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Abstract

Deep vein thrombosis (DVT) and pulmonary embolism are major causes of morbidity and mortality in patients during hospitalization; previous studies have proposed that an advanced age of more than 60 years is a risk factor for these conditions. This study analyzes the relative risk of DVT in very elderly patients older than 90 years of age compared with elderly patients aged 80 to 89 years. The study was performed at the Department of Internal Medicine, University Hospital of Saarland, Homburg/Saar, Germany, between 2004 and 2012. After completing ultrasound examinations, 20 (64.52%, 12 [60%] female patients, mean age 91.8 ± 1.83 years) of the 31 patients in the study group and 132 (62.26%, 87 [65.91%] female patients, mean age 83.84 ± 2.66 years) of the 212 patients in the control group were diagnosed with DVT. An increased relative risk of DVT was not discovered in the very elderly patients (relative risk, 1.04; P = .80).

Keywords

phlebothrombosis thrombus old age aging risk factors

Introduction

Deep vein thrombosis (DVT), which is the clotting of blood components in the veins located deep within the leg, is the third most common cardiovascular disease after heart attack and stroke.^1
–3 Deep vein thrombosis can create a high risk for the development of pulmonary embolism, which is a primary and potentially life-threatening complication of DVT. Therefore, early diagnosis and aggressive and proactive treatment of DVT is crucial in effectively preventing pulmonary embolism. Deep vein thrombosis and the development of pulmonary embolism are the main causes of morbidity and mortality in patients of all ages and medical backgrounds; nevertheless, elderly patients are at a higher risk of DVT than younger patients.⁴ Reduced physical mobility is relevant to the development of the condition, and elderly patients have reduced physical mobility and high hospitalization rates for illnesses that contribute to the development of DVT and induce a greater risk of generating pulmonary embolism.⁵ Previous studies have asserted that advanced age is a risk factor in the development of DVT and that the incidence of DVT increases significantly with increasing age.^4

–7 As the average life expectancy continues to increase, DVT will become a major health problem worldwide. Further, elderly patients develop common internal illnesses, such as congestive heart failure, chronic obstructive pulmonary disease (COPD), acute infection, and atherosclerotic vascular disease, which increase the risk of DVT.⁵ Since the detection of DVT can be a challenge, given that common symptoms of DVT may be absent, this study was conducted to accurately identify very elderly patients at risk of DVT. Ultimately, DVT can only be prevented when the risk factors and risk groups for DVT are understood and identified.

Hospital chart data from the Department of Internal Medicine, University Hospital of Saarland, Homburg/Saar, Germany, were analyzed for nonagenarian and octogenarian patients who were examined after DVT to assess the relative risk of DVT in this age-group. All outpatients treated at the Internal Medicine Emergency Department and all the Internal Medicine Department’s hospitalized patients aged older than 80 years were included in the study. Patients hospitalized in all other departments of the University Hospital were excluded from this study for better comparison of the study population by including possible internal medicine primary disease as a requirement of the study design. This study was also performed to identify the typical clinical manifestations of DVT in the very elderly patients as well as acute and chronic comorbidities as possible risk factors. Further, d-dimer was evaluated as an effective method for excluding DVT in very elderly low-risk patients. It is well known that d-dimer values vary with increasing age; therefore, it is currently suggested that d-dimer values should be adjusted for age^8,9 and that a cutoff d-dimer value greater than 500 ng/mL may be more helpful.¹⁰ The practice of age-adjusted d-dimer cutoff levels might be a useful method; however, the effect on sensitivity remains unidentified.¹⁰ Additionally, anticoagulant medication therapy for DVT is being studied among the very elderly patients after ultrasounds have confirmed that they have developed DVT.

Materials and Methods

Patients

All data pertaining to patients with risk factors for DVT based on clinical gestalt were collected at the Department of Internal Medicine of the University Hospital of Saarland, between 2004 and 2012. The relative risk of DVT in the last decade of a patient’s life was considered theoretically by assuming that the average life expectancy would be 100 years of age. For the control group, the second highest decade of life was chosen to avoid any distortion in the data analysis due to age. The second highest decade of life refers to patients between 80 and 89 years of age. Thus, the study population was composed of very elderly patients older than 90 years of age diagnosed with DVT, and the control group was composed of elderly patients between 80 and 89 years of age diagnosed with DVT. The relative risk was calculated from the ratio of the probability of the presence of DVT to the probability of the absence of DVT by examining duplex ultrasounds of patients in both the groups. Deep vein thrombosis is defined as a blood clot within a major vein with the primary location of the iliac vein, femoral vein, popliteal vein, and the lower leg veins in one or both legs at the same time. All patients suspected to have developed DVT based on the use of physician clinical gestalt assessment underwent venous ultrasound imaging after physical examinations to confirm or refute the diagnosis of DVT. This suspicion was established along with symptoms of likelihood of DVT including pain, erythema, swelling, and warmth in the affected leg. Although the probability of DVT can be calculated using either the Wells or the Revised Geneva scores, these calculations were not considered for this study since all patients underwent follow-up ultrasound testing. Therefore, the negative influence of the nonexamination of patients by means of ultrasound should be avoided since these 2 scores estimate the pretest probability of DVT.

The description of the location of DVT in the veins was classified into iliofemoral, femoropopliteal, popliteal, and calf DVT. The classification of DVT was performed according to the most recent edition of the International Classification of Disease (ICD I80.20) from 2004 to 2012. A d-dimer measurement was performed at the discretion of the treating physician as a screening test to exclude the existence of a blood clot. A positive d-dimer test did not necessarily mean that a patient had developed DVT since the condition was only confirmed by compression ultrasounds in this study. Plasma d-dimer concentrations were measured in citrated blood (1 + 10 mixture of 3.5% aqueous sodium citrate and blood; Sarstedt, Nürnbrecht, Germany) using a well-validated, commercial, particle-enhanced, and immunoturbidimetric assay (Innovance d-dimer; Siemens Medical Solutions, Erlangen, Germany) with the Behring Coagulation System analyzer (Dade Behring, Marburg, Germany). The normal reference range for d-dimer was <0.5 mg/L. A 12-lead electrocardiogram was used to detect cardiac arrhythmias. Contrast-enhanced chest computed tomography was evaluated to diagnose any patients suspected to have contracted pulmonary embolism caused by DVT. A previous DVT or pulmonary embolism was considered as a possible risk factor for DVT in all patients. Cardiovascular risk factors, such as hypertension, diabetes, hyperlipidemia, and obesity, were examined as potential risk factors for DVT in both groups. Tumor diseases were also determined to be risk factors for DVT in both the groups. Internal illnesses were analyzed in both the groups since they are predisposing factors for the formation of DVT. We also compared the incidence of various comorbidities in groups with and without DVT. Finally, the different medical treatment plans for DVT, duration of hospital stay, and mortality rate were analyzed for both the groups. Barring contraindications, patients admitted to the Department of Internal Medicine, University Hospital of Saarland, with an acute medical illness are routinely implemented thromboprophylaxis with low-molecular-weight heparin.¹¹ Reasons for withholding of thromboprophylaxis are bleeding risk, bleeding diseases, active gastrointestinal bleeding, hemoptysis, hemorrhagic diathesis, severe thrombocytopenia, known heparin allergy, known heparin-induced thrombocytopenia, gastrointestinal ulcers, impaired renal function with a creatinine clearance <30 mL/min, nephrolithiasis, parenchymal liver disease, uncontrolled hypertension, retinopathy with bleeding risk of cerebral artery aneurysms, florid endocarditis lenta, cavernous pulmonary tuberculosis, epilepsy, chronic alcoholism, and lack of patient compliance.¹² Due to the retrospective design of the study protocol, the institutional review board of the Medical Association of Saarland waived the need for informed consent.

Statistical Analysis

The data were expressed in proportion, mean, and standard deviation wherever appropriate. Relative risk and 95% confidence intervals (CIs) were calculated and compared between the very elderly patients and the elderly patients for the occurrence of DVT. Fisher exact test was used to compute the location of DVT in the legs, clinical signs for DVT in the very elderly patients and elderly patients, the difference in cardiovascular risk between the 2 groups, and the difference in acute and prior thromboembolic diseases in both the groups. The chi-square test was used to calculate sex difference, demographic data, clinical data, cardiovascular risk factors, acute and prior thromboembolic diseases, and acute and chronic internal illnesses. The Mann-Whitney U test was used to compare age difference, the difference in d-dimer value, and the duration of hospital stay. Sensitivity was calculated for d-dimer as a probability for true-positive results when DVT was present. Specificity was defined as a probability for true-negative results when DVT was not present. Positive likelihood ratio was described as a ratio between the probability of a positive test result given the presence of DVT and the probability of a positive test result given the absence of DVT. Negative likelihood ratio was defined as a ratio between the probability of a negative test result given the presence of DVT and the probability of a negative test result given the absence of DVT. Positive predictive value was calculated as a probability that DVT was present when the test was positive. Negative predictive value was expressed as a probability that DVT was not present when the test was negative. Survival rates for both the groups were calculated using the Kaplan-Meier method. All tests were expressed as 2 tailed, and a P value of <.05 was considered to be statistically significant.

Results

A total of 2770 patients who were believed to be at risk of DVT based on clinical features, such as pain, erythema, swelling, and warmth in legs, were examined for DVT at the Department of Internal Medicine of the University Hospital, in the study period from 2004 to 2012. Of these, 31 (1.12%) were in the study group and 212 (7.65%) were in the control group. The number of patients with DVT rose with the annual fluctuation rates between 2004 and 2012 (Figure 1). There was a significant difference in the number of cases between both the groups during the study period (P = .000287). There were 11 (35.48%) men and 20 (64.52%) women in the study group, and 74 (34.91%) men and 138 (65.09%) women in the control group (P = .9497). Deep vein thrombosis was diagnosed in 20 (64.52%; 95% CI, 47.68-81.36) patients in the study group and 132 (62.26%; 95% CI, 55.73-68.79) patients in the control group. More women were diagnosed with DVT in both groups but without statistical significance (P = .6053; Table 1). The relative risk (1.04; 95% CI, 0.78-1.37; P = .80) for the occurrence of DVT did not increase in the very elderly patients older than 90 years of age compared with elderly patients who were between 80 and 89 years of age. A significant difference in the age of patients with DVT was found between the 2 groups (P < .001). There was also no statistical difference in the frequency of the right or left leg being affected by DVT (P = .2875) and the location of DVT (P = .6272). The clinical symptoms of pain, erythema, swelling, and warmth were not statistically significant signs of DVT in the very elderly group compared with the control group (P = .2196). The numerical difference in the level of d-dimer revealed no statistical difference (P = .39166) in the study group (range 0.30-34.90 mg/L) compared with the control group (range 0.10-35 mg/L; Figure 2). The sensitivity and specificity of d-dimer as a prediction tool for DVT was lower in the study group (Table 2). No statistical difference was found in cardiovascular risk factors between the 2 groups (Table 3). There was also no statistical difference in acute and prior thromboembolic diseases (Table 4). Disorders such as acute infectious diseases, acute myocardial infarction, contusion, lung fibrosis, and sepsis have been previously recognized as particular risk factors for the occurrence of DVT in very elderly patients⁵; malignant neoplastic diseases also presented as a risk factor for the development of DVT (Table 4). Atrial tachyarrhythmia, cardiac decompensation, and pulmonary edema were more common in the very elderly patients with DVT (Table 5). A comparison of different chronic comorbidities of the elderly patients older than 80 years of age with and without DVT showed an increased incidence of hysterectomy, hyperthyroidism, arthritis, and decubitus ulcers in the group with DVT; however, increased dermatitis was found in the group without DVT (Table 6). Interestingly, more patients in the study group received phenprocoumon as a medical therapy in comparison with the control group (Table 7). The average length of hospital stay was 8.2 ± 8.23 days (range 0-31 days) in the study group and 7.98 ± 9.72 days (range 0-62 days) in the control group without a statistically significant difference (P = .714362). Statistically, there were more deaths in the study group (15%) in comparison with the control group (3.03%). The 3 deaths in the study group were caused by pulmonary embolism (33.33%), sepsis (33.33%), and bronchopulmonary infection (33.33%), whereas pulmonary embolism (50%), pneumonia (25%), and sepsis (25%) were the main causes of the 4 deaths in the control group. An increased risk of dying (relative risk, 0.6667; 95% CI, 0.1021-4.3540; P = .6719) from pulmonary embolism was not observed in the study group. Thus, the survival rate was 85% (95% CI, 68.02-101.97) in the study group and 96.97% (95% CI, 94-99.94) in the control group.

Figure 1.

Trends in rates of deep vein thrombosis in both the groups.

Figure 2.

Comparison of d-dimer values in both groups of elderly patients with deep vein thrombosis.

Table 1.

Demographic and Clinical Data of Patients with Deep Vein Thrombosis.^a

	Study Group (n = 20) (%)	Control Group (n = 132) (%)	P Value
Number of diagnosed DVT	20 (64.52)	132 (62.26)	.80
Men	8 (40)	45 (34.09)	.7211
Women	12 (60)	87 (65.91)	.899
Mean age, years ± SD	91.8 ± 1.83	83.84 ± 2.66	<.001
DVT in the right leg	9 (45)	63 (47.73)	.8199
DVT in the left leg	8 (40)	62 (46.97)	.561
DVT in both legs	3 (15)	7 (5.30)	.1031
Iliac vein DVT	1 (5)	19 (14.39)	.2468
Femoral vein DVT	9 (45)	46 (34.85)	.3786
Popliteal vein DVT	4 (20)	22 (16.67)	.7122
Calf DVT	6 (30)	45 (34.09)	.718
Pain	5 (25)	25 (18.94)	.5257
Erythema	1 (5)	1 (0.76)	.1208
Swelling	6 (30)	61 (46.21)	.1736
Warmth	0	1 (0.76)	.6961

Abbreviations: DVT, deep vein thrombosis; SD, standard deviation.

^aSignificant P value shown in bold.

Table 2.

Comparison of d-dimer as a Predictive Value for Deep Vein Thrombosis in Both Groups Including Patients With Exclusion of Thrombosis.

	Study Group (n = 31) (%)	95% CI	Control Group (n = 212) (%)	95% CI
Mean ± SD	5.16 ± 8.16		3.74 ± 5.67
True positive	13 (41.94)	24.57-59.31	76 (35.85)	29.39-42.31
True negative	2 (6.45)	−2.2-15.1	15 (7.08)	3.63-10.53
False positive	7 (22.58)	7.86-37.3	24 (11.32)	7.06-15.58
False negative	4 (12.90)	1.1-24.7	20 (9.43)	5.5-13.36
NP-d-dimer	5 (16.13)	3.18-29.08	77 (36.32)	29.85-42.79
Sensitivity	76.47%	50.10-93.04	79.17%	69.67-86.78
Specificity	22.22%	3.47-59.94	38.41%	23.38-55.38
Positive predictive value	65%	40.79-84.55	76%	66.43-83.97
Negative predictive value	33.33%	5.33-77.32	42.86%	26.33-60.64
Positive likelihood ratio	0.98	0.63-1.52	1.29	0.98-1.68
Negative likelihood ratio	1.06	0.24-4.71	0.54	0.31-0.94
DVT prevalence	65.38%	44.34-82.75	71.11%	62.69-78.58

Abbreviations: DVT, deep vein thrombosis; SD, standard deviation; CI, confidence interval; NP-d-dimer, number of patients who were not exposed to measure d-dimer.

Table 3.

Cardiovascular Risk Factors in Both Groups.

	Study Group (n = 20) (%)	Control Group (n = 132) (%)	P Value
Hypertension	13 (65)	56 (42.42)	.0588
Diabetes	4 (20)	21 (15.91)	.6456
Hyperlipidemia	4 (20)	13 (9.85)	.1795
Obesity	0	8 (6.06)	.258

Table 4.

Recognized Disorders as a Risk Factor for Deep Vein Thrombosis in Both Groups.^a

	Study Group (n = 20) (%)	Control Group (n = 132) (%)	P Value
Acute infectious diseases	11 (55)	36 (27.27)	.0124
Acute myocardial infarction	2 (10)	2 (1.52)	.0272
Cancers	0	39 (29.55)	.0048
Chronic obstructive pulmonary disease	1 (5)	12 (9.09)	.5421
Chronic venous insufficiency	0	4 (3.03)	.4301
Congestive heart failure	3 (15)	10 (7.58)	.2686
Contusion	2 (10)	1 (0.76)	.0056
Depression	0	2 (1.52)	.5795
Exsiccosis	1 (5)	11 (8.33)	.6064
Heparin-induced thrombocytopenia	0	3 (2.27)	.4959
History of orthopedic surgery	1 (5)	8 (6.06)	.8514
Inflammatory bowel disease	0	4 (3.03)	.4301
Lung fibrosis	2 (10)	0	.0003
Pacemaker	2 (10)	5 (3.79)	.2168
Parkinson disease	1 (5)	2 (1.52)	.2964
Prior deep vein thrombosis	2 (10)	17 (12.88)	.7168
Prior pulmonary embolism	2 (10)	5 (3.79)	.2168
Sepsis	2 (10)	2 (1.52)	.0272
State postmyocardial infarction	2 (10)	7 (5.30)	.4069
State poststroke	2 (10)	12 (9.09)	.8958
Systemic disease	3 (15)	7 (5.30)	.1031
Varicose veins	0	4 (3.03)	.4301

^aSignificant P value shown in bold.

Table 5.

Acute Comorbidities in the Study and Control Groups.^a

Acute Diseases	Study Group (n = 20) (%)	Control Group (n = 132) (%)	P Value
Acute coronary syndrome	0	3 (2.27)	.4959
Acute kidney injury	1 (5)	5 (3.79)	.7953
Anemia	0	14 (10.61)	.1264
Arterial bleeding	0	1 (0.76)	.6961
Arteriovenous fistula	0	1 (0.76)	.6961
Atrial tachyarrhythmia	4 (20)	4 (3.03)	.0015
Cardiac decompensation	6 (30)	12 (9.09)	.007
Circulatory collapse	0	1 (0.76)	.6961
Electrolyte disturbance	2 (10)	4 (3.03)	.1358
Gastritis	1 (5)	3 (2.27)	.4777
Gastroesophageal reflux disease	0	1 (0.76)	.6961
Gastrointestinal bleeding	0	2 (1.52)	.5795
Hematoma	0	1 (0.76)	.6961
Hemolysis	0	1 (0.76)	.6961
Hemoptysis	0	1 (0.76)	.6961
Hyperglycemia	0	2 (1.52)	.5795
Hypoglycemia	0	1 (0.76)	.6961
Hypotension	0	1 (0.76)	.6961
Lymphedema	0	1 (0.76)	.6961
Pancreatitis	0	1 (0.76)	.6961
Peptic ulcer	0	1 (0.76)	.6961
Phlegmasia cerulea dolens	0	1 (0.76)	.6961
Pleural effusion	0	4 (3.03)	.4301
Pulmonary edema	1 (5)	0	.01
Pulmonary embolism	5 (25)	48 (34.09)	.3203
Shock	0	1 (0.76)	.6961
Syncope	0	5 (3.79)	.3761
Thrombocytopenia	0	1 (0.76)	.6961
Ulcus cruris	0	4 (3.03)	.4301
Urinary obstruction	0	3 (2.27)	.4959

^aSignificant P value shown in bold.

Table 6.

Various Comorbidities in Elderly Patients Aged >80 Years With and Without Deep Vein Thrombosis.^a

Cardiovascular Disease	Elderly Patients >80 Years With Deep Vein Thrombosis (n = 152) (%)	Elderly Patients >80 Years Without Deep Vein Thrombosis (n = 91) (%)	P Value
Aneurysm	10 (6.58)	3 (3.30)	.2711
Cardiac dysrhythmia	20 (13.16)	11 (12.09)	.8088
Cardiomyopathy	2 (1.32)	1 (1.10)	.8822
Carotid stenosis	1 (0.66)	0	.4381
Cor pulmonale	14 (9.21)	5 (5.49)	.2963
Coronary artery disease	26 (17.11)	16 (17.58)	.9241
Hypertensive heart disease	7 (4.61)	3 (3.30)	.6192
Peripheral arterial occlusive disease	9 (5.92)	6 (6.59)	.8331
Valvular heart disease	24 (15.79)	7 (7.69)	.0671
Pulmonary disease
Bronchial asthma	1 (0.66)	0	.4381
Lung emphysema	2 (1.32)	0	.2719
Obstructive sleep apnea syndrome	3 (1.97)	1 (1.10)	.604
State postlung surgery	1 (0.66)	0	.4381
State posttuberculosis	0	1 (1.10)	.1953
Gastrointestinal diseases
Appendectomy	8 (5.26)	6 (6.59)	.6667
Barrett esophagus	2 (1.32)	0	.2719
Cholecystectomy	12 (7.89)	9 (9.89)	.5921
Choledocholithiasis	1 (0.66)	2 (2.20)	.2927
Colectomy	5 (3.29)	1 (1.10)	.2869
Diverticulosis	7 (4.61)	1 (1.10)	.1382
Esophageal varices	0	1 (1.10)	.1953
Fatty liver	4 (2.63)	0	.1187
Gallbladder stones	9 (5.92)	2 (2.20)	.1766
Gastrectomy	2 (1.32)	2 (2.20)	.601
Hepatitis	3 (1.97)	0	.1775
Intestinal polyps	0	1 (1.10)	.1953
Liver cirrhosis	0	2 (2.20)	.0665
Liver cyst	1 (0.66)	0	.4381
State postsplenic infarction	1 (0.66)	0	.4381
Stoma	5 (3.29)	1 (1.10)	.2869
Kidney disease
Adrenal adenomas	2 (1.32)	0	.2719
Atrophic kidney	1 (0.66)	0	.4381
Chronic kidney disease	24 (15.79)	11 (12.09)	.4264
Nephrectomy	2 (1.32)	1 (1.10)	.8822
Renal cyst	9 (5.92)	2 (2.20)	.1766
Disease of the genitourinary system
Benign prostatic hyperplasia	5 (3.29)	1 (1.10)	.2869
Hysterectomy	9 (5.92)	0	.018
Ovarian cyst	1 (0.66)	0	.4381
Urinary incontinence	1 (0.66)	1 (1.10)	.7127
Thyroid disease
Autonomous thyroid adenoma	1 (0.66)	1 (1.10)	.7127
Hyperparathyreosis	0	1 (1.10)	.1953
Hyperthyroidism	8 (5.26)	0	.0261
Hypothyroidism	8 (5.26)	4 (4.40)	.7626
Struma nodosa	3 (1.97)	0	.1775
Strumectomy	6 (3.95)	3 (3.30)	.7827
Ear, nose, and throat disease
Dizziness	1 (0.66)	0	.4381
Ménière disease	1 (0.66)	0	.4381
Tonsillectomy	1 (0.66)	0	.4381
Nervous system disorders
Epilepsy	1 (0.66)	1 (1.10)	.7127
Lumbago	1 (0.66)	2 (2.20)	.2927
Multiple sclerosis	1 (0.66)	0	.4381
Polyneuropathy	3 (1.97)	2 (2.20)	.9052
Spinal degenerative disease	1 (0.66)	0	.4381
Spinal disc herniation	2 (1.32)	0	.2719
Spinal stenosis	2 (1.32)	0	.2719
State postsubdural hematoma	1 (0.66)	0	.4381
Psychiatric disorders
Alcoholism	0	1 (1.10)	.1953
Dementia	18 (11.84)	6 (6.59)	.1844
Psychosis	2 (1.32)	1 (1.10)	.8822
Schizophrenia	2 (1.32)	0	.2719
Orthopedic disorders
Amputation	0	1 (1.10)	.1953
Arthritis	9 (5.92)	0	.018
Baker cyst	0	1.10	.1953
Osteoarthritis	9 (5.92)	9 (9.89)	.2529
Osteoporosis	7 (4.61)	5 (5.49)	.7568
Skin disorders
Allergy	2 (1.32)	0	.2719
Decubitus ulcers	7 (4.61)	0	.0378
Dermatitis	0	3 (3.30)	.0243
Psoriasis	3 (1.97)	0	.1775
State postherpes zoster	1 (0.66)	0	.4381
Ophthalmologic diseases	14 (9.21)	7 (7.69)	.6835
State after early trauma
State postbone fracture	19 (12.5)	9 (9.89)	.5374
State postfall	7 (4.61)	4 (4.40)	.9393
Gynecological disorders
Mastectomy	3 (1.97)	2 (2.20)	.9052
Uterine polyps	0	1 (1.10)	.1953

^aSignificant P value shown in bold.

Table 7.

Therapy of Deep Vein Thrombosis in Both Groups.^a

	Study Group (n = 20) (%)	Control Group (n = 132) (%)	P Value
Heparin	6 (30)	33 (25)	.6333
Low-molecular-weight heparin	15 (75)	105 (79.55)	.6422
Phenprocoumon	12 (60)	45 (34.09)	.0257
Thrombolytic therapy	0	1 (0.76)	.6961

^aSignificant P value shown in bold.

Discussion

Although previous studies postulated a higher risk of DVT with increasing age,^3

–7 the results of the current study showed relatively no increased risk of DVT in the very elderly patients older 90 years of age compared with the elderly patients between 80 and 89 years of age. Although the incidence of pulmonary embolism decreased in patients of all ages over time, the incidence of DVT in older men remained unchanged while it increased in older women.^7,13 The annual number of DVT diagnoses also increased in our study but was not continuous, with a marked rise and fall according to annual fluctuation rates. We diagnosed more elderly women with DVT than elderly men, but without statistical significance, corroborating the findings in the study by Silverstein et al.⁷ There was a considerably lower proportion of very elderly patients included in our study, and these patients did not have an increased risk of DVT in comparison with the elderly patients. The outcomes of our study could be affected by the small number of patients in the study group as well as the fact that our study was conducted in a single Department of Internal Medicine. Furthermore, the number of patients becomes smaller with increasing biological age.

Since the typical clinical symptoms of DVT may be absent or uncharacteristic,⁵ diagnosing DVT can be a challenge, and the illness can be easily overlooked. Accordingly, pain, erythema, swelling, and warmth were not statistically significant signs of DVT in the very elderly patients. In our study, the most common symptoms in both the groups were swelling and pain. In a study by Naess et al, DVT was described as originating in the left leg and then developing in the right leg, although DVT rarely occurred in both legs; in contrast, DVT was detected more often in the right leg in both the groups.¹⁴ Our study was in agreement with Naess et al, as we found no statistical significance in the detection of DVT in the right leg, and we detected more proximal DVT in both groups but without statistical significance. In a previous study by Zhu et al,¹⁵ the development of pulmonary embolism caused by DVT was detected in approximately 44% of cases. Likewise, in our study, pulmonary embolism was a common complication of DVT in both the groups. Further, we found that one-third of the deaths in the very elderly patients were caused by pulmonary embolism; however, in the study by Heit,⁶ up to one-quarter of sudden deaths in all age-groups was caused by pulmonary embolism. Longo et al¹⁶ observed that DVT was more frequently associated with pulmonary embolism and less frequently associated with neoplasms in elderly patients; further, they provided different data regarding the prevalence of DVT and sex differences. In the study by Longo et al,¹⁶ more elderly patients had DVT with different clinical features, and no differences were found between males and females regarding the prevalence of DVT.

Frailty has been identified as a risk factor for DVT in the elderly patients in a previous study by Folsom et al.¹⁷ However, we did not measure frailty in our study. Generally, frailty should be assumed to be more prevalent in the age-group studied herein. Folsom et al studied frailty based on weight loss, grip strength, feelings of exhaustion, walking time, and physical activity.¹⁷ These parameters have not been considered in detail in our study. Further studies are needed to examine the relationship between frailty and DVT in the very elderly patients. Previous studies reported minor injuries as a risk factor for venous thrombosis,¹⁸ this observation was made in our study in patients with contusions after a fall. Furthermore, a high prevalence of venous thromboembolism has been reported in patients with COPD.¹⁹ Although no significant increased risk of DVT was found in patients with COPD in our study, acute inflammatory diseases appeared to be a risk factor for the development of DVT. Acute respiratory and urinary infections were also described as a risk factor for DVT in a study by Smeeth et al.²⁰ General acute inflammatory diseases could increase the risk of developing DVT in very elderly patients. An association was found between atherosclerosis and venous thrombosis in a previous study by Prandoni et al²¹; this observation was made in patients with acute myocardial infarction in our study as well. A high risk of DVT was discovered in patients with heart failure in the study by Beemath et al.²² These findings were also confirmed in very elderly patients with cardiac decompensation due to heart failure in our study. Generally, cancer is considered a risk factor for DVT.^23
–25 In our study, cancer was found only in the elderly patients in the control group who were diagnosed with both cancer and DVT, probably due to the fact that patients with cancer included in our study did not reach the age of 90 years or older. Recent studies have reported an increased risk of DVT in patients with lung fibrosis.²⁶ Accordingly, analysis of the data in our study indicates that an association between lung fibrosis and DVT might exist. However, further investigations are required to clarify this relationship.

A correlation has been implied between sepsis and DVT.²⁷ The incidence of sepsis in the study population with DVT was increased in our study, although further studies are warranted. Comparison of various comorbidities in groups with and without DVT showed an elevated incidence of hysterectomy, hyperthyroidism, arthritis, and decubitus ulcers in the elderly patients aged older than 80 years with DVT in our study. In agreement, data of the latest studies show that the incidence of venous thromboembolism rises after major cancer surgery such as hysterectomy,²⁸ as is the case in our study. Following a small number of published studies, it remains unclear whether hyperthyroidism leads to an increased risk of venous thromboembolism through modifications of the hemostatic system causing a hypercoagulable condition.^29,30 Recent developments in the interpretation of blood coagulation processes support an inflammatory origin, such as osteoarthritis and rheumatoid arthritis, for thromboembolic events.³¹ These discoveries permit the administration of a pharmacological thromboprophylaxis in patients with osteoarthritis and rheumatoid arthritis. Finally, for the increased incidence of decubitus in patients with DVT, we could find no published data.

A negative d-dimer has been indicated to successfully exclude DVT in very elderly patients.³² However, the d-dimer value has been shown to have little predictive value for DVT in the elderly patients.³³ In agreement, in our study, the sensitivity and specificity of d-dimer as a predictive value for DVT were low for very elderly patients. Piazza et al found that elderly patients diagnosed with DVT received less medical treatment and prophylaxis for DVT.⁵ Interestingly, the study group received more phenprocoumon as a medical treatment for DVT in our study. Consequently, most acutely ill patients admitted to hospital with congestive heart failure or severe respiratory disease, or who are restricted to bed and have 1 or more additional risk factors, should receive thromboprophylaxis during hospitalization.³⁴

Study Limitations

This study examined very elderly patients diagnosed with DVT in one Department of Internal Medicine but did not investigate very elderly patients diagnosed with DVT in other medical departments. The differences in our descriptive results may be due to the age difference between both the groups and individual biological variations regarding limited life expectancy. Other limitations of this study include the small number of patients observed in the study group, the retrospective study design, and the single-center analysis.

Conclusions

The study group had no increased risk of DVT compared with the control group. The typical clinical symptoms of DVT may be absent in the very elderly patients. Common acute illnesses among the very elderly patients, such as congestive heart failure, respiratory and urinary infections, acute myocardial infarction, sepsis, atrial tachyarrhythmia, contusion, and pulmonary edema, increased the risk of DVT. Further, an increased risk of DVT was found for cancer, lung fibrosis, hysterectomy, hyperthyroidism, and arthritis. The d-dimer value had minimal predictive value for DVT in the very elderly patients. Elderly patients with acute diseases should receive prophylaxis for DVT during hospitalization.

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.

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Relative Risk of Deep Vein Thrombosis in Very Elderly Patients Compared With Elderly Patients

Abstract

Keywords

Introduction

Materials and Methods

Patients

Statistical Analysis

Results

Discussion

Study Limitations

Conclusions

Footnotes

Declaration of Conflicting Interests

Funding

References