ALBERT

Description: Sickle cell disease (SCD) is associated with chronic activation of coagulation and an increased risk of venous thromboembolism. Erythrocyte sickling, the primary pathologic event in SCD, results in dramatic morphological changes in red blood cells (RBCs) because of polymerization of the abnormal hemoglobin. We used a mouse model of SCD and blood samples from sickle patients to determine if these changes affect the structure, properties, and dynamics of sickle clot formation. Sickling of RBCs and a significant increase in fibrin deposition were observed in venous thrombi formed in sickle mice. During ex vivo clot contraction, the number of RBCs extruded from sickle whole blood clots was significantly reduced compared with the number released from sickle cell trait and nonsickle clots in both mice and humans. Entrapment of sickled RBCs was largely factor XIIIa–independent and entirely mediated by the platelet-free cellular fraction of sickle blood. Inhibition of phosphatidylserine, but not administration of antisickling compounds, increased the number of RBCs released from sickle clots. Interestingly, whole blood, but not plasma clots from SCD patients, was more resistant to fibrinolysis, indicating that the cellular fraction of blood mediates resistance to tissue plasminogen activator. Sickle trait whole blood clots demonstrated an intermediate phenotype in response to tissue plasminogen activator. RBC exchange in SCD patients had a long-lasting effect on normalizing whole blood clot contraction. Furthermore, RBC exchange transiently reversed resistance of whole blood sickle clots to fibrinolysis, in part by decreasing platelet-derived PAI-1. These properties of sickle clots may explain the increased risk of venous thromboembolism observed in SCD.

Description: Abstract 1414 Poster Board I-437 Introduction: Previous studies demonstrated that the incidence of venous thromboembolism (VTE) was very low among Thais (Lancet. 1975; 1: 1357-8, Arch Intern Med. 1988; 148: 1349-53). However, recent investigations in Asian countries strongly indicated that VTE is currently much more common, approaching rates in the western countries. Meanwhile, the latest National Health Surveys showed the inadequate vegetable and fruit intakes, as well as an obvious rise in prevalence of obesity in Thai population. Therefore, changing diet and behaviors are suspected to contribute to this marked increase in the VTE incidence. Patients and Methods The case-control study was conducted. Cases were objectively confirmed venous thromboembolism. Patients with underlying cancer, antiphospholipid syndrome and arterial thrombosis were excluded. Controls are age- and sex-matched healthy volunteers. Body mass indices, history of alcohol intake, smoking and exercise were obtained. Food consumptions were interviewed using a food frequency questionnaire modified from the Thailand National Health Examination Survey III previously validated in Thai population. Results: There were 97 cases and 195 controls. The mean age was 54.6 yr, ranging from 17-93 yr, and 70% were female. VTE was significantly associated with low vegetable intakes (below 3.5 standard servings per day) compared with controls (Odd ratio [OR] 2.5, 95% confidence interval [CI] 1.37-4.67), while there was no difference in fruit consumption (p values =0.53). Notably, low fish intakes (below 0.1 serving per day, OR 3.9, 95%CI 1.58-9.71) and having spicy food less than once a week (OR 1.9, 95%CI 1.15-3.18) also increased the risk. The meat, fat, carbohydrate, fast food or alcohol consumptions were similar. In addition, VTE was associated with overweight (OR 2.1, 95%CI 1.21-3.62) and obesity (OR 3.1, 95%CI 1.46-6.74, p values = 0.002 and 0.001, respectively). Furthermore, estrogen uses also increased the risk of VTE (OR 3.7, 95% CI 1.05-13.20, p=0.02), while smoking and lack of exercise did not. Conclusions: Low vegetable, fish and spicy food intakes, as well as obesity and hormonal uses, are the risk factors for VTE in Thai population. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Novel coronavirus infection (SARS CoV-2 or COVID-19) is associated with a high risk of thrombotic complications, including macro- and micro-thrombi in major organs, leading to increased morbidity and mortality. Anticoagulant use, mainly heparin, which has both anticoagulant and anti-inflammatory properties, has been suggested as potentially beneficial. However, the optimal dose of anticoagulant for patients with COVID-19 is unknown. Establishing the optimal thromboprophylaxis strategy and determining the role of biomarkers for patient risk stratification may help to improve outcomes in COVID-19. Methods: This single-center retrospective cohort study is part of an ongoing Quality Improvement project on the use of an anti-factor Xa-driven heparin protocol, which includes a low-dose intravenous (IV) unfractionated heparin (UFH) option, being conducted at our medical center. Data on the type, dose, and indication for anticoagulation as well as outcomes including thrombosis, bleeding and survival was collected for inpatients diagnosed with COVID-19 between mid-March and June 15, 2020. To address COVID-coagulopathy we developed a d-dimer-based anticoagulation protocol for patients with COVID-19 (Figure 1). We recorded anticoagulant use as either standard prophylactic, escalated prophylactic (low-dose intravenous unfractionated heparin titrated to achieve an anti-factor Xa level of 0.1-0.3 anti-Xa units or enoxaparin 0.5mg/kg subcutaneously every 12 hours) or standard therapeutic dose used during the hospitalization. The primary endpoints assessed were ISTH-defined major and clinically relevant non-major bleeding (CRNMB) events and survival. Secondary endpoints included incidence of breakthrough thrombosis and duration of hospitalization. Results: A total of 263 patients with COVID-19 were reviewed. Of these, 68.44% of patients received prophylactic, 12.55% escalated prophylactic and 19.01% therapeutic dosage. Of total, 129 (49%) were receiving ICU level of care. No major bleeding events were observed. The incidence of CRNMB was 4.56% in the whole cohort, which did not differ significantly between the escalated prophylactic and therapeutic groups (12% and 12.12%, respectively). Patients treated with standard prophylaxis had less CRNMB (1.11%), but this was not statistically significant in a multivariate analysis that included other confounding factors such as age, sex, ethnicity, BMI, comorbidity, HASBLED bleeding risk, and sepsis induced coagulopathy score (SICS). The mortality rate was 12.6% in the whole cohort (7.22%, 21.21% and 26% in prophylactic, escalated prophylactic, and therapeutic dosage, respectively). Factors significantly associated with increased mortality included age and ICU level of care (HR 1.10, 95%CI [1.05, 1.15] and HR 20.42, 95%CI [2.84, 146.72], respectively). The use of therapeutic dose heparin and high-flow nasal cannula demonstrate a survival benefit in multivariate analysis (HR 0.13, 95%CI [0.04,0.44] and HR 0.23, 95%CI [0.07, 0.72], respectively; Figure 2). Breakthrough thrombosis occurred in 7 (2.66%) patients; 1 (0.56%), 1 (3.03%) and 5 (10%)) in prophylactic, escalated prophylactic and therapeutic dosage, respectively but very few diagnostic tests were performed during this time period. Duration of hospitalization was significantly longer in the therapeutic dose group when compared to escalated prophylaxis and standard prophylactic groups. Conclusion: In this cohort of inpatients with COVID-19, there were no major bleeding events related to any dose of heparin or LMWH prophylaxis. By multivariate analysis, implementation of a d-dimer-titrated anticoagulation strategy was not associated with increased CRNMB. Therapeutic dose heparin based on a d-dimer-driven anticoagulation protocol was associated with a survival benefit in COVID19-infected patients. Limitations of this study include the retrospective observational nature and a lack of a uniform diagnostic protocol for patients with suspected VTE. Although no significant difference in bleeding events were observed in our study subgroups, randomized clinical trials are necessary to determine optimal thromboprophylaxis strategy in the COVID-19 population. Disclosures No relevant conflicts of interest to declare.