Background: Patients affected by COVID-19 are at risk of various venous and arterial thrombotic events, as well as embolic risks, the risk can vary from 17% to 78% according to the different published series. Therefore, thromboprophylaxis must be imperative.

Methods: Descriptive and analytical study in patients who presented pneumonia due to COVID-19 in April and May 2020, who received LMWH during their hospital stay and at discharge with rivaroxaban 10 mg / day for 2 months. D-dimer was measured at the beginning of the study and 1 month after discharge. Thrombotic or hemorrhagic episodes are controlled after 1 and 2 months of treatment (June – July 2020).

Results: 50 patients are included, twenty women (40%) and thirty (60%) men, with a median age of 42.9 years. 32 (64%) patients had mild pneumonia and 18 (36%) patients had severe pneumonia, mean initial d-dimer 556.5 (375.2 - 1233.7) ng / ml, 56% of patients had d-dimer ≥ 500 ng / ml at the time of hospital admission. Baseline D-dimer values were significantly higher among patients with severe pneumonia. In the follow-up at one and two months after hospital discharge, we found that D-dimer values were significantly higher among patients with severe pneumonia and also, in this group of patients, the percentage of patients with D-dimer levels ≥ 500 ng / mL in the first month of follow-up, was significantly higher in the group of patients who were hospitalized for severe pneumonia. During the first month of follow-up, there was a thrombotic event and a hemorrhagic event in the group of patients with a history of severe pneumonia; by the second month of follow-up, there was a hemorrhagic event in the group of patients with mild pneumonia, but this difference in frequencies was not statistically significant.

Conclusion: In this group of patients, the incidence of thrombotic and hemorrhagic events was low, so the thromboprophylaxis scheme used in patients with recovered pneumonia due to COVID-19 is recommended. Rivaroxaban is safe to use like thromboprophylaxis.

Keywords: rivaroxaban, thromboprophylaxis, COVID-19

The first descriptions of pneumonia associated with Sars Cov 2 associated it with severe hypoxemic acute respiratory failure, coupled with hyperinflammation that can lead to multiple organ failure, however, with the evolution of the case study, the participation of microvascular thrombosis was observed which added comorbidity and high mortality in these pictures, currently being considered a picture of thromboinflammation.^1,2 Clinically, it is expressed as hypoxemic pneumonia and initial coagulopathy with a high expression of D-dimer and fibrinogen degradation products, with abnormal clotting times and platelets being rare. The determination of elevated D-dimer (with a cut-off of 6.494ng/ml in a Chinese study of 158 patients) is considered a risk factor for developing deep vein thrombosis associated with COVID-19 and this has been established as having a high prevalence in this virus.^3-5 An Italian study studied venous thromboembolism, which includes deep vein thrombosis and its main complication, pulmonary embolism, which appears to occur with a higher incidence in seriously ill patients who require intensive care. This study revealed the presence of asymptomatic deep vein thrombosis and independent pulmonary embolism in patients with COVID-19.⁶

A Dutch study demonstrated venous thromboembolism in patients admitted to intensive care in 27% of 184 patients, of these 81% presented pulmonary embolism; also identified arterial thrombotic events in 3.7%.⁷ Other thrombotic manifestations include acute cerebrovascular disease (mainly ischemic) which was more common among 88 patients with severe COVID-19 than among those with non-severe disease (5.7% vs. 0.8%). Another study mentions that 1.5% of patients admitted to the emergency room or hospitalization present acute cerebral ischemia. A Chinese study of 1,875 cases reported 50 cases of acute cerebrovascular disease (90% ischemic and 10% hemorrhagic).^8-11 An American study in 3,556 patients diagnosed with COVID-19 reported that 0.9% had an acute stroke, of these 43.8% had a neurological deficit upon admission to the emergency room, and 56.2% developed the deficit during their hospital stay.¹²

Similarly, in patients with COVID-19, the presence of acute cardiac injury, shock and arrhythmias has been reported in 7.2%, 8.7% and 16.7% respectively, which may favor thrombotic coronary artery disease and embolism of cardiac origin.¹³

Given the above, the current concern is the management of prophylactic or therapeutic anticoagulation, there are recommendations for the use of LMWH during acute events and oral anticoagulants gaining ground in the convalescence phase, which incidentally is also considered to be of high thrombotic risk -embolic due to the long hospital stay, immobility of the patient, the presence of asymptomatic peripheral venous thrombosis and the high incidence of chronic degenerative diseases considered prothrombotic that are associated.

At the patient's discharge, it is recommended to maintain anticoagulation for at least 45 to 60 days due to post-COVID-19 thrombotic risks, preferring oral anticoagulants such as rivaroxaban, because they do not need monitoring, they can be administered in daily single doses and facilitate the discharge plan and management ambulatory.^14-16

A descriptive and analytical study is carried out in patients who presented pneumonia due to COVID-19 in April and May 2020 at the General Hospital 71 of the Veracruz North delegation of the Mexican Institute of Social Security, monitoring them for two months after discharge hospitable. Confirmation of pneumonia due to COVID-19 was by RT-PCR as well as by pulmonary axial tomography; a baseline D-dimer measurement was taken in the first 5 days of hospital admission, as well as a D-dimer control in the first month of discharge, taking values ​​greater than 500ng/mL as high thrombotic risk. All received low molecular weight heparin (enoxaparin) during their hospital stay at a dose of 1mg/kg/day, starting with rivaroxaban in a single dose of 10mg/day that was administered for 2 months.

We analyzed the data of 50 patients who had a hospital stay with a confirmed diagnosis of COVID-19 pneumonia by RT-PCR, twenty women (40%) and thirty (60%) men, with a median age of 42.9 (IQR 32.7 - 61.7) years. The most frequent comorbidity was diabetes mellitus in 25 (50%) patients, followed by systemic arterial hypertension with 15 (30%) patients, 3 (6.0%) patients with peripheral vascular insufficiency and 1 (2.0%) patient with a history of arrhythmia without anticoagulant treatment.

The results of the measurement of laboratory parameters are found in Table 1, which highlights the baseline median d-dimer [556.5 (375.2 - 1,233.7) ng/mL], 56% of the patients had d-dimer ≥500 ng/mL at the time of hospital admission. Regarding the type of pneumonia, we found that 32 (64%) patients had mild pneumonia and 18 (36%) patients had severe pneumonia; with a median of 7.0 (5.0 - 15.0) days of hospital stay. At one-month follow-up, 28 (56%) patients remained with d-dimer levels ≥500 ng/mL. During the first month one patient had an ischemic stroke and one patient had upper gastrointestinal bleeding. For the second month of follow-up, there was one patient who presented self-limited epistaxis. Measurement of demographic and clinical variables of patients with a confirmed diagnosis of COVID-19 stratified by type of pneumonia.

We performed a comparative analysis of the demographic and clinical variables stratified by the type of pneumonia that they presented during the hospital stay (Table 2); we found that in terms of gender there were no differences regarding the frequency of presentation of mild or severe pneumonia. However, the median age was lower in the group of patients with mild pneumonia compared to the median age of patients with severe pneumonia [35.5 (32.0 - 48.7) VS 56.6 (41.7 - 73.5) years, respectively) and that this difference was statistically significant (p = 0.001). Regarding comorbidities, we found that only diabetes mellitus was significantly more frequent among patients with severe pneumonia (72.2 VS 37.5%; p = 0.038). With regard to systemic arterial hypertension, vascular insufficiency, and a history of arrhythmia, there was a tendency to be more frequent in the group of patients with severe pneumonia, but it was not statistically significant.

Regarding the variables associated with COVID-19, we found the values ​​of lymphocytes [925.0 (645.0 1,210.0) VS 1,225.0 (1,020.7 - 1,617.5) lymphocytes; p = 0.005] were significantly lower in the group of patients with severe pneumonia. The white blood cell and platelet values ​​tended to be lower in the group of patients with severe pneumonia, but this difference was not statistically significant. Baseline dimer values ​​were significantly higher among patients with severe pneumonia [1,880.0 (1,175.0 - 3,187.0) VS 410.0 (341.7 - 556.7) ng/mL; p = 0.001]; in addition, the percentage of patients with baseline d-dimer ≥500 ng/mL with severe pneumonia (94.4 VS 34.4%; p = 0.001) and hospital stay [17.0 (14.0 - 20.2) VS 7.0 (5.0 - 7.0); p = 0.001], were also significantly higher among patients with severe pneumonia.

In the follow-up at one and two months after hospital discharge, we found that D-dimer values ​​were significantly higher among patients who had severe pneumonia [835.0 (655.0 - 1,125.0) VS 390.0 (349.2 - 463.2); p = 0.001]; Additionally, in this group of patients, the percentage of patients with d-dimer levels ≥500 ng/mL at the first month of follow-up was significantly higher in the group of patients who were hospitalized with severe pneumonia (88.9 vs. 6.3%; p = 0.001). During the first month of follow-up, there was a thrombotic event and a hemorrhagic event in the group of patients with a history of severe pneumonia; for the second month of follow-up, there was a hemorrhagic event in the group of patients who had mild pneumonia, but this difference in frequencies was not statistically significant.

In this group of patients, the incidence of thrombotic events associated with COVID-19 is low compared to that reported in the world literature, probably favored by the anticoagulation strategy applied with LMWH in the acute stage and rivaroxaban in the convalescent stage, and In the presence of overt prothrombotic (diabetes, hypertension) and thrombotic risk factors (pneumonia and elevated baseline D-dimer and persistently elevated in the convalescent phase), the incidence of bleeding events is low and with self-limited events. More studies based on this regimen are needed to give further weight to the recommendation.

The authors declare there are no conflicts of interest.

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