Isolated Calf Deep Venous Thrombosis: Prevalence, Clinical Characteristics and Implications for Ultrasound Evaluation

Objectives It remains controversial whether to include calf veins in the initial ultrasound evaluation of suspected deep venous thrombosis (DVT). We sought to investigate the prevalence and clinical characteristics of isolated calf DVT. Materials and Methods We retrospectively analyzed a cohort of 596 patients (median age 69 years, 52.3% women) evaluated with complete duplex ultrasound of the leg veins for suspected acute DVT within one year. Radiology reports were analyzed for the presence and localization of DVT. Electronic chart review was performed to collect clinical information. Results DVT was found in 157 patients (26.3%), of which 74 patients (47.1%) had isolated calf DVT. Isolated calf DVTs were most commonly located in the posterior tibial veins (22 patients, 29.7%), bular veins (41 patients, 55.4%) and muscle veins (19 patients, 25.7%). There were no differences in age or gender between patients with isolated calf DVT and patients with more proximal DVT. Isolated calf DVT was more commonly associated with leg pain (52.7% vs. 33.7%, p = 0.0234) and less commonly associated with subjective leg swelling (35.1% vs. 55.4%, p = 0.0158) and objectively measured difference in leg circumference (23% vs. 39.8%, p = 0.0268). D-Dimers were signicantly lower in patients with isolated lower leg DVT (median 2.3 vs. 6.8 mg/L, p < 0.0001) compared to patients with more proximal DVT. Conclusions Isolated calf DVT is almost as common as more proximal DVT. Our data supports performing complete duplex ultrasound including the calf veins in suspected DVT.


Introduction
Venous ultrasound is the standard imaging test for patients with suspected deep venous thrombosis (DVT). There is, however, great variability in the ultrasound technique performed for suspected DVT between institutions [1,2] and guidelines. [3][4][5][6][7] In particular, there is disagreement on whether to include the calf veins in the initial ultrasound evaluation of suspected DVT. Some institutions perform ultrasound examinations with a limited range from the groin to the knee -sometimes in the form of two-point or three-point compression ultrasound as the initial test. [8][9][10][11][12][13][14] If negative, this is typically followed by a second ultrasound examination within one week to safely exclude DVT. [15] The clinical importance of isolated calf-vein DVT is incompletely understood with regards to the risks for propagation into the popliteal and/or femoral vein, pulmonary embolism and the development of a postthrombotic syndrome. It is currently thought that approximately 15-20% of isolated asymptomatic distal DVTs will extend to the proximal veins if untreated. [16,17] Nevertheless, the bene t of treating patients with isolated calf DVT remains uncertain and controversial. [17][18][19][20][21][22][23] In light of this ongoing controversy, we sought to investigate the prevalence and clinical characteristics of isolated calf DVT on complete duplex ultrasound examination as the initial test in patients with

Material And Methods
Ethical approval, study design and patient selection The study was approved by our institutional review board with waiver of informed consent. The investigation was designed as a retrospective, single-center cohort study. We included all patients who were examined with venous ultrasound of the legs at our institution between January 1 and December 31, 2014 for suspected acute DVT. The year 2014 was chosen because during this year venous ultrasound evaluations were almost exclusively performed by two senior radiologists (initials blinded) with extensive experience in vascular ultrasound. We identi ed eligible patients through a retrospective query of our radiology information system. We excluded patients with other indications for venous ultrasound and follow-up examinations of patients with known DVT (Fig. 1). We also excluded patients referred for duplex ultrasound because of a recent diagnosis of acute pulmonary embolism under the assumption that isolated calf DVT in patients with pulmonary embolism may not be truly isolated calf DVT but rather the remnant of a more extensive proximal DVT, much of which has embolized.

Analysis of radiology reports
Radiology reports of all evaluations were retrospectively reviewed by a medical student (initials blinded) for the presence and location of DVT. If the localization could not be precisely determined from the radiology report alone, the images of the ultrasound examination stored in our PACS were also viewed by a board-certi ed radiologist. Patients were classi ed as having proximal DVT if any portion of the DVT was in the popliteal vein, femoral and/or iliac veins. In contrast, patients were classi ed as having isolated calf DVT, if DVT was exclusively in one or more veins below the knee (posterior tibial veins,

Discussion
Several previous studies have demonstrated that isolated calf vein DVT, that is, infra-popliteal DVT without extension to proximal veins (popliteal vein or above), is frequent and represents 30-70% of all lower-limb DVTs diagnosed on ultrasound series. [14,[24][25][26][27][28] Our results are in line with these earlier reports since we found that in our series 47% of DVTs diagnosed on complete duplex ultrasound as the initial tests were isolated calf vein DVTs. This suggests that an initial ultrasound evaluation performed with a limited range (from the groin to the popliteal vein) will miss almost half of DVT cases.
Our study goes beyond previously published data, as we analyzed the clinical characteristics of patients with isolated calf DVT compared to more proximal DVT. Interestingly, we observed that isolated calf DVT was more commonly associated with leg pain than more proximal DVT. It is generally thought that acute DVT triggers an in ammatory response [29] and that pain from DVT predominantly results from in ammation of the venous wall around the clot. A possible interpretation of our results would be that the local in ammatory response to DVT may be more pronounced in the smaller calf veins that in larger proximal veins.
Less surprisingly, we found that isolated calf DVT was less commonly associated with subjective leg swelling and objectively measured circumference difference. The most straightforward explanation for this nding is that in most patients, there is a single iliac, femoral and popliteal vein for each leg. DVT in these veins will thus occlude the entire deep venous system at this level. In contrast, there are multiple deep veins in the calf (typically paired peroneal veins, anterior and posterior tibial veins as well as muscle veins). Most cases of isolated calf DVT will occlude one or few of these veins and leave other deep calf veins patent.
Regarding laboratory values, we observed that levels of D-dimers were signi cantly lower in patients with isolated lower leg DVT compared to patients with more proximal DVT. This likely re ects the greater thrombus burden in patients with DVT in larger, more proximal veins compared to isolated calf DVT. In our analysis, 4.1% of patients with isolated calf DVT had "negative" D-dimers (reference value of our hospital laboratory < 0,5 mg/L) compared to 1 of 83 patients (1.2%) with more proximal DVT, suggesting that D-dimer testing is somewhat less sensitive for isolated calf DVT.
Our results should be interpreted in light of the controversies surrounding isolated calf DVT. It is known that venous ultrasonography is less accurate for isolated distal deep venous thrombosis than for proximal deep venous thrombosis. [30] Additionally, the clinical utility of including the calf veins in venous ultrasound is under debate because there is limited data about the natural course of isolated calf DVT and the bene t of anticoagulation. [21,22] Unlike for proximal DVT and PE, which have been extensively studied and for which management is well standardized, much less is known about the optimal management of isolated distal DVT. The rate of extension to the proximal veins and the rate of PE associated with distal DVT are highly variable from one study to another and signi cant variation exists in diagnostic and therapeutic practices. [16,19,22,31] In some centers, both the proximal veins and the calf veins are imaged in all patients with suspected DVT, and patients diagnosed with isolated calf DVT are treated with anticoagulant therapy. [32] There appears to be a positive effect of anticoagulation treatment on the proximal progression of the thrombus, PE and development of a postthrombotic syndrome [16][17][18][19][20][33][34][35].
According to the consensus guideline of the German, Swiss and Austrian Societies for Vascular Medicine [3] an additional advantage of whole-leg ultrasound is to identify differential diagnoses for example Baker's cyst, muscle ber tear, aneurysm, hematoma, tumor as the reason for the patient's symptoms if negative for acute DVT.
Several limitations of our investigation should be mentioned. This single-center study was performed at a university hospital. This may be a more selected cohort of patients than patients with suspected DVT seen by primary care physicians. No external reference standard is available to con rm ndings at ultrasound. Due to the retrospective nature of our investigation, Wells scores and D-Dimer levels were not available for all patients. Also, the precise time from symptom onset was not available in all cases. This may affect the ndings on D-Dimer levels, which typically change over the course of acute DVT.
In summary, we found that isolated calf DVT is almost as common as more proximal DVT. Venous ultrasound with a limited range from the groin to the knee will therefore miss almost half of DVT cases.
We conclude that it is prudent to perform complete duplex ultrasound including the calf veins in suspected DVT. Figure 1 Flow chart of patient inclusion