Venous Thromboembolism is common in acutely ill COVID-19 patients despite the use of prophylactic anticoagulation. It was reported that about 20-43% of VTE, mostly PE developed in ICU patients 3–5. Data are limited for inpatients admitted to regular medical floor. The pathophysiology of COVID-19 associated coagulopathy remains unclear. Two autopsy studies on post-mortem examination of COVID-19 individuals revealed that common causes of death are hypercoagulability and inflammation 6,7. One of the autopsy study revealed 7 out of 12 patients (58%) had DVT and PE and this was the direct cause of death in 4 patients 7. Here, we reported a case of asymptomatic COVID-19 patient with underlying malignancy and previous history of VTE who developed an acute VTE (both DVT and PE) despite being on therapeutic anticoagulation. Her inflammatory markers were all elevated. Initially, the patient’s Ddimer was trending down to 1859 ng/ml, later on, there was an increasing trend of Ddimer to 7786 ng/ml on day 8 of admission which prompted the suspicion of acute VTE. The initial CTA was negative which suggested that the previous PE had resolved.
Although this patient has multiple risk factors for VTE which included malignancy, immobility and previous history of VTE, the inflammation and severe endothelial dysfunction secondary to COVID-19 may trigger and worsen the hypercoagulable state despite the use of therapeutic dose of enoxaparin. Interestingly, the late presentation of VTE in COVID-19 patients also suggests that the hypercoagulable state persist even in recovery phase and also in asymptomatic patients. High Ddimer is an independent predictor of mortality in hospitalized patients with COVID-19 8. However, it is also important to trend Ddimer in asymptomatic COVID-19 patients in the hospital.
Recent study from Mount Sinai Hospital shows that therapeutic dose anticoagulation improved survival among hospitalized COVID-19 patient both in and out of ICU 9. Due to lack of data, the use of therapeutic anticoagulation in individuals with no documented VTE still remains controversial. American Society of Hematology (ASH) recommends the use of prophylactic anticoagulation for those who have not had confirmed VTE unless in patients with high risk probability in whom confirmatory test could not be performed. If VTE is suspected, confirmatory testing should be sought if possible. Despite the lack of evidence, many institutions have used an intermediate dose or therapeutic dose of anticoagulation on managing COVID-19 coagulopathy. Therefore, current clinical trials are focusing on studying the therapeutic or prophylactic dose of anticoagulation in preventing VTE in critically ill COVID-19 patients. It is also crucial to understand which phase of disease is associated with the highest risk of VTE to know the optimal timing and duration for therapeutic anticoagulation. It will be interesting to study the incidence of VTE in asymptomatic COVID-19 patients with high risk as well. In regards to the duration of anticoagulation, it is important to consider extended thromboprophylaxis after discharge depends on patient's VTE risk factors.
Heparins have been reported to have an anti-inflammatory and anti-viral activity in COVID-19. It binds tightly to COVID-19 spike proteins, downregulate IL-6 and directly dampens immune activation10–12. To date, no study compares whether unfractionated heparin (UFH) is better than low molecular weight heparin (LMWH) in COVID-19 coagulopathy. Koenig et al. reported that heparin, in addition to anticoagulation, has effects on the blocking of P- and L-selectin, which are being reduced or even eliminated by the switch to the low-molecular-weight heparins. P- and L-selectin, are a group of glycoproteins important in mediating the inflammation and interactions of endothelium in reperfusion injury13. Moreover, P-selectin ligation has been demonstrated to play a role in platelets activation as well as thrombus formation and micro-aggregation14. Although there is no direct comparison between heparin and LMWH, but it seems that heparin have more functional roles that have been reduced with conversion to LMWH and synthetic polysaccharides. Nonetheless, LMWH has more practical use due to less frequent dosing and omit the need for frequent monitoring of activated partial thromboplastin time (aPTT). However, UFH has better anti-inflammatory activity and is preferred in patients who may need reversibility for urgent intervention, morbid obesity or renal impairment. The other indication to use UFH is in patients who progressed despite being on anticoagulant therapy. More studies are still needed to dissect the roles and differences of UFH versus LMWH on its anti-inflammatory activity especially on COVID-19.