ABSTRACT

Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most discussed topics in the management of this disease. The aim of this position paper is to provide the opinion of Brazilian experts on the thromboprophylaxis and management of thrombotic events in patients with suspected COVID-19, in the sphere of healthcare in Brazil. To do so, the Brazilian Society of Thrombosis and Hemostasis (BSTH) and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) have constituted a panel of experts to carefully review and discuss the available evidence about this topic. The data discussed in this document was reviewed by May 9, 2020. Recommendations and suggestions reflect the opinion of the panel and should be reviewed periodically as new evidence emerges.

PMID:32565232 | PMC:PMC7293502 | DOI:10.1016/j.htct.2020.06.001

07:21

PubMed articles on: Cancer & VTE/PE

Risk factors for pediatric cerebral sinovenous thrombosis: A case-control study with case validation

Sellers A, et al. Thromb Res 2020.

ABSTRACT

INTRODUCTION: Cerebral sinovenous thrombosis (CSVT) represents the second most common type of venous thromboembolism (VTE) in children. Current literature includes limited evidence on risk factors for CSVT, particularly in the pediatric population. We sought to determine risk factors for CSVT in pediatric patients through a single-institutional case-control study. In addition, we evaluated thrombophilias, treatments and outcomes in CSVT among cases.

METHODS: A case-control study was performed at Johns Hopkins All Children's Hospital on patients admitted from March 31, 2006 through April 1, 2018. Cases were identified using diagnostic codes and confirmed based on electronic health record (EHR) and neuroimaging review. Controls were matched in a 2:1 fashion accounting for the month and year of admission.

RESULTS: A total of 60 CSVT cases and 120 controls were identified. Median (range) age was 4.8 years (0-21.3 years) for cases and 5.6 years (0-20.0 years) for controls. Factors putatively associated with CSVT in unadjusted analyses were: corticosteroid use, presence of a central venous catheter, mechanical ventilation, systemic infection, head/neck infection, head/neck trauma, and chronic inflammatory disease. In the multivariable model, head/neck infection (OR: 13.8, 95% CI: 4.87-38.7; P < 0.01), head/neck trauma (OR: 12.7, 95% CI: 2.88-56.2; P < 0.01), and mechanical ventilation (OR: 9.32, 95% CI: 2.35-36.9; P = 0.01) remained independent, statistically-significant risk factors. 61% of patients were subacutely treated with anticoagulants and of those, only two developed relevant bleeding after initiation of therapy.

CONCLUSIONS: This single-institutional case-control study reveals that head/neck infection, head/neck trauma, and mechanical ventilation are independent risk factors for pediatric CSVT. These findings will be further investigated via a cooperative registry of pediatric hospital-acquired VTE, by which a risk model for pediatric CSVT will be developed and validated, in order to inform future preventive strategies in at-risk pediatric patients.

PMID:32554256 | DOI:10.1016/j.thromres.2020.06.013

07:21

PubMed articles on: Cardio-Oncology

Echocardiography and biomarkers for the diagnosis of cardiotoxicity

Berliner D, et al. Herz 2020 - Review.

ABSTRACT

As a result of better treatment options for malignant cancer, the cardiovascular side effects of such therapies have increasingly come into focus in recent years. The new cardiological subspecialty of oncocardiology is developing strategies to prevent and/or detect those effects early in order to treat them in a timely and adequate manner. The diagnosis of cardiotoxic effects is based mainly on imaging and specific biomarkers. Echocardiography has become the main imaging technique due to its wide availability. In addition to quantitative determination of left ventricular function using two-dimensional methods, three-dimensional methods offer better precision and less variability in the detection of cardiac dysfunction. Furthermore, the analysis of the global longitudinal strain (GLS) reveals even subtle changes in left ventricular function and thus detects very early damage before left ventricular ejection fraction drops. Various biomarkers have been tested recently for their potential to detect cardiotoxicity. Cardiac troponins are currently the best investigated biomarkers and certainly have the highest impact. Due to contradicting results, the importance of natriuretic peptides has not yet been conclusively clarified. Results for myeloperoxidase are promising, as are the results for circulating microRNAs, which still mainly derive from experimental data. In this context, further studies still need to show the value of these in everyday clinical practice.

PMID:32564096 | DOI:10.1007/s00059-020-04957-5

07:21

PubMed articles on: Cancer & VTE/PE

High molecular weight kininogen contributes to early mortality and kidney dysfunction in a mouse model of sickle cell disease

Sparkenbaugh EM, et al. J Thromb Haemost 2020.

ABSTRACT

BACKGROUND: Sickle cell disease (SCD) is characterized by chronic hemolytic anemia, vaso-occlusive crises, chronic inflammation, and activation of coagulation. The clinical complications such as painful crisis, stroke, pulmonary hypertension, nephropathy and venous thromboembolism lead to cumulative organ damage and premature death. High molecular weight kininogen (HK) is a central cofactor for the kallikrein-kinin and intrinsic coagulation pathways, which contributes to both coagulation and inflammation.

OBJECTIVE: We hypothesize that HK contributes to the hypercoagulable and pro-inflammatory state that causes end-organ damage and early mortality in sickle mice.

METHODS: We evaluated the role of HK in the Townes mouse model of SCD.

RESULTS/CONCLUSIONS: We found elevated plasma levels of cleaved HK in sickle patients compared to healthy controls, suggesting ongoing HK activation in SCD. We used bone marrow transplantation to generate wild type and sickle cell mice on a HK-deficient background. We found that short-term HK deficiency attenuated thrombin generation and inflammation in sickle mice at steady state, which was independent of bradykinin signaling. Moreover, long-term HK deficiency attenuates kidney injury, reduces chronic inflammation, and ultimately improves of sickle mice.

PMID:32573897 | DOI:10.1111/jth.14972

07:22

PubMed articles on: Cardio-Oncology

Impact of the Iranian Registry of Infective Endocarditis (IRIE) and multidisciplinary team approach on patient management

Sadeghpour A, et al. Acta Cardiol 2020.

ABSTRACT

Backgrounds:The last 30 years have witnessed major improvements in understanding of all aspects of infective endocarditis (IE). The Iranian Registry of Infective Endocarditis (IRIE) was formed to address epidemiological aspects of IE vis-à-vis its main pathogens and underlying heart diseases over a 12-year period. Indeed, a multidisciplinary team (MDT) for IE was developed alongside.Methods: In a longitudinal observational study, data of adult patients with definite or possible IE based on modified Duke criteria were collected from 2007 to 2016 in our tertiary centre, Iran. From 2016 until 2019, we run a prospective observational study using formation of an IE MDT to provide better patient management and compared data before and after this.Results: Totally, 645 patients with mean age of 48 ± 17 years were enrolled. Data of 445 and 200 patients were compared before and after IRIE and MDT formation, respectively. We found significantly reduced type and number of applied antibiotics (p = 0.04) and higher rate of positive blood culture (p = 0.001). Hospital length of stay increased significantly after formation of the IRIE and IE MDT (p = 0.02). The rate of heart failure, new abscess formation and cerebral emboli were significantly decreased after IRIE and IE MDT (p < 0.001) and consequently in-hospital mortality reduced significantly (p = 0.05).Conclusion: Developing national registries and MDTs has potential to enhance patient management and reduce IE burden. Our results demonstrated that establishment of the Iranian IRIE and IE MDT conferred better diagnoses, standardised treatments and significantly reduced cardiac and extra cardiac morbidity.

PMID:32589112 | DOI:10.1080/00015385.2020.1781423

07:22

PubMed articles on: Cancer & VTE/PE

Resection of recurrent hepatocellular carcinoma with thrombi in the inferior vena cava, right atrium, and phrenic vein: a report of three cases

Tomita K, et al. World J Surg Oncol 2020.

ABSTRACT

BACKGROUND: Prognosis for patients with advanced hepatocellular carcinoma with a tumor thrombus in the inferior vena cava or right atrium is extremely poor due to cancer progression, pulmonary embolism, and congestion of the circulatory system caused by right heart failure. Surgical resection of the tumor thrombi may potentially yield better results than non-surgical treatments through prevention of sudden death. However, the benefits of surgical resection in patients with hepatocellular carcinoma and a tumor thrombus extending to the inferior vena cava, right atrium, and potentially in the phrenic vein are unclear. Here, we report three such cases.

CASE PRESENTATION: Of the total 136 patients who underwent hepatectomies for hepatocellular carcinoma in our institution, three patients with prior hepatectomies and recurrent hepatocellular carcinoma had tumor thrombi in the inferior vena cava, right atrium, and phrenic vein. Surgical resections were performed, as there was a possibility of sudden death, despite the risk of leaving residual tumor. For all patients, we performed resection of the tumor thrombi in the inferior vena cava and right atrium and combined diaphragm resection. Surgical resection was performed using the total hepatic vascular exclusion technique in all cases. Additional passive veno-venous bypass was also performed in two cases, in which complete tumor resections could not be achieved. The microscopic surgical margins of the combined resected diaphragms were positive in all cases. Progression-free survival was 20.2, 3.8, and 9.5 months for case 1, 2, and 3, respectively. The respective overall postoperative survival was 98.0, 38.9, and 30.9 months. The patients died due to liver cirrhosis, acute heart failure, and hepatocellular carcinoma, respectively. Sudden death did not occur for any of the patients.

CONCLUSION: Surgical resections may extend prognosis for patients with recurrent hepatocellular carcinoma with tumor thrombi in the inferior vena cava, right atrium, and phrenic vein, although the indications should be considered carefully.

PMID:32571339 | PMC:PMC7310451 | DOI:10.1186/s12957-020-01914-8

07:22

PubMed articles on: Cardio-Oncology

Variation in RARG increases susceptibility to doxorubicin-induced cardiotoxicity in patient specific induced pluripotent stem cell-derived cardiomyocytes

Christidi E, et al. Sci Rep 2020.

ABSTRACT

Doxorubicin is a potent anticancer drug used to treat a variety of cancer types. However, its use is limited by doxorubicin-induced cardiotoxicity (DIC). A missense variant in the RARG gene (S427L; rs2229774) has been implicated in susceptibility to DIC in a genome wide association study. The goal of this study was to investigate the functional role of this RARG variant in DIC. We used induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) from patients treated with doxorubicin. iPSC-CMs from individuals who experienced DIC (cases) showed significantly greater sensitivity to doxorubicin compared to iPSC-CMs from doxorubicin-treated individuals who did not develop DIC (controls) in cell viability and optical mapping experiments. Using CRISPR/Cas9, we generated isogenic cell lines that differed only at the RARG locus. Genetic correction of RARG-S427L to wild type resulted in reduced doxorubicin-induced double stranded DNA breaks, reactive oxygen species production, and cell death. Conversely, introduction of RARG-S427L increased susceptibility to doxorubicin. Finally, genetic disruption of the RARG gene resulted in protection from cell death due to doxorubicin treatment. Our findings suggest that the presence of RARG-S427L increases sensitivity to DIC, establishing a direct, causal role for this variant in DIC.

PMID:32587261 | PMC:PMC7316788 | DOI:10.1038/s41598-020-65979-x

07:22

PubMed articles on: Cardio-Oncology

Speckle-Tracking Echocardiography in Cardio-Oncology and Beyond

Quintana RA, et al. Tex Heart Inst J 2020.