Several studies have shown that coagulopathic complications are common in severe COVID-19 patients and are associated with increased mortality. COVID-19 can predispose patients to both venous and arterial thromboembolic disease, due to the activation of coagulation caused by excessive inflammation, activation of platelets, endothelial dysfunction, and stasis of blood flow due to immobility. Indications of disease severity and the establishment of coagulopathy may vary; these indications include increased D-dimer, thrombocytopenia, elevated D-dimer levels, prolongation (PT), and prolongation of aPTT in patients [7,8,9].
One of the hypercoagulable states can be enforced through the finding of an increased D-dimer value, where D-dimer is the end result of breaking down fibrin clots that have cross-links in the D-domain. Consequently, D-dimer can be used as one of the parameters for measuring thrombus formation. An increase in the D-dimer value indicates the presence of a fibrinolysis process in these patients, so that a negative value on the D-dimer examination can rule out the suspicion of a diagnosis of venous or arterial thrombosis; in contrast, an increase in the D-dimer value indicates a sign of thrombus formation [10,11].
In this study, it was found that outpatients who had confirmed COVID-19 with coagulopathy were mostly in the >60 year age group and comprised as many as 30 patients (30.6%) of the 98 patients studied. This result is in line with a study at Tongji Hospital that divided the sample into two groups of inpatients confirmed positive for COVID-19 and showed that there was a significant difference between the young and old age groups, with an increase in the D-dimer value of up to 1 g/mL, PT prolongation, and increased fibrinogen. It is also supported by research conducted at Union Hospital, Wuhan, China, which showed that of the 81 inpatients who were confirmed positive for COVID-19 and were evaluated for VTE, the age group of 60-69 years was the most common, comprising 28 patients (35%); 18 (22%) patients were in the 70-year age group [12,13].
In addition to the distribution by age, in this study, it was also found that the female gender had a slightly higher prevalence than men, namely, 51 patients (52%) of the 98 patients studied, although the difference shown was not very significant (47 male patients, 48%). The results of this study are in line with research conducted at Union Hospital, Wuhan, China, which showed that of the 81 hospitalized patients who were confirmed to be positive for COVID-19 with VTE being studied, the number of female patients was 44 (54%), and the number of male patients was 37 (46%). In general, female sex is a risk factor associated with hypercoagulation disorders, but in COVID-19 patients with native arterial occlusion, this is more common in men. In addition, women taking combined oral contraceptives (COC) and oestrogen replacement therapy (ERT) may have an exacerbated risk of VTE occurrence in COVID-19. COC use is associated with a 2- to 6-fold increase in the risk of VTE. The risk of VTE in COVID-19 can also be exacerbated in pregnancy (the risk increases by 4 to 5 times) and in postmenopausal women [13,14,15].
The value of D-dimer in this study when the patient first entered the hospital was found to be in the interval of 1.01–5 g FEU/mL in as many as 44 patients (44.9%), and the lowest D-dimer value was found in the interval <0.708 g FEU/mL, namely, in 8 patients (8.2%). The results of this study are in accordance with research at Tongji Hospital, which showed that 449 patients studied had a D-dimer value of 1.47 (0.78–4.16) g FEU/mL (315 patients), and the rest had a D-dimer value of 4.70 (1.42-21.00) g FEU/mL [16,17].
In this study, it was also shown that 63 patients with hypercoagulation complications used LMWH (fondaparinux) as an anticoagulant, with the highest group showing an increase of 16 patients (25.4%). However, the number of patients who experienced an increase rather than a decrease was only 25.4% of the total 63 patients studied. The second highest order was found in the decreased group (0.01±0.5 g FEU/mL), comprising 15 patients (23.8%). This is consistent with the study in which PVT disappeared completely and the target blood vessels were patent in 2 patients 7 days after drug administration, in 4 patients 14 days after drug administration, and in 1 patient 21 days after drug administration. The D-dimer value decreased significantly during treatment. Decreased D-dimer had a predictive value for portal vein recanalization (P = 0.018). No side effects, such as bleeding, hypohepatia, or thrombocytopenia, occurred in any of the patients. These results indicate that the decrease in the D‑dimer value is the result of fibrin formation and fibrinolysis caused by the administration of LMWH (fondaparinux) [18,19,20,21].
There are increasing data reporting a high incidence of coagulopathy and VTE among hospitalized patients with COVID-19. However, little is known about the potential association between antithrombotic therapy and COVID-19 or prognosis. Thromboprophylactic anticoagulants LMWH, low-dose UFH, or LMWH (fondaparinux) are recommended for acutely ill hospitalized medical patients with an increased risk of thrombosis. In this study, there was a slight difference between treatments in patients with hypercoagulable complications who were given UFH and LMWH (fondaparinux) p = 0.193 (p > 0.05). This is in line with research by Russo et al., who reported the main finding that the incidence of VTE and bleeding events, including MB and CRNMB, did not significantly differ between patients with COVID-19 who were taking LMWH (fondaparinux) and patients on UFH therapy. In addition, compared with the use of UFH, treatment with LMWH (fondaparinux) did not yield statistically significant differences in ARDS progression and in-hospital mortality, with numerically lower rates of both ARDS and event mortality .