logo RLK Srbije eng

Review article

Anticoagulants and corticosteroids in COVID-19 – what do we know so far?

Marija Milenković1,3, Marija Dukić2, Ivan Rović3, Đuro Šijan3, Adi Hadžibegović1, Višeslav Popadić2, Slobodan Klašnja2, Milica Brajković2, Marija Zdravković2,3
  • University Clinical Center of Serbia, Emergency Center, Belgrade, Serbia
  • University Hospital Medical Center "Bežanijska kosa", Belgrade, Serbia
  • University of Belgrade, Faculty of Medicine, Serbia

ABSTRACT

It has been a year and a half since the fight against the COVID-19 pandemic started. In today’s protocols for the treatment of COVID-19 and the prevention of its complications, corticosteroid therapy and anticoagulant therapy have a crucial part. The goal of this article is to show, based on available data, both the benefits and the disadvantages of corticosteroid and anticoagulant therapy in treating the infection caused by the Sars-CoV-2 virus.

At the very onset of the pandemic, an increased frequency of thrombotic events negatively impacting the course and outcome of the disease, was registered. It has been observed that increased values of D-dimer in patients with COVID-19 do not correlate with the presence of venous thrombosis and are not reliable in the detection of deep vein thrombosis and pulmonary thromboembolism. According to the National Protocol for Treating COVID-19 (Version 12), anticoagulant therapy is recommended in hospitalized patients. Due to the risk of different side effects, such as bleeding and heparin-induced thrombocytopenia, a careful use of anticoagulant therapy is necessary, as well as close monitoring of its effects.

With respect to corticosteroids, their efficacy in patients with moderate and severe clinical presentation of COVID-19, who are in need of oxygen support, was analyzed. Corticosteroids have proven efficient in decreasing mortality, decreasing the need for mechanical ventilation, decreasing the length of stay in intensive care units, as well as in shortening the length of hospital stay.

Assessing the individual benefits and risks before introducing these drugs into the therapy of a patient with confirmed COVID-19 is of vital importance for achieving the desired effects of the therapy.


INTRODUCTION

The first cases of atypical pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were registered in December 2019, in Wuhan (China) [1]. The disease very quickly spread all over the world and, on March 11, 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) pandemic [2]. The fight against the pandemic has been ongoing ever since. Despite all of the efforts made at the global level, the pandemic is still in full swing.

Patients suffering from this new infectious disease most commonly report the following symptoms: elevated body temperature, dry cough, fatigue, shortness of breath (dyspnea), and, less frequently, headache, haemoptysis, and diarrhea. Loss of the sense of smell (anosmia) and loss of the sense of taste (ageusia) also occur [3],[4].

Until the beginning of December 2021, more than 251.000.000 COVID-19 patients and more than five million COVID-19 related deaths were registered worldwide. During the same period, in Serbia, there were more than a million COVID-19 cases and more than eleven thousand COVID-19 related deaths [5].

At the beginning of the pandemic, it seemed that the infection was limited to the respiratory organs, however, as time elapsed, different manifestations of the disease were discovered, occurring at the level of the nervous, cardiovascular, gastrointestinal, renal, endocrine, muscular, sanguineous, i.e., within all body systems [6].

At present, there is no specific drug for this disease, and the treatment protocols vary, somewhat, from country to country. In Serbia, at present, treatment is carried out according to Version 12 of the National Protocol for Treating COVID-19 [7]. The development of treatment protocols started as of February 2020, and they have been changing over time, in keeping with new knowledge and experience coming from all regions of the world affected by COVID-19. An essential part of all current protocols is considering the introduction of corticosteroids and anticoagulants, but also preventing potential complications caused by the use of these drugs. Regardless of the evidence gathered so far on the benefits of their use, there is still an ongoing debate regarding the precise indications and contraindications in the application and dosing of these drugs.

Anticoagulant therapy has long been in use for the treatment of a wide range of diseases and pathological states [8]. This treatment modality is constantly being developed further with the advent of oral anticoagulants, which have now been added to the range of possible treatment, alongside existing intravenous and subcutaneous drugs, thus widening treatment options for thromboprophylaxis and anticoagulant therapy. Bearing in mind the pharmacokinetic and pharmacodynamic differences among the different drugs, an individualized approach is necessary in order to ensure and optimal treatment outcome [9].

Due to their anti-inflammatory, but also their immunosuppressive effects, the use of corticosteroids in the treatment of COVID-19 is being analyzed and assessed by clinicians all over the world [10],[11].

Bearing in mind that, in addition to benefits, the use of these drugs may also have adverse effects, it is necessary to have clearly defined indications and contraindications for their application. Differently designed studies have been carried out in a number of countries of the world, with the same goal – to assess the impact of corticosteroids on the course of the disease in patients with COVID-19. The results of these studies have been aggregated by the World Health Organization within the Sixth Protocol, published on September 24, 2021 [12].

COVID-19 AND THROMBOSIS

In the population of patients suffering from COVID-19, different disorders have been discovered with the help of hemostatic screening tests and specific hemostasis tests. Elevated levels of D-dimer, which correlate with the degree of severity of the disease, have especially drawn the attention of researchers and clinicians [13]. D-dimer has been reported as an independent predictor of mortality during in-hospital treatment, in a number of studies [14],[15],[16].

Thromboses are significant complications of COVID-19 as they have a considerably negative impact on the course and outcome of the disease. At the very onset of the pandemic, higher frequencies of thrombotic events were registered. In patients treated in intensive care units (ICU), deep vein thrombosis was registered in 25% of patients, as well as pulmonary thromboembolism [18]. Despite systematic anticoagulant prophylaxis, thrombosis (venous or arterial) develops in 31% of critically ill patients [19].

In a meta-analysis involving 1,599 critically ill patients, the frequency of venous thromboembolism was 28.4%, the frequency of deep vein thrombosis (DVT) was 25.6%, while the frequency of pulmonary embolism was 16.4%. A higher frequency of DVT was registered in studies including routine analysis of all patients than in studies where only patients with clinically suspected DVT were evaluated. The results of a meta-analysis involving 91 studies with a total of 35,017 patients speak also to that effect. The conclusion of that study is that the frequency of venous thrombosis in patients treated in ICUs is 24.1%, as opposed to 7.7% in patients treated outside ICUs. The frequency of thrombotic complications in children is low and amounts to 0.7%, more precisely, out of 537 SARS-CoV-2 positive children (median age: 61 months, IQR: 6 – 140), four of them developed venous thrombosis (68.5% of the total number were hospitalized, while 10.8% required treatment in the ICU) [20],[21].

In a meta-analysis involving 41,768 patients, the relative risk for thrombosis development was analyzed in COVID-19 patients and in patients suffering from other diseases of similar severity (the flu, ARDS resulting from causes other than COVID-19, out- of-hospital-pneumonia). In this study, an increased risk of thrombosis development was not registered in COVID-19. A significantly higher risk of thrombosis was registered in COVID-19 patients treated in ICUs [22]. Another study involving more than a million patients showed similar results [23].

Based on the above, one might conclude that venous thrombosis in SARS-CoV-2 positive patients has a high frequency, especially in patients requiring ICU treatment, as well as that venous thrombosis requires special attention in terms of prevention, early detection, and treatment.

The frequency of thrombotic complications indicates that, most probably, several different molecular interactions between the virus and the host body are at play, leading to this adverse effect. In the human body, the SARS-CoV-2 virus binds with angiotensin-converting enzyme 2 (ACE2), which converts angiotensin II into angiotensin 1-7, consequently leading to the increase in the level of angiotensin II (which has proinflammatory and prothrombotic effects) in the blood. On the other hand, due to the decrease in the level of angiotensin 1-7, positive anti-inflammatory and antithrombotic effects of this peptide are absent. Additionally, angiotensin II is a powerful mediator of oxidative stress, which leads to the formation of reactive forms of oxygen, while angiotensin 1-7 has opposing, antioxidative effects, through the induction of synthesis and the release of nitrogen monoxide from endothelial cells. The sum of these two – the increase in the reactive forms of oxygen and the decrease in the level of nitrogen monoxide, has a detrimental effect on the endothelium. In addition to the above stated consequences of the deregulation of the renin-angiotensin-aldosterone system on the endothelium, increased expression of LOX-1, COX-2, VEGF also occurs. Different studies have shown the existence of a powerful link between a dysfunctional endothelium and the development of thrombosis. Endothelial dysfunction leads to the activation of different coagulation mechanisms, and it is also linked to the increased expression of individual prothrombotic molecules on the cell surface [24],[25].

The potential mode of the stimulation of thrombocyte aggregation and thrombosis is the release of the Willebrand factor from subendothelial spaces, due to the dysfunction of the endothelium and its damage, which leads to its polymerization and activation [26].

In addition to all the above stated, thrombosis in COVID-19 can also potentially occur as the result of dysfunction within the immune system. The cytokine storm, which is known to occur within this disease, leads to the dysregulation of the coagulation system, due to the activation of different immune coagulation cascades, which consequently leads to the coagulation of blood [27],[28],[29].

D-dimer is routinely used in clinical practice when deep vein thrombosis and pulmonary embolism are suspected. In these conditions, D-dimer levels reach high values, which is why the measurement of this marker has a sensitivity above 95% [30]. However, using D-dimer for diagnostic purposes, i.e., detecting thrombosis, has been losing its significance. Elevated levels of D-dimer in COVID-19 patients do not correlate with the existence of venous thrombosis. D-dimer values are elevated as the body’s response to infection with the SARS-CoV-2 virus, which induces inflammation, consequently leading to bronchoalveolar hemostasis. One of the explanations would be that ‘protective’ microthrombi are formed, as the body’s response to the virus, in order to limit further invasion and damage. The degradation of these microthrombi is the result of elevated D-dimer levels [30]. It is for these reasons that, in this case, D-dimer levels are not a reliable parameter in the detection of deep vein thrombosis and pulmonary thromboembolism. Suspicion of venous thrombosis is warranted when unilateral swelling of an extremity occurs, as well as in case of the development of superficial thrombophlebitis, while pulmonary embolism may be suspected in the event of dyspnea, or if hypoxemia worsens despite improvement in radiological findings, as well as if there is an elevation in systolic pressure in the right ventricle with an increase of the D-dimer level (values above 5 mg/l; doubling of the value within 24 hours) [31].

ANTICOAGULANT THERAPY IN COVID-19

According to the National Protocol for Treating COVID-19 (Version 12), it is recommended that anticoagulant therapy should be used in hospitalized patients. Standard therapeutic doses are administered to patients who need to be treated in the ICU, while, in patients treated in hospital wards, in patients with suspected or confirmed venous thrombosis, as well as in patients on long-term anticoagulant therapy, the application of therapeutic doses of low-molecular-weight heparin (LMWH) is recommended [7] (Table 1).

Table 1. Recommendations for administering anticoagulant therapy in adults (based on the National Protocol, Version 12) [7]

07 01 en

At first glance, the application of therapeutic doses in noncritical patients seems confusing. However, when the National Protocol was being made, this decision was reached based on a multiplatform randomized controlled study, which has proven the positive effects of the use of therapeutic doses of heparin-based medication. The use of therapeutic doses reduces the risk of a lethal outcome during hospitalization, as well as the risk of adverse effects of respiratory and cardiovascular support [32].

However, the application of therapeutic doses of anticoagulant therapy did not demonstrate its advantage in critically ill SARS-CoV-2 positive patients treated in the ICU, as compared to the application of prophylactic doses, when it comes to intrahospital mortality and the number of days without cardiovascular or respiratory support [33].

The application of antiaggregation therapy (acetylsalicylic acid) and anticoagulant therapy is not recommended in COVID-19 patients who do not require in-hospital treatment. A study analyzing the effects of forty-five-day application of antiaggregation and anticoagulant therapy concluded that the said therapy did not reduce the risk of the occurrence of cardiovascular and pulmonary complications, as compared to the placebo, in patients not requiring in-hospital treatment [34].

As in prescribing and applying other medication, care should be taken in the application of anticoagulant therapy. The main adverse effect is acute bleeding. Although relatively rare, it can be life-threatening, which is why it is necessary that it should be recognized and stopped on time [35]. In case of minor bleeding, local hemostatic measures and anticoagulant therapy adjustment may be sufficient, and in case of major and clinically significant bleeding, hemodynamic support, transfusion of blood and blood derivatives, as well as hemostatic support need to be supplied, and the administration of appropriate antidotes (such as the use of vitamin K for vitamin K antagonists, protamine sulphate for heparin, etc.) needs to be considered [36]. Additionally, when heparin is applied, heparin-induced thrombocytopenia (HIT) may develop. It is an immunological reaction after drug use (most commonly unfractionated heparin, or less frequently LMWH) which leads to the prothrombotic state of the body, which is recognized by the development of thrombocytopenia in the space of a few days within the beginning of heparin therapy and the detection of antibodies to platelet-factor 4 [37],[38]. HIT can be linked to pulmonary embolism, ischemic necrosis of the extremities (which requires amputation), acute myocardial infarction, as well as stroke. In case of suspicion of HIT development, it is of utmost importance that the application of heparin is discontinued and that the patient is put on other, alternative anticoagulant therapy (not vitamin K oral anticoagulants), which is determined individually, for each patient [39].

In everyday clinical practice the “HIT 4t” score can be calculated (thrombocytopenia, time from heparin introduction to thrombocytopenia development, thromboses and other complications, other thrombocytopenia causes) for rapid orientation regarding the probability of HIT development (a score of 0 - 3 points signifies low risk; a score of 4 - 5 points signifies medium risk; a score of 6 - 8 points signifies high risk). If the score is low, the probability of HIT is low (indicating the necessity for further monitoring), while if the score is medium or high, serological tests must be performed (antibodies against heparin) and treatment must be started [40].

Therefore, anticoagulant therapy, just like any other medicamentous treatment, carries certain risks, which is why it is necessary to apply the postulates of modern medicine and individualize the therapy, as much as possible, as well as recognize and treat its adverse effects.

CORTICOSTEROIDS IN COVID-19

Well before the ongoing pandemic, corticosteroids represented one of the therapeutic choices in the treatment of acute respiratory distress syndrome (ARDS) of different etiology. This is why, with the outbreak of COVID-19, their use has become the topic of a large number of clinical studies. Due to the pathophysiological basis of the disease, but also due to the pharmacodynamics of corticosteroids, their use has proven justified. However, as the result of insufficient understanding of all the pathophysiological mechanisms of the development of this infection, as well as due to the possibility of complications resulting from corticosteroid therapy, opinions regarding the use of these drugs remain divided [41]. The cytokine storm, which occurs as the result of intensive production of proinflammatory cytokines, due to the dysregulation of immune response, has been characterized as the most severe complication of the infection [42]. In our body, corticosteroids have a primarily anti-inflammatory, but also an immunosuppressive role [43]. In this way, they reduce the release of major cytokine storm mediators, i.e., proinflammatory cytokines, by suppressing the genes responsible for their synthesis. Many studies have analyzed the effects of corticosteroid use in treating COVID-19 patients and have investigated the role of dexamethasone, methylprednisolone, and hydrocortisone. A multicentric, randomized study, carried out in Great Britain, on 6,425 patients, analyzed the effect of dexamethasone application, 6 mg/day, intravenously or orally, for 10 days. It was found that mortality in the first 28 days was lower in the group of patients who, along with standard therapy, received dexamethasone. Also, patients who were put on dexamethasone after the seventh day of disease onset, had a better prognosis. It has been proven that patients with the moderately severe and the severe form of the disease, who were on some form of oxygen therapy, benefitted the most from corticosteroid application. What is interesting is the fact that, according to this study, patients with the milder form of the disease, i.e., a form that did not require oxygen therapy, more frequently exhibited adverse reactions to corticosteroid effects, which is why the need for individual risk and benefit assessment in the application of corticosteroids was stressed as important [44],[45],[46].

Regarding the application of methylprednisolone, the GLUCOCOVID and MetCOVID studies examined its short-term use (GLUCOCOVID – 40 mg/12 h, and then 20 mg/12 h, intravenously, over a period of three days; MetCOVID – 0.5 mg/kg/12 h, intravenously, over a period of five days) [47],[48]. It has been shown that, in patients who, in addition to standard therapy, also received methylprednisolone, there was a lower risk of being admitted to the ICU, a lesser need for noninvasive and invasive mechanical ventilation, as well as lower mortality. Additionally, the universal conclusion of all the studies was that methylprednisolone application shortened hospital stay, by shortening the time necessary for recovery as well as the duration of necessary oxygen support. The comparison of the effects of dexamethasone and methylprednisolone demonstrated the superiority of methylprednisolone over dexamethasone, which is why patients who received methylprednisolone therapy less commonly had the need for mechanical ventilation, they had lower mortality, as well as a shorter stay in hospital [49],[50].

The least researched, but certainly not the least important, is hydrocortisone. Fixed, small doses of hydrocortisone affect better survival of patients in the first 21 days of illness [51],[52]. Additionally, in these patients, respiratory insufficiency occurs less frequently, as does the need for mechanical ventilation and the lethal outcome, however, the statistical significance of these results has not been confirmed.

All in all, whichever corticosteroid is administered in the treatment of COVID-19, it is important that it should not be given at the very beginning, but when it becomes clear, based on the clinical course of the disease and the laboratory analyses, which direction the disease is taking. Mild forms of the disease do not require the application of corticosteroids (Tables 2 and 3).

Table 2. Systematized overview of studies which have analyzed the effect of dexamethasone and hydrocortisone, with presented conclusions [53]

07 02 en

Table 3. Systematized overview of studies which have analyzed the effect of methylprednisolone and compared it to the effect of dexamethasone, with presented conclusions [53]

07 03 en

WHY ARE OPINIONS ON THE USE OF CORTICOSTEROIDS DIVIDED?

As is the case with other drugs and substances, corticosteroids may exhibit adverse effects. The most commonly occurring adverse effect is the disturbance of glucoregulation in patients already suffering from diabetes mellitus, however, this complication may also occur in other patients [54]. Bearing in mind that cor ticosteroids are a physiological product of the adrenal glands, their intake may lead to adrenal suppression, which may manifest as adrenal crisis, but also as iatrogenic Cushing’s syndrome [54]. Complications at the level of the cardiovascular system are also frequent, most commonly in the form of hypertension, ischemic heart disease, and hyperlipidemia [55]. Most of these adverse effects are dose-dependent, and, additionally, individuals with certain conditions have a higher tendency towards developing complications. This is why it is important, once more, to emphasize how significant it is to individually assess the benefit – risk ratio before making a decision on starting corticosteroid treatment.

CONCLUSION

The aim of this paper is to demonstrate the importance of the application of anticoagulant and corticosteroid therapy in the treatment of COVID-19. Bearing in mind the global importance of resolving the pandemic, emphasis is placed on treating the already existing infection and its complications, for which these two groups of drugs are important. Anticoagulant therapy is applied in the treatment of hospitalized patients suffering from the disease caused by the SARS-CoV-2 virus. When people suffering from this infectious disease are treated as outpatients, the use antiaggregation and anticoagulant therapy is not recommended. Bearing in mind the risk of the development of different adverse effects, such as bleeding and heparin-induced thrombocytopenia, an individualized approach to each patient as well as careful prescribing of anticoagulant therapy is necessary, as is the monitoring of its effects.

As far as the application of corticosteroids is concerned, the emphasis is on their efficiency in patients with moderate and severe clinical presentation which require some form of oxygen support. This efficiency is manifested in the decrease of mortality, the reduction of the need for mechanical ventilation and the reduction of the need for transferring patients to intensive care units, as well as in the shortened duration of hospitalization. Methylprednisolone has proven to be the most potent, although further studies are necessary to prove this, since it is known that the use of corticosteroids carries the risk of adverse effects, which, in certain categories of patients, or with certain doses, are expected more frequently.

Finally, it is important to emphasize that the individual assessment of benefits and risks, when these drugs are included in the treatment of patients with confirmed COVID-19, is of vital importance for achieving the desired effects of the therapy.

  • Conflict of interest:
    None declared.

Informations

Volume 3 No 1

Volume 3 No 1

March 2022

Pages 62-74
  • Received:
    20 November 2021
  • Revised:
    15 December 2021
  • Accepted:
    20 December 2021
  • Online first:
    18 March 2022
  • DOI:
Corresponding author

Marija Milenković
Emergency Center, University Clinical Center of Serbia
28 Rada Neimara Street, 11000 Belgrade, Serbia
E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.


  • 1. Lu H, Stratton CW, Tang YW. Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle. J Med Virol. 2020 Apr;92(4):401- 2. doi: 10.1002/jmv.25678.[CROSSREF]

    2. Neue Zürcher Zeitung. Die Corona-Epidemie ist jetzt eine Corona-Pandemie. Das ändert wenig [Internet]. Neue Zürcher Zeitung; 2020 Mar [pristupljeno 20. novembra 2021.]. Dostupno na: https://www.nzz.ch/wissenschaft/covid-19-who-erklaert-corona-epidemie-zur-pandemie-ld.1546030.[HTTP]

    3. Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020 Jul;75(7):1730-41. doi: 10.1111/all.14238.[CROSSREF]

    4. Boscolo-Rizzo P, Borsetto D, Fabbris C, Spinato G, Frezza D, Menegaldo A, et al. Evolution of Altered Sense of Smell or Taste in Patients With Mildly Symptomatic COVID-19. JAMA Otolaryngol Head Neck Surg. 2020 Aug 1;146(8):729-32. doi: 10.1001/jamaoto.2020.1379.[CROSSREF]

    5. Ministarstvo zdravlja Republike Srbije. COVID-19. [Internet]. [pristupljeno 29. novembra 2021.]. Dostupno na: https://www.zdravlje.gov.rs/sekcija/345852/covid-19.php.[HTTP]

    6. White-Dzuro G, Gibson LE, Zazzeron L, White-Dzuro C, Sullivan Z, Diiorio DA, et al. Multisystem effects of COVID-19: a concise review for practitioners. Postgrad Med. 2021 Jan;133(1):20-7. doi: 10.1080/00325481.2020.1823094.[CROSSREF]

    7. Službeni portal Doma zdravlja „Savski venac“.Terapijski portokol COVID-19 – 21. 09. 2021. VERZIJA 12. [Internet]. [pristupljeno 20. oktobra 2021.]. Dostupno na: https://www.dzsvenac.rs/sluzbeno/index.php/vesti-meni/11-ministarstvo-obavestenja/452-terapijski-protokol-covid19-v8.[HTTP]

    8. Mansory EM, Srigunapalan S, Lazo-Langner A. Venous Thromboembolism in Hospitalized Critical and Noncritical COVID-19 Patients: A Systematic Review and Meta-analysis. TH Open. 2021 Jul 6;5(3):e286-94. doi: 10.1055/s-0041-1730967.[CROSSREF]

    9. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Jul;191:145-7. doi: 10.1016/j.thromres.2020.04.013.[CROSSREF]

    10. Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N Engl J Med. 2005 Oct 20;353(16):1711-23. doi: 10.1056/NEJMra050541.[CROSSREF]

    11. Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG. Prevention and management of glucocorticoid-induced side effects: A comprehensive review: Gastrointestinal and endocrinologic side effects. J Am Acad Dermatol. 2017 Jan;76(1):11-6. doi: 10.1016/j.jaad.2016.02.1239.[CROSSREF]

    12. World Health Organization. Therapeutics and COVID-19. [Internet]. [pristupljeno 20. oktobra 2021.]. Dostupno na: https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2021.4.[HTTP]

    13. Popadic V, Klasnja S, Milic N, Rajovic N, Aleksic A, Milenkovic M, et al. Predictors of Mortality in Critically Ill COVID-19 Patients Demanding High Oxygen Flow: A Thin Line between Inflammation, Cytokine Storm, and Coagulopathy. Oxid Med Cell Longev. 2021 Apr 20;2021:6648199. doi: 10.1155/2021/6648199.[CROSSREF]

    14. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62. doi: 10.1016/S0140-6736(20)30566-3.[CROSSREF]

    15. Soni M, Gopalakrishnan R, Vaishya R, Prabu P. D-dimer level is a useful predictor for mortality in patients with COVID-19: Analysis of 483 cases. Diabetes Metab Syndr. 2020 Nov-Dec;14(6):2245-9. doi: 10.1016/j. dsx.2020.11.007.[CROSSREF]

    16. Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost. 2020 Jun;18(6):1324-9. doi: 10.1111/jth.14859.[CROSSREF]

    17. Poissy J, Goutay J, Caplan M, Parmentier E, Duburcq T, Lassalle F, et al.; Lille ICU Haemostasis COVID-19 Group. Pulmonary Embolism in Patients With COVID-19: Awareness of an Increased Prevalence. Circulation. 2020 Jul 14;142(2):184-6. doi: 10.1161/CIRCULATIONAHA.120.047430.[CROSSREF]

    18. Wu C, Liu Y, Cai X, Zhang W, Li Y, Fu C. Prevalence of Venous Thromboembolism in Critically Ill Patients With Coronavirus Disease 2019: A Meta-Analysis. Front Med (Lausanne). 2021 Apr 29;8:603558. doi: 10.3389/fmed.2021.603558.[CROSSREF]

    19. Mansory EM, Srigunapalan S, Lazo-Langner A. Venous Thromboembolism in Hospitalized Critical and Noncritical COVID-19 Patients: A Systematic Review and Meta-analysis. TH Open. 2021 Jul 6;5(3):e286-94. doi: 10.1055/s-0041-1730967.[CROSSREF]

    20. Aguilera-Alonso D, Murias S, Martínez-de-Azagra Garde A, Soriano-Arandes A, Pareja M, Otheo E, et al.; EPICO-AEP Working Group. Prevalence of thrombotic complications in children with SARS-CoV-2. Arch Dis Child. 2021 Nov;106(11):1129-32. doi: 10.1136/archdischild-2020-321351.[CROSSREF]

    21. Mai V, Tan BK, Mainbourg S, Potus F, Cucherat M, Lega JC, et al. Venous thromboembolism in COVID-19 compared to non-COVID-19 cohorts: A systematic review with meta-analysis. Vascul Pharmacol. 2021 Aug;139:106882. doi: 10.1016/j.vph.2021.106882.[CROSSREF]

    22. Tufano A, Rendina D, Abate V, Casoria A, Marra A, Buonanno P, et al. Venous Thromboembolism in COVID-19 Compared to Non-COVID-19 Cohorts: A Systematic Review with Meta-Analysis. J Clin Med. 2021 Oct 25;10(21):4925. doi: 10.3390/jcm10214925.[CROSSREF]

    23. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 May 2;395(10234):1417-8. doi: 10.1016/S0140-6736(20)30937-5.[CROSSREF]

    24. Dimitropoulou C, Chatterjee A, McCloud L, Yetik-Anacak G, Catravas JD. Angiotensin, bradykinin and the endothelium. Handb Exp Pharmacol. 2006;(176 Pt 1):255-94. doi: 10.1007/3-540-32967-6_8. [CROSSREF]

    25. Goshua G, Pine AB, Meizlish ML, Chang CH, Zhang H, Bahel P, et al. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet Haematol. 2020 Aug;7(8):e575-82. doi: 10.1016/S2352-3026(20)30216-7.[CROSSREF]

    26. Leebeek FW, Eikenboom JC. Von Willebrand's Disease. N Engl J Med. 2016 Nov 24;375(21):2067-80. doi: 10.1056/NEJMra1601561.[CROSSREF]

    27. Catanzaro M, Fagiani F, Racchi M, Corsini E, Govoni S, Lanni C. Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2. Signal Transduct Target Ther. 2020 May 29;5(1):84. doi: 10.1038/s41392-020-0191-1.[CROSSREF]

    28. Pulivarthi S, Gurram MK. Effectiveness of d-dimer as a screening test for venous thromboembolism: an update. N Am J Med Sci. 2014 Oct;6(10):491-9. doi: 10.4103/1947-2714.143278.[CROSSREF]

    29. Thachil J, Srivastava A. SARS-2 Coronavirus-Associated Hemostatic Lung Abnormality in COVID-19: Is It Pulmonary Thrombosis or Pulmonary Embolism? Semin Thromb Hemost. 2020 Oct;46(7):777-80. doi: 10.1055/s-0040-1712155.[CROSSREF]

    30. Iba T, Levy JH, Levi M, Connors JM, Thachil J. Coagulopathy of Coronavirus Disease 2019. Crit Care Med. 2020 Sep;48(9):1358-64. doi: 10.1097/CCM.0000000000004458.[CROSSREF]

    31. Du WN, Zhang Y, Yu Y, Zhang RM. D-dimer levels is associated with severe COVID-19 infections: A meta-analysis. Int J Clin Pract. 2021 Aug;75(8):e14031. doi: 10.1111/ijcp.14031.[CROSSREF]

    32. ATTACC Investigators; ACTIV-4a Investigators; REMAP-CAP Investigators, Lawler PR, Goligher EC, Berger JS, Neal MD, McVerry BJ, Nicolau JC, et al. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19. N Engl J Med. 2021 Aug 26;385(9):790-802. doi: 10.1056/NEJMoa2105911.[CROSSREF]

    33. REMAP-CAP Investigators; ACTIV-4a Investigators; ATTACC Investigators, Goligher EC, Bradbury CA, McVerry BJ, Lawler PR, Berger JS, Gong MN, et al. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19. N Engl J Med. 2021 Aug 26;385(9):777-89. doi: 10.1056/NEJMoa2103417.[CROSSREF]

    34. Connors JM, Brooks MM, Sciurba FC, Krishnan JA, Bledsoe JR, Kindzelski A, et al.; ACTIV-4B Investigators. Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients With Clinically Stable Symptomatic COVID-19: The ACTIV-4B Randomized Clinical Trial. JAMA. 2021 Nov 2;326(17):1703-12. doi: 10.1001/jama.2021.17272.[CROSSREF]

    35. Harter K, Levine M, Henderson SO. Anticoagulation drug therapy: a review. West J Emerg Med. 2015 Jan;16(1):11-7. doi: 10.5811/westjem.2014.12.22933.[CROSSREF]

    36. Sartori MT, Prandoni P. How to effectively manage the event of bleeding complications when using anticoagulants. Expert Rev Hematol. 2016 Jan;9(1):37-50. doi: 10.1586/17474086.2016.1112733.[CROSSREF]

    37. Lee GM, Arepally GM. Heparin-induced thrombocytopenia. Hematology Am Soc Hematol Educ Program. 2013;2013:668-74. doi: 10.1182/asheducation-2013.1.668.[CROSSREF]

    38. Daviet F, Guervilly C, Baldesi O, Bernard-Guervilly F, Pilarczyk E, Genin A, et al. Heparin-Induced Thrombocytopenia in Severe COVID-19. Circulation. 2020 Nov 10;142(19):1875-7. doi: 10.1161/CIRCULATIONAHA.120.049015.[CROSSREF]

    39. Tran PN, Tran MH. Emerging Role of Direct Oral Anticoagulants in the Management of Heparin-Induced Thrombocytopenia. Clin Appl Thromb Hemost. 2018 Mar;24(2):201-9. doi: 10.1177/1076029617696582.[CROSSREF]

    40. Hogan M, Berger JS. Heparin-induced thrombocytopenia (HIT): Review of incidence, diagnosis, and management. Vasc Med. 2020 Apr;25(2):160-73. doi: 10.1177/1358863X19898253.[CROSSREF]

    41. Chaudhuri D, Sasaki K, Karkar A, Sharif S, Lewis K, Mammen MJ, et al. Corticosteroids in COVID-19 and non-COVID-19 ARDS: a systematic review and meta-analysis. Intensive Care Med. 2021 May;47(5):521-37. doi: 10.1007/ s00134-021-06394-2.[CROSSREF]

    42. Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol. 2021 Jan;93(1):250-6. doi: 10.1002/jmv.26232.[CROSSREF]

    43. Añón JM, Villar J. Ten reasons why corticosteroid therapy reduces mortality in severe COVID-19. Intensive Care Med. 2021 Mar;47(3):355-6. doi: 10.1007/s00134-020-06330-w.[CROSSREF]

    44. Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al., on behalf of the RECOVERY Collaborative Group. Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report. MedRxiv. 2020.[CROSSREF]

    45. Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, et al.; COALITION COVID-19 Brazil III Investigators. Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1307-16. doi: 10.1001/jama.2020.17021.[CROSSREF]

    46. Villar J, Añón JM, Ferrando C, Aguilar G, Muñoz T, Ferreres J, et al.; DEXACOVID19 Network. Efficacy of dexamethasone treatment for patients with the acute respiratory distress syndrome caused by COVID-19: study protocol for a randomized controlled superiority trial. Trials. 2020 Aug 16;21(1):717. doi: 10.1186/s13063-020-04643-1.[CROSSREF]

    47. Corral-Gudino L, Bahamonde A, Arnaiz-Revillas F, Gómez-Barquero J, Abadía-Otero J, García-Ibarbia C, et al.; GLUCOCOVID investigators. Methylprednisolone in adults hospitalized with COVID-19 pneumonia : An open-label randomized trial (GLUCOCOVID). Wien Klin Wochenschr. 2021 Apr;133(7- 8):303-11. doi: 10.1007/s00508-020-01805-8.[CROSSREF]

    48. Jeronimo CMP, Farias MEL, Val FFA, Sampaio VS, Alexandre MAA, Melo GC, et al.; Metcovid Team. Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial. Clin Infect Dis. 2021 May 4;72(9):e373-81. doi: 10.1093/cid/ciaa1177.[CROSSREF]

    49. Ranjbar K, Moghadami M, Mirahmadizadeh A, Fallahi MJ, Khaloo V, Shahriarirad R, et al. Methylprednisolone or dexamethasone, which one is superior corticosteroid in the treatment of hospitalized COVID-19 patients: a triple-blinded randomized controlled trial. BMC Infect Dis. 2021 Apr 10;21(1):337. doi: 10.1186/s12879-021-06045-3.[CROSSREF]

    50. Ko JJ, Wu C, Mehta N, Wald-Dickler N, Yang W, Qiao R. A Comparison of Methylprednisolone and Dexamethasone in Intensive Care Patients With COVID-19. J Intensive Care Med. 2021 Jun;36(6):673-80. doi: 10.1177/0885066621994057.[CROSSREF]

    51. Dequin PF, Heming N, Meziani F, Plantefève G, Voiriot G, Badié J, et al.; CAPE COVID Trial Group and the CRICS-TriGGERSep Network. Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1298- 306. doi: 10.1001/jama.2020.16761.[CROSSREF]

    52. Angus DC, Derde L, Al-Beidh F, Annane D, Arabi Y, Beane A, et al.; The Writing Committee for the REMAP-CAP Investigators. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1317-29. doi: 10.1001/jama.2020.17022.[CROSSREF]

    53. Milenković M, Đukić M, Brajković M, Klašnja S, Tošković B, Zdravković M. Primena kortikosteroida u terapiji COVID-19 infekcije SJAIT.2021;(43)VII – IX.[HTTP]

    54. Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG. Prevention and management of glucocorticoid-induced side effects: A comprehensive review: Gastrointestinal and endocrinologic side effects. J Am Acad Dermatol. 2017 Jan;76(1):11-6. doi: 10.1016/j.jaad.2016.02.1239.[CROSSREF]

    55. Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG. Prevention and management of glucocorticoid-induced side effects: A comprehensive review: A review of glucocorticoid pharmacology and bone health. J Am Acad Dermatol. 2017 Jan;76(1):1-9. doi: 10.1016/j.jaad.2016.01.062.[CROSSREF]


References

1. Lu H, Stratton CW, Tang YW. Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle. J Med Virol. 2020 Apr;92(4):401- 2. doi: 10.1002/jmv.25678.[CROSSREF]

2. Neue Zürcher Zeitung. Die Corona-Epidemie ist jetzt eine Corona-Pandemie. Das ändert wenig [Internet]. Neue Zürcher Zeitung; 2020 Mar [pristupljeno 20. novembra 2021.]. Dostupno na: https://www.nzz.ch/wissenschaft/covid-19-who-erklaert-corona-epidemie-zur-pandemie-ld.1546030.[HTTP]

3. Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020 Jul;75(7):1730-41. doi: 10.1111/all.14238.[CROSSREF]

4. Boscolo-Rizzo P, Borsetto D, Fabbris C, Spinato G, Frezza D, Menegaldo A, et al. Evolution of Altered Sense of Smell or Taste in Patients With Mildly Symptomatic COVID-19. JAMA Otolaryngol Head Neck Surg. 2020 Aug 1;146(8):729-32. doi: 10.1001/jamaoto.2020.1379.[CROSSREF]

5. Ministarstvo zdravlja Republike Srbije. COVID-19. [Internet]. [pristupljeno 29. novembra 2021.]. Dostupno na: https://www.zdravlje.gov.rs/sekcija/345852/covid-19.php.[HTTP]

6. White-Dzuro G, Gibson LE, Zazzeron L, White-Dzuro C, Sullivan Z, Diiorio DA, et al. Multisystem effects of COVID-19: a concise review for practitioners. Postgrad Med. 2021 Jan;133(1):20-7. doi: 10.1080/00325481.2020.1823094.[CROSSREF]

7. Službeni portal Doma zdravlja „Savski venac“.Terapijski portokol COVID-19 – 21. 09. 2021. VERZIJA 12. [Internet]. [pristupljeno 20. oktobra 2021.]. Dostupno na: https://www.dzsvenac.rs/sluzbeno/index.php/vesti-meni/11-ministarstvo-obavestenja/452-terapijski-protokol-covid19-v8.[HTTP]

8. Mansory EM, Srigunapalan S, Lazo-Langner A. Venous Thromboembolism in Hospitalized Critical and Noncritical COVID-19 Patients: A Systematic Review and Meta-analysis. TH Open. 2021 Jul 6;5(3):e286-94. doi: 10.1055/s-0041-1730967.[CROSSREF]

9. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Jul;191:145-7. doi: 10.1016/j.thromres.2020.04.013.[CROSSREF]

10. Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N Engl J Med. 2005 Oct 20;353(16):1711-23. doi: 10.1056/NEJMra050541.[CROSSREF]

11. Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG. Prevention and management of glucocorticoid-induced side effects: A comprehensive review: Gastrointestinal and endocrinologic side effects. J Am Acad Dermatol. 2017 Jan;76(1):11-6. doi: 10.1016/j.jaad.2016.02.1239.[CROSSREF]

12. World Health Organization. Therapeutics and COVID-19. [Internet]. [pristupljeno 20. oktobra 2021.]. Dostupno na: https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2021.4.[HTTP]

13. Popadic V, Klasnja S, Milic N, Rajovic N, Aleksic A, Milenkovic M, et al. Predictors of Mortality in Critically Ill COVID-19 Patients Demanding High Oxygen Flow: A Thin Line between Inflammation, Cytokine Storm, and Coagulopathy. Oxid Med Cell Longev. 2021 Apr 20;2021:6648199. doi: 10.1155/2021/6648199.[CROSSREF]

14. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62. doi: 10.1016/S0140-6736(20)30566-3.[CROSSREF]

15. Soni M, Gopalakrishnan R, Vaishya R, Prabu P. D-dimer level is a useful predictor for mortality in patients with COVID-19: Analysis of 483 cases. Diabetes Metab Syndr. 2020 Nov-Dec;14(6):2245-9. doi: 10.1016/j. dsx.2020.11.007.[CROSSREF]

16. Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost. 2020 Jun;18(6):1324-9. doi: 10.1111/jth.14859.[CROSSREF]

17. Poissy J, Goutay J, Caplan M, Parmentier E, Duburcq T, Lassalle F, et al.; Lille ICU Haemostasis COVID-19 Group. Pulmonary Embolism in Patients With COVID-19: Awareness of an Increased Prevalence. Circulation. 2020 Jul 14;142(2):184-6. doi: 10.1161/CIRCULATIONAHA.120.047430.[CROSSREF]

18. Wu C, Liu Y, Cai X, Zhang W, Li Y, Fu C. Prevalence of Venous Thromboembolism in Critically Ill Patients With Coronavirus Disease 2019: A Meta-Analysis. Front Med (Lausanne). 2021 Apr 29;8:603558. doi: 10.3389/fmed.2021.603558.[CROSSREF]

19. Mansory EM, Srigunapalan S, Lazo-Langner A. Venous Thromboembolism in Hospitalized Critical and Noncritical COVID-19 Patients: A Systematic Review and Meta-analysis. TH Open. 2021 Jul 6;5(3):e286-94. doi: 10.1055/s-0041-1730967.[CROSSREF]

20. Aguilera-Alonso D, Murias S, Martínez-de-Azagra Garde A, Soriano-Arandes A, Pareja M, Otheo E, et al.; EPICO-AEP Working Group. Prevalence of thrombotic complications in children with SARS-CoV-2. Arch Dis Child. 2021 Nov;106(11):1129-32. doi: 10.1136/archdischild-2020-321351.[CROSSREF]

21. Mai V, Tan BK, Mainbourg S, Potus F, Cucherat M, Lega JC, et al. Venous thromboembolism in COVID-19 compared to non-COVID-19 cohorts: A systematic review with meta-analysis. Vascul Pharmacol. 2021 Aug;139:106882. doi: 10.1016/j.vph.2021.106882.[CROSSREF]

22. Tufano A, Rendina D, Abate V, Casoria A, Marra A, Buonanno P, et al. Venous Thromboembolism in COVID-19 Compared to Non-COVID-19 Cohorts: A Systematic Review with Meta-Analysis. J Clin Med. 2021 Oct 25;10(21):4925. doi: 10.3390/jcm10214925.[CROSSREF]

23. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 May 2;395(10234):1417-8. doi: 10.1016/S0140-6736(20)30937-5.[CROSSREF]

24. Dimitropoulou C, Chatterjee A, McCloud L, Yetik-Anacak G, Catravas JD. Angiotensin, bradykinin and the endothelium. Handb Exp Pharmacol. 2006;(176 Pt 1):255-94. doi: 10.1007/3-540-32967-6_8. [CROSSREF]

25. Goshua G, Pine AB, Meizlish ML, Chang CH, Zhang H, Bahel P, et al. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet Haematol. 2020 Aug;7(8):e575-82. doi: 10.1016/S2352-3026(20)30216-7.[CROSSREF]

26. Leebeek FW, Eikenboom JC. Von Willebrand's Disease. N Engl J Med. 2016 Nov 24;375(21):2067-80. doi: 10.1056/NEJMra1601561.[CROSSREF]

27. Catanzaro M, Fagiani F, Racchi M, Corsini E, Govoni S, Lanni C. Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2. Signal Transduct Target Ther. 2020 May 29;5(1):84. doi: 10.1038/s41392-020-0191-1.[CROSSREF]

28. Pulivarthi S, Gurram MK. Effectiveness of d-dimer as a screening test for venous thromboembolism: an update. N Am J Med Sci. 2014 Oct;6(10):491-9. doi: 10.4103/1947-2714.143278.[CROSSREF]

29. Thachil J, Srivastava A. SARS-2 Coronavirus-Associated Hemostatic Lung Abnormality in COVID-19: Is It Pulmonary Thrombosis or Pulmonary Embolism? Semin Thromb Hemost. 2020 Oct;46(7):777-80. doi: 10.1055/s-0040-1712155.[CROSSREF]

30. Iba T, Levy JH, Levi M, Connors JM, Thachil J. Coagulopathy of Coronavirus Disease 2019. Crit Care Med. 2020 Sep;48(9):1358-64. doi: 10.1097/CCM.0000000000004458.[CROSSREF]

31. Du WN, Zhang Y, Yu Y, Zhang RM. D-dimer levels is associated with severe COVID-19 infections: A meta-analysis. Int J Clin Pract. 2021 Aug;75(8):e14031. doi: 10.1111/ijcp.14031.[CROSSREF]

32. ATTACC Investigators; ACTIV-4a Investigators; REMAP-CAP Investigators, Lawler PR, Goligher EC, Berger JS, Neal MD, McVerry BJ, Nicolau JC, et al. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19. N Engl J Med. 2021 Aug 26;385(9):790-802. doi: 10.1056/NEJMoa2105911.[CROSSREF]

33. REMAP-CAP Investigators; ACTIV-4a Investigators; ATTACC Investigators, Goligher EC, Bradbury CA, McVerry BJ, Lawler PR, Berger JS, Gong MN, et al. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19. N Engl J Med. 2021 Aug 26;385(9):777-89. doi: 10.1056/NEJMoa2103417.[CROSSREF]

34. Connors JM, Brooks MM, Sciurba FC, Krishnan JA, Bledsoe JR, Kindzelski A, et al.; ACTIV-4B Investigators. Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients With Clinically Stable Symptomatic COVID-19: The ACTIV-4B Randomized Clinical Trial. JAMA. 2021 Nov 2;326(17):1703-12. doi: 10.1001/jama.2021.17272.[CROSSREF]

35. Harter K, Levine M, Henderson SO. Anticoagulation drug therapy: a review. West J Emerg Med. 2015 Jan;16(1):11-7. doi: 10.5811/westjem.2014.12.22933.[CROSSREF]

36. Sartori MT, Prandoni P. How to effectively manage the event of bleeding complications when using anticoagulants. Expert Rev Hematol. 2016 Jan;9(1):37-50. doi: 10.1586/17474086.2016.1112733.[CROSSREF]

37. Lee GM, Arepally GM. Heparin-induced thrombocytopenia. Hematology Am Soc Hematol Educ Program. 2013;2013:668-74. doi: 10.1182/asheducation-2013.1.668.[CROSSREF]

38. Daviet F, Guervilly C, Baldesi O, Bernard-Guervilly F, Pilarczyk E, Genin A, et al. Heparin-Induced Thrombocytopenia in Severe COVID-19. Circulation. 2020 Nov 10;142(19):1875-7. doi: 10.1161/CIRCULATIONAHA.120.049015.[CROSSREF]

39. Tran PN, Tran MH. Emerging Role of Direct Oral Anticoagulants in the Management of Heparin-Induced Thrombocytopenia. Clin Appl Thromb Hemost. 2018 Mar;24(2):201-9. doi: 10.1177/1076029617696582.[CROSSREF]

40. Hogan M, Berger JS. Heparin-induced thrombocytopenia (HIT): Review of incidence, diagnosis, and management. Vasc Med. 2020 Apr;25(2):160-73. doi: 10.1177/1358863X19898253.[CROSSREF]

41. Chaudhuri D, Sasaki K, Karkar A, Sharif S, Lewis K, Mammen MJ, et al. Corticosteroids in COVID-19 and non-COVID-19 ARDS: a systematic review and meta-analysis. Intensive Care Med. 2021 May;47(5):521-37. doi: 10.1007/ s00134-021-06394-2.[CROSSREF]

42. Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol. 2021 Jan;93(1):250-6. doi: 10.1002/jmv.26232.[CROSSREF]

43. Añón JM, Villar J. Ten reasons why corticosteroid therapy reduces mortality in severe COVID-19. Intensive Care Med. 2021 Mar;47(3):355-6. doi: 10.1007/s00134-020-06330-w.[CROSSREF]

44. Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al., on behalf of the RECOVERY Collaborative Group. Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report. MedRxiv. 2020.[CROSSREF]

45. Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, et al.; COALITION COVID-19 Brazil III Investigators. Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1307-16. doi: 10.1001/jama.2020.17021.[CROSSREF]

46. Villar J, Añón JM, Ferrando C, Aguilar G, Muñoz T, Ferreres J, et al.; DEXACOVID19 Network. Efficacy of dexamethasone treatment for patients with the acute respiratory distress syndrome caused by COVID-19: study protocol for a randomized controlled superiority trial. Trials. 2020 Aug 16;21(1):717. doi: 10.1186/s13063-020-04643-1.[CROSSREF]

47. Corral-Gudino L, Bahamonde A, Arnaiz-Revillas F, Gómez-Barquero J, Abadía-Otero J, García-Ibarbia C, et al.; GLUCOCOVID investigators. Methylprednisolone in adults hospitalized with COVID-19 pneumonia : An open-label randomized trial (GLUCOCOVID). Wien Klin Wochenschr. 2021 Apr;133(7- 8):303-11. doi: 10.1007/s00508-020-01805-8.[CROSSREF]

48. Jeronimo CMP, Farias MEL, Val FFA, Sampaio VS, Alexandre MAA, Melo GC, et al.; Metcovid Team. Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial. Clin Infect Dis. 2021 May 4;72(9):e373-81. doi: 10.1093/cid/ciaa1177.[CROSSREF]

49. Ranjbar K, Moghadami M, Mirahmadizadeh A, Fallahi MJ, Khaloo V, Shahriarirad R, et al. Methylprednisolone or dexamethasone, which one is superior corticosteroid in the treatment of hospitalized COVID-19 patients: a triple-blinded randomized controlled trial. BMC Infect Dis. 2021 Apr 10;21(1):337. doi: 10.1186/s12879-021-06045-3.[CROSSREF]

50. Ko JJ, Wu C, Mehta N, Wald-Dickler N, Yang W, Qiao R. A Comparison of Methylprednisolone and Dexamethasone in Intensive Care Patients With COVID-19. J Intensive Care Med. 2021 Jun;36(6):673-80. doi: 10.1177/0885066621994057.[CROSSREF]

51. Dequin PF, Heming N, Meziani F, Plantefève G, Voiriot G, Badié J, et al.; CAPE COVID Trial Group and the CRICS-TriGGERSep Network. Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1298- 306. doi: 10.1001/jama.2020.16761.[CROSSREF]

52. Angus DC, Derde L, Al-Beidh F, Annane D, Arabi Y, Beane A, et al.; The Writing Committee for the REMAP-CAP Investigators. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1317-29. doi: 10.1001/jama.2020.17022.[CROSSREF]

53. Milenković M, Đukić M, Brajković M, Klašnja S, Tošković B, Zdravković M. Primena kortikosteroida u terapiji COVID-19 infekcije SJAIT.2021;(43)VII – IX.[HTTP]

54. Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG. Prevention and management of glucocorticoid-induced side effects: A comprehensive review: Gastrointestinal and endocrinologic side effects. J Am Acad Dermatol. 2017 Jan;76(1):11-6. doi: 10.1016/j.jaad.2016.02.1239.[CROSSREF]

55. Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG. Prevention and management of glucocorticoid-induced side effects: A comprehensive review: A review of glucocorticoid pharmacology and bone health. J Am Acad Dermatol. 2017 Jan;76(1):1-9. doi: 10.1016/j.jaad.2016.01.062.[CROSSREF]

1. Lu H, Stratton CW, Tang YW. Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle. J Med Virol. 2020 Apr;92(4):401- 2. doi: 10.1002/jmv.25678.[CROSSREF]

2. Neue Zürcher Zeitung. Die Corona-Epidemie ist jetzt eine Corona-Pandemie. Das ändert wenig [Internet]. Neue Zürcher Zeitung; 2020 Mar [pristupljeno 20. novembra 2021.]. Dostupno na: https://www.nzz.ch/wissenschaft/covid-19-who-erklaert-corona-epidemie-zur-pandemie-ld.1546030.[HTTP]

3. Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020 Jul;75(7):1730-41. doi: 10.1111/all.14238.[CROSSREF]

4. Boscolo-Rizzo P, Borsetto D, Fabbris C, Spinato G, Frezza D, Menegaldo A, et al. Evolution of Altered Sense of Smell or Taste in Patients With Mildly Symptomatic COVID-19. JAMA Otolaryngol Head Neck Surg. 2020 Aug 1;146(8):729-32. doi: 10.1001/jamaoto.2020.1379.[CROSSREF]

5. Ministarstvo zdravlja Republike Srbije. COVID-19. [Internet]. [pristupljeno 29. novembra 2021.]. Dostupno na: https://www.zdravlje.gov.rs/sekcija/345852/covid-19.php.[HTTP]

6. White-Dzuro G, Gibson LE, Zazzeron L, White-Dzuro C, Sullivan Z, Diiorio DA, et al. Multisystem effects of COVID-19: a concise review for practitioners. Postgrad Med. 2021 Jan;133(1):20-7. doi: 10.1080/00325481.2020.1823094.[CROSSREF]

7. Službeni portal Doma zdravlja „Savski venac“.Terapijski portokol COVID-19 – 21. 09. 2021. VERZIJA 12. [Internet]. [pristupljeno 20. oktobra 2021.]. Dostupno na: https://www.dzsvenac.rs/sluzbeno/index.php/vesti-meni/11-ministarstvo-obavestenja/452-terapijski-protokol-covid19-v8.[HTTP]

8. Mansory EM, Srigunapalan S, Lazo-Langner A. Venous Thromboembolism in Hospitalized Critical and Noncritical COVID-19 Patients: A Systematic Review and Meta-analysis. TH Open. 2021 Jul 6;5(3):e286-94. doi: 10.1055/s-0041-1730967.[CROSSREF]

9. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Jul;191:145-7. doi: 10.1016/j.thromres.2020.04.013.[CROSSREF]

10. Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N Engl J Med. 2005 Oct 20;353(16):1711-23. doi: 10.1056/NEJMra050541.[CROSSREF]

11. Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG. Prevention and management of glucocorticoid-induced side effects: A comprehensive review: Gastrointestinal and endocrinologic side effects. J Am Acad Dermatol. 2017 Jan;76(1):11-6. doi: 10.1016/j.jaad.2016.02.1239.[CROSSREF]

12. World Health Organization. Therapeutics and COVID-19. [Internet]. [pristupljeno 20. oktobra 2021.]. Dostupno na: https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2021.4.[HTTP]

13. Popadic V, Klasnja S, Milic N, Rajovic N, Aleksic A, Milenkovic M, et al. Predictors of Mortality in Critically Ill COVID-19 Patients Demanding High Oxygen Flow: A Thin Line between Inflammation, Cytokine Storm, and Coagulopathy. Oxid Med Cell Longev. 2021 Apr 20;2021:6648199. doi: 10.1155/2021/6648199.[CROSSREF]

14. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62. doi: 10.1016/S0140-6736(20)30566-3.[CROSSREF]

15. Soni M, Gopalakrishnan R, Vaishya R, Prabu P. D-dimer level is a useful predictor for mortality in patients with COVID-19: Analysis of 483 cases. Diabetes Metab Syndr. 2020 Nov-Dec;14(6):2245-9. doi: 10.1016/j. dsx.2020.11.007.[CROSSREF]

16. Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost. 2020 Jun;18(6):1324-9. doi: 10.1111/jth.14859.[CROSSREF]

17. Poissy J, Goutay J, Caplan M, Parmentier E, Duburcq T, Lassalle F, et al.; Lille ICU Haemostasis COVID-19 Group. Pulmonary Embolism in Patients With COVID-19: Awareness of an Increased Prevalence. Circulation. 2020 Jul 14;142(2):184-6. doi: 10.1161/CIRCULATIONAHA.120.047430.[CROSSREF]

18. Wu C, Liu Y, Cai X, Zhang W, Li Y, Fu C. Prevalence of Venous Thromboembolism in Critically Ill Patients With Coronavirus Disease 2019: A Meta-Analysis. Front Med (Lausanne). 2021 Apr 29;8:603558. doi: 10.3389/fmed.2021.603558.[CROSSREF]

19. Mansory EM, Srigunapalan S, Lazo-Langner A. Venous Thromboembolism in Hospitalized Critical and Noncritical COVID-19 Patients: A Systematic Review and Meta-analysis. TH Open. 2021 Jul 6;5(3):e286-94. doi: 10.1055/s-0041-1730967.[CROSSREF]

20. Aguilera-Alonso D, Murias S, Martínez-de-Azagra Garde A, Soriano-Arandes A, Pareja M, Otheo E, et al.; EPICO-AEP Working Group. Prevalence of thrombotic complications in children with SARS-CoV-2. Arch Dis Child. 2021 Nov;106(11):1129-32. doi: 10.1136/archdischild-2020-321351.[CROSSREF]

21. Mai V, Tan BK, Mainbourg S, Potus F, Cucherat M, Lega JC, et al. Venous thromboembolism in COVID-19 compared to non-COVID-19 cohorts: A systematic review with meta-analysis. Vascul Pharmacol. 2021 Aug;139:106882. doi: 10.1016/j.vph.2021.106882.[CROSSREF]

22. Tufano A, Rendina D, Abate V, Casoria A, Marra A, Buonanno P, et al. Venous Thromboembolism in COVID-19 Compared to Non-COVID-19 Cohorts: A Systematic Review with Meta-Analysis. J Clin Med. 2021 Oct 25;10(21):4925. doi: 10.3390/jcm10214925.[CROSSREF]

23. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 May 2;395(10234):1417-8. doi: 10.1016/S0140-6736(20)30937-5.[CROSSREF]

24. Dimitropoulou C, Chatterjee A, McCloud L, Yetik-Anacak G, Catravas JD. Angiotensin, bradykinin and the endothelium. Handb Exp Pharmacol. 2006;(176 Pt 1):255-94. doi: 10.1007/3-540-32967-6_8. [CROSSREF]

25. Goshua G, Pine AB, Meizlish ML, Chang CH, Zhang H, Bahel P, et al. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet Haematol. 2020 Aug;7(8):e575-82. doi: 10.1016/S2352-3026(20)30216-7.[CROSSREF]

26. Leebeek FW, Eikenboom JC. Von Willebrand's Disease. N Engl J Med. 2016 Nov 24;375(21):2067-80. doi: 10.1056/NEJMra1601561.[CROSSREF]

27. Catanzaro M, Fagiani F, Racchi M, Corsini E, Govoni S, Lanni C. Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2. Signal Transduct Target Ther. 2020 May 29;5(1):84. doi: 10.1038/s41392-020-0191-1.[CROSSREF]

28. Pulivarthi S, Gurram MK. Effectiveness of d-dimer as a screening test for venous thromboembolism: an update. N Am J Med Sci. 2014 Oct;6(10):491-9. doi: 10.4103/1947-2714.143278.[CROSSREF]

29. Thachil J, Srivastava A. SARS-2 Coronavirus-Associated Hemostatic Lung Abnormality in COVID-19: Is It Pulmonary Thrombosis or Pulmonary Embolism? Semin Thromb Hemost. 2020 Oct;46(7):777-80. doi: 10.1055/s-0040-1712155.[CROSSREF]

30. Iba T, Levy JH, Levi M, Connors JM, Thachil J. Coagulopathy of Coronavirus Disease 2019. Crit Care Med. 2020 Sep;48(9):1358-64. doi: 10.1097/CCM.0000000000004458.[CROSSREF]

31. Du WN, Zhang Y, Yu Y, Zhang RM. D-dimer levels is associated with severe COVID-19 infections: A meta-analysis. Int J Clin Pract. 2021 Aug;75(8):e14031. doi: 10.1111/ijcp.14031.[CROSSREF]

32. ATTACC Investigators; ACTIV-4a Investigators; REMAP-CAP Investigators, Lawler PR, Goligher EC, Berger JS, Neal MD, McVerry BJ, Nicolau JC, et al. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19. N Engl J Med. 2021 Aug 26;385(9):790-802. doi: 10.1056/NEJMoa2105911.[CROSSREF]

33. REMAP-CAP Investigators; ACTIV-4a Investigators; ATTACC Investigators, Goligher EC, Bradbury CA, McVerry BJ, Lawler PR, Berger JS, Gong MN, et al. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19. N Engl J Med. 2021 Aug 26;385(9):777-89. doi: 10.1056/NEJMoa2103417.[CROSSREF]

34. Connors JM, Brooks MM, Sciurba FC, Krishnan JA, Bledsoe JR, Kindzelski A, et al.; ACTIV-4B Investigators. Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients With Clinically Stable Symptomatic COVID-19: The ACTIV-4B Randomized Clinical Trial. JAMA. 2021 Nov 2;326(17):1703-12. doi: 10.1001/jama.2021.17272.[CROSSREF]

35. Harter K, Levine M, Henderson SO. Anticoagulation drug therapy: a review. West J Emerg Med. 2015 Jan;16(1):11-7. doi: 10.5811/westjem.2014.12.22933.[CROSSREF]

36. Sartori MT, Prandoni P. How to effectively manage the event of bleeding complications when using anticoagulants. Expert Rev Hematol. 2016 Jan;9(1):37-50. doi: 10.1586/17474086.2016.1112733.[CROSSREF]

37. Lee GM, Arepally GM. Heparin-induced thrombocytopenia. Hematology Am Soc Hematol Educ Program. 2013;2013:668-74. doi: 10.1182/asheducation-2013.1.668.[CROSSREF]

38. Daviet F, Guervilly C, Baldesi O, Bernard-Guervilly F, Pilarczyk E, Genin A, et al. Heparin-Induced Thrombocytopenia in Severe COVID-19. Circulation. 2020 Nov 10;142(19):1875-7. doi: 10.1161/CIRCULATIONAHA.120.049015.[CROSSREF]

39. Tran PN, Tran MH. Emerging Role of Direct Oral Anticoagulants in the Management of Heparin-Induced Thrombocytopenia. Clin Appl Thromb Hemost. 2018 Mar;24(2):201-9. doi: 10.1177/1076029617696582.[CROSSREF]

40. Hogan M, Berger JS. Heparin-induced thrombocytopenia (HIT): Review of incidence, diagnosis, and management. Vasc Med. 2020 Apr;25(2):160-73. doi: 10.1177/1358863X19898253.[CROSSREF]

41. Chaudhuri D, Sasaki K, Karkar A, Sharif S, Lewis K, Mammen MJ, et al. Corticosteroids in COVID-19 and non-COVID-19 ARDS: a systematic review and meta-analysis. Intensive Care Med. 2021 May;47(5):521-37. doi: 10.1007/ s00134-021-06394-2.[CROSSREF]

42. Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol. 2021 Jan;93(1):250-6. doi: 10.1002/jmv.26232.[CROSSREF]

43. Añón JM, Villar J. Ten reasons why corticosteroid therapy reduces mortality in severe COVID-19. Intensive Care Med. 2021 Mar;47(3):355-6. doi: 10.1007/s00134-020-06330-w.[CROSSREF]

44. Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al., on behalf of the RECOVERY Collaborative Group. Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report. MedRxiv. 2020.[CROSSREF]

45. Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, et al.; COALITION COVID-19 Brazil III Investigators. Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1307-16. doi: 10.1001/jama.2020.17021.[CROSSREF]

46. Villar J, Añón JM, Ferrando C, Aguilar G, Muñoz T, Ferreres J, et al.; DEXACOVID19 Network. Efficacy of dexamethasone treatment for patients with the acute respiratory distress syndrome caused by COVID-19: study protocol for a randomized controlled superiority trial. Trials. 2020 Aug 16;21(1):717. doi: 10.1186/s13063-020-04643-1.[CROSSREF]

47. Corral-Gudino L, Bahamonde A, Arnaiz-Revillas F, Gómez-Barquero J, Abadía-Otero J, García-Ibarbia C, et al.; GLUCOCOVID investigators. Methylprednisolone in adults hospitalized with COVID-19 pneumonia : An open-label randomized trial (GLUCOCOVID). Wien Klin Wochenschr. 2021 Apr;133(7- 8):303-11. doi: 10.1007/s00508-020-01805-8.[CROSSREF]

48. Jeronimo CMP, Farias MEL, Val FFA, Sampaio VS, Alexandre MAA, Melo GC, et al.; Metcovid Team. Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial. Clin Infect Dis. 2021 May 4;72(9):e373-81. doi: 10.1093/cid/ciaa1177.[CROSSREF]

49. Ranjbar K, Moghadami M, Mirahmadizadeh A, Fallahi MJ, Khaloo V, Shahriarirad R, et al. Methylprednisolone or dexamethasone, which one is superior corticosteroid in the treatment of hospitalized COVID-19 patients: a triple-blinded randomized controlled trial. BMC Infect Dis. 2021 Apr 10;21(1):337. doi: 10.1186/s12879-021-06045-3.[CROSSREF]

50. Ko JJ, Wu C, Mehta N, Wald-Dickler N, Yang W, Qiao R. A Comparison of Methylprednisolone and Dexamethasone in Intensive Care Patients With COVID-19. J Intensive Care Med. 2021 Jun;36(6):673-80. doi: 10.1177/0885066621994057.[CROSSREF]

51. Dequin PF, Heming N, Meziani F, Plantefève G, Voiriot G, Badié J, et al.; CAPE COVID Trial Group and the CRICS-TriGGERSep Network. Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1298- 306. doi: 10.1001/jama.2020.16761.[CROSSREF]

52. Angus DC, Derde L, Al-Beidh F, Annane D, Arabi Y, Beane A, et al.; The Writing Committee for the REMAP-CAP Investigators. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1317-29. doi: 10.1001/jama.2020.17022.[CROSSREF]

53. Milenković M, Đukić M, Brajković M, Klašnja S, Tošković B, Zdravković M. Primena kortikosteroida u terapiji COVID-19 infekcije SJAIT.2021;(43)VII – IX.[HTTP]

54. Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG. Prevention and management of glucocorticoid-induced side effects: A comprehensive review: Gastrointestinal and endocrinologic side effects. J Am Acad Dermatol. 2017 Jan;76(1):11-6. doi: 10.1016/j.jaad.2016.02.1239.[CROSSREF]

55. Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG. Prevention and management of glucocorticoid-induced side effects: A comprehensive review: A review of glucocorticoid pharmacology and bone health. J Am Acad Dermatol. 2017 Jan;76(1):1-9. doi: 10.1016/j.jaad.2016.01.062.[CROSSREF]


© All rights reserved. Medical Chamber of Serbia.

To top