Tag: Covid DVT connection

Podiatry Today: Is There A Connection Between Deep Vein Thrombosis And COVID-19?

As is the case for so many aspects of the COVID-19 pandemic, information on clinical complications caused by this virus continues to emerge and evolve in real time. The majority of patients who have tested positive for COVID-19 present with symptoms of an acute respiratory illness including fever, body aches, lethargy, dry cough and breathing difficulties. However, it appears that the novel coronavirus may impact more than just the lungs, especially in severe cases.

Clinicians from around the globe report kidney damage, liver dysfunction, heart problems and, most recently, issues with blood clots such as deep vein thrombosis (DVT). These systemic complications appear to increase patient morbidity and mortality. In recent days, this issue was thrust into the media spotlight with coverage surrounding the April 12 leg amputation of Tony award-winning Broadway star Nick Cordero, who developed a DVT during his intensive care unit (ICU) hospitalization for COVID-19.

Deep vein thrombosis occurs when a blood clot forms in a large vein, usually in the calf. Swelling, pain and serious complications, such as pulmonary embolism (PE) or a sudden blockage in the lung, can occur and make DVTs a potentially fatal condition. Thus, rapid treatment is imperative. The use of venous duplex ultrasound enables clinicians to screen patients for whom there is a high clinical suspicion of thrombosis.

What We Know About DVTs 

Patients admitted to the ICU are at an increased risk for thrombolytic events due to multiple comorbidities, invasive tests and treatments, and prolonged immobilization. Physicians often attribute the elevated probability of DVT formation to Virchow’s triad, which consists of three major risk factors: venous stasis, vessel injury and hypercoagulability. The incidence of DVT during an ICU stay reportedly ranges between five and 15 percent.1 The COVID-19 virus induces a hyper-inflammatory state. Sources suggest that systemic inflammation induces endothelial injury. This will activate the coagulation cascade and impair fibrinolysis with disruption of the endothelial barrier and loss of physiologic antithrombotic factors.2 This may significantly elevate the risk for DVTs.

What Is The Latest Data On Thrombotic Events And COVID-19?

In my clinical experience, and in that of my hospital colleagues, in some severe cases, patients with COVID-19 crash hard and fast from cardiac episodes. This leads some clinicians to believe that these sudden arrests may stem from thrombolytic events, such as DVT, that they had not considered looking for. There is the hypothesis that critically-ill patients with COVID-19 patients may develop a pro-thrombotic form of disseminated intravascular coagulation (DIC) that is putting them at increased risk for thrombotic events. This concern is growing so much that the American Society of Hematology has identified this as a new pattern of clotting, which is referred to as COVID-19-associated coagulopathy or CAC.3

In a recent observational study of 184 patients, Klok and colleagues determined that the cumulative incidence of venous thrombotic complications was as high as 31 percent during ICU admissions for patients with COVID-19.4 That equates to at least a twofold increase over the median DVT occurrence rate in patients admitted to the ICU.1 The authors concluded that the study findings reinforce the addition of pharmacological thrombosis prophylaxis to treatment algorithms of all patients with COVID-19 admitted to the ICU.4

In a recent single-center retrospective analysis involving 81 COVID-19-positive patients in China who required ICU admission, Cui and coworkers evaluated patients for lower extremity DVT.5 The group found that the rate of DVT in patients with severe COVID was substantial with elevated D-dimer levels emerging as the best single predictor of clot development. In this patient cohort, a D-dimer greater than 1,500 ng/ml had an 85 percent sensitivity and 89 percent specificity for predicting which patients would develop DVT.

The American Society of Hematology recommends monitoring platelet count, partial thromboplastin time (PTT), activated partial thromboplastin time (aPTT), D-dimer and fibrinogen in all patients with COVID-19.3 Worsening of these parameters may indicate increasing severity of infection that needs more aggressive critical care. The society recommends prophylactic dosing of low-molecular weight heparin (LMWH) for all hospitalized patients with COVID-19 despite abnormal coagulation tests in the absence of active bleeding and holding off dosing only if platelet counts fall below 25×10L, or if fibrinogen is less than 0.5 g/L.3 Thromboprophylaxis via mechanical means is applicable when pharmacological prophylaxis is contraindicated.3

Although hematology experts recommend the use of low molecular weight heparin to decrease the risk of disseminated intravascular coagulation in severe cases of coronavirus, the efficacy is not yet validated. In a retrospective study conducted at Tongji Hospital in Wuhan, China, Tang and colleagues analyzed 449 patients with severe COVID-19 and 99 of these patients received low molecular weight heparin for seven days or longer.6 The 28-day mortality rate was lower in the heparin group versus the non-users in patients with a sepsis-induced coagulopathy (SIC) score of greater than four or a D-dimer greater than sixfold of the upper limit of normal. The authors concluded that anticoagulant therapy with low molecular weight heparin appears to be associated with better prognosis in patients with severe COVID-19 who meet sepsis-induced coagulopathy (SIC) criteria or have a markedly elevated D-dimer level.6 The use of anticoagulant therapy did not seem to influence mortality rate in patients without evidence of sepsis-induced coagulopathy or an elevated D-dimer level. Additional longitudinal randomized trials are necessary to validate these findings.

Are There Alternatives To Low-Molecular Weight Heparin Treatment?

Following several public promotions by President Donald Trump, the use of hydroxychloroquine to treat COVID-19 has increased. Historically, physicians use hydroxychloroquine to treat malaria, rheumatoid arthritis and lupus. Multiple clinical trials are ongoing to determine if this drug does in fact exhibit antiviral properties against the novel coronavirus. This past week media outlets reported on an unpublished analysis of the medical records of patients treated for coronavirus in Veterans Health Administration medical centers nationwide.7 This initial retrospective examination of 368 males estimates that roughly 28 percent of patients receiving hydroxychloroquine plus routine care died versus 11 percent of those receiving standard of care alone. One should note that this was not a controlled randomized clinical trial and the results are not yet vetted by the scientific community. Additional rigorous research is necessary to validate if this drug is or is not an effective therapeutic agent for the treatment of the novel coronavirus.7

Past studies demonstrate that hydroxychloroquine interferes with the immune activation of various cells such as monocytes and macrophages.8 This direct immunomodulatory effect results in inhibition of the production of pro-inflammatory cytokines, which can subsequently protect against cytokine-mediated inflammation.

Although hydroxychloroquine is not an anticoagulant, it is widely believed to have protective effects including inhibiting the development of thrombotic events such as DVT.8 This protective effect may be the most significant therapeutic benefit in patients with COVID-19. The complete mechanism of action of this drug is unknown and under investigation.

Where Do We Go From Here?

More clinical information is necessary before we can connect the dots linking COVID-19 and DVT. Until additional data is available, initiating full anticoagulation therapy to prevent DVT in these cases remains controversial. There is currently at least one clinical trial listed on clinicaltrials.gov investigating the prevalence and possible risk factors of DVT in 12 intubated and mechanically ventilated patients with COVID-19 admitted to the ICU at a single time point.9 For now, one should weigh both risks and benefits on a case-by-case basis. Going forward, podiatrists will play a vital role in prevention of DVTs in this patient population by ordering screenings for early detection and making proper referrals for patients needing prophylactic therapy. Together, we can help decrease complications and mortality in these patients.

Dr. Cole is the Medical Director of the Wound Care Center at University Hospitals Ahuja Medical Center in Beachwood, Ohio. She is also an Adjunct Professor and Director of Wound Care Research at the Kent State University School of Podiatric Medicine.

References

1. Boddi M, Peris A. Deep vein thrombosis in intensive care. Adv Exp Med Biol. 2017;906:167–181.

2. Yau JW, Teoh H, Verma S. Endothelial cell control of thrombosis. BMC Cardiovasc Disord. 2015;15:130.

3. American Society of Hematology. COVID-19 and coagulopathy: frequently asked questions. Available at: https://hematology.org/covid-19/covid-19-and-coagulopathy . Updated April 14, 2020. Accessed April 23, 2020.

4. Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020. Available at:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146714/ . Published April 10, 2020. Accessed April 23, 2020.

5. Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost. 2020. Available at: https://onlinelibrary.wiley.com/doi/abs/10.1111/jth.14830. Published April 9, 2020. Accessed April 23, 2020.

6. Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020. Available at: https://onlinelibrary.wiley.com/doi/abs/10.1111/jth.14817 . Published March 27, 2020. Accessed April 23, 2020.

7. Marchione M. Nationwide study finds malaria drug touted by President Trump leads to more deaths, no benefits in coronavirus patients. Time. Available at: https://time.com/5825398/hydroxychloroquine-study-coronavirus/ . Published April 22, 2020. Accessed April 28, 2020.

8. Schrezenmeier E, Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020;16(3):155–166.

9. U.S. National Library of Medicine.  Available at: https://clinicaltrials.gov/ct2/results?cond=COVID-19+AND+%22Embolism+and+Thrombosis%22 . Accessed April 23, 2020.

 

The National Library of Medicine: Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia.

Abstract

BACKGROUND:

Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan, China, and spread rapidly around the world. Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.

OBJECTIVES:

To determine the incidence of VTE in patients with severe NCP.

METHODS:

In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled. The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.

RESULTS:

The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died. The VTE group was different from the non-VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D-dimer, etc. If 1.5 µg/mL was used as the D-dimer cut-off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.

CONCLUSIONS:

The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis. The significant increase of D-dimer in severe NCP patients is a good index for identifying high-risk groups of VTE.

The Lancet Haematology: Attention should be paid to venous thromboembolism prophylaxis in the management of COVID-19

Since December, 2019, the coronavirus disease 2019 (COVID-19) has spread globally, infecting more than 1 million people and causing more than 70 000 deaths.

Among patients with COVID-19, especially those who are severely and critically ill, a variety of potential risk factors for venous thromboembolism exist, including infection, immobilisation, respiratory failure, mechanical ventilation, and central venous catheter use.

However, to the best of our knowledge, risk of venous thromboembolism in these patients has not yet been reported. Here we use a nationwide dataset from China to provide a delineation of venous thromboembolism risk in patients with COVID-19.

On behalf of the National Clinical Research Centre for Respiratory Disease, together with the National Health Commission of the People’s Republic of China, we collected data from 1099 patients with laboratory-confirmed COVID-19 in 31 provincial administrative regions throughout the country.

The study was supported by the National Health Commission, was designed by the investigators, and was approved by the institutional review board of the National Health Commission. Written informed consent from the patients was waived in light of the urgent need to collect data, and the fact that this was a retrospective analysis of deidentified data. Data were analysed and interpreted by the authors. Continuous variables were expressed as medians with IQR. Wilcoxon rank-sum tests were applied to continuous variables, and χ2 tests were used for categorical variables. To estimate the odds ratio (OR) associated with venous thromboembolism risk, variables including outcomes and laboratory findings that were adjusted by age (by use of logistic regression) were further analysed by logistic regression.

Research Square: COVID-19 presented with Deep Vein Thrombosis: An unusual case report

Background

On 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown cause detected in Wuhan City, Hubei Province, China. The pneumonia was caused by a virus called SARS-Cov-2, which was later named COVID-19. In this report, we present a patient with COVID-19 who developed deep vein thrombosis.

Case presentation

A 57-year-old woman presented to the clinic’s infectious department with no underlying illness due to pain, redness, and leg swelling. According to a patient report, she had a mild dry cough for the past 3 days and had no other symptoms. The patient had no history of prone thrombosis conditions. Initially, CT angiography was performed to rule out pulmonary thromboembolism, which showed no evidence of thrombosis. Dilatation and thrombosis were seen in the examinations of the paired veins of the leg, popliteal, superficial and left femoral joints, and no evidence of vascular flow suggesting acute DVT. Because of fever and lymphopenia, nasal swabs were used for sampling and SARS-CoV-2 nucleic acid was detected by RT-PCR. Chest X-ray also revealed bilateral patchy ground-glass opacity. Other tests including ANA, Anti-dsDNA, RF test and ACA test was normal. Heparin at a dose of 80 units/kg IV bolus, chloroquine 400 mg single dose and lopinavir/ritonavir (Kaletra) 400 mg twice daily were prescribed to treat illness and relieve symptoms. On illness day 3, fever stopped and nasal swab sample turned undetectable for SARS-CoV-2 by RT-PCR as well as swelling and tenderness on her leg had been disappeared gradually. She is under regular follow-up with no new symptoms to date.

Conclusion

The mechanism of DVT formation due to COVID-19 is unknown despite thrombocytopenia, and has not been investigated but it resolved as COVID-19 symptoms, tenderness, and leg pain improved. Although COVID-19 presented with Deep Vein Thrombosis is a rare condition, in middle-aged people with sudden onset of manifestations, we should recognize it from other diseases as an important and treatable differential diagnosis. Rapid diagnostic assays, efficient treatment, and prudent use of CT-scan are important to control future COVID-19 spread.

American Journal of Respiratory and Critical Care Medicine: Severe Acute Respiratory Syndrome and Venous Thromboembolism in Multiple Organs

Severe acute respiratory syndrome (SARS) is now known to be caused by a novel coronavirus, the SARS-associated coronavirus (SARS-CoV) (1). It is characterized by severe systemic symptoms in multiple organs, such as lung, immune system, and small vessels, and finally becomes respiratory failure. Initial autopsies reported the predominant pathological findings to be diffuse lung injury, injured immune organs, inflammatory response in systemic small vessels, and general toxic reaction (2).

Changes in coagulation and the development of thrombi have been reported in patients with SARS, but the extent of the effects of the SARS-associated coronavirus on the systemic circulation has yet to be established. Limited data are available on the extent of the damage to the systemic vasculature and circulation in patients with SARS. In the present study, an autopsy was performed on a 57-year-old man diagnosed with SARS and specimens from multiple organs were analyzed to assess pathological changes in the vasculature. Specimens from multiple organs, including the lungs, heart, liver, kidneys, adrenal glands, spleen, esophagus, stomach, intestine, vermiform appendix, pancreas, brain, cerebellum, brainstem, hilus of lung, mesenteric lymph node, and muscle tissues, were analyzed by light microscopy. Examination of all of the specimens revealed systemic circulatory disturbance and polyangiitis. Proliferation, swelling, and apoptosis of endothelial cells, and edema, inflammatory cell infiltration, and fibrinoid necrosis were observed in the walls of small blood vessels in specimens from the lungs, heart, liver, kidneys, adrenal glands, brain, gastrointestinal tract, and muscle tissues. In addition, thrombi were evident in the veins and microcirculation of the soft tissues surrounding the lungs, spleen, pancreas, kidneys, adrenal glands, and mesenteric lymph nodes (Figure 1A–1F).

This autopsy case report has demonstrated that in addition to the well-established diffuse alveolar damage and damage to the immune system, SARS is associated with systemic circulatory disturbance and polyangiitis, in particular thrombosis in the veins and microcirculation in multiple organs and tissues. To our knowledge, this is the first study to show the extent of the damage to the vasculature and circulation that can occur in patients with SARS.

Deep vein thrombosis and/or pulmonary embolism have been reported in patients with SARS previously (34). However, the pathogenesis of deep vein thrombosis in patients with SARS remains unknown. Emerging evidence suggests that viral infection may have a role in the onset of venous thromboembolism (56). The present study adds to this evidence by demonstrating widespread thrombosis associated with SARS.