A decision by Brigham and Women’s Hospital in the early days of the COVID-19 pandemic is helping patients hospitalized with the virus avoid two potentially fatal complications: deep vein thrombosis (DVT) and pulmonary embolism (PE). The Brigham’s protocol to give all hospitalized patients a prophylactic anticoagulant dose of low-molecular-weight heparin (LMWH) addresses blood clot risk factors that are particularly acute in patients with COVID-19.
“People with the virus, especially if they’re severely infected, have a strong pro-inflammatory response that drives up the levels of procoagulant proteins such as fibrinogen and factor VIII, and the virus damages the vascular endothelium,” explained Jean Marie Connors, MD, medical director, Anticoagulation Management and Stewardship Services, of the Brigham’s Hematology Division. “The damage from the inflammation, coupled with high procoagulant protein levels and an immobilized patient, sets the stage for harmful blood clots.”
According to Dr. Connors, this thromboinflammation relationship—in which inflammation interacts with and activates coagulation pathways and the proinflammatory cytokines that are produced in trying to fight off the virus—appears to be particularly strong in patients with COVID-19. When thromboinflammation results in DVT or PE blood clots, or in microvascular thrombosis, the lungs can’t get enough oxygen, leading to heart strain and the shortness of breath that is a common symptom of COVID-19.
Establishing COVID-19 Protocols
As part of its pandemic response, the Brigham quickly mobilized a hospital-wide incident command center and a COVID-19 management team. In addition to Dr. Connors and her colleagues in hematology, the COVID-19 team includes Brigham experts in infectious disease, surgical intensive care, cardiology, pulmonary critical care and other specialties.
The team created a set of COVID-19 Clinical Guidelines that are updated regularly based on pertinent published medical literature, national and state guidelines and/or expert consensus. In addition to giving all hospitalized patients a prophylactic dose of anticoagulants, the guidelines call for measuring patients’ coagulation factors including fibrinogen and D-dimer at admission and every three days thereafter.
“As the medical community continues to gather data on patients with COVID-19, we’re seeing a correlation between elevated D-dimer markers and increased mortality in patients who have more severe infections or have had the infection longer,” Dr. Connors said. “The Brigham is being aggressive by monitoring patients and providing prophylaxis anticoagulants to more than 93 percent of those hospitalized with COVID-19, and we’re starting to see a lower rate of venous thromboembolism compared with some other countries.”
As part of the multidisciplinary COVID-19 team, Dr. Connors regularly presents information about hematological implications of COVID-19 to other Brigham specialists. She recently shared details about coagulation to the surgical intensive care staff and fielded questions about how to manage patients with blood clots, how to deal with patients whose dialysis filters clot and considerations for moving patients with suspected PE from their bed to a CT scanner, among other topics.
Responding to an Evolving Threat
Dr. Connors cautioned that because COVID-19 is constantly evolving, patient data and practice guidelines are evolving as well. As of this writing, for example, she and Brigham colleagues in infectious disease and pulmonary critical care are discussing whether or not to move to higher doses of prophylactic LMWH in patients in the ICUs and are analyzing the incidence of blood clots in patients specifically at the Brigham.
“Prophylactic anticoagulant dosing is not well-studied in patients in the ICU because the overall rates are low in other situations,” she said.
Dr. Connors and the team are currently investigating performing clinical trials to address the question of appropriate dosage of anticoagulation in Brigham patients with COVID-19.
“However, we are starting to see randomized control trials of anti-inflammatories,” she concluded. “This is important because even if you prevent microvascular thrombosis or PE, if you don’t stop the inflammation, patients will not improve. That’s why the Brigham is focused on delivering the best care to prevent problematic blood clots and the inflammation associated with the infection.”