Prevalence and Prognostic Role of Lymphedema in Patients with Deep Venous Thrombosis and Thrombophlebitis

Abstract

Background:

Deep venous thrombosis (DVT) poses a substantial disease burden. Lymphedema may present with similar symptoms making the diagnosis process more difficult. Data on the epidemiology of lymphedema are lacking.

Methods:

The German nationwide inpatient sample served to analyze all patients hospitalized owing to DVT and/or thrombophlebitis (referred to as DVT) of the legs in Germany between 2005 and 2020. We stratified these patients for additional lymphedema and analyzed the impact of lymphedema on adverse in-hospital events.

Results:

Overall, 1,136,574 hospitalizations related to DVT were recorded in Germany during 2005–2020 (53.3% women; 51.3% aged ≥70 years). Lymphedema was coded in 9974 (0.9%) patient-cases (82.0% not elsewhere classified, 17.7% secondary lymphedema). Annual numbers of hospitalizations with lymphedema among DVT patients increased from 450 (2005) to 613 (2016) (β 0.57; 95% confidence interval [CI]: 0.48–0.66], p < 0.001) and decreased thereafter. Despite similar age, DVT patients with lymphedema had higher prevalence of cardiovascular diseases, chronic organ failure, and all types of investigated cancer. Prevalence of pulmonary embolism (PE) with shock/CPR (4.1% vs. 1.5%), acute renal failure (6.7% vs. 2.5%), and stroke (5.2% vs. 4.2%) was higher in DVT patients with lymphedema than without. Lymphedema was independently associated with PE with shock/CPR (OR: 2.1; 95% CI: 1.9–2.3) as well as death (OR: 1.3; 95% CI: 1.2–1.4).

Conclusions:

Comorbidity conditions like cancer, obesity, and cardiovascular risk factors, and also infectious complications, were more prevalent in DVT patients with lymphedema than in those without. Lymphedema was independently associated with severe in-hospital complications, particularly when its genesis was related to severe comorbidities.

Introduction

Deep venous thrombosis (DVT) occurs in 1 of 12 people over a lifetime and poses substantial burden in terms of early and long-term complications, including pulmonary embolism (PE) and postthrombotic syndrome.¹ In most patients, DVT occurs during hospitalization and in relation to other comorbidities.² Indeed, a number of medical conditions may present with similar signs and symptoms, resulting in under- or even misdiagnosis.³

Similar to DVT and chronic venous diseases, lymphedema can manifest as a limb swelling leading to a tightness feeling, skin fibrosis, and recurrent infections.⁴ Occurring spontaneously as a result of a genetic defect leading to a developmental abnormality of the lymphatic system (primary lymphedema) or secondary to other conditions like cancer, its clinical picture may partly overlap to that of DVT.⁵ Although lymphedema contributes to functional impairment, to more frequent hospitalizations, and increased financial burden, data on its epidemiology and global burden are lacking.⁶ The prevalence and incidence rates frequently cited in scientific literature are based on indirect data derived from cohort studies, rather than being derived from robust epidemiological analyses.

Furthermore, given the lack of expertise among practitioners, the diagnostic process may pose challenges, especially when dealing with patients who present with symptoms resembling lymphedema. In addition, there remains a scarcity of evidence regarding the most effective treatment strategies for this condition. Patients and their families often feel frustrated and discouraged owing to multiple office visits, misdiagnosis, and inadequate treatment, possibly endangering the doctor–patient alliance and patient-centered care.⁷

In our study, we aimed to provide initial population-based epidemiological data on the burden and early outcome of lymphedema and associated comorbidities in patients hospitalized for DVT and thrombophlebitis of the lower extremities (here referred to as DVT) in Germany between 2005 and 2020.

Methods

Data source, and funding sources

Statistical study analyses were performed on our behalf by the Research Data Center (RDC) of the Federal Bureau of Statistics (Wiesbaden, Germany). Statistical analysis was performed based on a predefined SPSS syntaxes prepared by the investigators (IBM Corp. Released 2011; IBM SPSS Statistics for Windows, Version 20.0; IBM Corp, Armonk, NY). The statistical code was sent to the RDC (source: RDC of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005–2020, own calculations), which ultimately provided aggregated statistic results with permission to publish these data. A detailed description of the methodology and data sources is provided in the following references.^8,9

No commercial support was provided for this study and no external influence on the preparation of this report has to be reported. Since our study did not include a direct access by the investigators on individual patient data but instead only an access of the investigators on summarized results provided by the RDC, an approval by an ethics committee as well as patients' informed consent were not required, in accordance with the German law.^8–10

ICD coding for diagnosis and procedures

Lymphedema cases were identified based on the following ICD codes: I89, Q82, I97.2x, and I97.8x. Based on their relative frequency, cases were primarily categorized into (1) lymphedema not elsewhere classified (ICD code I89) and (2) secondary lymphedema (postsurgery-associated lymphedema with ICD codes I97.2x, after mastectomy and/or I97.8x, after surgery at axillary/inguinal lymphatics). Hereditary lymphedema (Q82) was analyzed separately. These codes were searched among patient charts that reported on hospitalizations/admissions owing to DVT and/or superficial vein thrombosis of the legs, ICD code I80.x. encompassing superficial vein thrombosis (I80.0) and deep vein thrombosis (I80.1 plus I80.2). The use of the I80 code without distinction in subcodes was based on the following points: (1) the pathophysiology of DVT and superficial vein thrombosis is only partly different, (2) the two conditions are often coexisting, (3) both could lead to chronic vein insufficiency and are wrongly interpreted as lymphedema, (4) we do not have reassurance that they are used correctly and the use of a single code for both conditions was based on prior works.^11,12

During the year 2004, diagnoses- and procedures-related remuneration and reimbursement were introduced and implemented in the German health care system mandatory for German hospitals. In this context, coding according the German Diagnosis-Related Groups (G-DRG) system with coding of patient data with regard to patients' diagnoses, coexisting conditions, and to surgeries as well as to diagnostics/procedures/interventions is required, and the transfer of the codes to the Institute for the Hospital Remuneration System for German hospitals is mandatory to receive the reimbursement.^8–10 Patients' diagnoses have to be coded according the International Statistical Classification of Diseases and Related Health Problems (of the 10th revision with German modification, ICD-10-GM).^8–10 In addition, diagnostic, interventional and surgical procedures have to be coded with OPS codes (Operationen- und Prozedurenschlüssel).

Study outcomes

The primary study outcomes were in-hospital death (death of all causes during in-hospital stay), PE (ICD code I26), instable PE (patients with cardiopulmonary resuscitation and/or shock), and pneumonia (ICD codes J12–J18). In addition, we analyzed the prevalence of other adverse in-hospital events.

Statistical analysis

To compare DVT patients with and without lymphedema during the period 2005–2020 in Germany, we analyzed differences between these two groups with the help of Wilcoxon–Whitney U-test for continuous variables and Fisher's exact or chi-square test for categorical variables, as appropriate. In addition, we analyzed time-trends regarding the prevalence of lymphedema in DVT hospitalizations in Germany over the period 2005–2020. Linear regressions were used to assess these trends over time and the results are given as beta (β) with corresponding 95% confidence intervals (CI).

Univariate and multivariate logistic regression models were computed to investigate associations between lymphedema and the outcomes PE, pneumonia, and in-hospital death. The multivariate regression models were adjusted in two different ways:

Adjustment I: adjusted for age, sex, obesity, ischemic heart disease, heart failure, chronic lung disease, essential arterial hypertension, acute and chronic kidney disease, hyperlipidemia, diabetes mellitus, and atrial fibrillation/flutter;

Adjustment II: adjusted for age, sex, obesity, ischemic heart disease, heart failure, chronic lung disease, essential arterial hypertension, acute and chronic kidney disease, hyperlipidemia, diabetes mellitus, atrial fibrillation/flutter, and cancer.

We have chosen this epidemiological approach regarding the aforementioned adjustments to test statistically the widespread independence regarding the prognostic impact of lymphedema on adverse in-hospital events of these well-known causers of increased in-hospital case-fatality rate as well as differences in age and sex. The results were presented as odds ratios (OR) and 95% confidence intervals (CI). All statistical analyses were carried out with the SPSS software (IBM Corp. Released 2011; IBM SPSS Statistics for Windows, Version 20.0; IBM Corp). Only p-values <0.05 (two-sided) were considered to be statistically significant.

Results

A total of 1,136,574 hospitalizations related to DVT were recorded in Germany between 2005 and 2020: the slight majority of DVT hospitalizations were of female sex (606,217 [53.3%]) and aged 70 years or older (583,467 [51.3%]). Lymphedema was coded as diagnosis in 9974 (0.9%) hospitalization cases, including 8183 (82.0%) with lymphedema not elsewhere classified, and 1765 (17.7%) with secondary lymphedema, which emerged often in relation to surgical procedures (Table 1). An overview of interventions is provided in Supplementary Table S1: the most frequent procedures were gynecological, urological, or dermatological, as well as surgical thrombectomy.

Table 1.

Disease-Specific Characteristics and Genesis of Lymphedema in Hospitalized Patients with Deep Vein Thrombosis with Lymphedema

	Total (N = 9974)
Lymphedema not elsewhere classified	8183 (82.0%)
Lymphangitis	398 (4.0%)
Hereditary lymphedema	80 (0.8%)
Lymphedema following procedures	1563 (15.7%)
Lymphedema after (partial) mastectomy	202 (2.0%)
Lymphedema following procedures at the upper extremity	222 (2.2%)
Lymphedema following procedures at the lower extremity	74 (0.7%)
Secondary lymphedema	1765 (17.7%)

Table 2 provides the demographic and baseline characteristics of DVT hospitalizations stratified according to the presence of lymphedema. Despite a similar age, DVT patients with (vs. without) lymphedema had a higher prevalence of cardiovascular diseases and risk factors, chronic organ failure, psychological and behavioral disorders, and all types of investigated cancer. Not surprisingly, the prevalence of rare lymphedema-associated conditions and risk factors, such as polyneuropathy, phlegmons, erysipelas, congenital malformations, and wounds, was higher in patients with (vs. without) lymphedema (Table 3).

Table 2.

Baseline and Patient Characteristics Among 1,136,574 Hospitalizations in Patients with Deep Vein Thrombosis With Versus Without Lymphedema

	Total (N = 1,136,574)	Patients without lymphedema (n = 1,126,600)	Patients with lymphedema (n = 9974; 0.9%)
Age		70.0 (56.0–79.0)	70.0 (58.0–78.0)
Age ≥70 years	583,467 (51.3%)	578,414 (51.3%)	5053 (50.7%)
Women^*	606,217 (53.3%)	600,166 (53.3%)	6051 (60.7%)
Obesity	100,887 (8.9%)	99,114 (8.8%)	1773 (17.8%)
Diabetes mellitus	187,663 (16.5%)	185,662 (16.5%)	2001 (20.1%)
Arterial hypertension	569,529 (50.1%)	564,235 (50.1%)	5294 (53.1%)
Hyperlipidemia	136,067 (12.0%)	134,828 (12.0%)	1239 (12.4%)
Ischemic heart disease	114,216 (10.0%)	113,114 (10.0%)	1102 (11.0%)
Heart failure	139,503 (12.3%)	137,791 (12.2%)	1712 (17.2%)
Peripheral artery disease	31,103 (2.7%)	30,648 (2.7%)	455 (4.6%)
Atrial fibrillation/flutter	108,722 (9.6%)	107,455 (9.5%)	1267 (12.7%)
Chronic lung disease	90,354 (7.9%)	89,465 (7.9%)	889 (8.9%)
Chronic obstructive pulmonary disease	65,368 (5.8%)	64,754 (5.7%)	614 (6.2%)
Acute and chronic kidney disease	177,894 (15.7%)	175,539 (15.6%)	2355 (23.6%)
Cerebrovascular diseases	86,640 (7.6%)	85,807 (7.6%)	833 (8.4%)
Psychological and behavioral disorders	206,534 (18.2%)	204,524 (18.2%)	2010 (20.2%)
Cancer	144,991 (12.8%)	141,850 (12.6%)	3141 (31.5%)
Bladder cancer	6313 (0.6%)	6075 (0.5%)	238 (2.4%)
Breast cancer	16641 (1.5%)	16,168 (1.4%)	473 (4.7%)
Cervical cancer	2100 (0.2%)	1971 (0.2%)	129 (1.3%)
Endometrial cancer	4157 (0.4%)	3946 (0.4%)	211 (2.1%)
Ovarian cancer	5766 (0.5%)	5563 (0.5%)	203 (2.0%)
Vulva cancer	834 (0.1%)	704 (0.1%)	130 (1.3%)
Prostate cancer	13,130 (1.2%)	12,502 (1.1%)	628 (6.3%)
Colorectal cancer	19,087 (1.7%)	18,830 (1.7%)	257 (2.6%)
Head/neck cancer	1369 (0.1%)	1338 (0.1%)	31 (0.3%)
Melanoma cancer	1562 (0.1%)	1499 (0.1%)	63 (0.6%)
Lymphangiosarcoma	1103 (0.1%)	1053 (0.1%)	50 (0.5%)

Information available for 1,136,525 patients.

Table 3.

Prevalence of Lymphedema-Associated Conditions and Risk Factors in Hospitalized Patients with Deep Vein Thrombosis With Versus Without Lymphedema

	Patients without lymphedema (n = 1,126,600)	Patients with lymphedema (n = 9974; 0.9%)
Phlegmons	5236 (0.5%)	129 (1.3%)
Erysipelas	18,117 (1.6%)	565 (5.7%)
Wounds	7868 (0.7%)	190 (1.9%)
Monoplegia of upper limb	2752 (0.2%)	34 (0.3%)
Monoplegia of lower limb	1721 (0.15%)	36 (0.36%)
Paralytic syndromes	6109 (0.5%)	91 (0.9%)
Acute lymphadenitis	273 (0.02%)	11 (0.11%)
Congenital malformations, deformations and chromosomal abnormalities	14,098 (1.3%)	289 (2.9%)
Hereditary malformation syndrome involving multiple organ systems	251 (0.02%)	10 (0.10%)

During the period 2005–2020, the number of hospitalizations with lymphedema among DVT patients increased from 450 cases in 2005 to a maximum of 613 in the year 2016 (β 0.573; 95% CI: 0.484–0.662, p < 0.001) and decreased thereafter (Fig. 1A). The proportion of patients with lymphedema increased across age groups (β 0.052; 95% CI: 0.018–0.085, p = 0.002) with age comprising a maximum of 2371 cases in the eighth decade of life (Fig. 1B). The increase of lymphedema cases over time was more pronounced in secondary (β 1.135; 95% CI: 0.924–1.346, p < 0.001) than in lymphedema not elsewhere classified (β 0.461; 95% CI: 0.363–0.560, p < 0.001) (Fig. 1C). Although the increase of cases of lymphedema not elsewhere classified with age was statistically significant (β 0.078; 95% CI: 0.041–0.115, p < 0.001), the secondary lymphedema cases did not change with age (β −0.023; 95% CI: −0.102 to 0.057, p = 0.575) (Fig. 1D).

FIG. 1.

Time trends regarding total numbers of hospitalizations of patients with DVT or thrombophlebitis (blue bars) and among them those with lymphedema. (A) Time trends regarding total numbers of hospitalizations of patients with DVT and/or thrombophlebitis (blue bars) and proportion of lymphedema (orange line) stratified for treatment years. (B) Time trends regarding total numbers of hospitalizations of patients with DVT and/or thrombophlebitis (blue bars) and proportion of lymphedema (orange line) stratified for age-decade of life. (C) Time trends regarding total numbers of hospitalizations of patients with DVT and/or thrombophlebitis (blue bars) with lymphedema not elsewhere classified (light orange bars) and secondary lymphedema (dark orange bars) stratified for treatment years. (D) Time trends regarding total numbers of hospitalizations of patients with DVT and/or thrombophlebitis (blue bars) with lymphedema not elsewhere classified (light orange bars) and secondary lymphedema (dark orange bars) stratified for age-decade of life. DVT, deep vein thrombosis.

Among DVT patients, those with lymphedema were characterized by a higher prevalence of severe acute cardiovascular events, notably PE with shock/CPR (4.1% vs. 1.5%, respectively), acute renal failure (6.7% vs. 2.5%), and stroke (5.2% vs. 4.2) (Table 4). The same applied to bleeding events: intracerebral bleeding (0.7% vs. 0.3%), gastrointestinal (1.7% vs. 0.8%), or requiring transfusions (16.6% vs. 4.9%). The higher complexity of lymphedema patients (Charlson index 4.9 vs. 3.8) translated into longer stays in hospital: an average of 10 (Q1–Q3 5–19) days for lymphedema vs. 7 (Q1–Q3 4–12) for nonlymphedema patients. Overall, up to 1% of DVT patients required an invasive strategy including endovascular or surgical thrombus removal.

Table 4.

Charlson Index, Length of In-Hospital Stay and Adverse Events in Hospitalized Patients with Deep Vein Thrombosis With Versus Without Lymphedema

	Patients without lymphedema (n = 1,126,600)	Patients with lymphedema (n = 9974; 0.9%)	p-value
Charlson index	3.81 ± 2.74	4.93 ± 3.14	<0.001
In-hospital stay (days), median (Q1–Q3)	7 (4–12)	10 (5–19)	<0.001
In-hospital death	35,360 (3.1%)	600 (6.0%)	<0.001
Pulmonary embolism	485,103 (43.1%)	3931 (39.4%)	<0.001
Pulmonary embolism with hemodynamic instability (shock/CPR)	16,944 (1.5%)	412 (4.1%)	<0.001
Pneumonia	129,506 (11.5%)	1143 (11.5%)	0.912
Acute kidney injury	28,649 (2.5%)	665 (6.7%)	<0.001
Stroke (ischemic or hemorrhagic)	47,473 (4.2%)	522 (5.2%)	<0.001
Intracerebral bleeding	3932 (0.3%)	65 (0.7%)	<0.001
Gastrointestinal bleeding	8464 (0.8%)	171 (1.7%)	<0.001
Transfusion of blood constituents	54,652 (4.9%)	1659 (16.6%)	<0.001

p Values of < 0.05 (two-sided) were considered as statistically significant and are marked in bold.

At logistic regression analysis (Table 5), it appeared that the risk of experiencing PE with shock/CPR or death was higher in patients with lymphedema (OR: 2.1; 95% CI: 1.9–2.3 and OR: 1.3; 95% CI: 1.2–1.4, respectively). This risk was driven by those with secondary lymphedema, who most often underwent surgical procedures and were characterized by higher prevalence of comorbidities. Lymphedema not elsewhere classified was not associated with increased risk of developing PE, pneumonia, and of dying. These results were confirmed in two different multivariable analyses accounting for multiple potential confounding factors.

Table 5.

Impact of Lymphedema on In-Hospital Death and Occurrence of Pulmonary Embolism as Well as Pneumonia (Univariable and Multivariable Logistic Regression Models)

	Univariable regression model, OR (95% CI)	Multivariable regression model (adjustment I)^a, OR (95% CI)	Multivariable regression model (adjustment II)^b, OR (95% CI)
All patients with lymphedema
In-hospital death	1.975 (1.818–2.147)	1.763 (1.618–1.922)	1.279 (1.172–1.396)
Pulmonary embolism	0.860 (0.826–0.896)	0.808 (0.775–0.842)	0.701 (0.672–0.731)
Pulmonary embolism with hemodynamic instability (shock/CPR)	2.822 (2.554–3.118)	2.215 (1.998–2.456)	2.056 (1.854–2.280)
Pneumonia	0.997 (0.937–1.060)	0.932 (0.875–0.993)	0.886 (0.832–0.944)
Lymphedema not elsewhere classified
In-hospital death	1.379 (1.239–1.536)	1.270 (1.138–1.418)	0.911 (0.815–1.018)
Pulmonary embolism	0.674 (0.644–0.706)	0.642 (0.613–0.673)	0.555 (0.529–0.582)
Pulmonary embolism with hemodynamic instability (shock/CPR)	1.214 (1.033–1.427)	1.008 (0.855–1.188)	0.932 (0.790–1.098)
Pneumonia	0.701 (0.648–0.758)	0.678 (0.626–0.734)	0.644 (0.595–0.697)
Secondary lymphedema
In-hospital death	5.198 (4.551–5.939)	4.065 (3.528–4.683)	3.025 (2.619–3.495)
Pulmonary embolism	2.562 (2.322–2.827)	2.264 (2.048–2.503)	1.974 (1.784–2.184)
Pulmonary embolism with hemodynamic instability (shock/CPR)	11.502 (10.083–13.120)	7.348 (6.372–8.474)	6.804 (5.901–7.846)
Pneumonia	2.752 (2.475–3.060)	2.248 (2.014–2.509)	2.134 (1.912–2.382)

Adjustment I: Adjusted for age, sex, obesity, ischemic heart disease, heart failure, chronic lung disease, essential arterial hypertension, acute and chronic kidney disease, hyperlipidemia, diabetes mellitus, and atrial fibrillation/flutter.

Adjustment II: Adjusted for age, sex, obesity, ischemic heart disease, heart failure, chronic lung disease, essential arterial hypertension, acute and chronic kidney disease, hyperlipidemia, diabetes mellitus, atrial fibrillation/flutter, and cancer.

CPR, cardiopulmonary resuscitation; OR, odds ratio.

Discussion

In this nationwide analysis spanning over a 16-year period, we provide for the first time, large-scale data on the burden of lymphedema and patients with DVT. Our data indicate that the majority (∼80%) of these patients were classified having a lymphedema not elsewhere classified with only a tiny minority having primary/hereditary lymphedema. Comorbidity conditions like cancer, obesity, and cardiovascular risk factors, and also infectious complications, appeared to be more prevalent in patients with (vs. without) lymphedema. Unexpectedly, we could establish that lymphedema correlated with a higher burden of severe in-hospital complications even after adjustment for age, sex, and important other conditions, if its genesis was considered secondary to other diseases. Our results may help to define the epidemiological and prognostic impact of lymphedema in this particular population of hospitalized patients.

Both DVT groups, namely those with and without lymphedema, revealed a high Charlson comorbidity index, which is known to significantly impact the 1-year survival.¹³ Of importance, patients with lymphedema had in general a higher Charlson comorbidity index, compatible with the higher death risk during hospitalization, being approximately two times higher compared with patients without lymphedema independent of age, sex, and important comorbidities, notably cancer. Overall, patients with lymphedema appeared to be characterized by higher burden of complications including organ failure, bleedings, and PE. These results were mainly driven by the subgroup of patients with secondary lymphedema. Although one cannot conclude that lymphedema and its direct complications (i.e., wounds, erysipelas, monoplegia, malformations) are pathophysiologically involved in the genesis of these events, rather it may represent a marker of disease severity requiring longer hospitalization periods and more aggressive treatments.

In our study cohort of patients admitted owing to DVT, indeed, clinical signs and symptoms may only partially differ from lymphedema. The main symptoms of DVT are acute swelling with skin discoloration and pain, whereas lymphedema leads typically to chronic swelling and progressive skin changes¹⁴ making it difficult to differentiate lymphedema from DVT.^14–16 This may explain at least in part the more severe presentation of DVT, namely in the case of hemodynamically unstable or fatal PE, in this vulnerable patient group beside other comorbidities.^15,16

An optimal management of lymphedema may lead not only to improved patient satisfaction, quality of life, and an improvement of functionality, but overall to less complications and a significant reduction of hospital admissions. The implementation of outpatient care comprising manual lymph drainage, compression techniques, and potential surgical interventions is expected to enhance the management of lymphedema and potentially diminish the necessity for hospital admissions. In addition, an early recognition mainly of DVT or of early associated complications would substantially improve patient prognosis.

There are some limitations that should be mentioned: (1) study analyses are based on ICD codes and OPS codes of hospitalized patients, which might be accompanied by underreporting or undercoding; (2) because these data comprise only information of the in-hospital course, we are not able to provide data of later follow-up and we could not study the temporal or causal effect between the two conditions; (3) the severity of disease cannot be determined, so potential associations between lymphedema severity and whether a patient receives outpatient treatment or not cannot be established.

Nonetheless, the use of codes for acute conditions is usually reserved for patients who have just experienced that complication, and not for those who had it in the personal history. Therefore, also in consideration of the expected high prevalence of PE, we are confident that the DVT events were acutely diagnosed.

Moreover, the majority of patients (8183 of 9974) were classified as having a lymphedema not elsewhere classified. It is known from cohort studies that secondary lymphedema patients exceed those with primary or hereditary lymphedema. Therefore, no clear assumptions can be made for the group of patients with lymphedema not elsewhere classified and one cannot exclude misclassification.

Conclusion

In this nationwide analysis covering a 16-year period, we provide a large-scale database concerning the burden of lymphedema in patients with DVT. To our knowledge, this represents one of the first ad hoc epidemiological analyses in the field of lymphedema. In this group, the majority of patients had a lymphedema not elsewhere classified, reinforcing the need of a more accurate coding and possibly diagnostic process, particularly if comorbidities are present. Despite this, severe comorbidities were more prevalent in patients with (vs. without) lymphedema, being independently associated with severe in-hospital complications. Our results may contribute to define more precisely the epidemiological and prognostic impact of lymphedema in a selected population of hospitalized patients with DVT.

Footnotes

Acknowledgment

The authors thank the Federal Statistical Office of Germany (Statistisches Bundesamt, DEStatis) for providing the data/results and the kind permission to publish these data.

Authors' Contributions

A.G.: conceptualization (lead); writing—original draft (lead); writing—review and editing (equal); N.L.: review and editing (equal); I.L.: review and editing (equal); L.H.: review and editing (equal); S.K.: review and editing (equal); T.M.: review and editing (equal); S.B.: conceptualization (lead); writing original draft (lead); writing—review and editing (equal); K.K.: conceptualization (lead); writing original draft (lead); statistical analysis (lead); writing—review and editing (equal).

Author Disclosure Statement

S.B. reports institutional research grants from Concept Medical, Bard, Bentley, Boston Scientific, INARI, Sanofi, and Bayer; and personal fees from Concept Medical, Bayer, Boston Scientific, and INARI, all not related to this study. S.K. reports grants or contracts from Bayer A.G.; consulting fees from Bayer, Daiichi Sankyo, and Boston Scientific; and payment or honoraria from Bayer, INARI Medical, MSD, Pfizer, and Bristol-Myers Squibb, all not related to this study. L.H. reports having received lecture honoraria from MSD. T.M. is P.I. of the DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany. K.K. reports no conflicts of interest. N.L. acts as a symposium speaker and clinical advisor for Medical Microinstruments (MMI). A.G. and I.L. report no conflict of interest.

Funding Information

This study was conducted at the University Medical Center Mainz and at the University Hospital Zurich and no funding was received for this article.

Supplementary Material

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