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Tareq Abadl on NETs: A Clinical and Laboratory Overview for Thrombosis Management
Nov 24, 2025, 14:10

Tareq Abadl on NETs: A Clinical and Laboratory Overview for Thrombosis Management

Tareq Abadl, Medical Laboratory Specialist and Director of the Blood Bank at Dr. Abdelkader Al-Mutawakkil Hospital, posted on LinkedIn:

“Neutrophil Extracellular Traps (NETs) and Platelet–Neutrophil Aggregates

  • Short Introduction

NETs are mesh-like webs of chromatin coated with neutrophil proteins (histones, MPO, elastase). They trap pathogens but also create a procoagulant scaffold that binds platelets, activates coagulation, and promotes thrombosis. NET-driven thrombosis is seen in sepsis, severe COVID-19, cancer, autoimmune diseases, and device-related clotting.

  • When to Suspect NET-Driven Thrombosis

Unexplained or recurrent thrombosis with significant inflammation (↑ CRP, ↑ ferritin) or neutrophilia.

Thrombosis with severe infection, malignancy, autoimmune flare, ECMO/LVAD/HD devices, or poor response to standard anticoagulation.

Microvascular thrombosis with organ dysfunction out of proportion to typical causes.

  • Practical Laboratory Assays

MPO–DNA or nucleosome ELISA → detects NET fragments (sensitive, limited specificity).

Citrullinated histone H3 (H3Cit) ELISA/Western → more specific for PAD4-dependent NETosis.

Cell-free DNA (cfDNA) → sensitive but non-specific.

Flow cytometry for platelet–neutrophil aggregates (CD45+/CD15+/CD66b+ with CD41+/CD61+).

Functional assays: thrombin generation ± DNase or NET inhibitors.

Histology/IF (DNA + MPO/H3Cit colocalization) → gold standard for NET-rich thrombus.

  • Specimen and Pre-Analytical Requirements

Tube type: follow assay SOP; avoid heparin in DNA-based assays.

Processing: double-spin plasma; avoid buffy coat contamination.

Storage: aliquot, freeze at −80°C, avoid repeated freeze–thaw.

Documentation: infection status, inflammatory markers, device exposure, anticoagulation therapy, processing times.

  • How to Interpret

↑ MPO–DNA or H3Cit → supports NET involvement; must correlate clinically.

↑ Platelet–neutrophil aggregates → indicates platelet-driven neutrophil activation/NET potential.

Functional confirmation: reduced thrombin generation after DNase supports NET-dependent clotting.

Trend > single value: rising markers before events are more meaningful.

  • Clinical Implications

NETs may be targeted using DNase, anti-inflammatory therapy, or investigational PAD4 inhibitors—coordinate with hematology/critical care.

Device-related NET-rich thrombosis may require optimizing device flow/coating plus tailored anticoagulation.

NET markers are adjunctive, not a replacement for standard diagnostics.

  • Pitfalls and Limitations

NET assays lack standardization; always report method and reference ranges.

Delayed processing or leukocyte lysis can cause false elevations.

cfDNA is non-specific; H3Cit is more specific but assay-dependent.

Many assays are still research-level rather than routine clinical tests.”

Tareq Abadl on NETs: A Clinical and Laboratory Overview for Thrombosis Management

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Autoimmune Diseases cancer Cell-free DNA (cfDNA) Citrullinated histone H3 (H3Cit) Covid-19 device-related clotting Health Hematology Hemostasis Hemostasis Today Medicine Neutrophil Extracellular Traps (NETs) Platelet–Neutrophil Aggregates Tareq Abadl Thrombosis Management
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