ABSTRACT
Background : Several thrombotic manifestations have been reported with SARS-Cov-2 infection including liver vascular involvement. Aims : We present a dramatic case of acute liver necrosis in a 36-year-old SARS-Cov-2 positive Italian woman with no respiratory symptoms and triple positive antiphospholipid syndrome (APS). Methods : The patient was referred to our University Hospital for acute hypertransaminasemia and liver failure (Figure). She had systemic lupus erythematosus (positivity for: ANA, anti-dsDNA, complement activation, Coombs;thrombocytopenia, previous arthritis). Anti-phopspholipid antibodies (aPL) were detected for the first time in 2015 during routine pregnancy screening and chronically treated with aspirin. Apparently, no venous/arterial nor obstetric events were recorded up to the recent hospitalization. FIGURE 1 Results : At arrival, US-Doppler and CT-scan were consistent with signs of chronic liver disease and occlusion of the three hepatic veins defining a Budd-Chiari syndrome. We opted for a stepwise approach considering anticoagulation (clexane 100 UI/Kg b.i.d) the first line of therapy before any invasive intervention. Dexamethasone 6 mg/ day b.i.d., 6 sessions of plasma-exchange, i.v.-immunoglobulin were sequentially planned to revert the liver damage sustained by aPL. After 5-days, two hepatic-veins resulted recanalized in association with amelioration of liver-enzyme/function and aPL quantification. Then we performed hepatic vein catheterization and transjugular liver biopsy. The histology showed multiple areas of necrosis associated with liver cirrhosis. Unexpectedly, no signs of acute Budd-Chiari were observed (e.g. intraparenchymal hemorrhages, centrilobular congestion, sinusoidal dilation). Other etiologies were also excluded and we hypothesized the involvement of small arteries of the liver in a triple positive APS in a patients with SLE. We finally addressed the patient to a liver transplant program and a tight multispecialistic follow-up. Conclusions : Thrombosis of arterial/venous vessels or microcirculation causes liver damage in some patients with aPL. Our report suggests that SARS-Cov-2 can exacerbate this prothrombotic condition determining a life-threatening complication such as acute liver failure.
ABSTRACT
Background : The novel coronavirus disease 2019 (COVID-19) presents an important and urgent threat to global health. Identifying strong predictors of mortality could assist medical staff in treating patients and allocating limited healthcare resources. Aims : The primary aim of this paper was to study the effect of ddimer levels at admission as a predictive marker for in-hospital mortality. Methods : This was a retrospective cohort study evaluating hospitalized patients (age > 18 years), who were positive for COVID-19 based on real-time PCR at one of nine COVID-19 units during the period of the first COVID-19 wave in Lombardy, Italy. The primary endpoint was in-hospital mortality. Information was obtained from patient records. Statistical analyses were performed using a Fine-Gray competing risk survival model. Predictive power was assessed using Harrell's C-index. Results : Out of 1049 patients that were admitted to the emergency department and subsequently hospitalized, 501 patients had evaluable data for d-dimer. Of these 501 patients, 96 did not survive. Cumulative incidence of in-hospital mortality within 30 days was 20%, and the majority of deaths occurred within the first 10 days. (Figure 1) When compared to patients in the lowest quartile of d-dimer blood concentration, the hazard ratio of in-hospital mortality for patients in the 2 nd , 3 rd and 4 th quartile was 3.9 (95CI: 1.5-10.0), 5.8 (95CI: 2.3-14.7), and 4.6 (95CI: 1.8-11.5) respectively, after multivariable adjustment for age, sex and number of comorbidities. The C-statistic of d-dimer for in-hospital mortality was 0.67 (95CI: 0.62-0.71). (Table 2) Conclusions : Higher d-dimer levels were strongly associated with inhospital mortality. However, the predictive power of d-dimer alone was not high enough to be useful as a risk prediction score. Future research should focus on the added value of d-dimer as part of a larger risk prediction score.
ABSTRACT
Background : Covid-19 infection is associated with a widespread global activation of coagulation and affected patients are at an increased risk of thrombosis. Aims : Heparin therapy is effective in various setting in preventing thromboembolic complications and aim of this study was to assess heparin response in COVID-19 patients through anti-FXa test. Methods : In 52 patients, M:F ratio 59:41, median age 59 years old, admitted in different intensity of care units of our hospital, treated with different regimens of heparin (100 U/kg every 24 h in low intensity care, 70 U/kg every 12 h in intermediate intensity care and 100 U/kg every 12 h in intensive care unit), anti-FXa levels were measured immediately before and 3 h after subcutaneous enoxaparin administration. On the same samples thrombin generation tests were performed. Results : Patients treated with 100 U/kg every 24 h and 70 U/ kg every 12 h had median anti-FXa basal levels in the prophylactic range, respectively 0.18 and 0.22 U/ml, while patients treated with 100 U/kg every 12 h were in the anticoagulant range (0.37 U/ ml). Despite heparin therapy thrombin generation was elevated in COVID-19 patients, indicating a high level of coagulation activation. Conclusions : In conclusion we demonstrated that the biological response to enoxaparin in COVID-19 patients is in the expected range using anti-FXa assay and patients are not resistant to heparin therapy.