ABSTRACT
Background: A novel acquired coagulopathy characterized by a severe procoagulant imbalance is common in COVID-19 patients and is associated with the clinical severity of the disease. Aim(s): Our study aims to elucidate the underlying mechanisms of coagulation activation in COVID-19 patients. Method(s): Symptomatic COVID-19 patients during Milan first wave were consecutively enrolled and stratified into 3 groups based on the intensity of care: Low, requiring only high-flow oxygen by nasal cannula;intermediate, requiring continuous positive airway pressure;high, requiring mechanical ventilation. Blood samples were tested for markers of activation of the intrinsic pathway (FXIa, FXIIa) together with its physiologic inhibitor (C1-inhibitor), of the extrinsic pathway (FVIIa), of global activation of the coagulation cascade (D-dimer, FDP, FM) and of fibrinolysis (plasminogen, t-PA, alpha2-antiplasmin, PAI-1). Result(s): 111 patients were included: 26 at low, 42 intermediate and 43 high care-intensity. Median age was 59 +/- 12 (34 patients >65 years);32 patients (29%) developed a venous thrombosis and 12 (11%) died (Table). Median D-dimer, FDP and FM plasma levels were higher in COVID-19 patients compared to controls, with a gradient of increase across the three care intensities, while all the fibrinolytic pathway parameters were in the normal range. Median plasma levels of FVIIa were lower in COVID-19 patients (27.5 mU/ml) than in controls (40.1 mU/ml) while median plasma levels of FXIIa and FXIa were higher in COVID-19 patients (11.2 and 11.3 mU/ml) than in controls (7.2 and 5.5 mU/ml), with a gradient of increase across the three care intensities. C1-inhibitor plasma levels were above the normal range in all the 3 COVID-19 patients' groups (Figure). Conclusion(s): Our study showed a prevalent activation of the contact pathway over the extrinsic pathway of the coagulation cascade in COVID-19 patients, which is proportional to the clinical severity of the infection, opening the possibility for targeted anticoagulant therapies. (Table Presented).
ABSTRACT
Background: Thrombotic thrombocytopenic purpura (TTP) has occasionally been described after vaccination. Since the availability of anti-SARS- CoV- 2 vaccines, 12 cases have been described on a possible association with TTP onset. Aim(s): This study aims to evaluate the relapse rates in patients affected by TTP undergoing anti-SARS- CoV- 2 vaccination. Method(s): All consecutive TTP patients undergoing anti-SARS- CoV- 2 vaccination from March to May 2021 were enrolled. Blood samples were collected before vaccination (T0), 2 weeks after the first (T1) and the second dose (T2) to evaluate ADAMTS13 activity and anti-ADAMTS13 antibody titer. Result(s): A total of 49 TTP patients were enrolled (48 acquired and 1 congenital), all vaccinated with an mRNA vaccine. No patients had a clinical TTP relapse, with an ADAMTS13 relapse rate of 1.36% per month. Mean levels of ADAMTS13 activity were stable among the three timepoints (Figure). In only two patients a significant drop in ADAMTS13 levels occurred after the first dose (from 28% to <3% and from 101% to 82%), and both remained stable after the second dose, with negative anti-ADAMTS13 antibodies. Due to a stable undetectable ADAMTS13, the first patient was treated with 4 doses of weekly 375 mg/m2 rituximab with a rapid ADAMTS13 response. One patient had positive basal anti-ADAMTS13 antibodies with a titer remaining stable after the two vaccine doses, while in another patient anti-ADAMTS13 antibodies became detectable after the first dose, with no corresponding drop in ADAMTS13 levels and a stable titer after the second dose. Conclusion(s): The result of our study prospectively evaluating the effect of anti-SARS- CoV- 2 vaccination on the risk of relapse in a large cohort of patients with TTP in Milan showed a lower than reported relapse rate (1.36% vs 2.6%) with an observed to expected incidence rate ratio of 0.52, confirming the safety of mRNA-based anti-SARS- CoV- 2 vaccination in TTP patients.
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.