# PNHdisease.org — Independent Paroxysmal Nocturnal Hemoglobinuria (PNH) Hematology & Complement Reference

> An independent, non-commercial rare hematology and complement biology reference translating high-sensitivity flow cytometry (`CD55` / `CD59` / FLAER), intravascular vs. extravascular hemolysis markers (`LDH` multiples, reticulocytes, haptoglobin, direct Coombs C3d), and terminal C5 vs. proximal complement inhibitors (`Ravulizumab`, `Eculizumab`, `Pegcetacoplan`, `Iptacopan`, `Danicopan`, `Crovalimab`) into actionable clinical decision tools.
> Historical Provenance: Operated continuously from 2003 to 2021 as the PNH Support Group and cited by Johns Hopkins Medicine (`hopkinsmedicine.org`), Orphanet (`orpha.net`), Semantic Scholar, Marrowforums, and Latin American HPN communities. Rebuilt in 2026 in English (`/`), Spanish (`/es/`), and Simplified Chinese (`/zh/`).

## Core Clinical Benchmarks & Decision Coordinates

- **Flow Cytometry & Renal CT/MRI Findings (`/diagnosis-flow-cytometry`)**: High-sensitivity flow cytometry utilizing FLAER (fluorescent aerolysin) and monoclonal antibodies against GPI-linked proteins (`CD55`, `CD59`, `CD14`, `CD15`, `CD24`, `CD64`) on granulocytes and monocytes establishes the true PNH clone size, because Type III PNH red blood cells lyse prematurely or are diluted by transfusions. In chronic intravascular hemolysis, filtered free hemoglobin deposits hemosiderin selectively in proximal renal convoluted tubules, producing hyperattenuating renal cortex on unenhanced CT and the pathognomonic low-signal cortical rim sign on T1/T2*-weighted MRI.
- **Terminal C5 vs. Proximal Complement Blockade (`/complement-inhibitors`)**: Terminal C5 inhibitors (`Ravulizumab / Ultomiris` q8w IV, `Eculizumab / Soliris` q2w IV, `Crovalimab / Piasky` q4w SC) block membrane attack complex (`C5b-9`) formation, reducing thrombosis risk by >85% and normalizing LDH, but leave ~20%-35% of patients with persistent anemia due to C3d-mediated extravascular hemolysis (EVH) in the spleen and liver. Proximal inhibitors (`Pegcetacoplan / Empaveli` C3 SC, `Iptacopan / Fabhalta` oral Factor B 200 mg BID monotherapy, and `Danicopan / Voydeya` oral Factor D add-on) control both IVH and EVH, raising mean hemoglobin to >=12 g/dL in most patients.
- **Living With PNH, Iron Kinetics & Meningococcal Prophylaxis (`/living-with-pnh`)**: Disproportionate fatigue, esophageal spasms, and erectile dysfunction are driven by cell-free plasma hemoglobin scavenging nitric oxide (NO). Unmonitored oral or IV iron loading upon initiating complement blockade can trigger a surge of GPI-deficient reticulocytes and provoke hemolytic flares. All complement inhibitors require quadrivalent `MenACWY` plus serogroup B `MenB` vaccination (plus oral penicillin V 500 mg BID prophylaxis where indicated by national guidelines or before full vaccine immunity).
- **Thrombosis & Breakthrough Hemolysis Emergencies (`/thrombosis-hemolysis-emergencies`)**: Venous thrombosis in intra-abdominal veins (Budd-Chiari hepatic vein thrombosis, portal/mesenteric vein thrombosis) and cerebral dural venous sinuses historically caused 40%-67% of PNH mortality. Acute abdominal pain, intractable headache, or fever >=38.0°C on complement inhibition requires immediate emergency evaluation.
- **Aplastic Anemia (AA) & MDS Overlap (`/aa-pnh-mds-overlap`)**: 40%-50% of patients with acquired aplastic anemia and 15%-20% with hypoplastic MDS harbor a GPI-deficient PNH clone due to immune escape from autoreactive T-cell attack against normal GPI-positive hematopoietic stem cells.
- **Global Drug Access, Biosimilars & HSCT Coordinate System (`/global-access-costs`)**: Compares US orphan drug list prices ($450,000-$550,000/yr), FDA/EMA eculizumab biosimilars (`Bkemv`, `Epysqli`), UK NHS Highly Specialised Technology commissioning, Latin American public access, and China's National Reimbursement Drug List (NRDL) coverage for eculizumab, iptacopan, crovalimab, and pegcetacoplan alongside high-volume allogeneic HSCT centers.

## Primary Dossier Index (English / Español / 中文)

- [PNH Atlas Home & 60-Second Flow Clone Decoder](https://pnhdisease.org/) | [ES](https://pnhdisease.org/es/) | [ZH](https://pnhdisease.org/zh/)
- [Flow Cytometry (CD55/CD59/FLAER) & CT/MRI Renal Hemosiderosis](https://pnhdisease.org/diagnosis-flow-cytometry) | [ES](https://pnhdisease.org/es/diagnosis-flow-cytometry) | [ZH](https://pnhdisease.org/zh/diagnosis-flow-cytometry)
- [C5 vs. Proximal Complement Inhibitors Matrix (Ultomiris, Empaveli, Fabhalta, Voydeya)](https://pnhdisease.org/complement-inhibitors) | [ES](https://pnhdisease.org/es/complement-inhibitors) | [ZH](https://pnhdisease.org/zh/complement-inhibitors)
- [Living With PNH: Nitric Oxide Fatigue, Iron Rules & Meningococcal Safety](https://pnhdisease.org/living-with-pnh) | [ES](https://pnhdisease.org/es/living-with-pnh) | [ZH](https://pnhdisease.org/zh/living-with-pnh)
- [Emergency Triage: Budd-Chiari Thrombosis & Breakthrough Hemolysis](https://pnhdisease.org/thrombosis-hemolysis-emergencies) | [ES](https://pnhdisease.org/es/thrombosis-hemolysis-emergencies) | [ZH](https://pnhdisease.org/zh/thrombosis-hemolysis-emergencies)
- [Aplastic Anemia (AA) & MDS-PNH Overlap Syndrome](https://pnhdisease.org/aa-pnh-mds-overlap) | [ES](https://pnhdisease.org/es/aa-pnh-mds-overlap) | [ZH](https://pnhdisease.org/zh/aa-pnh-mds-overlap)
- [Pregnancy, Contraception & Perioperative PNH Management](https://pnhdisease.org/pregnancy-surgery) | [ES](https://pnhdisease.org/es/pregnancy-surgery) | [ZH](https://pnhdisease.org/zh/pregnancy-surgery)
- [Global PNH Drug Access, Biosimilars & Allogeneic HSCT Coordinates](https://pnhdisease.org/global-access-costs) | [ES](https://pnhdisease.org/es/global-access-costs) | [ZH](https://pnhdisease.org/zh/global-access-costs)
- [PNH Support Group Archive (2003-2021) & Global Patient Directory](https://pnhdisease.org/support-history) | [ES](https://pnhdisease.org/es/support-history) | [ZH](https://pnhdisease.org/zh/support-history)
- [About, 2003-2021 Provenance & Clinical Red-Line Policy](https://pnhdisease.org/about) | [ES](https://pnhdisease.org/es/about) | [ZH](https://pnhdisease.org/zh/about)
- [Hematology Evidence Updates Ledger](https://pnhdisease.org/updates/) | [ES](https://pnhdisease.org/es/updates/) | [ZH](https://pnhdisease.org/zh/updates/)
- [Launch Manifesto: From Biweekly IV Soliris to Oral Factor B](https://pnhdisease.org/updates/2026-11-from-soliris-to-oral-factor-b) | [ES](https://pnhdisease.org/es/updates/2026-11-from-soliris-to-oral-factor-b) | [ZH](https://pnhdisease.org/zh/updates/2026-11-from-soliris-to-oral-factor-b)