Authors: Dhauna P. Karam, MD1
Incidence of thrombotic complications in patients with COVID-19 who are critically ill is high, with an estimated incidence of 31% for arterial or venous thromboembolism (VTE), acute pulmonary embolism, ischemic stroke, and myocardial infarction. On the basis of the study by Klok et al,1 pulmonary embolism was the most common thrombotic complication in critically ill patients with COVID-19 despite being on standard anticoagulation. Prevention of thromboembolism with anticoagulants is recommended in all critically ill patients with COVID-19.
The American Society of Hematology (ASH) guideline panel (updated April 7, 2021) recommends prophylactic anticoagulation in all critically ill patients with COVID-19 without suspected or confirmed venous thromboembolism (VTE). ASH defines patients with COVID-19 critical illness as someone who is suffering from a life-threatening condition, typically admitted in an intensive care unit. It is recommended that individualized assessment of the patient’s thrombotic and bleeding risk needs to be performed before deciding on anticoagulation.2 What about hospitalized patients with COVID-19 who are not critically ill? What are some clinical parameters that can be used to guide decisions on anticoagulant use in such patients?
The accompanying manuscript by Gaddh et al3 reports guidelines used in a large academic institution, Emory University School of Medicine, Atlanta, Georgia, to determine anticoagulation in hospitalized patients with COVID-19. The guidelines were created by a multidisciplinary panel of experts and were incorporated into frontline care at Emory. The three-tiered algorithm was used to risk stratify patients admitted with a primary diagnosis of COVID-19. It was not recommended for use in patients incidentally found to have COVID-19 during hospitalization for other causes. On the basis of the guidelines, patients with normal D-dimer, no evidence of thromboembolism and not critically ill were given prophylactic anticoagulation (group 1). Patients with elevated D-dimer (> 6 times upper limit normal) with no evidence of thromboembolism and not critically ill were given intermediate-dose anticoagulation. Patients critically ill without any evidence of thromboembolism and without elevation of D-dimer were also given intermediate-dose anticoagulation. Patients with confirmed thromboembolism or those with other markers of possible thromboembolism (worsening hypoxia or pulmonary status without identifiable cause and limb edema) received therapeutic anticoagulation. Anticoagulation was continued for 1 week after discharge in group 1 patients. Group 2 received anticoagulation for 4-6 weeks after discharge. Finally, group 3 received anticoagulation for minimum 3 months postdischarge. Preliminary findings revealed low bleeding complications. Data on type of anticoagulant used, incidence of thromboembolism in the hospitalized group following the above guidelines, and improvement in morbidity and mortality rates were not provided. The algorithm is a simple, practical statement, which can guide frontline caregivers until evidence-based recommendations become available. Group 1 and 3 recommendations are supported by major organizational guidelines such as ASH and International Society on Thrombosis and Haemostasis (ISTH). Preliminary guidelines from these organizations refrain from commenting strongly on intermediate-dose anticoagulation in the absence of supporting data from clinical trials but do support anticoagulant dose escalation on the basis of clinician’s assessment for high-risk patients.2,4
For More Information: https://ascopubs.org/doi/full/10.1200/OP.21.00359
Authors: Geoffrey D Wool 1, Jonathan L Miller 2
Coronavirus disease 2019 (COVID-19) causes a spectrum of disease; some patients develop a severe proinflammatory state which can be associated with a unique coagulopathy and procoagulant endothelial phenotype. Initially, COVID-19 infection produces a prominent elevation of fibrinogen and D-dimer/fibrin(ogen) degradation products. This is associated with systemic hypercoagulability and frequent venous thromboembolic events. The degree of D-dimer elevation positively correlates with mortality in COVID-19 patients. COVID-19 also leads to arterial thrombotic events (including strokes and ischemic limbs) as well as microvascular thrombotic disorders (as frequently documented at autopsy in the pulmonary vascular beds). COVID-19 patients often have mild thrombocytopenia and appear to have increased platelet consumption, together with a corresponding increase in platelet production. Disseminated intravascular coagulopathy (DIC) and severe bleeding events are uncommon in COVID-19 patients. Here, we review the current state of knowledge of COVID-19 and hemostasis.
For More Information: https://pubmed.ncbi.nlm.nih.gov/33049751/
Authors: Jia Yu, Xuan Yuan, Hang Chen, Shruti Chaturvedi, Evan M. Braunstein, Robert A. Brodsky
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious respiratory virus that can lead to venous/arterial thrombosis, stroke, renal failure, myocardial infarction, thrombocytopenia, and other end-organ damage. Animal models demonstrating end-organ protection in C3-deficient mice and evidence of complement activation in humans have led to the hypothesis that SARS-CoV-2 triggers complement-mediated endothelial damage, but the mechanism is unclear. Here, we demonstrate that the SARS-CoV-2 spike protein (subunit 1 and 2), but not the N protein, directly activates the alternative pathway of complement (APC). Complement-dependent killing using the modified Ham test is blocked by either C5 or factor D inhibition. C3 fragments and C5b-9 are deposited on TF1PIGAnull target cells, and complement factor Bb is increased in the supernatant from spike protein–treated cells. C5 inhibition prevents the accumulation of C5b-9 on cells, but not C3c; however, factor D inhibition prevents both C3c and C5b-9 accumulation. Addition of factor H mitigates the complement attack. In conclusion, SARS-CoV-2 spike proteins convert nonactivator surfaces to activator surfaces by preventing the inactivation of the cell-surface APC convertase. APC activation may explain many of the clinical manifestations (microangiopathy, thrombocytopenia, renal injury, and thrombophilia) of COVID-19 that are also observed in other complement-driven diseases such as atypical hemolytic uremic syndrome and catastrophic antiphospholipid antibody syndrome. C5 inhibition prevents accumulation of C5b-9 in vitro but does not prevent upstream complement activation in response to SARS-CoV-2 spike proteins.
For More Information: https://ashpublications.org/blood/article/136/18/2080/463611/Direct-activation-of-the-alternative-complement
Authors: Richard N. Fogoros, MD
The D-dimer test is a blood test that indicates whether blood clots are being actively formed somewhere within a person’s vascular system. This test is most often helpful in the diagnosis of pulmonary embolus and deep vein thrombosis, but it can also be useful in diagnosing other medical conditions in which blood clots play a role.
However, there are limitations to the D-dimer test, and it can be tricky to evaluate the results. In order to avoid being misled by it, doctors need to make sure they are using this test at the appropriate times and must take due care in interpreting the results.
For More Information: https://www.verywellhealth.com/d-dimer-test-4173338
Authors: T Schutte 1, A Thijs, Y M Smulders
D-dimer is routinely measured as part of the clinical diagnosis algorithms for venous thromboembolism (VTE). In these algorithms, low D- dimer cut-off values are used to generate a dichotomous test result that is sensitive, but very non-specific for VTE. A consequence of any test dichotomisation is loss of information that is hidden in the continuous spectrum of results. For D-dimer, the information conveyed by extremely elevated results may be particularly relevant. Our aim was to assess the differential diagnosis of extremely elevated D-dimer levels in a hospital setting.
For More Information: https://pubmed.ncbi.nlm.nih.gov/27966438/