Pathophysiology and Management of Hypercoagulation in Infectious Diseases

Numerous systemic infections may have hypercoagulation as one of the complications, which may range from asymptomatic presentation of elevation of biochemical markers of coagulation such as that of fibrin and thrombin generation, to a much severe, symptomatic, life-threatening, disseminated intravascular coagulation (DIC), which results in the formation of thrombi in the microvasculature of various organs. This phenomenon contributes to increase in morbidity and mortality in various infectious diseases. The current review discusses various mechanisms of hypercoagulation during infections such as tissue factor activation, endothelial cell activation, inhibition of physiological anticoagulant pathways, and fibrinolysis inhibition. The review also discusses pathophysiological changes in the coagulation system and its management in the recent pandemic of COVID-19. The article also discusses role of various parenteral and oral anticoagulants in the management of infectious diseases. The review provides clinical data on various anticoagulants used during hospitalization and extended prophylaxis for the management of venous thromboembolism in various infections. Methodology Because this is a review of published literature and no humans or animals were involved, ethical committee approval was not required and patient consent was not required.

Thrombosis with Thrombocytopenia Syndrome After Administration of AZD1222 or Ad26.COV2.S Vaccine for COVID-19: A Systematic Review.

BACKGROUND: Cases of thrombosis with thrombocytopenia syndrome (TTS) have been reported following vaccination with AZD1222 or Ad26.COV2.S. This review aimed to explore the pathophysiology, epidemiology, diagnosis, management, and prognosis of TTS. METHODS: A systematic review was conducted to identify evidence on TTS till 4th September 2021. Case reports and series reporting patient-level data were included. Descriptive statistics were reported and compared across patients with different sexes, age groups, vaccines, types of thrombosis, and outcomes. FINDINGS: Sixty-two studies reporting 160 cases were included from 16 countries. Patients were predominantly females with a median age of 42.50 (22) years. AZD1222 was administered to 140 patients (87·5%). TTS onset occurred in a median of 9 (4) days after vaccination. Venous thrombosis was most common (61.0%). Most patients developed cerebral venous sinus thrombosis (CVST; 66.3%). CVST was significantly more common in female vs male patients (p = 0·001) and in patients aged <45 years vs ≥45 years (p = 0·004). The mortality rate was 36.2%, and patients with suspected TTS, venous thrombosis, CVST, pulmonary embolism, or intraneural complications, patients not managed with non-heparin anticoagulants or IVIG, patients receiving platelet transfusions, and patients requiring intensive care unit admission, mechanical ventilation, or inpatient neurosurgery were more likely to expire than recover. INTERPRETATION: These findings help to understand the pathophysiology of TTS while also recommending diagnostic and management approaches to improve prognosis in patients. FUNDING: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Coronavirus Pandemic: An Update on the Transmission, Diagnosis, Clinical Features and Managment

The novel coronavirus, designated as "Severe Acute Respiratory Syndrome Coronavirus 2" (SARS-CoV-2), is a new coronavirus that has evolved as a global pandemic recently, and it has created a widespread interest in coronaviruses causing human infections. This article compares the pathogenesis, distribution, clinical characteristics, and treatment of the three highly pathogenic coronaviruses that caused epidemics, namely, "Severe Acute Respiratory Syndrome Coronavirus" (SARS), "Middle East Respiratory Syndrome" (MERS), and SARS-CoV-2. This narrative review is prepared using the data compiled from literature search using relevant MeSH terms. The clinical manifestation of SARS-CoV-2 infection (COVID-19) is mild with relatively low fatality rate than the other two coronaviruses;however, its overall capability to cause explosive spread of the disease and reach a pandemic level is greater. Unlike SARS and MERS, COVID-19 has no accepted treatment protocols at present. Extensive studies and analyses on COVID-19 are necessary before making strong recommendations for or against any particular treatment, although some recent medications have shown great potential. COVID-19 still needs further investigation, where all of the lessons gained from previous outbreaks of SARS and MERS and the experience from the countries that managed COVID-19 seem to be the best approaches to counteract this new global hazard at present until effective preventive vaccines are available in sufficient quantity for mass vaccination programs worldwide.

Factors associated with disease severity and mortality among patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: Understanding the factors associated with disease severity and mortality in Coronavirus disease (COVID-19) is imperative to effectively triage patients. We performed a systematic review to determine the demographic, clinical, laboratory and radiological factors associated with severity and mortality in COVID-19. METHODS: We searched PubMed, Embase and WHO database for English language articles from inception until May 8, 2020. We included Observational studies with direct comparison of clinical characteristics between a) patients who died and those who survived or b) patients with severe disease and those without severe disease. Data extraction and quality assessment were performed by two authors independently. RESULTS: Among 15680 articles from the literature search, 109 articles were included in the analysis. The risk of mortality was higher in patients with increasing age, male gender (RR 1.45, 95%CI 1.23-1.71), dyspnea (RR 2.55, 95%CI 1.88-2.46), diabetes (RR 1.59, 95%CI 1.41-1.78), hypertension (RR 1.90, 95%CI 1.69-2.15). Congestive heart failure (OR 4.76, 95%CI 1.34-16.97), hilar lymphadenopathy (OR 8.34, 95%CI 2.57-27.08), bilateral lung involvement (OR 4.86, 95%CI 3.19-7.39) and reticular pattern (OR 5.54, 95%CI 1.24-24.67) were associated with severe disease. Clinically relevant cut-offs for leukocytosis(>10.0 x109/L), lymphopenia(< 1.1 x109/L), elevated C-reactive protein(>100mg/L), LDH(>250U/L) and D-dimer(>1mg/L) had higher odds of severe disease and greater risk of mortality. CONCLUSION: Knowledge of the factors associated of disease severity and mortality identified in our study may assist in clinical decision-making and critical-care resource allocation for patients with COVID-19.