No abstract

No abstract

The actual Coronavirus Disease (COVID 19) pandemic is due to Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a member of the coronavirus family. Besides the respiratory involvement, COVID 19 patients frequently develop a pro-coagulative state caused by virus-induced endothelial dysfunction, cytokine storm and complement cascade hyperactivation. It is common to observe diffuse microvascular thrombi in multiple organs, mostly in pulmonary microvessels. Thrombotic risk seems to be directly related to disease severity and worsens patients' prognosis. Therefore, the correct understanding of the mechanisms underlying COVID-19 induced prothrombotic state can lead to a thorough assessment of the possible management strategies. Hence, we review the pathogenesis and therapy of COVID 19-related thrombosis disease, focusing on the available evidence on the possible treatment strategies and proposing an algorithm for the anticoagulation strategy based on disease severity. Keywords COVID-19 • SARS-CoV-2 • Thrombosis • Anticoagulation Highlights • SARS-CoV-2 induced complement hyperactivation, endothelial dysfunction and cytokine storm have a prothrombotic effect. • COVID 19 patients develop a pro-coagulative state directly related to disease severity. • In COVID 19 critical patients, thrombotic lesions in pulmunary microvessels have a prevalence twice higher than critical non-COVID 19 patients. • Anticoagulant treatment is associated with lower mortality. Hence, we propose an algorithm for the anticoagulation strategy based on disease severity.

BACKGROUNDAlthough experimental studies have demonstrated an important role of insulin‐like growth factor I (IGF‐I) in hepatocarcinogenesis, the clinical data about IGF‐I in patients with hepatocellular carcinoma (HCC) are scarce and controversial. To the authors' knowledge, this is the first prospective study investigating the longitudinal correlation between modifications in serum IGF‐I levels and the development of HCC in a cohort of patients with hepatitis C virus (HCV)‐related cirrhosis.METHODSOne hundred fourteen consecutive patients with HCV‐related Child Grade A cirrhosis were followed prospectively at the Second University of Naples for 56.4 ± 12.0 months with ultrasound examinations of the liver and serum α‐fetoprotein determination every 6 months. At each clinical evaluation, the severity of disease was graded according to the established Child–Pugh scoring system. Serum IGF‐I levels were measured prospectively at the study entry and at least every 12 months throughout follow‐up.RESULTSTwenty patients (19.2%) developed HCC during follow‐up. Eleven of these patients had persistent Child Grade A cirrhosis for the whole study, whereas the other 9 patients developed HCC after their cirrhosis progressed from Child Grade A to Grade B. In patients who remained free of HCC for the whole study, serum IGF‐I concentrations did not modify significantly during follow‐up. Conversely, in patients who developed HCC, IGF‐I levels decreased significantly during follow‐up (from 72.6 ± 29.9 μg/L to 33.8 ± 14.5 μg/L; P = 0.001). In these patients, the significant decrease occurred both in patients with persistent Child Grade A cirrhosis and in patients with cirrhosis that progressed from Child Grade A to Grade B. The reduction in IGF‐I level preceded the diagnosis of HCC by 9.3 ± 3.1 months.CONCLUSIONSThis prospective study demonstrates that, in patients with HCV‐related cirrhosis, 1) the development of HCC is accompanied by a significant reduction of serum IGF‐I levels independent of the grade of impairment of liver function; and 2) modification of the IGF‐I level precedes the morphologic appearance of HCC, permitting a precocious diagnosis of the tumor. Cancer 2002;95:2539–45. © 2002 American Cancer Society.DOI 10.1002/cncr.11002