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Abstract

Background:

Distal deep venous thrombosis (DVT) accounts for approximately half of all the cases of lower limb thrombosis. The impact and management of this condition is still controversial. This study aims to evaluate the incidence of pulmonary embolism (PE) in patients with distal DVT in comparison to proximal DVT and evaluate the correlation between DVT and PE extension.

Methods:

100 patients with acute lower limb DVT diagnosed with whole leg Doppler ultrasound from January 2006 to December 2014 were retrospectively analyzed. Active investigation for PE was carried out in all patients using multislice computed tomography angiography. Classification of DVT and PE was based on the proximal extension of the thrombus.

Results:

The overall incidence of PE in our sample patients was 72%. In the subgroup analysis, incidence of PE was equal in both the proximal and distal DVT groups (77%, p > 0.99). PE was detected in 43% of the patients with isolated calf vein thrombosis (ICVT). No statistical difference was observed between the distribution of lobar, segmental and subsegmental PE in the 3 DVT subgroups (p = 0.665); however, truncular PE was only observed in the proximal DVT group.

Conclusion:

Distal DVT is associated with a high incidence of PE compared to proximal DVT. Distal DVT and ICVT can provoke PE with involvement of proximal vessels in the pulmonary arterial tree, even in asymptomatic patients. Our study arises discussion in the controversial debate regarding the need for routine anticoagulation in distal DVT.

Keywords

pulmonary embolism deep venous thrombosis anticoagulants

Introduction

Venous thromboembolism (VTE) is a prevalent and potentially fatal condition that affects over 900 000 in the United States and over 1 million people in Europe annually.^1,2 Pulmonary embolism (PE) is the most feared complication of deep venous thrombosis (DVT) with a case fatality rate of approximately 15%, exceeding the rate reported for myocardial infarction.³ Distal DVT accounts for approximately half of all the cases of lower limb DVT diagnosed on whole leg compression ultrasonography.⁴

Studies have demonstrated that the incidence of silent PE in patients with DVT varies between 32% and 50%.^5
–7 These outcomes are apparently underestimated, since they are based on imaging studies with lower accuracy, such as pulmonary scintigraphy or computed tomography angiography (CTA) scans with thicker slices. Furthermore, the literature discloses a common knowledge that the prevalence of PE in patients with proximal DVT is significantly higher when compared to distal DVT, inferring a lower severity of the latter condition.⁸

The management of distal DVT is still controversial. Recent studies and guidelines have suggested that this condition can be treated conservatively without routine need for anticoagulation, however, with weak levels of recommendation. The American College of Chest Physicians (CHEST) guidelines for the first time in 2012 attempted to differentiate treatment strategies for patients with distal and proximal DVT, nonetheless, the decision to administer anticoagulation is based upon the presence of clinical symptoms and physician’s experience without any clear consensus.^9,10 There are currently ongoing trials comparing treatment versus placebo for distal DVT.¹¹

The aim of this study was to evaluate the incidence of PE in patients with distal DVT in comparison to proximal DVT, based on the use of modern gold-standard CTA scans, and to evaluate the correlation between DVT and PE extension. As a secondary outcome, we aim to analyze how the laboratorial biomarkers C-reactive protein (CRP), d-dimer, and red cell distribution width (RDW) may predict the severity of thromboembolic events.

Methods

This retrospective transverse study was carried out in accordance with the Ethics Committee of our institution. Due to the observational and retrospective nature of the study, informed consent terms were dismissed. Medical records of 120 consecutive patients followed by our vascular surgery team, with the diagnosis of acute DVT of the lower limb between January 2006 and December 2014 were retrospectively analyzed.

We included patients who reported to the emergency department of our institution with an acute onset of inferior limb DVT and were submitted to chest CTA for active investigation of PE upon admission. All included patients reported leg pain and/or edema and had no initial complain of respiratory symptoms. Twenty patients who were not submitted to CTA due to renal impairment (creatinine levels over 1.5 mg/dL), pregnancy, and/or hypersensitivity to iodinated contrast media were excluded from our analysis. All the patients were immediately treated with full-dose enoxaparin (1 mg/kg twice daily) for at least 48 hours prior to the introduction of an oral anticoagulant therapy.

Relevant epidemiologic characteristics including age, sex, body mass index (BMI), and comorbidities were registered. We considered as risk factors patients older than 75 years, BMI ≥ 25, positive thrombophilia testing, recent trauma or surgical intervention (within the last 4 weeks), use of oral contraceptives, recent travel (over 8 hours in the last 4 weeks), and active malignancy.

Certified radiologists in our institution performed the color Doppler ultrasound examinations. The CTA scans were performed in 16- or 64-row multislice scanners (Toshiba Medical Systems, Tokyo, Japan) with reconstructed axial images of 1 mm thickness. Intravenous iodinated contrast (iobitridol 350 mg/mL, Henetix^®, France) was used in all cases with doses ranging from 90 to 120 mL, administered by a power injector with an approximate rate of 4.0 mL/s.

Information regarding the site of affected vein, laterality of thrombus, and extent of DVT and PE was recorded. We reviewed blood samples collected from the study patients upon admission and analyzed red and white cell tests (including RDW), basic biochemistry, CRP using chemiluminescence assay (reference range 0-3.0 mg/L), and d-dimer using automated immunoturbidimetry assay (STA^® Liatest^® D-Di, Stago, USA). Prothrombin and factor V Leiden mutations were also reviewed and recorded.

Deep Venous Thrombosis and PE Classification

Patients with DVT were classified into 3 subgroups: proximal, distal, or isolated calf thrombosis (ICVT) according to the proximal location of the thrombus. Clots affecting popliteal, femoral, or iliac veins were classified as proximal, clots affecting axial leg veins (tibial or fibular veins) were classified as distal, whereas isolated clots in soleus or gastrocnemius veins were defined as ICVT. To evaluate clot burden, we counted the number of individual venous segments involved (ie, the sum of the number of veins with clots as reported in the Doppler ultrasound).

Pulmonary embolism was classified into 4 categories based on the anatomical site of the pulmonary arterial tree affected by the clot.¹² Clots involving the main pulmonary artery or its bifurcation were classified as truncular, and clots affecting the second, third, and fourth bifurcations of the pulmonary artery were classified as lobar, segmental, or subsegmental, respectively.

Control Group

A control group including patients admitted in the emergency department of the same institution, in the same time period, followed by other vascular surgery teams was studied. We used the hospital’s official database and surveyed the cases of DVT using the International Classification of Diseases, Tenth Revision (ICD-10) coding system. The codes analyzed were I82.8 (embolism and thrombosis of other specified veins) and I82.9 (embolism and thrombosis of unspecified vein). Cases of thrombosis in sites other than inferior limbs, cases of isolated superficial thrombophlebitis, and cases of PE with no detected DVT were excluded from the control group analysis. Comparisons between baseline epidemiological characteristics of the patients included in our internal validation sample and our study group were performed.

Statistical Analysis

Qualitative variables were described using absolute frequencies and percentages. Quantitative variables were described using medians and interquartile intervals, since normal distribution could not be verified using the Shapiro-Wilk test.

Variables of interest were tested for the presence of PE using χ² or Fisher test in the case of categorical variables. In the case of continuous variables, Mann-Whitney U test or Kruskal-Wallis test was used.

The association between RDW, CRP, and d-dimer with the number of affected venous segments was evaluated using Kruskal-Wallis test. In case of P value less than .05, we performed multiple comparisons adjusted by Bonferroni method.

The association between RDW, CRP, and d-dimer with the occurrence of PE was analyzed using logistic regression models and receiver–operating characteristic curves. The results were described as odds ratio, 95% confidence interval, P values, and area under the curve. In case of association, we presented a cutoff based on the sum of sensitivity and specificity. Analysis was performed using the R statistical package.¹³ A 5% level of significance was used.

Results

General Characteristics of the Study Population and Comparison With the Control Group

The clinical baseline characteristics of the study patients in the 3 DVT subgroups are outlined in Table 1. Gender, age, BMI, and laterality of DVT were similar in the 3 groups. We observed bilateral DVT involvement in 3 cases of the proximal group.

Table 1.

Baseline Characteristics of Patients With DVT.

	Proximal, n = 60	Distal, n = 26	ICVT, n = 14	P
Gender				.611
Female	30 (50.0)	13 (50.0)	5 (35.7)
Male	30 (50.0)	13 (50.0)	9 (64.3)
Age, median (range)	48.0 (37.8-70.0)	44.5 (38.0-52.5)	46.0 (39.8-53.5)	.430
BMI, median (range)	27.5 (25.7-29.9)	27.7 (22.2-29.7)	28.7 (25.3-31.5)	.643
Laterality of DVT				.616
Right	26 (43.3)	10 (38.5)	7 (50.0)
Left	31 (51.7)	16 (61.5)	7 (50.0)
Bilateral	3 (5.0)	0 (0.0)	0 (0.0)
Vein involvement
Cava	2 (3.3)	0 (0.0)	0 (0.0)
Iliac	18 (30.0)	0 (0.0)	0 (0.0)
Femoral	35 (58.3)	0 (0.0)	0 (0.0)
Popliteal	47 (78.3)	0 (0.0)	0 (0.0)
Axial vein	33 (55.0)	25 (96.2)	0 (0.0)
Calf vein	13 (21.7)	6 (23.1)	14 (100.0)

Abbreviations: BMI, body mass index; DVT, deep venous thrombosis; ICVT, isolated calf thrombosis.

Table 2 outlines the comparison between demographic and clinical characteristics of the study and control groups. Age was significantly higher in the control group. Among the studied risk factors, recent surgery was significantly more prevalent in the protocol group (P = .011).

Table 2.

Comparative Analysis Between Baseline Characteristics of Protocol and Control Group.

	Protocol Group, n = 100	Control Group, n = 80	P
Age			.032
Median	46.5	56.8
1Q-3Q	38.0-64.0	41.6-70.5
Gender			.907
Female	48 (48.0%)	40 (50.0%)
Male	52 (52.0%)	40 (50.0%)
Laterality of DVT			.028
Right	43 (43.0%)	20 (25.0%)
Left	54 (54.0%)	54 (67.5%)
Bilateral	3 (3.0%)	6 (7.5%)
Proximal site of DVT			.022
Isolated calf vein	16 (16.0%)	14 (17.5%)
Axial vein	28 (28.0%)	9 (11.2%)
Popliteal	19 (19.0%)	15 (18.8%)
Femoral	21 (21.0%)	29 (36.2%)
Iliac	16 (16.0%)	13 (16.2%)
Risk factors
Age >75 years	12 (12.0%)	18 (22.5%)	.094
Recent surgery	26 (26.0%)	8 (10.0%)	.011
Cancer	13 (13.0%)	11 (13.8%)	>.99
Recent trauma	13 (13.0%)	8 (10.0%)	.697

Abbreviation: DVT, deep venous thrombosis.

Risk Factor Analysis According to the Severity of the Thromboembolic Event

The association between risk factors and the severity of the thromboembolic event, defined by occurrence of PE and extension of DVT, is presented in Table 3. Recent travel and recent surgical intervention were the only variables significantly associated with the occurrence of distal DVT. None of the other studied risk factors were predictive of the severity of the thromboembolic event.

Table 3.

Risk Factor Analysis According to the Presence of PE and Classification of DVT (Proximal or Distal).

	PE			DVT
	No = 28	Yes = 72	P	Distal = 40	Proximal = 60	P
Age ≥ 75 years	4 (14.3)	8 (11.1)	.735	3 (7.5)	9 (15.0)	.414
BMI ≥ 25	20 (71.4)	54 (76.1)	.618	26 (66.7)	48 (80.0)	.209
Active cancer	4 (14.3)	9 (12.5)	.753	3 (7.5)	10 (16.7)	.302
Recent surgery	6 (21.4)	20 (27.8)	.617	13 (32.5)	13 (21.7)	.328
Recent trauma	5 (17.9)	8 (11.1)	.508	9 (22.5)	4 (6.7)	.045
Use of OC	3 (17.6)	5 (16.7)	>.99	5 (27.8)	3 (10.3)	.252
Recent travel >8 hours	2 (7.1)	5 (6.9)	>.99	6 (15.0)	1 (1.7)	.031
G20210A mutation	0 (0.0)	6 (10.3)	.329	0 (0.0)	6 (12.8)	.102
FV Leiden	5 (25.0)	5 (8.6)	.113	4 (12.9)	6 (12.8)	>.99
Previous DVT	3 (10.7)	7 (9.7)	>.99	3 (7.5)	7 (11.7)	.736

Abbreviations: BMI, body mass index; DVT, deep venous thrombosis; FV, factor V; G20210A, prothrombin gene; ICVT, isolated calf thrombosis; OC, oral contraceptives.

Incidence and Severity of Asymptomatic PE in the DVT Groups

The overall incidence of PE in our sample patients was 72%. In the subgroup analysis, incidence of PE was equal in both the proximal and the distal DVT groups (77%, P > .99), as shown in Figure 1. Pulmonary embolism was detected in 43% of the patients with ICVT. No statistical difference was observed between the distribution of lobar, segmental, and subsegmental PE in the 3 DVT subgroups (P = .665), however, truncular PE was only observed in the proximal DVT group (Figure 2).

Figure 1.

Incidence of pulmonary embolism (PE) in the deep venous thrombosis (DVT) groups.

Figure 2.

Proximal site of pulmonary embolism (PE) thrombus location in the deep venous thrombosis (DVT) groups.

Association Between Laboratorial Biomarkers (CRP, RDW, and d-Dimer) and Clot Burden

Only d-dimer and CRP were predictive of clot burden (P = .001 and P < .001, respectively) as demonstrated in Figure 3. The values of these 2 markers rose according to the number of affected venous segments. d-Dimer values over 4000 ng/mL and CRP over 5.0 mg/L were associated with DVT involving 3 or more venous segments. The RDW values were similar, despite the increase in venous segments affected.

Figure 3.

Association between number of affected venous segments laboratorial biomarkers.

Predictive Value of d-Dimer for PE

d-Dimer values upon admission were significantly associated with the occurrence of PE (P = .004). The d-dimer values were analyzed to try and identify a cutoff level predictive of PE. Values greater that 1380 ng/mL were discriminant of PE (area under the curve: 0.82) with a sensitivity of 80% and a specificity of 75% (Figure 4). The positive and negative predictive values for this point were 47.8% and 8.3%, respectively. Red cell distribution width and CRP were not significantly associated with PE.

Figure 4.

Receiver–operating characteristic (ROC) curve for d-dimer.

Discussion

The observed overall incidence of 72% of asymptomatic PE in patients with acute DVT is higher than any data shown in the current literature. The equal incidence of PE in patients with proximal and distal DVT with a similar distribution of lobar and segmental clots is yet unpublished information. Our incidence of PE in patients with ICVT is similar to what is expected for proximal DVT according to recent papers.

The general concept that distal DVT is less likely to lead to PE has been well accepted in clinical practice and supported by recent publications.¹⁴ Recent thrombosis guidelines do not recommend routine anticoagulation for distal DVT.⁹ Our findings demonstrating an equal risk of PE among patients with proximal and distal DVT (77%, P > .99) may influence change in the clinical management of these patients. These results strongly encourage a need for standardizing mandatory use of anticoagulation in all cases of distal DVT.

The high incidence of PE in patients with ICVT (43%) shows that findings from a systematic review published in September 2014 describing a 13.1% prevalence of asymptomatic PE in patients with this condition are underestimated.¹⁵ Despite the asymptomatic nature of incidental PE, treatment is mandatory due to the increased risk of symptomatic and fatal recurrence.¹⁶ Watchful waiting can no longer be an option for patients with distal DVT, considering an almost 80% risk of associated PE. Furthermore, these undiagnosed and untreated patients are in risk of developing chronic thromboembolic pulmonary hypertension (CTPH), a condition that is frequently recognized in a late phase when prognosis is poor.¹⁷

Although truncular PE was only observed in the proximal DVT group, lobar and segmental PE similarly affected the 3 DVT subgroups. This alerts to the higher potential severity of PE in patients with proximal DVT but does not minimize the concern with PE in distal or ICVT. Despite the lower clot burden in distal DVT, proximal sites of the pulmonary arterial tree (ie, lobar arteries) are affected in around 20% of the cases.

The lower median age observed in our sample patients together with the similarity of relevant baseline characteristics between our sample and control groups was important to further validate our outcomes. These findings ensure that the high incidence of PE is not likely to be attributed to a selection bias of critically ill patients. The higher incidence of recent surgery observed in our protocol group emphasizes the need for adequate prophylactic measures in surgical patients. Special attention should be given to orthopedic interventions that were highly prevalent in our sample.

None of the studied risk factors were predictive of PE occurrence. Recent surgery consisted of 77% of orthopedic interventions and was significantly associated with distal DVT. This association corroborates with the results of a recent observational study including 50 000 patients, which demonstrated a higher prevalence of distal DVT (60% distal vs 33% proximal) in orthopedic surgical patients.¹⁸ Recent travel was also significantly associated with distal DVT as also demonstrated in a 2006 literature review of the quantitative risk of VTE following air travel.¹⁹

Despite the enthusiasm of previous studies in demonstrating a significant association between RDW and PE and severity of DVT,^20,21 this outcome was not reproduced in our research. Red cell distribution width did not show association with incidence of PE, location of proximal DVT thrombus, or DVT clot load. The observation that RDW does not show predictive value for the diagnosis of DVT has also been demonstrated in a study that analyzed patients undergoing total joint arthroplasty.²⁰

Our results showed that both CRP and d-dimer levels increased according to the number of affected venous segments and were significantly higher in patients with involvement of more than 4 segments. The suggestion that these biomarkers can be useful in determining clot load and extent of DVT is biologically plausible and in accordance with previous studies.^22,23 The presence of a systemic inflammatory response, regardless of its nature, seems to play an important role in the prothrombotic state in patients with VTE.²⁴

d-Dimer was the only laboratory marker that was significantly associated with PE, and the value of that best distinguished PE occurrence was 1380 ng/mL. These findings are comparable to previous studies that have analyzed ranges of d-dimer and demonstrated that levels >1.0 μg/mL are at a higher risk for PE.²⁵ This reproducibility of a d-dimer threshold predictive of PE allows the use of this parameter to reduce routine screening, minimizing radiation and contrast exposure.

Limitations

Our study was based on a retrospective analysis of electronic medical records, therefore, information loss is inevitable, despite the strict documentation protocol used by our group. Information regarding risk factors such as tobacco use was lacking in most of the analyzed medical records and was therefore excluded from our analysis.

Overexposure to radiation and contrast is a point of concern in our study. Despite the lack of conclusive data, this exposure may have implications in the renal function of predisposed patients and increased risk for certain types of radiation-induced cancers. However, modern CTA scanners require increasingly lower radiation doses,²⁶ and a recent systematic review and meta-analysis have reported that intravenous, as opposed to intra-arterial, contrast infusion is not associated with an increase in contrast-induced nephropathy.²⁷ Furthermore, this concern is what motivated our d-dimer analysis in order to suggest a predictive cutoff value, useful in limiting the need for routine PE screening.

Our findings of asymptomatic PE may represent an overdiagnosis of a condition with debatable clinical relevance, since favorable outcomes with complete thrombus recanalization are expected after full anticoagulation for DVT treatment. On the other hand, assuming the current recommendations in light of our results, almost half of the patients with ICVT will not be adequately treated for PE, leaving them at risk of sudden death or future pulmonary implications such as the development of CTPH.¹⁷

Conclusion

Distal DVT is associated with a high incidence of PE comparable to proximal DVT, around 77%. Distal DVT and ICVT can provoke PE with involvement of proximal vessels in the pulmonary arterial tree, including lobar and segmental branches even in asymptomatic patients. Our study arises discussion in the controversial debate regarding the need for routine anticoagulation in distal DVT.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

References

Heit

Cohen

Anderson

Jr ; VTE Impact Assessment Group. Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US. Blood. 2005;106(11):267a.

Cohen

Agnelli

Anderson

. Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007;98(4):756–764.

Stein

Kayali

Olson

. Estimated case fatality rate of pulmonary embolism, 1979 to 1998. Am J Cardiol. 2004;93(9):1197–1199.

Galanaud

Bosson

Quéré

. Risk factors and early outcomes of patients with symptomatic distal vs. proximal deep-vein thrombosis. Curr Opin Pulm Med. 2011;17(5):387–391.

Stein

Matta

Musani

Diaczok

. Silent pulmonary embolism in patients with deep venous thrombosis: a systematic review. Am J Med. 2010;123(5):426–431.

Huisman

Buller

ten Cate

. Unexpected high prevalence of silent pulmonary embolism in patients with deep venous thrombosis. Chest. 1989;95(3):489–502.

Meignan

Rosso

Gauthier

. Systematic lung scans reveal a high frequency of silent pulmonary embolism in patients with proximal deep venous thrombosis. Arch Intern Med. 2000;160(2):159–164.

Monreal

Ruíz

Olazabal

Arias

Roca

. Deep venous thrombosis and the risk of pulmonary embolism. A systematic study. Chest. 1992;102(3):677–681.

Kearon

Akl

Comerota

. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e419s–e494s.

10.

Sule

Chin

Handa

Earnest

. Should symptomatic, isolated distal deep vein thrombosis be treated with anticoagulation? Int J Angiol. 2009;18(2):83–87.

11.

University Hospital, Geneva. Randomized Controlled Trial of Anticoagulation vs. Placebo for a First Symptomatic Isolated Distal Deep-vein Thrombosis (IDDVT) (CACTUS-PTS). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000. Web site. http://clinicaltrials.gov/show/NCT00421538. Updated January 7, 2016. Accessed August 25, 2015.

12.

Boyden

. Segmental Anatomy of the Lungs. New York, NY: McGraw-Hill; 1995.

13.

A language and environment for statistical computing

2015. Web site. http://www.R-project.org/. Updated January 7, 2016.

14.

Singh

Yakoub

Giangola

. Early follow-up and treatment recommendations for isolated calf deep venous thrombosis. J Vasc Surg. 2010;55(1):136–140.

15.

Hughes

Stein

Matta

. Silent pulmonary embolism in patients with distal deep venous thrombosis: systematic review. Thromb Res. 2014;134(6):1182–1185.

16.

Douketis

Kearon

Bates

Duku

Ginsberg

. Risk of fatal pulmonary embolism in patients with treated venous thromboembolism. JAMA. 1998;279(6):458–462.

17.

Olsson

Meyer

Hinrichs

Vogel-Claussen

Hoeper

Cebotari

. Chronic thromboembolic pulmonary hypertension. Dtsch Arztebl Int. 2014;111(50):856–862.

18.

Lapidus

Ponzer

Pettersson

de Bri

. Symptomatic venous thromboembolism and mortality in orthopaedic surgery—an observational study of 45 968 consecutive procedures. BMC Musculoskelet Disord. 2013;14:177.

19.

Aryal

Al-Khaffaf

. Venous thromboembolic complications following air travel: what’s the quantitative risk? A literature review. Eur J Vasc Endovasc Surg. 2006;31(2):187–199.

20.

Cay

Unal

Kartal

Ozdemir

Tola

. Increased level of red blood cell distribution width is associated with deep venous thrombosis. Blood Coagul Fibrinolysis. 2013;24(7):727–731.

21.

Zöller

Melander

Svensson

Engström

. Red cell distribution width and risk for venous thromboembolism: a population-based cohort study. Thromb Res. 2014;133(3):334–339.

22.

Reiter

Bucek

Koca

Dirisamer

Minar

. Deep vein thrombosis and systemic inflammatory response: a pilot trial. Wien Klin Wochenschr. 2003;115(3-4):111–114.

23.

Roumen-Klappe

den Heijer

van Uum

van der Ven-Jongekrijg

van der Graaf

Wollersheim

. Inflammatory response in the acute phase of deep vein thrombosis. J Vasc Surg. 2002;35(4):701–706.

24.

Bakirci

Topcu

Kalkan

. The role of the nonspecific inflammatory markers in determining the anatomic extent of venous thromboembolism. Clin Appl Thromb Hemost. 2015;21(2):181–185.

25.

Gimber

Leong

Todoki

Yoon

. Avoiding unnecessary pulmonary CT angiography by using a combination of clinical criteria and d-dimer thresholds. Open J Radiol. 2013;3(2):78–84.

26.

Szucs-Farkas

Christe

Megyeri

. Diagnostic accuracy of computed tomography pulmonary angiography with reduced radiation and contrast material dose: a prospective randomized clinical trial. Invest Radiol. 2014;49(4):201–208.

27.

McDonald

Comin

. Frequency of acute kidney injury following intravenous contrast medium administration: a systematic review and meta-analysis. Radiology. 2013;267(1):119–128.

Rediscussing Anticoagulation in Distal Deep Venous Thrombosis

Abstract

Background:

Methods:

Results:

Conclusion:

Keywords

Introduction

Methods

Deep Venous Thrombosis and PE Classification

Control Group

Statistical Analysis

Results

General Characteristics of the Study Population and Comparison With the Control Group

Risk Factor Analysis According to the Severity of the Thromboembolic Event

Incidence and Severity of Asymptomatic PE in the DVT Groups

Association Between Laboratorial Biomarkers (CRP, RDW, and d-Dimer) and Clot Burden

Predictive Value of d-Dimer for PE

Discussion

Limitations

Conclusion

Footnotes

Declaration of Conflicting Interests

Funding

References