Thrombosis is the leading cause of morbidity and mortality in PNH. Anticoagulation management requires specialist haematology involvement.

Scenario Recommendation
Acute thrombosis Immediate therapeutic anticoagulation (heparin → warfarin or DOAC) PLUS initiation of C5 inhibitor if not already receiving. Thrombolysis for life-threatening events (e.g., Budd–Chiari).
Prior thrombosis (on C5 inhibitor) Long-term anticoagulation — usually warfarin (INR 2.0–3.0) or DOAC; specialist decision. Do NOT cease anticoagulation when starting eculizumab.
No prior thrombosis (on C5 inhibitor) Primary thromboprophylaxis: individualised decision. C5 inhibitor therapy itself reduces thrombotic risk significantly. Low-dose aspirin may be considered but evidence is limited. DOAC/warfarin prophylaxis considered if high-risk features (large clone, prior history, pregnancy).
No C5 inhibitor therapy Higher thrombotic risk. Consider anticoagulation prophylaxis in all patients with large PNH clones (>50% GPI-deficient granulocytes). Warfarin preferred over DOACs due to more limited evidence in PNH.

Supportive Care

  • Iron supplementation: Treat iron deficiency aggressively (IV iron preferred if severe, oral iron may exacerbate haemolysis in some patients). Target ferritin >50 µg/L, transferrin saturation >20%.
  • Folic acid: 5 mg PO daily (increased folate demand from chronic haemolysis).
  • Folic acid: 5 mg PO daily to support erythropoiesis.
  • Blood transfusion: Leucodepleted, CMV-safe red cells. Avoid unnecessary transfusions to minimise alloimmunisation risk.
  • EPO: Consider if anaemia persists despite C5 inhibitor and iron repletion (limited evidence).
  • Renal monitoring: Regular eGFR monitoring; manage chronic kidney disease per standard guidelines.
  • Pulmonary hypertension screening: Echocardiography at baseline and annually if symptoms (dyspnoea) develop.

Allogeneic Haematopoietic Stem Cell Transplantation (HSCT)

Allogeneic HSCT is the only curative therapy for PNH, replacing the defective haematopoietic stem cell clone. However, transplant-related morbidity and mortality (10–30% depending on conditioning and donor type) limit its role. In the era of C5 inhibitors, HSCT is reserved for:

  • PNH with severe aplastic anaemia component refractory to immunosuppressive therapy
  • C5 inhibitor–refractory disease (breakthrough haemolysis despite adequate complement inhibition, or evolving to aplastic anaemia / MDS)
  • Life-threatening thrombotic events despite adequate C5 inhibitor therapy and anticoagulation
  • Young patients with matched sibling donors and high-risk features (specialist decision)

Transplant should be performed at experienced haematopoietic stem cell transplant centres (e.g., Royal Adelaide Hospital, Westmead Hospital, Peter MacCallum Cancer Centre). Consultation with a transplant physician is essential for all patients at diagnosis for risk stratification and future planning.

Special Populations

🤰 Pregnancy
High-risk pregnancy — multidisciplinary management (haematologist, obstetric medicine, maternal–fetal medicine).
Thrombotic risk increases significantly during pregnancy and the postpartum period. Eculizumab can be continued throughout pregnancy and breastfeeding (limited but reassuring data; crosses placenta minimally in 2nd/3rd trimester). Ravulizumab: insufficient pregnancy data — eculizumab preferred. Anticoagulation: LMWH throughout pregnancy; warfarin contraindicated (teratogenic). Monitor LDH closely.
👶 Paediatric
Paediatric PNH is rare; usually presents in the context of inherited bone marrow failure syndromes or aplastic anaemia.
Eculizumab approved for children ≥18 kg. Ravulizumab data expanding. Weight-based dosing per SmPC. Meningococcal vaccination schedule per Australian National Immunisation Programme with additional doses. Regular growth and development monitoring.
🫘 Renal Impairment
Chronic kidney disease is common in PNH due to haemoglobin-mediated tubular injury.
No dose adjustment required for eculizumab or ravulizumab in renal impairment. Monitor eGFR regularly. Manage CKD per standard KDIGO guidelines. Ensure adequate hydration during haemolytic crises.
👴 Elderly
Late-onset PNH can present with thrombosis as the first manifestation.
Assess comorbidities and bleeding risk before anticoagulation decisions. Eculizumab/ravulizumab remain standard of care regardless of age. Fall risk assessment important if on anticoagulation.
🛡️ Immunocompromised
PNH often coexists with aplastic anaemia requiring immunosuppressive therapy (ATG + ciclosporin).
C5 inhibition does not address the underlying aplastic component. Monitor for infection (neutropenia) and bleeding (thrombocytopenia) in addition to haemolysis. Coordinate immunosuppressive and complement-inhibitor therapies.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

PNH is rare and there are no population-specific prevalence data for Aboriginal and Torres Strait Islander Australians. However, the high burden of comorbid chronic disease, barriers to specialist access, and unique cultural considerations require specific attention when caring for Indigenous patients with PNH.

Geographic access
C5 inhibitor therapy (eculizumab/ravulizumab) requires regular IV infusions at specialist centres. Aboriginal and Torres Strait Islander patients in remote and very remote areas face significant barriers to accessing infusion services. Telehealth monitoring, outreach infusion programmes, and patient-assisted travel schemes (PATS) should be explored. Ravulizumab's extended 8-weekly dosing interval may reduce travel burden.
Specialist services
Haematology specialist services are concentrated in metropolitan and major regional centres. Aboriginal Community Controlled Health Services (ACCHS) and remote area nurses play a critical role in facilitating referrals, blood monitoring (LDH, FBC), and medication adherence. Two-way communication between specialist and primary care is essential.
Thrombosis awareness
Aboriginal and Torres Strait Islander Australians have higher rates of cardiovascular and thromboembolic disease. Education on recognising thrombosis symptoms — particularly atypical presentations (abdominal pain from Budd–Chiari, headache from cerebral sinus thrombosis) — should be provided in culturally appropriate formats. Ensure emergency plans are in place in remote settings.
Cultural safety
Ensure culturally safe care: involve Aboriginal Health Workers (AHWs) and Aboriginal Liaison Officers in care planning; respect kinship obligations and family involvement in health decisions; provide health education in language where needed; acknowledge the impact of intergenerational trauma on healthcare engagement. Use the AIHW and RHDAustralia frameworks for culturally safe chronic disease management.
Vaccination
Meningococcal vaccination is mandatory before C5 inhibitor therapy. Ensure completion of MenACWY and MenB vaccination ≥2 weeks before first dose, with ongoing antibiotic prophylaxis. Coordinate with local immunisation programmes and ACCHS.

Monitoring

Ongoing monitoring of PNH patients on C5 inhibitor therapy requires a structured approach, ideally coordinated through a specialist haematology centre.

Baseline (pre-treatment)
Flow cytometry (clone size), LDH, FBC, reticulocytes, iron studies, renal function (eGFR), echocardiography (screen for pulmonary hypertension), bone marrow biopsy if aplastic anaemia suspected. Meningococcal vaccination (ACWY + B). Commence antibiotic prophylaxis (penicillin V 500 mg BD).
Week 1–4 (induction)
Weekly bloods (LDH, FBC). Monitor for infusion reactions. Assess for early haematological response (reticulocyte rise, LDH fall).
Months 1–6 (early maintenance)
LDH and FBC every 2–4 weeks. Confirm LDH normalisation or near-normalisation. Monitor transfusion requirements. Assess symptoms (fatigue, haemoglobinuria, dysphagia).
Ongoing (stable maintenance)
LDH and FBC every 3 months. Annual eGFR and iron studies. Annual echocardiography if prior pulmonary hypertension or symptoms. Flow cytometry annually or if clinical concern (clone size may fluctuate). Reinforce meningococcal prophylaxis adherence at every visit.
⚠️
Breakthrough haemolysis: Rising LDH on C5 inhibitor therapy may indicate breakthrough haemolysis (e.g., missed/delayed dose, complement amplification from infection, or extravascular haemolysis from C3 opsonisation). Investigate and treat triggers; consider dose optimisation or switch between eculizumab and ravulizumab. Rarely, patients develop anti-drug antibodies.

📚 References

  1. 1. Hill A, DeZern AE, Kinoshita T, Brodsky RA. Paroxysmal nocturnal haemoglobinuria. Nature Reviews Disease Primers. 2017;3:17028.
  2. 2. Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106(12):3699–3709.
  3. 3. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124(18):2804–2811.
  4. 4. Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. New England Journal of Medicine. 2006;355(12):1233–1243.
  5. 5. Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019;133(6):530–539.
  6. 6. Kulasekararaj AG, Hill A, Rottinghaus ST, et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor–experienced adult patients with PNH: the 302 study. Blood. 2019;133(6):540–549.
  7. 7. Socié G, Caby-Tosi MP, Marantz JL, et al. Eculizumab in paroxysmal nocturnal haemoglobinuria and pregnancy. European Journal of Haematology. 2019;102(2):150–158.
  8. 8. De Latour RP, Mary JY, Salanoubat C, et al. Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories. Blood. 2008;112(8):3099–3106.
  9. 9. Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook. Australian Government Department of Health; 2024. Meningococcal disease chapter.
  10. 10. Australian Institute of Health and Welfare (AIHW). Aboriginal and Torres Strait Islander health performance framework. Canberra: AIHW; 2023.
  11. 11. Richards SJ, Hill A, Hillmen P. Recent advances in the diagnosis, monitoring, and management of patients with paroxysmal nocturnal hemoglobinuria. Cytometry Part B: Clinical Cytometry. 2007;72B(5):291–298.
  12. 12. Röth A, Rottinghaus ST, Hill A, et al. Ravulizumab (ALXN1210) in patients with paroxysmal nocturnal hemoglobinuria: results of two phase 3 studies (301/302). Blood. 2019;134(Supplement_1):2043.