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SPECIAL SECTION on COVID-19 and PM&R

Screening for Deep Vein Thrombosis in Persons With COVID-19 Upon Admission to an Inpatient Rehabilitation Hospital

Kirshblum, Steven C. MD; DeLauter, Gabrielle MPH; Eren, Fatma MD; Pomeranz, Bruce MD; DeLuca, Robert BS; Hammerman, Samuel MD; Gans, Bruce M. MD

Author Information
American Journal of Physical Medicine & Rehabilitation: May 2021 - Volume 100 - Issue 5 - p 419-423
doi: 10.1097/PHM.0000000000001729
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Abstract

What Is Known

  • An increased risk of deep vein thrombosis (DVT) has been reported in hospitalized patients with COVID-19 infection in intensive and nonintensive care units. However, there have been no data regarding the incidence of DVT in patients being admitted to an acute inpatient rehabilitation hospital (IRH) nor any recommended surveillance for DVT upon admission to an IRH.

What Is New

  • This study reports a high rate of lower limb DVT in asymptomatic patients admitted to an IRH with a diagnosis of COVID-19 and strongly suggests greater surveillance of such patients.

COVID-19 (coronavirus disease 2019), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions of people around the world. COVID-19 was labeled a global pandemic by the World Health Organization on March 11, 2020,1 and as of February 02, 2021, the virus has caused more than 2,248,365 deaths worldwide with more than 446,272 of them in the United States.2

COVID-19 predisposes patients to venous thromboembolic (VTE) disorders, which encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE), due to numerous factors including excessive inflammation, hemostatic abnormalities, endothelial dysfunction, and stasis.3 In addition, the severe inflammatory response, critical illness, and underlying traditional risk factors of immobility may all predispose for thrombotic events. Numerous studies have documented high rates of VTE in hospitalized patients with COVID-19.4–21 These studies most commonly report rates of 15%–30% of acutely hospitalized patients developing VTE, with wide variability. For example, Zhang et al.18 reported an incidence of lower limb DVT in 46.2% of their hospitalized sample, whereas a larger study of nonintensive care unit (ICU) hospitalized patients reported a 3.6% incidence of VTE, although, in this later study, patients were only evaluated if symptomatic.5 Incidence of DVT seems to be higher in patients who required treatment in the ICU versus those in general hospital beds and with an increased incidence of PE relative to DVT.5,7,10,13,20,22 From a systematic review and meta-analysis by Nopp et al.,13 VTE occurred in 22.7% of patients with COVID-19 in the ICU, but VTE risk was also increased in non-ICU hospitalized patients. Of note was that COVID-19 patients who developed VTE had D-dimer levels that on average were 3.26 μg/ml higher than COVID-19 patients who did not develop a VTE.13 This is consistent with other studies that found that elevated D-dimer while in medical wards increased the risk of being diagnosed with a DVT.19,23,24

Asymptomatic VTE can lead to significant medical complications.25 For this reason, screening duplex scanning of the lower limbs for DVT was performed in a number of studies on acutely hospitalized patients diagnosed with COVID-19.6,8,14,18,19,21,22 In the ICU setting, Llitjos et al.21 performed routine duplex ultrasound screening and detected a DVT in 54% of patients. Nahum et al.14 performed screening at admission to the ICU (n = 34) and observed DVT in 65% of patients, with 24% having a proximal DVT. An additional 15% of patients were diagnosed with a DVT when the scans were performed 48 hrs after ICU admission.14 After the screening of all patients admitted to the ICU between 5 and 10 days after admission, Longchamp et al.8 found that 24% (6/25) had a proximal DVT despite adequate thromboprophylaxis. Ren et al.6 reported a high overall DVT rate of 85.4% (41/48), with 10.4% (5/48) being a proximal DVT, in their ICU patients on screening ultrasound. Zhang et al.18 reported a prevalence of 16.1% proximal DVT by screening ultrasound in both ICU and non-ICU patients with COVID-19. In the non-ICU setting, Demelo-Rodríguez et al.19 reported an incidence of 14.7% of asymptomatic DVT by screening patients with COVID-19 pneumonia with elevated D-dimer levels.

One autopsy study of 12 consecutive COVID-19–positive deaths revealed DVT in 58% of the patients in whom VTE was not suspected before death, and PE was the direct cause of death in four patients (33%).16 On this basis, screening for DVT is extremely important in this high-risk population.

Although DVT is known to be an early complication of COVID-19, studies with longer follow-up have shown that a considerable number of occurrences were diagnosed during the weeks after acute hospital admission including after hospital discharge, revealing that DVTs may arise in any phase of COVID-19.7,22,26 As such, longer-term monitoring of patients with the diagnosis of COVID-19 for VTE especially during postacute care hospitalization is important. Artifoni et al.23 evaluated non-ICU patients who were hospitalized with COVID-19 for more than 48 hrs by performing bilateral lower limb duplex ultrasounds at the time of discharge and found a rate of 18.8% (13/69) having an asymptomatic DVT. Roberts et al.26 reported nine VTE episodes associated with COVID-19 within 42 days of 1877 hospital discharges with a rate of 4.8 per 1000 discharges. Of those, two individuals had a proximal DVT and seven experienced a PE.

The frequency of a positive DVT in acute rehabilitation hospitals with routine duplex screening has varied, and generally, rates are between 6.5% and 18% for higher-risk groups including in persons with traumatic spinal cord and brain injury, as well as amputations.27,28 Patients with severe COVID-19 who survive the hospitalization often have neurologic or other functional deficits that require acute in-patient rehabilitation.29 However, to date, there has been no information regarding the incidence of DVT in patients admitted to a rehabilitation hospital published. In addition, no recommended surveillance guideline for VTE incidence upon admission to such facilities has been available.

New York City and Northern New Jersey were particularly hard hit early in the COVID-19 pandemic.30 Three acute inpatient rehabilitation hospitals (IRHs) located in Northern New Jersey that serve counties that had the largest numbers of COVID-19 cases in the state and are in close proximity to New York City were included in this study. The recommendation within this health system of care was to screen all admissions for DVT using duplex ultrasonography, although each physician made the decision to do so independently. The objective of this retrospective study was to describe the rate of DVT in patients admitted to our IRH who were diagnosed with COVID-19. We hypothesized that the frequency of previously undiagnosed DVT detected by duplex ultrasound screening in patients diagnosed with COVID-19 would be similar or greater than other high-risk groups upon admission to the IRH.

MATERIALS AND METHODS

After the institutional review board review and approval, the medical records of all patients with laboratory-proven COVID-19 admitted to one of the three IRHs between April 4 and May 23, 2020, were reviewed. (The initial plan was for a sample of 150 patients.) Patients with a diagnosis of VTE during their acute hospital course before transfer, as well as patients who had received a screening ultrasound test within 3 days before transfer, were excluded. (These patients were excluded as we focused on undiagnosed DVTs close to the time of transfer to the IRH.)

For patients found to be eligible, factors recorded included age, sex, race, body mass index (BMI), medical comorbidities, ventilator use during their acute hospitalization, and type of VTE thromboprophylaxis received in the acute care hospital. In addition, admission Section GG: Functional Abilities and Goals subscale scores from the Inpatient Rehabilitation Facility–Patient Assessment Instrument were combined to calculate a patient’s average self-care and mobility score. These subscale scores combined the scores from the following actions: eating, hygiene (oral and toileting), shower/bathe, upper/lower dressing, footwear, sit to lie down, sit to stand, chair transfer, toilet transfer, walk 10 feet, walk 50 feet, one step, bladder, and bowel were recorded. Lastly, length of the rehabilitation hospitalization and days since diagnosis of COVID-19 to the IRH admission were captured. The screening duplex ultrasound study of both lower limbs was performed within 72 hrs of admission to the rehabilitation hospital.

The primary outcome measure was the presence of a lower limb DVT, including proximal to the knee (located in the popliteal, femoral, or iliac veins) and distal clots, on duplex ultrasound scan. A board-certified radiologist completed all readings. Secondary factors included potential risk factors for screening positive for a DVT.

Statistical Analysis

Descriptive analyses were conducted to study the association between variables in relation to a positive DVT scan. Pearson χ2 and Fisher exact tests were conducted for categorical variables, as appropriate. Welch t test was also used for all continuous variables. In addition, univariate and multivariate logistic regressions were performed on clinical comorbidities in relation to a positive DVT scan and a positive proximal DVT scan. The analysis was conducted using R Studio Version 1.3.1056 and was considered statistically significant at a P value of less than 0.05.

RESULTS

One hundred sixty-nine persons with COVID-19 confirmed in the acute hospital were admitted to one of the three acute IRH during the time designated for this study and met the inclusion criteria. Of these, 113 (67%) received a duplex ultrasound scan of both lower limbs. Of the 56 patients not screened, 36 (64%) were already on full-dose anticoagulation for other diagnoses (e.g., atrial fibrillation), so the attending physician chose not to order the test. For the remainder of patients (n = 20), the physician indicated that the patient did not need a study because of their mobility status, and in a few cases, there was no documented reason for not ordering the test.

Patients from the three IRHs did not significantly differ in age, BMI, sex, number of days from COVID-19 diagnosis to rehabilitation admission, ventilator status during the acute care hospitalization, or self-care and mobility ability at admission and therefore were combined for analysis (Table 1).

TABLE 1 - Demographic data and results of overall sample
All Patients (N = 169) Patients Not Tested (n = 56) Patients Tested (n = 113)
Age, yr 65.6 (21–101) 65.6 (31–95) 65.5 (21–101)
Mean (range)
Sex (female:male) 64:105 19:37 45:68
Race
 White 109 39 70
 Black 38 10 28
 Asian 7 3 4
 Other 15 4 11
BMI
 Mean 28.4 29 28
 Median 27.7 28.1 27.7
 Range 14.9–56 19–56 15–51.7
Days from diagnosis of COVID to rehabilitation, mean (range) 22.5 (3–69) 19.6 (3–54) 23.8 (3–69)
Rehabilitation LOS, mean (range) 20.9 (4–93) 17 (4–55) 22.9 a (5–93)
Ventilation during acute hospitalization, n (%) b 70 (41.4) 22 (39.3) 48 (42.5)
GG scores
 GG subscale admit 40.8 43.1 39.7
GG, Section GG: Functional Abilities and Goals subscale scores from the Inpatient Rehabilitation Facility–Patient Assessment Instrument; LOS, length of stay.
aIndicates a significant P < 0.05.
bAcute care ventilation status was missing for one patient.

Of the patients tested (n = 113) on admission to our facilities, 22% (25/113) were found to have a lower limb DVT. Of those 25 patients, 32% (8/25) had a proximal lower limb DVT, accounting for 7.1% of the total sample screened (Table 2). Risk factors for a positive DVT included sex (male > female, P = 0.039) and having been on a ventilator during the acute care hospitalization (P = 0.049). Sixty percent of the patients who were on a ventilator at the acute hospital before transfer screened positive. Younger age was also strongly correlated with screening positive (P = 0.024). Race, BMI, and days to rehabilitation were not risk factors for screening positive for a DVT.

TABLE 2 - Demographic and risk factor data for patients screened with lower limb duplex scan upon admission
Duplex Negative on Admission (n = 88, 77.9%) Duplex Positive on Admission (n = 25, 22.1%) Proximal (n = 8) Distal (n = 17)
Age, yr 67.3 59.5 a 59.9 59.3
Mean (range) (21–101) (33–87) (45–71) (33–87)
Sex (female:male) 40:48 (88.9%:70.6%) 5:20 a (11.1%:41.7%) 1:7 4:13
Race
 White 54 (77.1%) 16 (22.9%) 5 11
 Black 21 (75%) 7 (25%) 2 5
 Asian 3 (75%) 1 (25%) 1 0
 Other 10 (90.9%) 1 (9.1%) 0 1
BMI
 Mean 28 28.3 28.7 28.1
 Median 27.32 27.9 28.2 27.7
 Range 14.9–27.3 16–39.6 21.7–34.7 16.0–39.6
Medical comorbidities
 HTN 21 (80.8%) 5 (19.2%) 1 4
 Obesity 9 (75%) 3 (25%) 0 3
 DM 26 (76.5%) 8 (23.5%) 4 4
 Kidney disease 16 (66.7%) 8 (33.3%) 1 7
 Respiratory disease 12 (80%) 3 (20%) 1 2
 Immunosuppression 10 (76.9%) 3 (23.1%) 1 2
 Cardiac disease 45 (77.9%) 13 (22.4%) 4 9
 DVT 10 (62.5%) 6 (37.5%) 2 4
Medication on transfer
 Prophylactic dosages
  Lovenox 44 (80%) 11 (20%) 4 7
  ASA 0 (0%) 1 (100%) 0 1
  Heparin 5000 BID/TID 6 (60%) 4 (40%) 1 3
 Treatment dosage
  Eliquis 11 (77.3%) 4 (26.7%) 2 2
  High-dose Lovenox 11 (78.6%) 3 (21.4%) 1 2
  Warfarin 2 (100%) 0 (0%) 0 0
  Xarelto 1 (50%) 1 (50%) 0 1
  None 13 (92.9%) 1 (7.1%) 0 1
Days from diagnosis of COVID to rehabilitation, mean (range) 23.6 (3–69) 24.5 (5–67) 22.9 (13–41) 25.2 (5–67)
Rehabilitation LOS, mean (range) 21.5 (5–93) 28 (7–64) 28.8 (14–63) 22.5 (5–93)
Ventilation during acute hospitalization 33 (37.5%) 15 a (60%) 4 (57.1%) 44 (41.9%)
GG scores
 GG subscale admit 39.8 39.4 40.3 (19–73) 39.6 (18–83)
ASA, acetylsalicylic acid; BID, twice a day; DM, diabetes mellitus; GG, Section GG: Functional Abilities and Goals subscale scores from the Inpatient Rehabilitation Facility–Patient Assessment Instrument; HTN, hypertension; LOS, length of stay; TID, 3 times a day.
aIndicates a significant P < 0.05.

The use of aspirin or unfractionated heparin (either 2 or 3 times per day) was associated with a positive ultrasound study relative to prophylactic low–molecular-weight heparin (e.g., enoxaparin sodium at 30 mg twice a day or 40 mg/d); 20% (11/55) vs 45.5% (5/11), but this observation was not statistically significant (P = 0.12).

There was no statistically significant difference between certain comorbidities, including hypertension, diabetes mellitus, kidney disease, obesity, cardiac disease, respiratory disease, being immunocompromised (including diagnoses such as multiple sclerosis and rheumatoid arthritis), and screening positive for a DVT on IRH admission. Age, BMI, sex, comorbidities, number of days from COVID-19 diagnosis to rehabilitation admission, ventilator status during the acute care hospitalization, or self-care and mobility ability at admission did not differ with the location of the DVT being proximal or distal.

DISCUSSION

This study sought to test the hypothesis that the frequency of silent DVT detected by duplex ultrasound screening in patients diagnosed with COVID-19 would be similar or greater than patients with high-risk diagnoses being admitted to an IRH. Despite chemoprophylaxis, this study found a high rate (22%) of lower limb DVT, including 7.1% with a proximal DVT. Risk factors associated with a positive scan included being male, younger in age, and having required ventilator management during the acute hospitalization. This is an important finding and emphasizes the continued risk for the development of VTE in persons with COVID-19. Although the importance of longer-term prophylaxis in patients with COVID-19 has been documented,3,31 this is the first documentation of the high rate of undetected DVT in persons transferring to an IRH.

The risk factor of requiring ventilator management is not surprising, given the previous data suggesting that requiring ICU care was a risk factor.5,7,10,13,20,22 Ventilator status was viewed as a marker of severity of COVID-19 illness, as this information was documented in all transfer information, whereas determining whether the patient had been in the ICU was more difficult to obtain. Similar to acute hospital studies, the rate of DVT on admission to an IRH was considerable in asymptomatic patients including in patients on appropriate thromboprophylaxis. The rates of positive scans at admission to an IRH interestingly were similar to those found during acute hospitalizations,8,14,15,18–20,23 although higher than other studies.7,22 A noticeable portion of individuals on therapeutic treatment doses of anticoagulants for other reasons also had a positive scan, perhaps reflecting their high risk overall. Younger age being a risk factor has been described as Poissy et al.17 reported younger age as a risk factor in COVID-19 patients who experienced a PE. In contrast, Zhang et al.18 reported that older age was associated with positive DVT in hospitalized patients with COVID-19. Marone et al.7 found that male individuals were predominant among those found positive for a DVT, which is similar to the findings in our study. Similar to previous findings,6 there did not seem to be differences in risk factors for patients who developed a proximal lower limb DVT to those who developed distal lower limb DVT.

Given the significant risk of developing VTE after severe COVID-19, these results suggest a low threshold of suspicion to conduct screening duplex scans upon admission to an IRH, especially for those patients with risk factors. Further study is needed to better understand the duration of the risk of VTE in patients with COVID-19, but this study can help guide the design of controlled trials on VTE surveillance.

Study Limitations

A limitation of this study was that not all patients upon admission were scanned. Nevertheless, most admitted patients (83%; 113/133) were studied. Another limitation was that D-dimer was not used to determine risk factors, as these tests were not available in our sample. In the future, this risk factor would be important to consider.32

CONCLUSIONS

This is the first study to evaluate the frequency of silent DVT in patients with a diagnosis of COVID-19 upon admission to an IRH. Despite chemoprophylaxis, a high rate of 22% for lower limb DVT was diagnosed upon admission to an IRH among patients with a previous diagnosis of COVID-19. This high rate suggests that the risk of VTE remains strong for an extended period in these patients. Surveillance screening of high-risk patients including those with previously diagnosed severe COVID-19 (as defined by previous requirement of mechanical ventilation) should be undertaken in postacute care venues to prevent future thromboembolic complications. Future studies should consider the association between elevated D-dimer and VTE among COVID-19 patients within postacute setting.

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Keywords:

Deep vein Thrombosis; COVID-19; Duplex Ultrasonography

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