IMHA, NETs, and the Clotting Risk

Immune-Mediated Hemolytic Anemia (IMHA) is one of the deadliest diseases in veterinary medicine, not just because of the anemia, but because of the clots. Pulmonary Thromboembolism (PTE) kills many IMHA dogs even after they survive the initial crisis.

For years, we blamed "hypercoagulability" in general terms. Now, we know that cell-free DNA is a specific culprit.

Neutrophil Extracellular Traps (NETs)

In IMHA, the immune system is in overdrive. Neutrophils become activated and undergo NETosis. They explode, releasing their DNA into the bloodstream in the form of sticky webs (NETs).

* Jeffery et al. (2017) found that dogs with IMHA have significantly elevated cfDNA compared to healthy controls.
* UC Davis Research: Further work has linked these NET markers directly to thrombotic risk.

How DNA Causes Clots

DNA is negatively charged. In the blood, these floating DNA webs act as a scaffold. They bind platelets. They activate the contact pathway of coagulation. Essentially, the NETs are "clot starters."

Clinical Implications

1. Biomarker of Risk: A very high cfDNA/nucleosome level in an IMHA dog might identify the subset of patients at highest risk for PTE, justifying more aggressive anticoagulation (e.g., dual therapy with Clopidogrel and Xarelto).
2. Therapeutic Target: This has opened the door to a new idea: DNase Therapy. In human medicine (and experimental veterinary models), giving enzymes that digest DNA (DNase) can break down the NETs and stop the clotting. While not yet standard of care, it represents the bleeding edge of translational research.

Takeaway: In IMHA, high cfDNA is not just a byproduct of the disease; it is a driver of the disease.