Iliofemoral Deep Vein Thrombosis Despite Repeatedly Negative D‐Dimer Results

ABSTRACT

A 75‐year‐old man presented with a three‐week history of left lower‐limb pain and repeatedly negative D‐dimer results. Doppler ultrasonography ultimately revealed extensive iliofemoral deep vein thrombosis (DVT). This case highlights that a negative D‐dimer result does not exclude subacute DVT and that clinical suspicion should prevail over biomarker findings.

1. Case Presentation

A 75‐year‐old man was admitted with a three‐week history of left lower limb pain, without any identifiable precipitating factor. His medical history included hypertension, a previous ischemic stroke without residual deficits, and obstructive sleep apnea. On admission, he was hemodynamically stable and afebrile. He denied chest pain and had no respiratory symptoms. Physical examination revealed painful edema involving the left thigh and calf, with a positive Homans' sign. No cutaneous lesions or rash were observed. According to the Wells clinical prediction rule, DVT was considered likely (score = 2). D‐dimer levels were measured on three separate occasions and remained below the laboratory threshold (380 ng/mL FEU; laboratory cut‐off < 500 ng/mL FEU). Given the patient's age of 75 years, the age‐adjusted D‐dimer threshold was 750 ng/mL FEU (age × 10). The measured value remained below both the conventional and age‐adjusted thresholds. Despite these negative results, persistent symptoms prompted lower‐limb venous Doppler ultrasonography, which demonstrated an extensive left iliofemoral DVT. Duplex ultrasonography showed a large occlusive thrombus within the common femoral vein, characterized by a color Doppler filling defect and a corresponding abnormal spectral Doppler waveform (Figure 1). Duplex ultrasonography further demonstrated a heterogeneous hypoechoic thrombus on B‐mode imaging within the color Doppler sampling window, along with a flat spectral Doppler waveform indicating an absence of flow (Figure 2). These findings are consistent with a subacute component. Therapeutic anticoagulation with apixaban was initiated.

FIGURE 1.

Duplex ultrasonography demonstrating a large occlusive thrombus in the common femoral vein, with color Doppler showing a persistent filling defect and spectral Doppler demonstrating the corresponding abnormal waveform.

FIGURE 2.

Duplex ultrasonography showing a heterogeneous hypoechoic thrombus on B‐mode imaging within the color Doppler sampling window, associated with a flat spectral Doppler waveform demonstrating the absence of flow, consistent with subacute thrombosis.

Deep vein thrombosis is a common condition associated with a potentially serious risk of pulmonary embolism, particularly when the thrombus involves the proximal iliofemoral veins. Current diagnostic strategies rely on a combination of clinical pretest probability assessment, most commonly using the Wells score, and D‐dimer testing. In patients with a low clinical pretest probability, a negative D‐dimer result is generally sufficient to exclude DVT. In contrast, in patients with a higher pretest probability (Wells score ≥ 2), venous Doppler ultrasonography should be performed immediately [1]. In the present case, despite a moderate clinical probability (Wells score = 2), D‐dimer levels remained repeatedly negative. This could have falsely reassured the clinician, whereas venous Doppler ultrasonography ultimately revealed an extensive proximal iliofemoral DVT. Although uncommon, false‐negative D‐dimer results have been reported and may occur in the setting of delayed presentation, subacute or chronic thrombosis, reduced fibrinolytic activity, or prior anticoagulant therapy [2, 3]. D‐dimer concentrations reflect the degradation of cross‐linked fibrin and therefore depend on ongoing fibrinolytic activity. Because D‐dimers have a relatively short circulating half‐life, their levels progressively decline once active fibrinolysis decreases. In subacute thrombosis, thrombus organization and reduced fibrin turnover may result in low circulating D‐dimer concentrations despite the persistence of a substantial thrombotic burden. Given the three‐week interval between symptom onset and diagnosis and the ultrasonographic features of subacute thrombosis, this mechanism is the most likely explanation for the repeatedly negative D‐dimer results observed in our patient [2, 3]. In retrospect, repeated D‐dimer testing did not provide additional diagnostic value and may have contributed to delaying definitive imaging. When clinical suspicion of DVT persists, venous Doppler ultrasonography should be performed rather than repeating laboratory testing, even in the presence of apparently reassuring D‐dimer results. This case highlights both the potential for false‐negative D‐dimer results in subacute iliofemoral DVT and the importance of timely imaging when clinical findings remain suggestive of venous thromboembolism.

Author Contributions

Rova Malala Fandresena Randrianarisoa: data curation, writing – original draft, writing – review and editing, investigation, conceptualization. Mounia Harici Stamboul: data curation. Yassine Haoues: data curation. Gerda Menzato: data curation. Amirouche Bessaoudi: data curation. Mostefa Koroghli: data curation. Catherine Letrillard: visualization, validation, supervision.

Funding

The authors have nothing to report.

Consent

The patient was informed of the objectives of the publication and how their information would be used for research purposes. Written informed consent was obtained for the publication of this case report.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.