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Background: Cancer-associated venous thromboembolism (CAT) has detrimental impact on patients' clinical outcomes and quality of life. Data on CAT education, communication, and awareness among the general cancer population are scanty. Methods: We present the preliminary results of an ongoing patient-centered survey including 27 items covering major spheres of CAT. The survey, available in 14 languages, was promoted and disseminated online through social networks, email newsletters, websites, and media. Results: As of September 20, 2022, 749 participants from 27 countries completed the survey. Overall, 61.8% (n = 460) of responders were not aware of their risk of CAT. Among those who received information on CAT, 26.2% (n = 56) were informed only at the time of CAT diagnosis. Over two thirds (69.1%, n = 501) of participants received no education on signs and symptoms of venous thromboembolism (VTE); among those who were educated about the possible clinical manifestations, 58.9% (n = 119) were given instructions to seek consultation in case of VTE suspicion. Two hundred twenty-four respondents (30.9%) had a chance to discuss the potential use of primary thromboprophylaxis with health-care providers. Just over half (58.7%, n = 309) were unaware of the risks of bleeding associated with anticoagulation, despite being involved in anticoagulant-related discussions or exposed to anticoagulants. Most responders (85%, n = 612) valued receiving CAT education as highly relevant; however, 51.7% (n = 375) expressed concerns about insufficient time spent and clarity of education received. Conclusions: This ongoing survey involving cancer patients with diverse ethnic, cultural, and geographical backgrounds highlights important patient knowledge gaps. These findings warrant urgent interventions to improve education and awareness, and reduce CAT burden.

Many patients with advanced illness have unrealistic survival expectations, largely due to cognitive biases. Studies suggests that when people are motivated to be accurate, they are less prone to succumb to these biases. Using a randomized survey design, we test whether offering advanced cancer patients ( n = 200) incentives to estimate their prognosis improves accuracy. We also test whether presenting treatment benefits in terms of a loss (mortality) rather than a gain (survival) reduces willingness to take up a hypothetical treatment. Results are not consistent with the proposed hypotheses for either accuracy incentives or framing effects.

Objective Many patients with advanced illness are unrealistically optimistic about their prognosis. We test for the presence of several cognitive biases, including optimism bias, illusion of superiority, self-deception, misattribution, and optimistic update bias, that could explain unrealistically optimistic prognostic beliefs among advanced cancer patients and quantifies the extent to which hope exacerbates these biases. Methods A cross-sectional survey was administered to 200 advanced cancer patients with physician-estimated prognoses of one year or less. Hope was measured using the Herth Hope Index (HHI). Hypotheses were tested using linear and logistic regressions and a structural-equation model. Results Results are consistent with the presence of optimism bias, illusion of superiority, self-deception, and misattribution. All of these biases are amplified by higher levels of hope. Each 1-point higher HHI is associated with a 6% (OR: 1.06; 95% CI: 1.01-1.11) greater odds of believing their illness is curable, a 0.33-year (95% CI: 0.17-0.49) longer expected survival, a 6% (OR: 1.06; 95% CI: 1.02-1.11) higher probability of believing that survival outcomes are better than the average patient, a 5% higher odds of believing primary intent of treatment is curative (OR: 1.05; 95% CI: 1.00-1.10), and a 12% (OR: 1.12; 95% CI: 1.05-1.17) higher odds of believing they are well-informed. Mediation analyses revealed that hope significantly mediates the effect of mental-well-being and loneliness on expected survival. Conclusions Results suggest advanced cancer patients succumb to several cognitive biases which are exacerbated by greater levels of hope. As a result, they are susceptible to possible over-treatment and regret.

Background Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients. Method and results This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16). Conclusions Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.

Management of adult patients with immune thrombocytopenia (ITP) is often unsatisfactory, due to variable efficacy of treatment, risk of life-threatening bleeding if disease control is poor, and side effects associated with treatment. Lack of data on the platelet count threshold associated with bleeding and infection risk associated with ITP treatment limits risk/benefit clinical decision making. We reviewed medical records of all ITP patients who were admitted to our hospital between 2012 and 2017 to evaluate the platelet count threshold for bleeding, infection burden associated with treatment, and real-world efficacy of second-line treatment. We demonstrated fair discrimination between platelet count and occurrence of bleeding, with 15 × 109/L being the optimal cut-off for predicting any bleeding while 20 × 109/L had the highest negative predictive value for severe bleeding. In multivariable analyses, patients who were treated with corticosteroids for at least 2 months were 5.3 times as likely to have an infection. In addition, rituximab response was strongly associated with response to frontline corticosteroids and infection was associated with older age ≥ 65 years and corticosteroid dependence. If corticosteroids are initiated, physicians should aim for the shortest duration of treatment before switching to effective second-line agents for hemostatic platelet counts.

Objectives Pregnancy-associated venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with increased risk of maternal mortality and morbidity. This study aimed to assess potential risk factors for pregnancy-associated VTE. Methods In this case-control study, women with pregnancy-associated VTE were identified via International Classification of Diseases codes and included if they had been objectively diagnosed with VTE during pregnancy or within six weeks postpartum, from 2004 to 2016, at KK Women’s and Children’s Hospital or Singapore General Hospital in Singapore. Controls, i.e. pregnant women without VTE, were selected from a prospective longitudinal study. The odds ratio (OR) for VTE was computed for a range of maternal and obstetric factors. Results and conclusions From 2004 to 2016, 89 cases of pregnancy-associated VTE and 926 controls were identifed and analysed using logistic regression. The most significant risk factors for pregnancy-associated VTE were smoking (OR 5.44, p=0.0002) and preterm delivery (OR 5.06, p=0.023). Malay race, multiparity, non-O blood group and caesarean section, were also identified to be of higher risk. These risk factors should be useful in the development of thromboprophylaxis strategies for pregnancy and the postpartum period, especially in Singapore.

Objective To determine the cumulative incidence, time of occurrence and risk factors of pregnancy-associated pulmonary embolism (PE) in Singapore, and to review the maternal mortality ratio of PE over the last four decades. Study design and setting In this retrospective epidemiology review, women with pregnancy-associated PE were identified via International Classification of Diseases codes and included if they had been objectively diagnosed on imaging with PE during pregnancy or within 6 weeks postpartum from 2004 to 2016 at KK Women's and Children's Hospital (KKH) and Singapore General Hospital (SGH) in Singapore. The medical records were reviewed and the time of occurrence of confirmed PE cases and risk factors for PE were noted. Results There were 18 PE cases out of 174 708 deliveries, of which two were fatal, giving a cumulative incidence of PE at 1.03 per 10 000 deliveries and a mortality rate of 11.1%. The maternal mortality ratio is 1.14 per 100 000 deliveries, the lowest compared to that of the previous three decades (2.5-4.9 per 100 000 deliveries). Majority of PE (66.7%) occurred during the first 2 weeks postpartum. Cumulative incidence of postpartum PE was four times more in caesarean section compared to vaginal delivery at 1.58 per 10 000 deliveries and 0.40 per 10 000 deliveries, respectively. Conclusion Although the cumulative incidence of pregnancy-associated PE in Singapore is low, it is comparable to the United Kingdom (UK) and United States (US). Risk assessment and thromboprophylaxis have decreased PE mortality significantly during this period.

The International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a free, web-based mobile phone application. The 2022 clinical practice guidelines, which are based on a literature review up to Jan 1, 2022, include guidance for patients with cancer and with COVID-19. Key recommendations (grade 1A or 1B) include: (1) low-molecular-weight heparins (LMWHs) for the initial (first 10 days) treatment and maintenance treatment of cancer-associated thrombosis; (2) direct oral anticoagulants for the initial treatment and maintenance treatment of cancer-associated thrombosis in patients who are not at high risk of gastrointestinal or genitourinary bleeding, in the absence of strong drug-drug interactions or of gastrointestinal absorption impairment; (3) LMWHs or direct oral anticoagulants for a minimum of 6 months to treat cancer-associated thrombosis; (4) extended prophylaxis (4 weeks) with LMWHs to prevent postoperative venous thromboembolism after major abdominopelvic surgery in patients not at high risk of bleeding; and (5) primary prophylaxis of venous thromboembolism with LMWHs or direct oral anticoagulants (rivaroxaban or apixaban) in ambulatory patients with locally advanced or metastatic pancreatic cancer who are treated with anticancer therapy and have a low risk of bleeding.

The Universal Health Coverage goals call for access to affordable palliative care to reduce inequities in “total pain” and suffering. To achieve this, a patient-centred understanding of these inequities is required. To assess association of total pain and suffering (i.e. physical, psychological, social, and spiritual health outcomes) and perceived health care quality with financial difficulties among stage IV solid malignancy patients. Using baseline data from the COMPASS cohort study, we assessed total pain and suffering including physical (physical and functional well-being, pain, symptom burden), psychological (anxiety, depression, emotional well-being), social (social well-being), and spiritual (spiritual well-being, hope) outcomes and perceived health care quality (physician communication, nursing care, and coordination/responsiveness). Financial difficulties were scored by assessing patient perception of the extent to which their resources were meeting expenses for their treatments, daily living, and other obligations. We used multivariable linear/logistic regression to test association between financial difficulties and each patient-reported outcome. Six hundred stage IV solid malignancy patients in Singapore. Thirty-five percent reported difficulty in meeting expenses. A higher financial difficulties score was associated with worse physical, psychological, social, spiritual outcomes, and lower perceived quality of health care coordination and responsiveness (i.e. greater total pain and suffering) (all p

COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and other respiratory viral (non-CoV-2-RV) infections are associated with thrombotic complications. The differences in prothrombotic potential between SARS-CoV-2 and non-CoV-2-RV have not been well characterised. We compared the thrombotic rates between these two groups of patients directly and further delved into their coagulation profiles. In this single-center, retrospective cohort study, all consecutive COVID-19 and non-CoV-2-RV patients admitted between January 15th and April 10th 2020 were included. Coagulation parameters studied were prothrombin time and activated partial thromboplastin time and its associated clot waveform analysis (CWA) parameter, min1, min2 and max2. In the COVID-19 (n = 181) group there were two (1.0 event/1000-hospital-days) myocardial infarction events while one (1.8 event/1000-hospital-day) was reported in the non-CoV-2-RV (n = 165) group. These events occurred in patients who were severely ill. There were no venous thrombotic events. Coagulation parameters did not differ throughout the course of mild COVID-19. However, CWA parameters were significantly higher in severe COVID-19 compared with mild disease, suggesting hypercoagulability (min1: 6.48%/s vs 5.05%/s, P 2 vs 0.74%/s2, P = 0.033). In conclusion, the thrombotic rates were low and did not differ between COVID-19 and non-CoV-2-RV patients. The hypercoagulability in COVID-19 is a highly dynamic process with the highest risk occurring when patients were most severely ill. Such changes in haemostasis could be detected by CWA. In our population, a more individualized thromboprophylaxis approach, considering clinical and laboratory factors, is preferred over universal pharmacological thromboprophylaxis for all hospitalized COVID-19 patients and such personalized approach warrants further research.

OBJECTIVE: We investigated patient-reported roles of families, physicians, and patients themselves in treatment decision making and whether discordance between perceived and preferred roles is associated with psychological distress and perceived quality of care among patients with cancer.METHODS: We analyzed cross-sectional survey data from 599 adults with stage IV solid malignancy in Singapore. Stuart-Maxwell tests were used to compare patients' perceived and preferred roles in decision making. Types of discordance were categorized as follows: involvement at a lesser level than preferred, involvement at a greater level than preferred, and no change in patient involvement. Ordinary least squares regressions examined the associations between types of discordance and patient outcomes, controlling for patient characteristics.RESULTS: Discordance between perceived and preferred roles was observed in 16% of patients. Amongst patients with discordance, 33% reported being involved at a lesser level than they preferred, 47% reported being involved at a greater level than they preferred, and 19% reported discordance where level of patient involvement did not change. Multivariable analyses showed that lesser involvement than preferred and discordance with no change in patient involvement were associated with poorer quality of physician communication (β = - 9.478 [95% confidence interval {CI} - 16.303 to - 2.653] and β = - 9.184 [95% CI - 18.066 to - 0.301]) and poorer care coordination (β = - 11.658 [95% CI - 17.718 to - 5.597] and β = - 8.856 [95% CI - 16.744 to - 0.968]) compared with concordance.CONCLUSIONS: Most patients reported participating at their desired level. Despite this finding, our results suggest that involving patients at a lesser level than they prefer can lead to poorer perceived quality of physician communication and care coordination and that encouraging patient participation is a safe approach to minimizing poor outcomes.

Infections cause varying degrees of haemostatic dysfunction which can be detected by clot waveform analysis (CWA), a global haemostatic marker. CWA has been shown to predict poor outcomes in severe infections with disseminated intravascular coagulopathy. The effect of less severe bacterial and viral infections on CWA has not been established. We hypothesized that different infections influence CWA distinctively. Patients admitted with bacterial infections, dengue and upper respiratory tract viral infections were recruited if they had an activated partial thromboplastin time (aPTT) measured on admission. APTT-based CWA was performed on Sysmex CS2100i automated analyser using Dade Actin FSL reagent. CWA parameters [(maximum velocity (min1), maximum acceleration (min2) and maximum deceleration (max2)] were compared against control patients. Infected patients (n = 101) had longer aPTT than controls (n = 112) (34.37 ± 7.72 s vs 27.80 ± 1.59 s, p 2; 0.74 ± 0.16%/s2), bacterial infection has higher CWA results (6.92 ± 1.60%/s; 1.04 ± 0.28%/s2; 0.82 ± 0.24%/s2, all p 2; 0.43 ± 0.14%/s2, all p 2; 0.73 ± 0.18%/s2, all p > 0.05). CWA parameters demonstrated positive correlation with C-reactive protein levels (min1: r = 0.54, min2: r = 0.44, max2: r = 0.34; all p

Testing for polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene is still a standard part of thrombophilia testing in many laboratories. However, it is clear that these polymorphisms are not risk factors for arterial or venous thrombosis and therefore should not be part of thrombophilia testing. Eliminating MTHFR from thrombophilia testing will reduce patient concerns and health care costs.

Race is touted as an independent risk factor for venous thromboembolism (VTE), although the basis for this is varied and contentious. Comparison of plasma thrombin generation (TG) using calibrated automated thrombogram (CAT) across races offers a modality that objectively measures global hemostatic function to evaluate this influence. Direct comparative data across races are currently not available. Aim is to establish the influence of race on plasma TG. Sixty normal participants, matched for age and gender, equally representing 4 races—Caucasian, Chinese, Indian, and Malay—were recruited. Thrombin generation parameters (lag time, time to peak, peak, and endogenous thrombin potential [ETP]) in platelet-poor plasma were measured using CAT. The mean ETP (standard deviation) for the different races were Caucasians: 1338.18 (194.19) nM·min; Chinese, 1318.91 (108.90) nM·min; Indians, 1389.81 (182.61) nM·min; and Malays, 1436.21 (184.24) nM·min. Caucasians had the longest mean lag time of 2.59 ± 0.37 seconds; Indians had the highest mean peak of 284.22 ± 30.74 nM, and Malays had the longest mean time to peak of 5.47 ± 0.59 seconds. Analysis based on race did not demonstrate any significant difference for all TG parameters. The greatest mean difference of ETP between any 2 races (Malays and Chinese) was 117.30 nM·min (95% confidence interval: −45.86 to 280.46 nM·min) which was within the predefined limit of equivalence. In a cohort of healthy participants, TG mediated by plasma factors is not influenced by race and does not explain the reported racial differences in VTE incidence. For the 4 racial groups studied, the use of separate normal ranges for plasma TG might not be essential.

Introduction An increasing number of evidence have reported the association of COVID-19 with increased incidence of thrombotic events. High incidences were initially reported in critically ill COVID-19 patients, but subsequently an increased incidence was also noticed in non-critically ill general ward patients. This has led to a universal recommendation of thromboprophylaxis for all COVID-19 patients by ASH and ISTH. As the data on COVID-19 and thrombosis continue to develop and evolve, we examined the data in two aspects. Firstly, other non-SARS-CoV-2 viral respiratory infections have also been reported to be associated with thrombotic events, be it arterial or venous. Thus, we aimed to compare the thrombotic rates between these two groups of patients directly to hopefully ascertain the actual thrombotic tendency in COVID-19 infections. Secondly, global hemostatic assays such as thromboelastogram and clot waveform analysis (CWA) have been used to demonstrate hypercoagulability in COVID-19 patients, albeit in a small group of patients and only in the critically ill. Incorporating these laboratory results into the management of thromboprophylaxis in COVID-19 is an attractive notion but more data and studies are definitely needed. Here, we evaluate the dynamic changes of hemostatic assays in patients with COVID-19 to better understand the overall coagulation profiles of COVID-19 infection. Methods We performed a single center, retrospective cohort study. All consecutive patients admitted to our hospital between 15 January and 10 April 2020 that were tested positive for COVID-19 or other non-SARS-CoV-2 respiratory viruses were included in our study. The main coagulation assays studied were prothrombin time and activated partial thromboplastin time and its associated CWA, min1, min2 and max2. Findings We included a total of 181 COVID-19 patients and 165 patients with non-SARS-CoV-2 respiratory viral infections. The respiratory viruses were rhinovirus (n=65), influenza A and B (n=46), adenovirus (n=13), human coronavirus 229E/NL63/OC43 (n=15), human enterovirus (n=3), metapneumovirus (n=6), parainfluenza virus 1 to 4 (n=11), respiratory syncytial virus (n=6) and human bocavirus 1 to 4 (n=0). The median age of COVID-19 patients was 37 (interquartile range [IQR], 30.5-51 years) versus 35 (IQR, 29-51.5) in the non-SAR-CoV-2 respiratory viruses group (P=0.12). Comorbidities, assessed by Charlson score, was also not statistically different between both groups (median score 0 (IQR, 0-1) in both groups, P=0.39). Majority of our patients had relatively mild infection as reflected by the low proportions of them requiring oxygen supplementation (11.0% in COVID-19 vs 4.8% in non-SARS-COV-2, P=0.035). COVID-19 patients had longer hospital stay (7 days (IQR, 5.5-13) vs 3 days (IQR, 2-3), P Conclusion The thrombotic rates were low in both groups and did not differ significantly between COVID-19 and Non-SARS-CoV-2 patients. Nonetheless, our analysis of hemostatic parameters demonstrated hypercoagulability in COVID-19 as a dynamic process with the risk highest when the patients are critically ill. These changes in hemostasis could be detected by CWA. With our findings, we suggest that a more individualized thromboprophylaxis approach, considering clinical and laboratory factors, is probably preferred over universal pharmacological thromboprophylaxis for all hospitalized COVID-19 patients and warrants further research. Disclosures Lee: Sanofi: Honoraria, Other: travel grants; Pfizer: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees, Other: travel grants ; Medtronics: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

Objective Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients. This study aims to describe the thrombotic and bleeding rates in COVID-19 patients admitted to intensive care units (ICU) in Singapore. Design Retrospective observational study involving all consecutive adult COVID-19 patients who required ICU admission between 23 January 2020 and 30 April 2020. Setting National multicenter study involving all eight public hospitals in Singapore. Patients 111 consecutive COVID-19 patients who required ICU admission were included. Measurements and Main Results Primary outcome was any venous or arterial thrombotic events occurred in ICU. Other measures included (1) the overall, venous and arterial thrombotic events throughout the hospitalisation, (2) major and minor bleeding events. The overall thrombotic rate in ICU was 11.7% (n=13), with 1.8% (n=2) venous and 9.9% (n=11) arterial events. The overall thrombotic rates throughout hospitalisation, censored at 30 April 2020, increased to 18.0% (n=20) with 6.3% (n=7) venous and 11.7% (n=13) arterial events. Major and minor bleeding rates were 14.8% (n=16) and 3.7% (n=4), respectively. Two-third of the patients received pharmacological thromboprophylaxis in ICU. Conclusions Critically ill COVID-19 patients in Singapore have lower VTE but higher arterial thrombosis rates with higher bleeding manifestations than other reported cohorts. Standard thromboprophylaxis may be sufficient to prevent thrombotic complications in patients with similar demographics. Disclosures No relevant conflicts of interest to declare.

Background: COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and other respiratory viral (non-CoV-2-RV) infections are associated with thrombotic complications. The differences in prothrombotic potential between SARS-CoV-2 and non-CoV-2-RV have not been well characterised. We compared the thrombotic rates between these two groups of patients directly and further delved into their coagulation profiles. Methods: In this single-center, retrospective cohort study, all consecutive COVID-19 and non-CoV-2-RV patients admitted between January 15th and April 10th 2020 were included. Coagulation parameters studied were prothrombin time and activated partial thromboplastin time and its associated clot waveform analysis (CWA) parameter, min1, min2 and max2. Findings: In the COVID-19 (n=181) group there were two (1.0 event/1000-hospital-days) thrombotic events while one (1.8 event/1000-hospital-day) was reported in the non-CoV-2-RV (n=165) group. All of these events were myocardial infarction occurring in the intensive care unit. Coagulation parameters did not differ throughout the course of mild COVID-19. However, CWA parameters were significantly higher in severe COVID-19 compared with mild disease, suggesting hypercoagulability (min1: 6.48%/s vs 5.05%/s, P

The 2020 Congress of the International Society of Thrombosis and Haemostasis (ISTH) was held virtually July 12-15, 2019, due to the coronavirus disease 2019 pandemic. The congress convenes annually to discuss clinical and basic topics in hemostasis and thrombosis. Each year, the program includes State of Art (SOA) lectures given by prominent scientists. Presenters are asked to create Illustrated Capsules of their talks, which are concise illustrations with minimal explanatory text. Capsules cover major themes of the presentation, and these undergo formal peer review for inclusion in this article. Owing to the shift to a virtual congress this year, organizers reduced the program size. There were 39 SOA lectures virtually presented, and 29 capsules (9 from talks omitted from the virtual congress) were both submitted and successful in peer review, and are included in this article. Topics include the roles of the hemostatic system in inflammation, infection, immunity, and cancer, platelet function and signaling, platelet function disorders, megakaryocyte biology, hemophilia including gene therapy, phenotype tests in hemostasis, von Willebrand factor, anticoagulant factor V, computational driven discovery, endothelium, clinical and basic aspects of thrombotic microangiopathies, fibrinolysis and thrombolysis, antithrombotics in pediatrics, direct oral anticoagulant management, and thrombosis and hemostasis in pregnancy. Capsule authors invite virtual congress attendees to refer to these capsules during the live presentations and participate on Twitter in discussion. Research and Practice in Haemostasis and Thrombosis will release 2 tweets from @RPTHJournal during each presentation, using #IllustratedReview, #CoagCapsule and #ISTH2020. Readers are also welcome to utilize capsules for teaching and ongoing education., peer-reviewed

Introduction We describe our experience with managing an unusual case of acquired Factor V deficiency (aFVd) in a myeloma patient with demonstrated amyloidosis. Methods Following diagnosis, records of previous investigations were sought. Specific clotting factors and inhibitors were tested. The clinical progress and treatment response measured by serial factor V levels and coagulation parameters was then prospectively tracked. Results A 57 year-old woman presented with spontaneous right knee haemarthrosis in association with bilateral symmetrical polyneuropathy and proteinuria. Coagulation screen showed prolongation of both PT (18.6 s, normal range [9.9–11.4 s]) and aPTT (41.4 s, normal range [25.7–32.9 s]), which were both fully correctable following a mixing study. Liver function, fibrinogen, clotting factor II/VIII/X assays and disseminated intravascular coagulopathy screen was normal. FV level was reduced (19%, normal range [70–170%]). Inhibitor titer was undetectable. Congenital FVd was excluded as her previous coagulation screen was normal. Bone marrow investigation performed for suspected underlying plasma cell dyscrasia showed 60% neoplastic plasma cells. Congo red staining was positive for amyloid within vascular walls of the marrow trephine. She was diagnosed with light chain myeloma and aFVd. She received Bortezomib/Cyclophosphamide/Dexamethasone (VCD) chemotherapy. After one cycle of VCD, serum kappa free light chain (SFLC) was reduced from 6951 mg/L to 3354 mg/L with serial measurements of FV levels showing increment to 76% and normalization of PT/aPTT. Conclusion Plasma cell dyscrasia with amyloidosis should be sought as a cause for aFVD, in particular one where bleeding manifestation is profound even with the absence of demonstrable inhibitors.

International audience; Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.

BackgroundFamily caregivers of patients with advanced cancer have been reported to provide long hours of care and be at risk for poor psychological outcomes. Although research has focused on the nature of caregiving burden, little attention has been paid to identifying protective factors that improve caregiver psychological outcomes.AimWe examined the relationship between caregivers’ time spent caregiving and the following psychological outcomes: anxiety, depression and caregiving esteem. Subsequently, we explored the main and moderating effects of caregiver-perceived self-competency and sense of meaning on caregiver psychological outcomes.Design/participantsCross-sectional analysis was conducted using the baseline data from an ongoing cohort study. Family caregivers of advanced cancer patients (n=287) were recruited from two tertiary hospitals in Singapore.ResultsTime spent caregiving was not significantly associated with caregiver anxiety, depression or caregiving esteem. However, significant main effects of self-competency on anxiety and caregiving esteem; and sense of meaning on anxiety, depression and caregiving esteem were observed. Moderator analyses further indicated that self-competency attenuated the positive relationship between time spent caregiving and anxiety, while sense of meaning attenuated the negative relationship between time spent caregiving and caregiving esteem.ConclusionGreater perceived self-competency and sense of meaning are related to better caregiver psychological outcomes, and protect caregivers from worsening outcomes as caregiving hours increase. Our findings suggest that screening caregivers for distress is an important part of care, and that supportive interventions for caregivers should aim to enhance their perceived caregiving competencies and the ability to make meaning of their caregiving role.

Increasing awareness and availability of tests for anti-PF4/heparin complex antibodies has raised concerns about indiscriminate testing and inappropriate diagnosis of heparin-induced thrombocytopenia. A retrospective review of HITS testing at a large tertiary centre was performed to determine test patterns and incidence of HITS. Records of anti-PF4 tests over 4 years were reviewed. Positive results were matched against patient medical records and records of heparin utilisation for the diagnosis of HITS. Total of 33,308 patients (9.89 % of admissions) were exposed to at least 1 day of unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Of 346 anti-PF4 antibody assays performed, 52 (15 %) were positive. Seventeen patients (4.9 % of total) were determined to have HITS. Of these, 13 cases (76 %) were patients who were initiated on haemodialysis via central venous catheters. Five patients (29 %) subsequently experienced thrombosis. The rate of HITS in patients given UFH was 0.33 %. HITS occurred in only one patient given LMWH. Of 1337 patients with chronic renal failure initiated on long term haemodialysis, the incidence of HITS was 0.97 %. Despite increased awareness of HITS, testing frequency remains conservative. An overwhelming majority of HITS cases were diagnosed among patients initiated on haemodialysis.

Introduction: A hypercoagulable state is a predisposition for venous thromboembolism (VTE). The activated partial thromboplastin time (aPTT)-based clot waveform analysis (CWA) is a global haemostatic measure but its role in assessment of hypercoagulability and thrombotic disorders is uncertain. We aimed to study the changes of CWA parameters in acute VTE. We hypothesized that patients with acute VTE would demonstrate higher CWA values than control patients without VTE and having elevated CWA parameters is associated with acute VTE. Materials and methods: Clot waveform analysis data from patients (N = 45) with objectively proven acute VTE who had an aPTT performed prior to initiation of anticoagulation were compared with controls (N = 111). The CWA parameters measured were min1, min2, max2 and delta change. Results: While the mean aPTT between VTE patients and controls did not differ (P = 0.830), the mean CWA parameters were significantly higher among VTE patients than controls (min1, P < 0.001; min2, P = 0.001; max2, P = 0.002; delta change, P < 0.001). There were significantly more cases within the VTE group exhibiting CWA values above their reference intervals than the control group (all P < 0.001), with the odds ratios for VTE of 8.0, 5.2, 4.8 and 18.6 for min1, min2, max2 and delta change, respectively (all P < 0.001). Conclusions: Patients with acute VTE had elevated aPTT-based CWA parameters than controls. Higher CWA parameters were significantly associated with acute VTE.

Introduction: Direct oral anticoagulants (DOACs) are establishing themselves as principle choices for the treatment of a variety of thrombotic disorders. DOACs are also known to affect common coagulation tests which are routinely performed for patients in clinical practice. An understanding of their varied effects is crucial for the appropriate ordering of coagulation tests and their interpretation. Materials and Methods: Laboratories in public and private healthcare institutions and commercial sectors were surveyed on coagulation tests offered and their methods. A Medline and bibliography search, including a search on search engines, was performed for publications reporting the effects of dabigatran, apixaban and rivaroxaban on these coagulation tests. These papers were reviewed and summarised for consensus recommendations. Results: Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are variably affected by the DOACs and dependent of the coagulation assays used. Clinicians must know which laboratory has performed these tests to logically interpret test results. A normal PT or aPTT does not exclude the presence of residual DOACs effect. The thrombin time is sensitive to dabigatran but not apixaban or rivaroxaban. Specialised coagulation tests such as thrombophilia tests are also variably affected by the DOACs. All laboratories in Singapore however, employ similar test methods permitting a common set of recommendations for specialised coagulation testing. Conclusion: Knowledge of the effects of DOACs on coagulation testing is essential to determine the appropriateness of performing such tests and interpreting them coherently. Practical recommendations which are tests and location-specific are set out in this paper. Key words: Apixaban, Dabigatran, Laboratory testing, Rivaroxaban

Non-transfusion-dependent thalassaemia (NTDT) is associated with a hypercoagulable state with thrombotic risk highest after splenectomy. Various mechanisms have been proposed. Although an antiplatelet agent is commonly recommended as thromboprophylaxis in NTDT, the role of platelets contributing to this hypercoagulable state is not well-defined. This study aims to evaluate the role of platelets contributing to hypercoagulability in NTDT patients using thrombin generation (TG). Platelet-rich (PRP) and platelet-poor plasma (PPP) were collected from NTDT patients (n = 30) and normal controls (n = 20) for TG measurement and compared. Controls had higher endogenous thrombin potential (ETP) in PPP (1204.97 nM.min vs 911.62 nM.min, p

The group of new oral anticoagulants or NOACs, now termed direct oral anticoagulants or DOACs, with their favourable results from large scale phase III clinical trials, represent a major advancement and expanded armamentarium in antithrombotic therapy. Dabigatran, rivaroxaban, apixaban and edoxaban are now in clinical routine use for prevention and treatment of arterial and venous thrombotic diseases as addressed in their clinical trials. Usage of the DOACs is expected to increase as clinicians gain more experience and reassurance with data from the real world studies which are generally consistent with that from clinical trials. Development of specific antidotes in management of bleeding complications and development of coagulation assays for their plasma levels will further boost the confidence in the DOACs. Nonetheless, there are still limitations associated with the DOACs. Many patients in need of anticoagulant therapy for indications not studied in the clinical trials will not be eligible for treatment with a DOAC. Conditions where more data is required include DOACs use in the paediatric age group, patients with atrial fibrillation and valvular heart disease, thrombosis associated with the anti-phospholipid syndrome and cancer associated thrombosis. The affordability and access to these drugs may pose an issue for many patients under healthcare systems not providing for these medications. With four new anticoagulants coming onboard very quickly, the focus has shifted to the practical approach and management in real life as many clinicians are not yet familiar with the DOACs. Clinicians need to be educated on how to manage this new class for drugs, from choosing the appropriate drug to prevention and managing bleeding complications as a lack of knowledge and understanding in these drugs will lead to inappropriate use and compromise on patient safety.

Extramedullary leukaemic involvement is not uncommon as part of the presentation in acute myeloid leukaemia (AML). However, infiltrative peripheral neuropathy due to AML was rarely reported. We report a case of extramedullary leukaemic infiltration of the brachial plexus in a patient with relapsed AML.Akut miyeloid löseminin (AML) bir parçası olarak ekstramedüller lösemik tutulum nadir bir durum değildir. Ancak AML’ye bağlı infiltratif periferik nötropati nadiren bildirilmiştir. Burada, relaps AML’li bir hastada brakiyal pleksusun ekstramedüller lösemik infiltrasyonu vakasını sunuyoruz.

Purpose Herbs with “blood-activating” properties by traditional medicine theory often raise concerns for their possible anti-platelet or anticoagulation effects based on reports from in vitro studies. Such herbs have been implicated for bleeding manifestations based on only anecdotal reports. In particular, the combination of such herbs with anti-platelet agents is often empirically advised against despite lack of good clinical evidence. Here we studied 3 commonly used herbal preparations Curcuma longa, Angelica sinensis and Panax ginseng on their respective anti-platelet and anticoagulation effect, alone and in combination with aspirin. Study design This is a randomized, double-blind, placebo-controlled trial involving 25 healthy volunteers for each herbal preparation. Methods Each subject underwent 3 phases comprising of herbal product alone, aspirin alone and aspirin with herbal product, where each phase lasted for 3 weeks with 2 weeks of washout between phases. PT/APTT, platelet function by light transmission aggregometry and thrombin generation assay by calibrated automated thrombogram were measured at baseline and after each phase. Information on adverse reaction including bleeding manifestations was collected after each phase. Results On the whole there was no clinically relevant impact on platelet and coagulation function. With the exception of 5 of 24 subjects in the Curcuma longa group, 2 of 24 subjects in the Angelica sinensis group and 1 of 23 subjects in the Panax ginseng group who had an inhibition in arachidonic-acid induced platelet aggregation, there was no effect of these 3 herbals products on platelet aggregation by other agonists. Combination of these herbal products with aspirin respectively did not further aggravate platelet inhibition caused by aspirin. None of the herbs impaired PT/APTT or thrombin generation. There was no significant bleeding manifestation. Conclusions This study on healthy volunteers provides good evidence on the lack of bleeding risks of Curcuma longa, Angelica sinensis and Panax ginseng either used alone or in combination with aspirin.

Strokes can have a catastrophic impact on patients' health-related quality of life (HRQoL). In addition to warfarin, two novel oral anticoagulants, i.e., dabigatran and rivaroxaban, have been approved to prevent strokes. This study aimed to use direct measures to elicit patient-reported utilities (i.e., preferences) for anticoagulant-related outcomes. A cross-sectional survey was administered to 100 patients taking warfarin in an anticoagulation clinic. Utilities for six long-term and four short-term anticoagulant-related health states were elicited by the visual analogue scale (VAS) and standard gamble (SG) methods. Health states with the highest SG-derived mean utility values were "well on rivaroxaban" (mean ± SD = 0.90 ± 0.15), "well on warfarin" (0.86 ± 0.17), and "well on dabigatran" (0.83 ± 0.18). Approximately half of the patients considered major ischemic stroke (-1.57 ± 6.77) and intracranial hemorrhage (-1.99 ± 6.98) to be worse than death. The percentages of patients who considered a particular health state worse than death ranged from 0 to 55 % among various health states assessed. The VAS had similar findings. Good logical consistency was observed in both VAS- and SG-derived utility values. Ischemic stroke and intracranial hemorrhage had a significant impact on patients' HRQoL. Greater variation in patients' preferences was observed for more severely impaired health states, indicating the need for individualized medical decision-making. In this study, both long-term and short-term health states were included in the utility assessment. The findings of this study can be used in cost-utility analysis of future anticoagulation therapies.

Background: The use of herbal medicine is prevalent worldwide. Curcuma longa(CL), Angelicae sinensis (AS) and Panax Ginseng(PG), commonly known as Tumeric, Dong Quai and Ginseng respectively, are frequently used herbal medicines but were cautioned to have "blood thinning" effects and generally advised not to be taken with anti-platelets and anticoagulants. However, their effects on haemostasis and interaction with aspirin are unknown and occurrence of bleeding symptoms rarely documented. Aim: To investigate the in-vivo effects of CL (Tumeric), AS (Dong Quai) and PG (Ginseng) with and without aspirin on platelet function and thrombin generation. Methods: A randomized, double-blind, placebo-controlled crossover study was carried out for each herb. 75 healthy volunteers were recruited with 25 assigned to each of the 3 herb-groups (Tumeric, Dong Quai and Ginseng). The study subjects were first assigned to {herbal only} for 3 weeks, followed by a 2-week wash out period, after which they were randomly assigned to {aspirin + herbal} or {aspirin + placebo} for 3 weeks. Following another 2 week washout, the subjects crossed over to receive {aspirin + placebo} and {aspirin + herbal capsule} respectively for next 3 weeks. Dosages of herbs are Tumeric 500mg, Dong Quai 1000mg or Ginseng 1000 mg and aspirin 100mg once daily. Blood samples were analysed at baseline and after each intervention phase for full blood counts (FBC), PT/aPTT, platelet function tests (PFT) and thrombin generation assays. PFT measured platelet aggregation using light transmission in platelet-rich plasma, induced with Adenosine diphosphate (ADP), Arachidonic acid (AA), Collagen, Epinephrine and Ristocetin. Thrombin generation (TG) assays on platelet poor plasma measured Endogenous Thrombin Potential(ETP), Time to peak (ttPeak), Peak height and Lag time (LT). All clinical events experienced by the subjects were recorded during each phase. Non-parametric statistical analysis was carried out through Wilcoxon-signed rank tests (SPSS Version 21, USA) and deemed significant if p Results: FBC, PT and aPTT were normal at baseline and for all 3 phases in all 3 herbs, with and without aspirin. For PFTs, Tumeric resulted in impaired AA-induced aggregation in 5, Dong Quai in 2 and Ginseng in 1 subjects. 2 other subjecys in Dong Quai group and 1 in Ginseng group also had reduction in Epinephrine-induced aggregation. Aspirin, as expected suppressed platelet aggregation to AA, Epinephrine, collegen and ADP but this was not further suppressed by concomitant administration of any of the 3 herbs. All TG assays were normal in all 3 herbs with one exception where Tumeric showed a significant proplongation in LT over baseline. Aspirin reduced ETP and peak height which was not further aggravated by concomitant administration of any of the 3 herbs. There was no significant clinical events reported, in particular no bleeding complications. Conclusion: Overall, there was no meaningful nor severe suppression of PFTs. Only a few subjects demonstrated decreased % platelet aggregation while on one of these herbs. In each of these subjects, this was restricted to platelet aggregation by 1 inducer and normal for the rest. Hence, the overall platelet hemostatic function should not be significantly compromised as to cause clinical events. Importantly, addition of herb did not further impair PFTs due to aspirin alone TG assays are more sensitive to subtle changes in global plasma hemostatic functions compared to conventional clotting times. Apart from a prolongation of LT seen in the Tumeric group, TG assays were largely unaffected by these herbs, indicating that these 3 herbs did not significantly affect the global plasma hemostatic function. Importantly, suppressed TG assays by aspirin was not further impaired by concomitant administration of any of the 3 herbs with aspirin, inferring that the herb addition to aspirin did not further impair hemostatic functions. The widely held notion of "blood thinning" properties of Tumeric, Dong Quai and Ginseng were not demonstrated through PFT and TG assays. The concurrent usage of aspirin with these herbs individually did not result in compromise of hemostatic functions and was safe with no clinical bleeding. These findings will help mitigate the anxiety over bleeding complications of these 3 herbs, especially for patients who are on aspirin. Larger studies with more numbers will be required for further verifications. Disclosures No relevant conflicts of interest to declare.