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Heghine Khachatryan: Diagnosing PNH in Resource-Limited Settings
Heghine Khachatryan/LinkedIn
Apr 12, 2026, 21:24

Heghine Khachatryan: Diagnosing PNH in Resource-Limited Settings

Heghine Khachatryan, Editor-in-Chief of Hemostasis Today, Head of Hemophilia and Thrombosis Center at Yeolyan Hematology and Oncology Center, shared a post on LinkedIn:

“Diagnosing PNH in Resource-Limited Settings

A Suspicion-Driven, Algorithmic Approach for Modern Clinical Practice

Paroxysmal nocturnal hemoglobinuria (PNH) is frequently underdiagnosed – not because it is rare, but because it is insufficiently suspected. In middle – and low-income settings, the diagnostic gap is driven by limited access to high-sensitivity flow cytometry and the protean nature of clinical presentation.

This necessitates a shift from technology-driven diagnosis to suspicion-driven medicine.

Step 1 — Recognize the Clinical Signal

PNH should be actively considered in patients with:

  • Coombs-negative hemolytic anemia
  • Unexplained cytopenias or marrow failure syndromes
  • Aplastic anemia / hypoplastic bone marrow
  • Thrombosis at unusual sites (hepatic, portal, cerebral)
  • Hemoglobinuria or iron deficiency of unclear origin

Clinical pattern recognition remains the most powerful diagnostic tool.

Step 2 — Build the Hemolysis Profile (Accessible Layer)

Even in constrained settings, a structured laboratory panel can establish high suspicion:

  • CBC plus reticulocyte count
  • High LDH
  • High indirect bilirubin
  •  Low Haptoglobin
  • Direct antiglobulin test (negative)
  • Urine hemoglobin / hemosiderin

These findings do not confirm PNH, but define the population requiring definitive testing.

Step 3 — Confirm with High-Sensitivity Flow Cytometry

According to International Society on Thrombosis and Haemostasis and European Hematology Association:

  • Detection of GPI-deficient cells is the diagnostic cornerstone
  • FLAER-based assays are preferred
  • Neutrophil and monocyte clones provide the most reliable estimate of disease burden

RBC-based assays alone may underestimate clone size, particularly in hemolysis or post-transfusion states.

Step 4 — Adapt Strategy to Resource Availability

In low-resource environments, the optimal pathway is:

Suspect early – screen intelligently – refer strategically

  • Prioritize sample referral to regional centers
  • Avoid reliance on low-sensitivity or outdated assays
  • Interpret negative results cautiously if methodology is limited

Why This Matters

Delayed diagnosis directly translates into:

  • Missed prevention of life-threatening thrombosis
  • Prolonged morbidity from untreated hemolysis
  • Failure to identify bone marrow failure overlap syndromes

Key Insight

PNH is not difficult to diagnose.

It is difficult to think of.

In resource – limited settings, diagnostic excellence begins with clinical suspicion, not technology.”

Heghine Khachatryan

More posts featuring Heghine Khachatryan on Hemostasis Today.

Diagnosing PNH Health Heghine Khachatryan Hematology Hemostasis Hemostasis News Hemostasis Today Medicine middle - and low-income settings Resource-Limited Settings
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