D-Dimer Levels: A Tool for Diagnosing Vascular Anomalies

Graeme M. Lipper, MD


January 15, 2010

Elevated D-Dimer Level in the Differential Diagnosis of Venous Malformations

Dompmartin A, Ballieux F, Thibon P, et al
Arch Dermatol. 2009;145:1239-1244


Venous malformations (VMs) are congenital vascular malformations composed of ectatic venous channels deficient in normal smooth muscle cells.[1] Clinical features include a characteristic dusky red to blue color, firmness and compressibility, and associated pain. Lesions can be unifocal or multifocal, localized or widespread, and accompanied by capillary, arterial, or lymphatic malformations. Distinguishing between VMs and other vascular malformations can be challenging, especially early in life when clinical features such as color are less distinctive. Tests to confirm the diagnosis of VMs include Doppler ultrasonography (typically showing slow flow for VMs), magnetic resonance imaging, arteriography, and, if necessary, biopsy.[2,3]

Study Summary

Recently, Dompmartin and associates[4] reported a strong association between venous malformations and localized intravascular coagulopathy (LIC), especially in cases of large VMs, intramuscular VMs, or VMs containing phleboliths. Independently, Mazoyer and colleagues[5] described a cohort of patients with VM (n = 118) in whom 58% had D-dimer levels greater than 0.5 mg/mL.

Building on these data, Dompmartin and colleagues now report results from a prospective study of 280 patients (184 women; mean age 23 years) with cutaneous, subcutaneous, and/or mucosal vascular abnormalities. They sought to determine whether elevated D-dimer levels can be used as specific or sensitive predictors of VMs.

The cohort featured a wide range of vascular malformations, including VMs (n = 154), glomuvenous malformations (n = 16), blue rubber bleb nevus syndrome (n = 2), capillary malformations (n = 22), lymphatic anomalies (n = 20), arteriovenous malformations (n = 26), and syndromic malformations (11 with Klippel-Trenaunay syndrome; 4 with Maffucci syndrome).

During a 26-month study period, the investigators noted the following:

  1. Using a combination of clinical features, Doppler ultrasonography, imaging studies (eg, MRI), and D-dimer levels, a VM was diagnosed in 195 of 280 patients.

  2. Eighty-three of the 195 patients with VMs had elevated D-dimer levels (sensitivity = 42.6%).

  3. Among the 85 patients without VMs, only 3 patients showed elevated D-dimer levels (specificity = 96.5%); all 3 “false positives” could be explained by other clinical features (eg, the presence of venous insufficiency, inflammatory bowel disease, etc.)

  4. Elevated D-dimer levels predicted VMs that could otherwise only be detected with imaging studies such as MRI.

  5. D-dimer levels could reliably distinguish between slow-flow vascular malformations (VMs, Klippel-Trenaunay syndrome) and fast-flow vascular malformations (arteriovenous malformations, Parkes Weber syndrome).

  6. Lymphatic malformations and capillary malformations were not associated with elevated D-dimer levels (unless these lesions also had an underlying VM component).

  7. Small or superficial VMs were less likely to be associated with elevated D-dimer levels; in contrast, large VMs, multifocal VMs (eg, blue rubber bleb nevus), and intramuscular VMs were almost always associated with elevated D-dimer levels.

  8. Patients with elevated D-dimer levels often experienced lesion-associated pain, which responded well to low-molecular-weight heparin therapy.

  9. Glomuvenous malformations were not associated with elevated D-dimer levels, assisting in differentiation of this type of vascular malformation from VMs.


Much practical information can be gleaned from this important study. As reviewed by Frieden and colleagues,[1] the presence of LIC provides a powerful diagnostic clue, helping the clinician to differentiate VMs from other vascular malformations. D-dimer levels are cheap and easy to obtain. In contrast to MRI and arteriography, D-dimer assessment does not require general anesthesia. In addition, elevated D-dimer levels correlate with patient morbidity and intralesional pain, suggesting that this subset of patients may benefit from anticoagulant therapies such as low-molecular-weight heparin or low-dose aspirin.[1,4,5]

As an important side note, LIC should be distinguished from the consumptive coagulopathy seen in Kasabach-Merritt phenomenon -- a rare, life-threatening condition caused by platelet entrapment within vascular tumors such as kaposiform hemangioendotheliomas and tufted angiomas. In contrast, LIC is far more common, does not deplete platelet or fibrinogen levels, and can be found in a wide range of disorders featuring sluggish venous flow such as superficial and deep venous thrombosis.[6]



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