Charles Greenberg: What If D-dimer Isn’t ‘Non-Specific’ At All?
Charles Greenberg, Professor of Medicine at Medical University of South Carolina, shared a post on LinkedIn:
”After studying D-dimer biology for many years, I’ve started to wonder if we’ve been misunderstanding one of the most common tests in medicine.
What if D-dimer isn’t ‘non-specific’ at all?
For decades we’ve used D-dimer mainly for one purpose:
ruling out venous thromboembolism.
If the level is normal and the clinical probability is low, we safely exclude DVT or pulmonary embolism. In that role the test performs remarkably well.
But when D-dimer is elevated, clinicians often dismiss it:
- Infection
- Inflammation
- Cancer
- Trauma
- Pregnancy
- Aging
In other words: ‘non-specific’
But the biology tells a different story.
D-dimer appears only when cross-linked fibrin is broken down.
And that cross-linking step is controlled by Factor XIII, which stabilizes fibrin architecture and determines how resistant a clot is to fibrinolysis.
So the D-dimer signal actually integrates several biological systems:
- Fibrin architecture — Factor XIII crosslinking
- Inflammation — endothelial injury and coagulation activation
- Genetic susceptibility — emerging polygenic thrombotic risk
- Disease biology — cancer, sepsis, COVID, systemic stress
The COVID-19 pandemic highlighted this clearly.
Patients with severe disease often had markedly elevated D-dimer levels, sometimes without clear thrombosis on imaging, yet those levels strongly predicted clinical outcomes.
Seen this way, D-dimer may not simply be a clot marker.
It may be a systems-level biomarker of fibrin turnover reflecting the interaction between coagulation, inflammation, and tissue injury.
As genomics and multi-omics frameworks evolve, laboratory markers we once labeled ‘non-specific’ may actually be reporting complex biological networks that we are only beginning to understand.
D-dimer might just be the first example.
Discussion
Are we underestimating what so-called ‘non-specific’ biomarkers are actually telling us about systemic disease biology?
References
Adam SS et al. Blood. 2009
Righini M et al. JAMA. 2014
Tang N et al. J Thromb Haemost. 2020
Ay C et al. Blood. 2012
Muszbek L et al. Physiol Rev. 2011”
Stay updated with Hemostasis Today.
-
Oct 21, 2026, 03:36Steve Watson: Ligand Epitope Ratios Influence Antagonist Inhibition
-
Oct 21, 2026, 03:18Stephen D. Coombs: Superficial Venous Thrombosis in Athletes and Importance of Early Recognition and Referral
-
Oct 21, 2026, 02:52Aymar Akilimali: Bleeding During Anticoagulation as a Potential Signal of Occult Cancer
-
Oct 21, 2026, 00:58Anees Ur Rahman: Completing a Two-Week Clinical Rotation at Haemophilia Treatment Centre Rawalpindi
-
Oct 21, 2026, 00:56Caitlyn Mooney: Pulmonary Embolism in Athletes, Recognition and Return to Sport
-
Oct 21, 2026, 00:54Hani Karrar: Pleased to Share Our Review on Emicizumab in Hemophilia A Management
-
Oct 21, 2026, 00:53Akshay Sharma: HSCT Leads to Sustained Improvements in Sickle Cell Cardiomyopathy for Up to 3 Years
-
Oct 21, 2026, 00:51Prateek Meena: The F. A. T. R. N. Mnemonic for Recognizing TTP
-
Oct 20, 2026, 23:51Registration Is Open for WFH CCS 2027 – World Federation of Hemophilia