Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.

INTRODUCTION: The prevalence of thrombotic complications in lymphoma patients ranges from 1.5% up to 59.5%. Lymphoma patients have a 10-fold higher risk for the development of venous thrombosis than patients with lung and gastrointestinal cancers. The pathogenesis of thromboembolic disease in hematological malignancies is complex and multifactorial and can be due to the underlying disorder or related to therapy. A number of biomarkers are associated with the occurence of VTE in cancer patients. Biomarkers reflect activation of coagulation and increased inflammatory potential. This study aimed to profile hemostatic and inflammatory biomarkers in patients with Hodgkin lymphoma, non-Hodgkin lymphoma, and chronic lymphocytic leukemia/ small lymphocytic lymphoma. METHODS: Citrated plasma samples were collected from lymphoma patients (n=96) under an IRB approved protocol Clinic for hematology, Lymphoma Center, University of Belgrade in Serbia. Samples were shipped to Loyola University Chicago and analyzed in batches via commercially available ELISA kits to profile biomarkers of coagulation activation and inflammation. Markers in Coagulation Activation: von Willebrand Factor (vWF), Factor XIIIa, Protein S, β2Glycoprotein I (β2GPI), D-dimer, Microparticles (MP), Urokinase-type Plasminogen Activator Antigen (uPA), Fibronectin. Markers of Inflammation included: Human Tumor Necrosis Factor- α (TNF- α), C-Reactive Protein (CRP), Plasminogen Activator Inhibitor Type 1 (PAI-1). The lymphoma patient population for each biomarker was compared to normal human pooled plasma (repeated 3 times for each biomarker), which consisted of 25 male and 25 females. RESULTS: The mean patients' age was 56 years (range, 19-80 years); 52.4% were males. Most patients were newly diagnosed and had advanced stage disease. A total of 42 patients (43.8%) had high-grade NHL; 17 (17.7%) had low-grade NHL; 24 (25.0%) had HLL; 7(7.3%) had HL; 6 (6.3%) had other forms. Lymphoma patients had significantly dysregulated following markers of coagulation: vWF, β2GPI, D-dimer, MP, uPA, and Fibronectin (Figure 1) (p<0.001 for all in comparison to controls). TNF-α and CRP as markers of inflammation were also significantly increased in lymphoma patients (Figure 1) (p<0.001 for both in comparison to controls). In lymphoma population 12 patients had thrombosis. Patients with thrombosis had significantly higher Factor XIIIa in comparison to lymphoma patients without thrombosis (106±9 vs. 85±256; p<0.001). CONCLUSION: Hemostatic dysregulation and inflammation is present in lymphoma patients, which may reflect increased thrombogenic potential. Further studies are required to link clinical data and biomarker levels, with special emphasis on the involvement of FXIII in the development of thrombotic events in lymphoma patients. Biomarker profiling of lymphoma patients will also help in the understanding of the pathophysiologic mechanisms involved in the observed thrombotic complications and differentiating the sub-groups. Figure 1 Disclosures No relevant conflicts of interest to declare.

Background Lymphomas are characterized by elevated synthesis of inflammatory soluble mediators that could trigger the development of venous thromboembolism (VTE). However, data on the relationship between specific immune dysregulation and VTE occurrence in patients with lymphoma are scarce. Therefore, this study aimed to assess the association between inflammatory markers and the risk of VTE development in patients with lymphoma. Methods The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase (LDH), total protein (TP), and albumin were assessed in 706 patients with newly diagnosed or relapsed lymphoma. Data were collected for all VTE events, while the diagnosis of VTE was established objectively based on radiographic studies. ROC (receiver operating characteristic) curve analysis was performed to define the optimal cutoff values for predicting VTE. Results The majority of patients was diagnosed with aggressive non-Hodgkin lymphoma (58.8%) and had advanced stage disease (59.9%). Sixty-nine patients (9.8%) developed VTE. The NLR, PLR, ESR, CRP, and LDH were significantly higher in the patients with lymphoma with VTE, whereas the TP and albumin were significantly lower in those patients. Using the univariate regression analysis, the NLR, PLR, TP, albumin, LDH, and CRP were prognostic factors for VTE development. In the multivariate regression model, the NLR and CRP were independent prognostic factors for VTE development. ROC curve analysis demonstrated acceptable specificity and sensitivity of the parameters: NLR, PLR, and CRP for predicting VTE. Conclusion Inflammatory dysregulation plays an important role in VTE development in patients with lymphoma. Widely accessible, simple inflammatory parameters can classify patients with lymphoma at risk of VTE development.

Venous thromboembolism (VTE) is a multifactorial disease that can possibly affect any part of venous circulation. The risk of VTE increases by about 2 fold in pregnant women and VTE is one of the major causes of maternal morbidity and mortality. For decades superficial vein thrombosis (SVT) has been considered as benign, self-limiting condition, primarily local event consequently being out of scope of well conducted epidemiological and clinical studies. Recently, the approach on SVT has significantly changed considering that prevalence of lower limb SVT is twice higher than both deep vein thrombosis (DVT) and pulmonary embolism (PE). The clinical severity of SVT largely depends on the localization of thrombosis, when it concerns the major superficial vein vessels of the lower limb and particularly the great saphenous vein. If untreated or inadequately treated, SVT can potentially cause DVT or PE. The purpose of this review is to discuss the complex interconnection between SVT and risk factors in pregnancy and to provide evidence-based considerations, suggestions, and recommendations for the diagnosis and treatment of this precarious and delicate clinical entity.

INTRODUCTION: Thromboembolism (TE) in lymphoma patients is gathering substantial attention due to its impact on morbidity and mortality of those patients. The association between lymphoma and increased risk for TE development, especially venous thromboembolism (VTE), has lately been well established through numerous publications. Thrombosis Lymphoma (ThroLy) score has been initially developed as a simple risk assessment model for the risk of TE development in lymphoma patients. It has been both internally and externally validated in several studies, which dominantly included patients with non-Hodgkin lymphoma (NHL). Therefore, aim of our study is to analyse and validate ThroLy score in an extensive cohort of Hodgkin lymphoma (HL) patients. METHODS: A total of 5509 newly diagnosed HL patients, from the German Hodgkin Study Group (GHSG) HD13-15 trials, were included in this study. Data has been obtained for all venous and arterial TE events in HL patients from time of diagnosis to 3 months after the last cycle of therapy. TE was diagnosed objectively based on radiographic studies (duplex venous ultrasound, contrast-enhanced thoracic computed tomography scan, magnetic resonance imaging (MRI) - for central nervous system (CNS) thrombosis, or angiograms (for arterial thrombosis), clinical examination and laboratory evaluation. Based on ThroLy score, patients were divided in three risk categories: low (score 0-1), intermediate (score 2-3) and high risk (score &gt;3). Patients with intermediate and high-risk score were classified at risk. The validation was conducted through Chi-square test, ROC analysis and logistic regression. RESULTS: The mean patients' age was 35.9 years (range, 18-75 years); 55.7% were males. The majority of patients had limited or intermediate stage of disease: Ann Arbor stage I 10.6%, and stage II 57.5%. 190 (3.4%) patients developed thromboembolic events, 173 patients with VTE (3.14%), and 17 with arterial TE (0.31%), respectively. Chi-square test showed statistically significant association between TE and ThroLy score, both in three risk groups (chi-square = 18.236, p≤0.001) and two risk groups: low and at risk (chi-square = 18.029, p≤0.001). The sensitivity, specificity, negative and positive predictive value were 49%, 65%, 95%, and 97%, respectively. Binary logistic regression of ThroLy score showed statistically significant performance in prediction of TE events in HL patients, with satisfactory validity indicators (Ombinus Test chi-square = 11.668, p=0.001; AIC=44.956, BIC = 97.869). Diagnostic accuracy of ThroLy score was calculated via ROC curve (area under curve (AUC)=0.57). CONCLUSION: ThroLy score demonstrated its capability of risk prediction for TE events in HL patients. The limited statistical performance of the ThroLy score requires further research towards possible score enhancement. Disclosures Engert: AstraZeneca: Honoraria; MSD Sharp & Dohme: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding; Affimed Therapeutics: Research Funding; Sandoz: Honoraria; Takeda: Honoraria, Research Funding.