Editor’s note: Our understanding of the clinical picture of COVID-19 is rapidly evolving as the current pandemic unfolds. One important aspect of the disease is what appears to be a greater risk of blood clots, particularly in people with severe disease. Unfortunately, clinicians are faced with managing patients with this serious complication without complete knowledge of the exact cause, best diagnostic approach, or best treatment for each individual.
The International Society on Thrombosis and Haemostasis has collected a number of studies and case reports on thrombosis in COVID-19 patients. The Journal of American College of Cardiology released a review of current understanding, citing many of the studies and case reports which are on the ISTH site. This COVID-19 pandemic challenges us to use current knowledge and innovate new approaches to care for patients diagnosed with COVID-19.
This article seeks to summarize some of the current knowledge about thrombosis in COVID-19 patients, knowing that future studies and case reports will undoubtedly refine the statements made below.
However, this is the way that science works. It is continually evolving and improving based on current data and understanding. With that, this article offers some insights about VTE in patients admitted to the hospital who have been diagnosed with COVID-19. Pat Salber, MD, Editor-in-Chief
Greater Risk of Blood Clots in COVID-19 Patients
Authors*: Michael Wong, JD; Laurie Paletz, RN, Thereza Ayad, RN
There have been reports about the development of venous thromboembolism (VTE) in patients with COVID-19. Such reports highlight a lack of awareness of evidence-based best practices in managing VTE in different subsets of patients, including the following:
- Patients who have been diagnosed with COVID-19
- People at risk of developing COVID-19
- Patients that are currently on anticoagulant therapy for other chronic medical conditions
Given the uncertainty of exactly what constitutes proven best practices, we felt it important to review what is currently known and what is not about the management of blood clots in patients with COVID-19.
The challenge of practicing without sufficient evidence-based best practices on blood clots in COVID-19 patients
Hypothesizing a solution to a high criticality problem like COVID-19 may result in harm and death. Massachusetts General Hospital in its hematology guidance for COVID-19 patients cautions against the administering tPA, saying, “currently, there is insufficient data to suggest using more advanced therapies (such as tPA) in critically ill COVID-19 patients and we do not recommend it at this time.” (tPA is commonly referred to as a “clot buster” and is administered intravenously for ischemic or thrombotic stroke.)
The LA Times reported that a doctor in New York, “took a gamble” by administering “a low-dose drip of tPA for about 24 hours, together with a blood thinner.” While this bought the patient “a few more days of life. A sudden, different complication killed her” a few days later. The LA Times article notes that whether the doctor’s actions were correct or not, it is all guesswork without sufficient evidence-based best practices:
“We’re taking care of extremely ill patients that are dying in front of us, and we can’t get any diagnostic testing, yet still have to make treatment decisions,” said Dr. Steven Pugliese, a pulmonologist at the University of Pennsylvania.
What do we currently know about treating blood clots in COVID-19 patients?
Our understanding of COVID-19 symptomatology is evolving as the current pandemic unfolds. However, there are current studies and patient case reports that provide us some insights about VTE in patients admitted to the hospital who have been diagnosed with COVID-19.
#1 – Patients with COVID-19 have an increased incidence of thrombotic complications
Frederikus A. Klok MD, Ph.D. (Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, Netherlands) and his colleagues studied 184 ICU admitted patients diagnosed with COVID-19 and found that 31% of these patients developed thrombotic complications (published in April 2020 in Thrombosis Research).
In addition, in studying 198 hospitalized patients diagnosed with COVID-19, Saskia Middeldorp, MD and her colleagues at the University of Amsterdam, in the Netherlands found [confidence intervals removed] “33 patients (17%) were diagnosed with VTE of whom 22 (11%) had symptomatic VTE, despite routine thrombosis prophylaxis. The cumulative incidences of VTE at 7 and 14 days were 15% and 34%, respectively. For symptomatic VTE, these were 11% and 23%. VTE appeared to be associated with death. The cumulative incidence of VTE was higher in the ICU than on the wards.”
#2 – Thrombotic complications are occurring even in young patients with COVID-19
In a letter submitted and published in the New England Journal of Medicine (April 2020), doctors at Mount Sinai in New York reported five patients who suffered large vessel strokes in patients under the age of 50. What these Mount Sinai found troubling is that all five of these patients “presented with new-onset symptoms of large-vessel ischemic stroke.” The youngest patient was 33 and only one patient had a history of stroke.
#3 – High mortality rates occur in COVID-19 patients presenting with thrombotic complications
Ning Tang, MD et al (Tongji Medical College in Wuhan, China) studied the results and outcomes of 183 consecutive patients admitted to their hospital who were diagnosed with COVID-19. In their research published April 2020 in the Journal of Thrombosis and Haemostasis, they found “abnormal coagulation results” and a mortality of 11.5%.
Recommendations for clinicians treating COVID-19 patients with suspected blood clots
Do these studies and case reports indicate the best course of detection, diagnosis, and therapeutic treatment? Probably not.
What may seem like logical inferences to laypeople remain just unproven observations in the realms of science and medicine, where incorrect inferences may lead to adverse events and patient deaths.
However, given the need for urgent care of patients diagnosed with COVID-19, caring for critically-ill and dying COVID-19 patients may not be able to wait for randomized clinical trial evidence.
Consequently, there is an immediate need for guidelines and recommendations that clinicians can use to help prevent and treat thrombosis in COVID-19 patients.
Here are two recommendations for clinicians, which could be a start for these guidelines and recommendations:
#1 – Understand that diagnosis of VTE in COVID-19 patients is challenging
Of the 183 patients studied by Dr. Tang and his colleagues, “non-survivors revealed significantly higher D-dimer and fibrin degradation product (FDP) levels.”
Elevated D-dimer and elevated fibrinogen may be two indicators of VTE onset in COVID-19 patients. However, as Suzanne C Cannegieter MD, Ph.D. and Frederikus A Klok MD, Ph.D. write in their commentary, “COVID-19 associated coagulopathy and thromboembolic disease,” diagnosis of VTE in COVID-19 patients may be difficult:
“For several reasons, diagnosing VTE in patients with COVID-19 may be challenging: as described above, elevated D-dimer levels is a common nonspecific finding in patients with COVID. However, clinical probability dependent D-dimer levels could be used even in these patients. For critical patients with severe ARDS who require prone positioning, radiological imaging for PE may not be directly possible.
An option may be to consider echocardiography to assess for signs of worsening right ventricular overload, especially in patients experiencing hemodynamic collapse. Nevertheless, suspicion for VTE should be high in the case of hypoxemia disproportionate to other known respiratory pathologies, acute unexplained right ventricular dysfunction, or unexplained leg swelling or pain. In the latter situation, (bedside) 2-point compression ultrasonography may help in avoiding CT scanning if proximal DVT is confirmed.”
In terms of relevance for optimal patient care, perhaps a diagnosis of VTE in COVID-19 patients should not be a pre-condition for treatment administration. This leads to guidance #2.
#2 – Administer VTE prophylaxis to all COVID-19 patients admitted to hospital
The assessment of clinical experts is that all admitted patients with COVID-19 should be administered VTE prophylaxis and this prophylaxis should be started early. (See ISTH’s webinar, “Thrombotic and Hemostatic Issues in Critical Care Units Managing COVID-19” given by Jerrold H. Levy, MD, Anesthesiologist at Duke University Medical Center, Nicole P. Juffermans, MD, PhD., Professor of Translational Intensive Care Medicine at the University of Amsterdam’s Faculty of Medicine, and Jean Marie Connors, MD Associate Professor of Hematology, Harvard Medical School).
Massachusetts General Hospital (MGH) in its hematology guidance for COVID-19 patients recommends that “All patients admitted to MGH for COVID-19 (including non-critically ill) should receive standard prophylactic anticoagulation with LMWH [bolded by MGH].” LMWH (low-molecular-weight heparin) is a class of anticoagulant medications. They are used in the prevention of blood clots and treatment of venous thromboembolism (deep vein thrombosis and pulmonary embolism) and in the treatment of myocardial infarction.
In patients who are bed-ridden, which may be most if not all critically-ill COVID-19 patients, the World Health Organization recommends mechanical VTE prophylaxis (e.g. intermittent pneumatic compression) be considered.
Sharing clinical information about blood clots in COVID-19 patients is important
In addition to the need for guidelines and recommendations, we would encourage the sharing of information through:
- Continuing medical/nursing education courses, lectures, and webinars which would allow clinicians to learn from their colleagues and other clinical experts.
- A consortium of clinical experts, who could prepare guidelines and recommendations, and revise these based on new scientific knowledge.
- A chat line or other social sharing network (such as Facebook) where clinicians could consult with and learn from colleagues and other clinical experts and share best practices such as changes to policies and new clinical practice guidelines as they emerge.
Questions, answers, and recommendations for patients concerned about COVID-19 and blood clots
For patients, which means all of us including those working in healthcare, what can be concluded from this?
Below are three questions that patients diagnosed with cardiovascular disease may have:
Q1: If I have been diagnosed with cardiovascular disease, am I more at risk of getting COVID-19?
According to the American College of Cardiology (ACC), 10.5% of people (about 1 in 10) who died from coronavirus had a cardiovascular condition.
To put this into perspective, the ACC highlights these statistics about deaths due to COVID-19:
- 8% were patients 70-79 years old and 14.8% were patients older than 80 years old.
- Death in patients who were also diagnosed with:
- Cancer: 5.6%
- Hypertension: 6.0%
- Chronic respiratory disease: 6.3%
- Diabetes: 7.3%
Q2: If I’m taking an anticoagulant, does this increase my risk of getting COVID-19?
According to the International Society on Thrombosis and Haemostasis:
- Taking an anticoagulant will not increase your risk of getting COVID-19 (commonly called “coronavirus”).
- However, if you have an underlying condition, treatment of that condition may cause your body’s immune system to be suppressed. That suppression could increase your risk of getting COVID-19.
Q3 – If I go to the hospital to get treated, will I just get infected by COVID-19 there?
If you are ill and this is a medical emergency, please call 9-1-1 or go to the nearest emergency department. A delay in treatment may only make your illness worse.
As the Mount Sinai doctors reported, a previously healthy 33-year-old woman “delayed seeking emergency care because of fear of Covid-19” By the time she was admitted to hospital, her National Institutes of Health Stroke Scale (NIHSS) was 19 (a score of 16 or more forecasts a high probability of death or severe disability whereas a score of less than or equal to 6 forecasts a good recovery). Thankfully, she was treated and discharged to a rehabilitation facility.
Hospitals around the country have taken precautions to ensure your safety, including:
- Testing admitted patients.
- Ensuring patients diagnosed with COVID-19 are separated from non-positive patients.
- Ensuring the hospital staff wears masks and other protective gear.
- Prohibiting/limiting visitors to decrease the number of people gathering.
- Encouraging as much physical distancing as possible
The CV Virtual Clinic offers help to get your questions about COVID-19 and blood clots answered
If you have other questions, the Physician-Patient Alliance for Health & Safety recently launched a free online service (the CV Virtual Clinic) where patients can speak with experienced registered nurses and get personalized answers to their questions.
The CV Virtual Clinic has been made possible by the generous grant support of BMS-Pfizer Alliance, as well as the efforts and resources of the the following organizations:
- American Heart Association,
- AC Forum,
- Heart Rhythm Society,
- Mended Hearts, and
- Preventive Cardiovascular Nurses Association.
To read more about it, please click here.
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*This article was authored by Michael Wong (Founder/Executive Director, Physician-Patient Alliance for Health & Safety), Laurie Paletz, BSN PHN RN BC SCRN (Manager, Stroke Program Department of Neurology, Cedars-Sinai), and Thereza B. Ayad, RN, MSN, DNP, CNOR (Assistant Professor, University of Massachusetts Medical School-Graduate School of Nursing; Surgical Services Clinical Staff Educator, North Shore Medical Center). It was also reviewed by Sue Koob, Chief Executive Officer, Preventive Cardiovascular Nurses Association.