Anticoagulation as a therapeutic strategy for hospitalised patients with COVID-19.

The COVID-19 pandemic has devastated the global community and continues to cause significant morbidity and mortality worldwide. The development of effective vaccines has represented a major step towards reducing transmission and illness severity but significant challenges remain, particularly in regions where vaccine access has been limited. COVID-19 is associated with hypercoagulability and increased risk of thrombosis, with greatest risk among the critically ill. Interestingly, early observational data suggested that anticoagulant therapy might improve clinical outcomes, aside from thrombotic events, in patients with COVID-19. In this review we summarise data generated from three published randomised clinical trials which have sought to determine the effect of therapeutic heparin anticoagulation on efficacy and safety outcomes in hospitalised patients with COVID-19: the multiplatform REMAP-CAP, ACTIV-4a and ATTACC randomised controlled trials and the RAPID trial. In the multiplatform REMAP-CAP, ACTIV-4a and ATTACC randomised controlled trials, therapeutic heparin was not associated with benefit in critically ill patients with COVID-19 compared with usual care (adjusted proportional odds ratio (OR) for increased organ-support free days up to day 21: 0.83; 95% credible interval, 0.67-1.03, posterior probability of futility 99.9%). Conversely, among hospitalised patients without critical illness, therapeutic heparin was associated with an increased probability of organ support-free days alive (adjusted OR, 1.27; 95% credible interval, 1.03-1.58). The RAPID trial also evaluated the effect of therapeutic heparin compared with prophylactic heparin in non-critically ill patients. In this study, therapeutic heparin did not significantly reduce the odds of the primary composite outcome (death, mechanical ventilation or intensive care unit admission) (OR 0.69; 95% confidence interval [CI], 0.43 to 1.10; p = 0.12) but was associated with a significant reduction in all-cause mortality [OR, 0.22 (95%-CI, 0.07 to 0.65)]. Collectively these studies suggest that therapeutic anticoagulation with heparin may reduce the severity of illness and potentially even confer a survival benefit in hospitalised, non-critically ill patients with COVID-19. No benefit for therapeutic anticoagulation with heparin was evident in critically ill patients with COVID-19. Therefore, while the results of additional studies in this evolving field are pending, it is important to approach decisions regarding therapeutic heparin in moderately ill hospitalised patients with COVID-19 in a measured and individualised manner.

Dual endothelin-1 receptor antagonism attenuates platelet-mediated derangements of blood coagulation in Eisenmenger syndrome.

Essentials Eisenmenger syndrome is characterised by thrombotic and hemorrhagic risks of unclear aetiology. Calibrated automated thrombography was used to assess these coagulation derangements. Platelet activity supported abnormalities in procoagulant and anticoagulant pathway function. Endothelin-1 antagonism appeared to ameliorate these derangements. SUMMARY: Aims The mechanisms underlying the competing thrombotic and hemorrhagic risks in Eisenmenger syndrome are poorly understood. We aimed to characterize derangements of blood coagulation and to assess the effect of dual endothelin-1 receptor antagonism in modulating hemostasis in this rare disorder. Methods In a 10-month recruitment period at a tertiary cardiology referral center, during which time there were over 14 000 outpatient consultations, consecutive subjects with Eisenmenger syndrome being considered for macitentan therapy (n = 9) and healthy volunteers (n = 9) were recruited. Plasma thrombin generation in platelet-rich and platelet-poor plasma was assessed by calibrated automated thrombography prior to and following therapy. Results Median peak plasma thrombin generation was higher in platelet-rich plasma obtained from Eisenmenger syndrome subjects relative to controls (median peak thrombin [25th-75th percentile]: 228.3 [206.5-258.6] nm vs. 169.9 [164.3-215.8] nm), suggesting a critical mechanistic role for platelets in supporting abnormal hypercoagulability in Eisenmenger syndrome. Abnormal enhanced sensitivity to the anticoagulant activity of activated protein C was also observed in platelet-rich plasma in Eisenmenger syndrome, suggesting that derangements of platelet activity may influence the activity of anticoagulant pathways in a manner that might promote bleeding in this disease state. Following 6 months of macitentan therapy, attenuations in the derangements in both procoagulant and anticoagulant pathways were observed. Conclusions Abnormal platelet activity contributes to derangements in procoagulant and anticoagulant pathways in Eisenmenger syndrome. Therapies targeting the underlying vascular pathology appear to ameliorate these derangements and may represent a novel strategy for the management of the competing prothrombotic and hemorrhagic tendencies in this disorder.

Ionizing radiation exposure as a result of diagnostic imaging in patients with lymphoma

Purpose: Survival rates among patients with lymphoma continue to improve. Strategies aimed at reducing potential treatment-related toxicity are increasingly prioritized. While radiological procedures play an important role, ionizing radiation exposure has been linked to an increased risk of malignancy, particularly among individuals whose cumulative radiation exposure exceeds a specific threshold (75 millisieverts). Methods: Within this retrospective study, the cumulative radiation exposure dose was quantified for 486 consecutive patients with lymphoma. Results: The median estimated total cumulative effective dose (CED) of ionizing radiation per subject was 69 mSv (42-118). However, younger patients (under 40 years) had a median CED of 89 mSv (55-124). Conclusion: This study highlights the considerable radiation exposure occurring among patients with lymphoma as a result of diagnostic imaging. To limit the risk of secondary carcinogenesis, consideration should be given to monitoring cumulative radiation exposure in individual patients as well as considering imaging modalities, which do not impart an ionizing radiation dose (AU)

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Ionizing radiation exposure as a result of diagnostic imaging in patients with lymphoma.

PURPOSE: Survival rates among patients with lymphoma continue to improve. Strategies aimed at reducing potential treatment-related toxicity are increasingly prioritized. While radiological procedures play an important role, ionizing radiation exposure has been linked to an increased risk of malignancy, particularly among individuals whose cumulative radiation exposure exceeds a specific threshold (75 millisieverts). METHODS: Within this retrospective study, the cumulative radiation exposure dose was quantified for 486 consecutive patients with lymphoma. RESULTS: The median estimated total cumulative effective dose (CED) of ionizing radiation per subject was 69 mSv (42-118). However, younger patients (under 40 years) had a median CED of 89 mSv (55-124). CONCLUSION: This study highlights the considerable radiation exposure occurring among patients with lymphoma as a result of diagnostic imaging. To limit the risk of secondary carcinogenesis, consideration should be given to monitoring cumulative radiation exposure in individual patients as well as considering imaging modalities, which do not impart an ionizing radiation dose.

Coagulation indices in very preterm infants from cord blood and postnatal samples.

BACKGROUND: Very premature infants are at high risk of bleeding complications; however, few data exist on ranges for standard coagulation tests. OBJECTIVES: The primary objective of this study was to measure standard plasma coagulation tests and thrombin generation in very premature infants compared with term infants. The secondary objective was to evaluate whether an association existed between coagulation indices and intraventricular hemorrhage (IVH). PATIENTS/METHODS: Cord and peripheral blood of neonates < 30 weeks gestational age (GA) was drawn at birth, on days 1 and 3 and fortnightly until 30 weeks corrected gestational age. Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen and coagulation factor levels were measured and tissue factor-stimulated thrombin generation was characterized. Control plasma was obtained from cord blood of term neonates. RESULTS: One hundred and sixteen infants were recruited. Median (range) GA was 27.7 (23.7-29.9) weeks and mean (SD) birth weight was 1020 (255) g. Median (5th-95th percentile) day 1 PT, APTT and fibrinogen were 17.5 (12.7-26.6) s, 78.7 (48.7-134.3) s and 1.4 (0.72-3.8) g L(-1) , respectively. No difference in endogenous thrombin potential between preterm and term plasma was observed, where samples were available. Levels of coagulation factors II, VII, IX and X, protein C, protein S and antithrombin were reduced in preterm compared with term plasma. Day 1 APTT and PT were not associated with IVH. CONCLUSION: In the largest cross-sectional study to date of very preterm infants, typical ranges for standard coagulation tests were determined. Despite long clotting times, thrombin generation was observed to be similar in very preterm and term infants.

Thromboprophylaxis in myeloma: what is happening outside of clinical trials?

Patients with myeloma are at high risk of venous thromboembolism (VTE). There is no consensus about what agent to use or what haematologists are doing in clinical practice. A survey was sent to haematologists treating patients with myeloma in Ireland. 32/45 (71%) responded. 13/28 (46%) felt that VTE affected < 5% of patients. However, 8/28 (29%) felt it affected 10-19%. Thromboprophylaxis was most commonly used in patients on lenalidomide; 25/28 (89%) and thalidomide; 23/28 (82%). 23/28 (82%) used LMWH and 20/28 (71%) used aspirin either very frequently or frequently. 3/28 (11%) had used dabigatran/rivaroxaban despite there being little evidence to support their use. Efficacy was the most important factor in choosing an agent for 25/28 (89%). Bleeding was not felt to be an issue 15/29 (52%) were not using thromboprophylaxis guidelines. This survey demonstrated wide variation in the beliefs and practices regarding the burden of VTE in patients with myeloma and the need for thromboprophylaxis.

Cancer and venous thromboembolic disease: from molecular mechanisms to clinical management.

Venous thromboembolism (vte) represents a major challenge in the management of patients with cancer. The malignant phenotype is associated with derangements in the coagulation cascade that can manifest as thrombosis, hemorrhage, or disseminated intravascular coagulation. The risk of vte is increased by a factor of approximately 6 in patients with cancer compared with non-cancer patients, and cancer patients account for approximately 20% of all newly diagnosed cases of vte. Postmortem studies have demonstrated rates of vte in patients with cancer to be as high as 50%. Despite that prevalence, vte prophylaxis is underused in hospitalized patients with cancer. Studies have demonstrated that hospitalized patients with cancer are less likely than their non-cancer counterparts to receive vte prophylaxis. Consensus guidelines address the aforementioned issues and emerging concepts in the area, including the use of risk-assessment models, biomarkers to identify patients at highest risk of vte, and use of anticoagulants as anticancer therapy. Despite those guidelines, a gulf exists between current recommendations and clinical practice; greater efforts are thus required to ensure effective implementation of strategies to reduce the incidence of vte in patients with cancer.

Percutaneous vertebroplasty in osteoporosis, myeloma and Langerhans' cell histiocytosis.

This review aims to assess the effectiveness of percutaneous vertebroplasty as a treatment for the severe refractory pain associated with vertebral fracture, in a group of patients with fractures secondary to either osteoporotic or neoplastic disease. A retrospective review of 20 patients treated with percutaneous vertebroplasty in Cork University Hospital up until March 2007 was carried out and a questionnaire was prepared and distributed. Prior to vertebroplasty, patients had been symptomatic with severe pain for a mean of 20.9 weeks. Of those thirteen whom replied to a postal questionnaire, 12 (92.3%) reported pain relief and this improvement occurred within 7 days in 9 (81.8%). This was associated with decreased analgesic requirements, as determined on chart review. Prior to the procedure only 5 (38.4%) were independently mobile and this figure rose to 10 (76.9%) afterwards, occurring within one week in the majority. Subjective outcomes were better in the group of patients with neoplasm-induced fractures.