Clotting Issue

Infection with the COVID-19 virus is characterized by overactivation of the immune system leading to acute respiratory distress syndrome (ARDS) and high mortality rates in some patients.  Another disturbing finding in most (if not all) COVID-19 patients is the presence of an environment conducive to the formation of blood clots.  This pro-thrombotic milieu was noted among the earliest experiences of doctors in Wuhan, China.  The sickest patients tended to have significantly elevated D-dimer levels over patients who were less severely affected.  D-dimer is a fibrin degradation product whose presence suggests clot formation.  Patients who later “relapsed” after release from the hospital were noted to have higher D-dimer levels at the time of their discharge than those who remained well after going home.  Postmortem autopsies on Chinese patients who died from COVID-19 exhibited blood clots in the lungs, heart, liver, and kidneys.  Doctors in the U.S. are seeing similar widespread blood clots, particularly in the lungs, at autopsy.   Due to the frequency of venous thromboembolism (VTE) and thrombotic stroke the International Society on Thrombosis and Hemostasis (ISTH) recommended that all COVID-19 patients admitted to the hospital be given prophylactic doses of low molecular weight heparin (LMWH).  Exceptions to the recommendations would be in patients with evidence of active bleeding or in those with low platelet counts (<25,000).  Some hospitals are using threshold values before initiating anticoagulants such as a D-dimer >1,500 ng/mL and/or fibrinogen >800 mg/mL.  Unfractionated heparin may be a superior choice over LMWH with inpatients since it possesses anti-inflammatory properties.  In addition heparin could easily be stopped in the event of unexpected bleeding.  Some medical facilities are routinely screening COVID-19 patients for VTE and/or a pulmonary embolus (PE).  If the screening procedures are positive or if the D-dimer exceeds a given threshold (i.e. 2500-2600ng/mL) then therapeutic anticoagulant doses would be administered.  Screening procedures in the sickest patients may not be feasible and treatment could be initiated based on an elevated D-dimer level alone.  Research work performed in France found that measurements above 2,660ng/mL had a 100% sensitivity and 67% specificity for finding a PE when a CT was subsequently performed.

There is near unanimous agreement on the inpatient use of LMWH, the question is whether anticoagulation should be continued after discharge and for how long.  It is unknown for how long the pro-thrombotic state persists in COVID-19 patients.  Many physicians are considering the continuation of prophylactic doses of LMWH or direct oral anticoagulants (DOACs) for up to 45 days after hospital discharge taking into  consideration each patient’s risk for bleeding.  We know that the COVID-19 virus enters cells via the angiotensin converting enzyme 2 (ACE2) receptors.  These receptors are most abundant in the alveoli of the lungs and the endothelial cells of the vasculature.  Inflammation and thrombosis induced by the body’s response to the virus results in hypoxemia and multi-organ failure.  The finding that remdesivir interferes with viral replication and shortens hospital stay suggests that these processes are abated or prevented by the drug.  We know a correlation exists between length of hospital stay and mortality.  Anything that gets patients out of the hospital sooner lessens the likelihood of an adverse event and decreases the burden on the healthcare system.



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