Using Daily D-Dimer Trends to Guide Anticoagulation Strategies for COVID-19 Patients

COVID-19 and D Dimer Anticoagulation

COVID-19 patients with lower admission and peak D dimer values seem to have better clinical outcomes. These results corroborate previous international work stating that daily D dimer trends correlate with survival and oxygenation requirements.

D dimer levels and oxygen requirements exhibited similar trends in which they increased over time and reached a maximum value around days 24-26 before decreasing subsequently. Therefore, assessing daily D dimer trends may be beneficial in guiding therapeutic anticoagulation strategies for COVID-19 patients.

Prognosis

D-dimer is frequently elevated in COVID-19 patients out of proportion to other coagulation parameters and suggests pulmonary microvascular thrombosis. This reflects an imbalance of thrombin generation and fibrin degradation due to inflammation-induced coagulopathy (PIC).

However, the absence of characteristic findings of disseminated intravascular clotting or DIC in autopsies suggests that this process is limited to certain organs. Thus, it may be important to determine if the increase in D-dimer is caused by localized or disseminated thrombosis, and whether this could be potentially treated with anticoagulation.

We performed a retrospective study to evaluate the correlation between daily D-dimer trends and patient survival. The patients were divided into two groups based on admission D-dimer value and oxygen requirements, and the trend of D-dimer was compared to patient survival. We found that patients who had a decreasing D-dimer trend and low oxygen requirements survived. The results suggest that daily D-dimer trends can be used to predict COVID-19 patient survival and can help guide the use of a therapeutic dose of LMWH to reduce COVID-19 death.

Diagnosis

D-dimer is frequently elevated in COVID-19 patients, out of proportion to changes in other coagulation parameters, reflecting the immunothrombosis caused by infection. However, the absence of characteristic features of DIC (e.g., fibrinogen 1 g/L) indicates that the elevated D-dimer may be limited to localized pulmonary microvascular thrombosis.

Moreover, high admission and peak D-dimer values correlate with worse clinical outcomes including intubation and mortality. Therefore, noting D-dimer trends early in a patient’s COVID-19 course allows physicians to provide intervention in time to potentially avoid these adverse events.

As increasing trends in D-dimer correlate with oxygen requirements, titration of anticoagulation dose based on daily D-dimer trend may be a useful tool to improve survival. This strategy can shorten the days a patient requires organ support and reduce death from COVID-19. This was not evaluated in a randomized study, but was a naturalistic observation from our clinical experience with the pandemic. However, this strategy is not without risks and should be considered carefully.

Treatment

While it is known that noncritically ill patients with COVID-19 can have a high mortality, the exact cause remains unclear. One hypothesis is that an overwhelming burden of microthrombi results in acute respiratory distress syndrome or death. Anticoagulation can prevent thrombi from growing and may thus save lives.

Several studies have shown that a prophylactic dose of low molecular weight heparin (LMWH) results in lower COVID-19 related mortality when compared to patients not treated with LMWH. The ATTACC, ACTIV-4a, and REMAP-CAP trials all show a survival benefit of anticoagulation in mechanically ventilated patients.

Dr Kabir’s retrospective study showed that non-critically ill patients who received an intermediate dose of anticoagulation (e.g., Enoxaparin 40 mg SQ twice a day) had a significantly better survival rate compared to those who were either treated with low or high doses of anticoagulants. It is recommended to start with an intermediate dose of anticoagulation and titrate the dosage depending on D-dimer trends and patient’s condition.

Monitoring

D-dimer is a sensitive early marker of clot formation and correlates with outcome in COVID-19 patients. However, the SIC scoring system does not include D-dimer in its evaluation of CIC, and thus may miss its potential to predict anticoagulation benefit.

We analyzed the relationship between daily D-dimer levels, oxygenation requirements and survival in COVID-19 patients. Patients who required intubation had significantly higher admission and peak D-dimer values than those who avoided intubation. Furthermore, patients with a D-dimer > 2 ug/mL died during hospitalization and had significantly higher death odds than those with a D-dimer of 2 ug/mL.

We suggest that daily D-dimer trends could be used to predict COVID-19 patient survival and oxygenation requirements. Patients with high bleeding risk should be started on moderate dose anticoagulants and titrated based on daily D-dimer trends to prevent life-threatening hemorrhage. It is also important to re-assess bleeding risk every day to decide whether or not to increase or decrease the anticoagulation dose.

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