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Cerebral venous sinus thrombosis is an uncommon adverse event in immune thrombocytopenia (ITP) patients treated with thrombopoietin receptor agonists. We reported two cases of cerebral venous sinus thrombosis after eltrombopag administration. The first case is a 29-year-old ITP woman who recently initiated eltrombopag one month before admission. She presented with progressive headache, visual disturbance, and nausea for six days with unremarkable physical examination except for bilateral optic disc edema. She was treated with enoxaparin and switched to edoxaban when discharged. The second case is a 75-year-old man with a history of vaccine-induced ITP. He was initially treated with dexamethasone and eltrombopag. One month later, he developed acute cerebral venous thrombosis with hemorrhagic infarction in bilateral frontal lobes. Even though he was treated with intravenous heparin, his status was not improved. He received the best supportive care. The pathophysiology of TPO-RAs-associated cerebral venous sinus thrombosis remained unclear but might associate with platelet activation. Careful use and closed monitoring might prevent this event.

Background: Cardiovascular events are the most serious complications for patients with myeloproliferative neoplasms (MPNs). There was limited data regarding arterial stiffness in these patients. Methods: This was a cross-sectional study aiming to determine the prevalence of arterial stiffness that was evaluated by cardio-ankle vascular index (CAVI) in patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We defined arterial stiffness as a mean CAVI of 8.0 or more. We compared the prevalence of arterial stiffness in non-MPN patients with cardiovascular risk by matching age, sex, and Thai CV risk score. Results: A total of 80 patients were enrolled (PV, n = 50; ET, n = 24; PMF, n = 6) with median age of 63.5 years (IQR 50.9-76.1). The prevalence of arterial stiffness in patients with MPNs was 63.8%, and among patients with ET, PV, and PMF was 70.8%, 60.0%, 66.7%, respectively (p = 0.655). After matching, the prevalence of arterial stiffness was not statistically significant difference when compared to the non-MPN population with cardiovascular risk (65.2% vs 60.9%, P = 0.539). Conclusion The prevalence of arterial stiffness in patients with MPNs was 63.8% which was comparable to non-MPN patients with cardiovascular risk.

Background Antifibrinolytic agents such as tranexamic acid (TXA) are commonly used as adjunctive therapies to prevent and treat excessive bleeding. In non-surgical settings, TXA is known to reduce bleeding related mortality. However, impact of TXA use on thrombosis is uncertain. Methods We systematically searched the MEDLINE, EMBASE, and CENTRAL databases from January 1985 to August 2018. Studies with the following characteristics were included: (i) RCT design; (ii) compared systemic (oral or intravenous) TXA for prevention or treatment of bleeding for non-surgical indications and placebo or no TXA, and (iii) reported thrombotic events or mortality. A Mantel-Haenzel, random-effects model was used to calculate risk ratios, and risk of bias was assessed using the Cochrane risk of bias tool. Results Our search identified 22 studies representing 49,538 patients. Those receiving TXA had a significantly lower risk of death from any cause (RR = 0.92; 95% CI = 0.87–0.98; I2 = 0%). There was no significant increase in the risk of stroke (RR = 1.10; 95% CI = 0.68–1.78; I2 = 31%), myocardial infarction (RR = 0.88; 95% CI = 0.43–1.84; I2 = 46%), pulmonary embolism (RR = 0.97; 95% CI = 0.75–1.26; I2 = 0%), or deep vein thrombosis (RR = 0.99; 95% CI = 0.70–1.41; I2 = 0%) from use of TXA. The results were similar when restricted to studies at low risk of bias. Conclusions In our systematic review and meta-analysis, the use of tranexamic acid reduced all-cause mortality without increased risk of venous or arterial thrombotic complications.

Background: The prognosis and management of primary thrombocytosis (PT) and secondary thrombocytosis (ST) are different. This study aims to evaluate the role of platelet function tests by light transmission platelet aggregometry (LTA), plasma von Willebrand factor antigen (vWF:Ag), ristocetin cofactor activity (vWF:RCo) and inflammatory markers [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)] for the differentiation between PT and ST. Methods: This prospective study was carried out in patients with platelet counts greater than 450 x 109/L. Primary outcomes were the sensitivity and specificity of platelet function tests by LTA for the differentiation of PT and ST. Secondary outcomes were sensitivity and specificity of ESR, CRP, vWF:Ag, and vWF:RCo for the differentiation of PT and ST. Results: Fifty-two patients were enrolled onto the study of which 26 (50%) had PT. The sensitivity and specificity of epinephrine, collagen, and arachidonic acid (AA) induced abnormal LTA for the differentiation of PT from ST were sensitivity of 50%, 38.5%, 26.9% and specificity of 88.5%, 100%, 100% respectively. The sensitivity and specificity of abnormal ESR, CRP, and either abnormal ESR or CRP in the differentiation of ST from PT were sensitivity of 88.5%, 80.8%, 100% and specificity of 65.4%, 61.5%, 46.2% respectively. The sensitivity and specificity of low vWF:Ag and vWF:RCo in the differentiation of PT from ST were sensitivity of 7.69%, 42.3% and specificity of 100%, 88.5% respectively. Conclusions: Abnormal platelet function determined by LTA with collagen, AA, epinephrine had high specificity ratings enabling the differentiation between PT and ST. vWF:RCo, ESR and CRP levels could be helpful in differentiating between PT and ST.

Recent data on acute lymphoblastic leukemia (ALL) treatment with multi-agent chemotherapy showed excellent response in pediatric patients in terms of long-term survival; however, the clinical needs for adult patients are still unmet. Adolescent and young adults' (AYA) ALL could benefit from a pediatric-inspired regimen with a higher rate of long-term remission. This retrospective study sought to investigate the efficacy of treatment of adult ALL in a single center over the past decade. We analyzed 107 ALL patients with a median age of 26 years (range 15-63 years). Of these, 67.3% received adult regimen and 32.7% received pediatric-inspired regimen. The median follow-up time was 11.6 months (range 1-120). Complete remission (CR) was similarly achieved in over 80% in both schemes. Relapse and refractory rates were higher in the adult group (75%) than in the pediatric (45.7%) group. Two-year disease-free survival in the pediatric group was significantly superior to the adult group (47.1% vs 24.7%, hazard ratio [HR], 1.73, 95% CI 1.22-3.03). Two-year overall survival was higher in pediatric group as compared to adult group (50.8% versus 31.2%, HR 1.52, 95% CI 0.83-2.78). Thus, these findings show that the pediatric-inspired regimen should be considered for the treatment of adult ALL.

Objectives The primary objective was to compare the efficacy of intermediate-dose cytarabine (IDAC) and high-dose cytarabine (HiDAC) as consolidation chemotherapy for acute myeloid leukemia (AML) in terms of a one-year-relapse-free survival rate (RFS). The secondary objectives were one-year-overall survival rate (OS) and adverse effects. Methods This was a retrospective study conducted at Chiang Mai University Hospital. AML patients who achieved complete remission after 7 + 3 induction regimen and received consolidation therapy with either IDAC or HiDAC during January 2015 and January 2018 were eligible. Data about clinical characteristics, efficacy and safety of IDAC and HiDAC regimens were collected. Results Sixty-two AML patients were enrolled (30 patients in IDAC and 32 patients in the HiDAC regimen). The one-year RFS in the IDAC group was 63.33% and 46.87% in the HiDAC group (P = 0.137). The 1-year OS was 93.33% and 84.37% in the IDAC and HiDAC, respectively (P = 0.691). The duration of grade 3-4 thrombocytopenia was significantly shorter in IDAC than HiDAC (mean duration 14.69 vs. 23.84 days; P = 0.045). There was no significant difference in other parameters including hemoglobin nadir, absolute neutrophil count nadir, platelet nadir, febrile neutropenia, duration of grade 3-4 neutropenia, and duration of hospitalization. Discussion and conclusions There was no significant difference in the one-year RFS and OS between IDAC and HiDAC. The IDAC regimen is an acceptable option for consolidation treatment in AML.

Hepcidin is a key iron-regulatory hormone, the production of which is controlled by iron stores, inflammation, hypoxia and erythropoiesis. The regulation of iron by hepcidin is of clinical importance in thalassemia patients in which anemia occurs along with iron overload. The present study aimed to evaluate the correlation between serum hepcidin and ferritin levels in thalassemia patients. This cross-sectional study investigated 64 patients with thalassemia; 16 β-thalassemia major (BTM), 31 β-thalassemia/hemoglobin (Hb) E (BE), and 17 Hb H + AE Bart’s disease (Hb H + AE Bart’s). The levels of serum hepcidin and ferritin, and Hb of the three groups were measured. The median values of serum ferritin and Hb were significantly different among the three groups, whereas serum hepcidin values were not observed to be significantly different. The correlation of the serum hepcidin and ferritin levels was not statistically significant in any of the three groups of thalassemia patients with BTM, BE, or Hb H + AE Bart’s (r = −0.141, 0.065 and −0.016, respectively). In conclusion, no statistically significant correlations were observed between serum hepcidin with any variables including serum ferritin, Hb, age, labile plasma iron (LPI), and number of blood transfusion units among the three groups of thalassemia patients. Likely, the regulation of hepcidin in thalassemia patients is affected more by erythropoietic activity than iron storage.

BACKGROUND Autologous stem cell transplantation (ASCT) has become a standard procedure in multiple myeloma (MM) patients. Cryopreservation (CRYO) of stem cells may be associated with adverse reactions of dimethyl sulfoxide. Previous studies showed that stem cell storage at 4°C (non-cryopreserved [NC] method) may have some advantages. This analysis focused on comparing the transplant-related outcomes of the 2 preservation methods. MATERIAL AND METHODS This was a cohort study of consecutive MM patients who underwent ASCT at Chiang Mai University from 2014 to 2019. Primary outcomes were time to neutrophil and platelet engraftment. Key secondary outcomes were the incidence of infusion reactions, duration of hospitalization, cost, and survival. RESULTS A total of 42 MM patients underwent ASCT. Of these, 26 patients and 16 patients underwent NC and CRYO stem cell collections, respectively. There was no difference in time to neutrophil engraftment (median 12 vs. 10.5 days, P=0.203) or platelet engraftment (median 14 vs. 12 days, P=0.809) between groups. The incidence of infusion reactions and duration of hospitalization were similar in both groups. The average cost of ASCT was 10% lower in the NC group. There was no difference in progression-free survival (median 16 vs. 22 months, P=0.701) or overall survival between NC and CRYO groups. CONCLUSIONS ASCT in MM using the NC preservation method is effective and safe compared to the CRYO method in both short-term and survival outcomes.

Background : The intestinal bacterial flora of febrile neutropenic patients has been found to be significantly diverse and may play a role in clinical decisions regarding antimicrobial de-escalation with predictive complications. However, there are few reports of microbiota alteration of adult acute myeloid leukemia (AML) patients. Methods : Stool samples of each treatment-naïve AML patient were collected the day before the initiation of induction chemotherapy (pretreatment), on the first date of neutropenic fever and first date of bone marrow recovery. Bacterial DNA was extracted from stool samples and bacterial 16s ribosomal RNA genes were sequenced by next-generation sequencing. Relative abundance, overall richness, Shannon's diversity index and Simpson's diversity index were calculated. Results : Ten AML patients (4 men and 6 women) were included with a median age of 39 years (range: 19-49). Twenty-four stool samples were collected and assigned into three groups: (1) pretreatment (n = 10); (2) first date of febrile neutropenia (n=9); and (3) first date of bone marrow recovery (n=5). All of patients developed febrile neutropenia; three patients had detectable infectious organisms and all of these cases had invasive pulmonary aspergillosis with two being co-infected with Pseudomonas pneumonia and Escherichia coli septicemia. Median absolute neutrophil count was 2.85 x 109/L (range: 1.42-7.67 x 109/L), 0.04 x 109/L (range: 0.01-0.43 x 109/L) and 3.65 x 109/L (range: 2.09-5.78 x 109/L) at pretreatment, first date of febrile neutropenia and first date of bone marrow recovery, respectively. At the phylum level, Firmicutes dominated over the period of neutropenic fever, subsequently declining after bone marrow recovery a pattern in contrast to that shown by Bacteroidetes and Proteobacteria. At the genus level, Enterococcus was more abundant in the febrile neutropenia period compared to pretreatment (mean difference of 20.2, [95%CI (5.9, 34.6)]; P Conclusions : Adult AML patients with a first episode of febrile neutropenia after initial intensive chemotherapy demonstrated a significant decrease in gut microbiota diversity and the level of diversity remained constant despite recovery of bone marrow. Figure Disclosures No relevant conflicts of interest to declare.

Background Cardiorenal syndrome (CRS), a serious condition with high morbidity and mortality, is characterized by the coexistence of cardiac abnormality and renal dysfunction. There is limited information about CRS in association thalassemia. This study aimed to investigate the prevalence of CRS in thalassemia patients and also associated risk factors. Methods Thalassemia patients who attended the out-patient clinic of a tertiary care university hospital from October 2016 to September 2017 were enrolled onto this cross-sectional study. Clinical and laboratory findings from 2 consecutive visits, 3 months apart, were assessed. The criteria for diagnosis of CRS was based on a system proposed by Ronco and McCullough. Cardiac abnormalities are assessed by clinical presentation, establishment of acute or chronic heart failure using definitions from 2016 ESC guidelines or from structural abnormalities shown in an echocardiogram. Renal dysfunction was defined as chronic kidney disease according to the 2012 KDIGO guidelines. Results Out of 90 thalassemia patients, 25 (27.8%) had CRS. The multivariable analysis showed a significant association between CRS and extramedullary hematopoiesis (EMH) (odds ratio (OR) 20.55, p = 0.016); thalassemia type [β0/βE vs β0/β0 thalassemia (OR 0.005, p = 0.002)]; pulmonary hypertension (OR 178.1, p = 0.001); elevated serum NT-proBNP (OR 1.028, p = 0.022), and elevated 24-h urine magnesium (OR 1.913, p = 0.016). There was no association found between CRS and frequency of blood transfusion, serum ferritin, liver iron concentration, cardiac T2*, type of iron chelating agents, or urine neutrophil gelatinase-associated lipocalin level. Conclusions CRS is relatively common in thalassemia patients. Its occurrence is associated with laboratory parameters which are easily measured in clinical practice.

Introduction Recruiting blood donors remains a challenging process to ensure sufficient blood product supplies. There were several interventions implemented in order to promote the retention of first-time donors, including short messaging service (SMS). However, the efficacy of SMS for promoting the retention of blood donation has never been demonstrated in a randomized controlled trial. Here, we report the interim analysis of the TEXT study. Methods This is a single center, randomized- controlled trial. We enrolled participants 18 years of age or older who were first-time blood donors and who were able to read and understand text messages. Participants were excluded if the purposes of blood donation were as follows, autologous donation, apheresis or blood letting. Participants were also excluded if they had no cell phone number or lived temporarily in the area. Participants were randomized within 24 hours followed the blood donation in a 1:1 ratio (text group vs control group). Only participants who were allocated in the "text group'' would receive a computer-generated text message once his/her blood product was dispatched from the transfusion service. The content of text message was "We would like to inform you that your blood has been used for patients on DD.MM.YYYY. Because of your blood donation, patients' lives will be saved." The primary outcome of the study was the rate of returning for the second donation at 6 months. Odds ratio (OR) and 95% confidence interval (CI) for retention rate was calculated based-on a modified intention-to-treat analysis. Results In a modified intention-to-treat analysis, there were 867 participants allocated to the text group and 864 participants to the control group (Figure 1). Mean age was 26.1 (standard deviation, SD 9.2) and 26.2 (SD 9.4) years, respectively. The primary outcome occurred in 120 of 867 (13.8%) in the text group and 89 of 864 (10.3%) in the control group, OR 1.40 (95%CI 1.04 to 1.87, P-value=0.02). Number needed to treat was 29. Figure 2 demonstrates the Kaplan-Meier curves of participants who returned for the second blood donation comparing between text and control groups. The median time for returning was 119 days (interquartile range, 95.5-150.5) in text group and 119 days (interquartile range, 98-148) in control group. Subgroup analysis does not show significant interactions between participants' characteristics and outcome. Conclusion Among first-time blood donors, text messaging after blood product being dispatched is a simple, inexpensive and effective intervention to increase the retention rate for second donation at 6 months duration. Disclosures No relevant conflicts of interest to declare.

Pulmonary hypertension (PH) is emerging as a complication of myeloproliferative neoplasms (MPNs). This was a prospective study conducted at Chiang Mai University Hospital. The primary objective was to determine the prevalence of high echocardiographic probability of PH in MPNs patients. The secondary objectives were to determine risk factors of PH and the correlation between risk factors and peak tricuspid regurgitation velocity (TRVmax). All MPNs patients aged over 18 years, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), were enrolled. All eligible patients underwent echocardiography for evaluation of the probability of PH in line with the 2015 European Society of Cardiology (ESC) and the European Respiratory Society (ERS) Guidelines. Sixty-six patients with a median age of 59 years were enrolled. There were 35 PV, 25 ET, and 6 PMF patients included. The prevalence of high echocardiographic probability of PH was 4.55% (2 ET and 1 PMF). Risk factors associated with high echocardiographic probability of PHT were not analyzed. There were three risk factors associated with increased TRVmax, specifically lower hemoglobin, older age, and the presence of JAK2V617F mutation. The prevalence of high echocardiographic probability of PH in MPNs patients was 4.55%.

Introduction There are limited data on the impact of haemophilia on health status and health-related quality of life (HRQL) in people with non-severe (mild and moderate) haemophilia. Aim To evaluate the health status of people living with mild or moderate haemophilia. Methods Data on respondents with no bleeding disorder (NoBD), mild and moderate haemophilia patients were drawn from the PROBE study. Respondents were enrolled using network patient organizations. This analysis was performed as a cross-sectional study. Primary outcomes were reported bleeding, acute and chronic pain, activities of daily living and HRQL. Results A total of 862 respondents with NoBD (n = 173), mild (n = 102) and moderate (n = 134) haemophilia were eligible, with a median age of 33, 42 and 43, respectively. In relation to haemophilia-related sequalae, 53% of male and 29% of female patients with mild and 83% of males with moderate haemophilia had more than 2-3 bleeds in the last 12 months. Reporting of acute and chronic pain is less in those with NoBD compared to the mild and moderate cohorts for both genders. Multivariate analysis demonstrates significant reductions in quality of life using VAS, EQ-5D-5L and PROBE for males with mild and moderate haemophilia (P ≤ .001) with only PROBE indicating a significant reduction for females with mild (P = .002). Conclusion People affected by mild or moderate haemophilia report a significant HRQL impact due to haemophilia-related bleeding. Future research is needed to identify the optimal care management of patients with mild and moderate haemophilia.

Background The Patient Reported Outcomes, Burdens and Experiences (PROBE) study aims to develop and validate questionnaire for assessing health status in patients with haemophilia and participants without bleeding disorders. Objective To investigate the test-retest properties of the PROBE questionnaire. Methods The PROBE questionnaire covers four domains and is comprised of 29 questions. People with haemophilia (PWH) and participants without bleeding disorder were invited to participate in this study. All participants were asked to complete the PROBE questionnaire three times (paper-based survey on two consecutive days: T1 and T2 and then a web-based version: T3). Test-retest properties and percentage agreement were analysed. Results A total of 63 participants were enrolled in this study with a median age of 50 (range: 17-76) years. Of these, 30 (47.6%) were PWH. On the questions common to PWH and participants without bleeding disorder, Kappa coefficients ranged from 0.69 to 1.00, indicating substantial to almost perfect agreement (T1 vs T2). For haemophilia-related questions (T1 vs T2), Kappa coefficients ranged from 0.5 to 1.0. Of these, 5 of 11 items were in perfect agreement (Kappa = 1.0). The web-based questionnaire (T3) showed substantial to almost perfect agreement with the paper version (T1 test-retest properties were comparable between PWH and individuals without a bleeding disorder). Conclusions The results suggest that PROBE is a reliable tool to assess patient-reported outcomes for PWH and benchmark data in participants without bleeding disorder. The web-based questionnaire and the standard paper-based version can be used interchangeably.

Background Infection is a major complication in aplastic anemia (AA) patients. Primary objectives of this study were to determine the prevalence of infections and to determine types of pathogens associated with infections in patients with AA. Secondary objectives were to evaluate overall survival after infections as well as risk factors of infections in patients with AA. Methods The authors retrospectively evaluated the infectious episodes (IEs), type of infections, associated pathogens, and outcomes of infections in patients with AA who were diagnosed and treated at Chiang Mai University between January 2010 and December 2015. Results Sixty-seven patients with a median age of 51 years (range, 15–87 years) were enrolled. Forty two patients (62.6%) were severe AA. Median absolute neutrophil count (ANC) was 984 /mm3 (range, 120–5500/mm3). Twenty five patients (37.3%) received antithymocyte globulin plus cyclosporine A, 41 patients (61.1%) received anabolic hormone, and 2 patients (2.9%) underwent allogeneic hematopoietic stem cell transplantation. Overall, 31 IEs were documented in 22 patients (32.8%). The most common microbiologically documented site of infection was bloodstream infection (23.4%) followed by pulmonary infection (14.9%). Culture-negative febrile neutropenia occurred in 12.7%. Common pathogens identified were bacteria (73.9%), mainly gram-negative (52.9%) including Acinetobacter baumannii (23.5%) and Pseudomonas aeruginosa (17.6%). Fungal infections were diagnosed in 21.7% and all were Aspergillus spp. Six patients (9%) died during the study period. All of them died from infection which gram-negative bacteria were most common pathogens (66.7%). Patients with infections had 5-year overall survival of 72% that is significantly less than patients without infection (100%) (p = 0.0002). Only risk factor that correlates with high probability of infection was ANC

Background: Salvage chemotherapy is the mainstay for the treatment of relapsed/refractory peripheral T-cell lymphomas (R/R PTCLs). ESHAP regimen, consisting of etoposide, methylprednisolone, high-dose Ara-C, and cisplatin is considered one of the well-accepted regimens for R/R lymphoma. Though, the evidence of long-term efficacy of ESHAP on R/R PTCLs is limited. This study aims to determine the efficacy and safety of ESHAP as a first salvage regimen, not followed by autologous stem cell transplantation (ASCT), in R/R PTCLs. Methods: Patients with PTCLs, who progressed after one prior therapy and received ESHAP as a salvage treatment without subsequent ASCT, were recruited from the prospective observational study in the patients with lymphoma. Results: From January 2005 to April 2015, 33 patients with R/R PTCLs received ESHAP as first salvage regimen at Chiang Mai University Hospital. The overall response rate was 46% (complete remission (CR) 39%). The median duration of response was 18 months. Median second progression-free survival (PFS) and overall survival (OS) were 8.0 and 11.0 months, respectively. Patients having late relapse had more favorable OS than those having early relapsed or refractory disease with a median OS of 21, 17 and 3 months, respectively (P = 0.001). Patients achieving CR after ESHAP had significantly better median OS (39, 7 and 5 months, P < 0.0001) and second PFS (33, 2 and 2 months, P < 0.0001) than those achieving PR or having progressive disease. Grade 3-4 neutropenia (45.5%) and thrombocytopenia (33.4%) were common but manageable. Conclusions: ESHAP offers a long-term survival in some transplant ineligible patients with PTCLs who were chemosensitive with late relapse after front-line therapy. These results require further investigation in a prospective study. J Hematol. 2018;7(4):131-139 doi: https://doi.org/10.14740/jh459w

Essentials In venous thromboembolism (VTE), benefits of extended treatment are balanced by bleeding risks. This is a meta-analysis of reduced-dose direct oral anticoagulants (DOACs) in extended treatment. Reduced-dose DOACs are as effective as full anticoagulation with bleeding risks similar to placebo. Reduced-dose DOACs are an attractive option for patients in the extended phase of VTE treatment. Summary Background Extended-duration anticoagulation is beneficial for preventing recurrent venous thromboembolism (VTE). Reduced-dose direct oral anticoagulants (DOACs) may be preferable if they preserve efficacy and cause less bleeding. We conducted a systematic review and meta-analysis of trials comparing reduced-dose DOACs with full-dose DOACs and aspirin or placebo in the extended phase of VTE treatment. Methods A literature search was conducted by use of the MEDLINE, EMBASE and CINAHL databases, supplemented by hand-searching. One thousand three hundred and ninety-nine titles were screened, with data from accepted studies being extracted by two independent reviewers. Major outcomes analyzed included recurrent VTE and major and clinically relevant non-major bleeding events, presented as risk ratios (RRs) and 95% confidence intervals (CI). Results Two trials met the prespecified inclusion criteria. Data from 5847 patients were analyzed for efficacy outcomes, and from 5842 patients for safety outcomes. Reduced-dose DOACs were as effective as full-dose treatment in preventing recurrent VTE at 1 year (RR 1.12 [95% CI 0.67-1.87]), and more effective than aspirin or placebo (RR 0.26 [95% CI 0.14-0.46]). Rates of major or clinically relevant non-major bleeding events were similar between patients receiving reduced-dose DOACs and and those receiving aspirin or placebo (RR 1.19 [95% CI 0.81-1.77]). There was a trend towards less bleeding when reduced-dose and full-dose DOACs were compared (RR 0.74 [95% CI 0.52-1.05]). Conclusions Extended-duration treatment of VTE with reduced-dose DOACs may be as efficacious as full-dose treatment, with rates of major bleeding being similar to those in patients receiving treatment with aspirin or placebo, but further long-term studies are needed.

Introduction Data on management of upper extremity deep vein thrombosis (UEDVT) in patients with cancer is limited. The objective of this study was to determine risk factors for UEDVT and the rates of recurrence and bleeding in a real-world setting. Methods Retrospective review of consecutive patients assessed for cancer-associated UEDVT. Outcome measures were recurrent venous thromboembolism (VTE), and major and clinically relevant non-major bleeding (CRNMB). Risk factors for recurrent VTE and bleeding were assessed. Results Mean duration of follow-up was 7.2 months. Two hundred cases were identified; 69% were associated with a central line. Non-line associated UEDVT occurred more frequently in the setting of breast cancer, lung cancer and documented local mass effect. The incidence of recurrent VTE was 18.5%, of which 14 (37.8%) were ipsilateral UEDVT. The risk of recurrence is higher with male gender (HR 2.0, 95% CI; 1.0–4.0). Major and CRNMB occurred in 1% and 11.5%, respectively. Concurrent use of an antiplatelet agent was associated with a higher risk of CRNMB compared to anticoagulant therapy alone (HR 3.9, 95% CI; 1.4–10.7). Conclusions Presence of a venous catheter was the primary risk factor for UEDVT, however, extrinsic compression by local tumour may be just as important for some cancer types. Furthermore, the majority of recurrent events did not occur in the same upper limb suggesting that UEDVT may be predictive of increased thrombotic risk rather than just a local effect of catheters.

Background The interest of health care agencies, private payers and policy makers for patient-reported outcomes (PRO) is continuously increasing. There is a substantial need to improve capacity to collect and interpret relevant PRO data to support implementation of patient-centered research and optimal care in haemophilia. The Patient Reported Outcomes, Burdens and Experiences (PROBE) Project aims to develop a patient-led research network, to develop a standardized questionnaire to gather patient-reported outcomes and to perform a feasibility study of implementing the PROBE questionnaire. Methods A pilot questionnaire was developed using focus group methodology. Content and face validity were assessed by a pool of persons living with haemophilia (PWH) and content experts through interactive workshops. The PROBE questionnaire was translated with the forward-backward approach. PROBE recruited national haemophilia patient non-governmental organizations (NGOs) to administer the questionnaire to people with and without haemophilia. PROBE measured the time to complete the questionnaire and gathered feedback on its content and clarity; staff time and cost required to implement the questionnaire were also collected. Results The PROBE questionnaire is comprised of four major sections (demographic data, general health problems, haemophilia-related health problems and health-related quality of life using EQ-5D-5L and EQ-VAS). Seventeen NGOs participated in the pilot study of the PROBE Project, recruiting 656 participants. Of these, 71% completed the questionnaire within 15 min, and all participants completed within 30 min. The median total staff and volunteer time required for the NGOs to carry out the study within their country was 9 h (range 2 to 40 h). NGO costs ranged from $22.00 to $543.00 USD per country, with printing and postage being the most commonly reported expenditures. Conclusions The PROBE questionnaire assesses patient-important reported outcomes in PWH and control participants, with a demonstrated short completion time. PROBE proved the feasibility to engage diverse patient communities in the structured generation of real-world outcome research at all stages. Trial registration Trial registration: NCT02439710. Electronic supplementary material The online version of this article (10.1186/s40814-018-0253-0) contains supplementary material, which is available to authorized users.

The primary objective was to demonstrate the different risk factors among patients presenting with usual and unusual site venous thromboembolism (VTE). The secondary objectives were to compare clinical characteristics and outcomes in each group. This was a retrospective observational cohort study. Patients admitted in Chiang Mai University Hospital who were diagnosed with VTE during January 2010 through December 2012 were included and classified into two groups: the usual and unusual site VTE. The usual sites of VTE included pulmonary embolism and lower extremity deep vein thrombosis. Clinical characteristics, risk factors, treatment, recurrence, bleeding rates, and deaths were collected. There were 165 patients included in the study, 82 in usual site group and 83 in unusual site group. Patients in usual site group were older than unusual site group (mean 58 vs. 50 years, P = 0.003) and were more symptomatic (89 vs. 49.4%, P < 0.001). The higher proportion of patients in usual site group had prolonged immobilization (22.0 vs. 2.4%, P < 0.001), prior surgery (12.2 vs. 1.2%, P = 0.005), and a history of chemotherapy (25.6 vs. 3.6%, P < 0.001). Local inflammation was significantly more common in unusual site group (0 vs. 8.5%, P < 0.001). The recurrent VTE and major bleeding rates were not statistically different between groups. The 3-year mortality rate was significantly higher in usual site VTE group (73.1 vs. 57.8%, P = 0.049). The study revealed the different risk factors and clinical characteristics between usual and unusual VTE sites.

In chronic lymphocytic leukemia (CLL) patients with mutated IGHV, 3 recent studies have demonstrated prolonged progression-free survival (PFS) after treatment with fludarabine-cyclophosphamide-rituximab (FCR) chemoimmunotherapy. We performed a systematic review to assess the benefit of FCR for patients with CLL and identified 5 randomized trials that met our inclusion criteria. FCR improved complete remission, PFS and overall survival vs the comparator; median PFS was not reached in the subgroup of CLL patients with mutated IGHV.

Essentials The association of body weight and patient-important outcomes remains unknown. Phase III randomized controlled trials of direct oral anticoagulants (DOACs) were searched. Risk of outcomes varying among body weight subgroups is not attributable to anticoagulant type. Dose adjustment of DOACs, outside that recommended, is unlikely to improve the outcomes. Click to hear Dr Braunwald's perspective on antithrombotic therapy in cardiovascular disease SUMMARY: Background Concerns have arisen in direct oral anticoagulant (DOAC)-treated patients about safety and efficacy in extremes of body weight. The aims of this systematic review were to investigate the association of body weight and patient-important outcomes in patients treated with DOACs or warfarin, and to demonstrate the fixed-dose effect of DOACs. Methods MEDLINE and EMBASE were searched until November 2016. Phase III randomized controlled trials (RCTs) using DOACs in atrial fibrillation (AF) and acute venous thromboembolism (VTE) were included. Relative risk and 95% confidence interval were calculated. The pooled estimates were performed using a Mantel-Haenszel random effects model. Results A total of 11 phase III RCTs were included. Low body weight was associated with increased risk of thromboembolism compared with non-low body weight (relative risk [RR], 1.57; 95% confidence interval [CI], 1.34-1.85). High body weight was not associated with risk of thromboembolism compared with non-high body weight (RR, 0.88; 95% CI, 0.63-1.23). The subgroup of AF patients with high body weight had a lower risk of thromboembolism compared with non-high body weight (RR, 0.43; 95% CI, 0.28-0.67). Bleeding outcomes were comparable for all body weight comparisons. There were no clear interactions between types of anticoagulant in all outcomes. Conclusion The pooled effect of both the DOAC and comparison arms was likely to be attributable to differences in baseline thrombotic risk in each body weight category, rather than an effect of the type or dose of DOAC used for each indication. Dose adjustment of DOACs, outside that recommended in the package insert, is unlikely to improve safety or efficacy.

Additional file 1: Table S1. Criteria for diagnosis of heart failure (all 3 criteria required). Table S2. Cardiac and renal abnormalities (n = 90).

Objectives To evaluate any association between pre-transfusion hemoglobin (Hb) levels and thalassemia complications and to identify the Hb cutoff values to predict thalassemia complications. Methods We performed a cross-sectional study in thalassemia patients who attended the Adult Hematology Clinic of the tertiary care University Hospital from October 2017 to October 2018. A point-biserial correlation was used to identify any association between Hb levels and thalassemia complications. A receiver operating characteristic (ROC) curve was used to identify the diagnostic ability of Hb levels to predict thalassemia complications and identify Hb cutoff values. Results Out of the 102 patients, there were 53 transfusion dependent thalassemia (TDT) patients and 49 non-transfusion dependent thalassemia (NTDT) patients. In theTDT group, Hb levels showed a negative correlation with severe hepatic iron overload and hypogonadism. The cutoff Hb levels to predict severe hepatic iron overload and hypogonadism were ≤7.01 and 6.81 g/dL, respectively, at which points the area under the ROC curve (AUC) were 0.721 and 0.708, respectively. In the NTDTgroup, Hb levels were negatively correlated with hepatic iron overload, osteoporosis, and pulmonary hypertension. The cutoff values of Hb levels to predict hepatic iron overload, osteoporosis, and pulmonary hypertension were ≤8.24, 7.16, and 7.16 g/dL, respectively, at which points the AUC were 0.923, 0.715, and 0.725, respectively. Conclusions Lower Hb level was associated with more frequent complications in both TDT and NTDT patients. The Hb cutoff levels to predict these complications were identified.

Background: Thalassemia is a hereditary hemolytic anemia with a severity ranging from mild, non-transfusion dependent to severe chronic anemia requiring lifelong transfusion. Transfusional iron overload is a major complication in patients with transfusion-dependent thalassemia (TDT). Telomeres are sequences of nucleotides forming the end caps of chromosomes that act as a DNA repair system. Iron overload in thalassemia can cause increased oxidative stress which leads to cellular damage and senescence. This may result in telomere length shortening. The degree of telomere length shortening may reflect the severity of thalassemia. Methods: This research aimed to study the telomere length in patients with TDT in comparison to non-thalassemic individuals and to identify the clinical and laboratory parameters that are associated with telomere length. We conducted a cross-sectional study in patients with TDT aged ³18 years. Telomere length was measured by real-time quantitative PCR. Results: Sixty-five patients with TDT were enrolled onto the study. There were 37 female patients (54.4%). The median age was 27 (18-57) years, and mean pre-transfusion hemoglobin (Hb) was 7.1 (± 1.07) g/dL. The mean telomere terminal restriction fragment (TRF) length of patients with TDT and the controls was 6.11 (± 0.61) kb and 6.79 (± 0.84) kb, respectively (p Conclusions: Our study showed that TDT patients had shorter telomere length compared with controls. Telomere shortening in TDT was an aging-dependent process and associated with lower hemoglobin level.

Background Among transfused patients, the effect of the duration of red blood cell storage on mortality remains unclear. This study aims to compare the mortality of patients who were transfused with fresher versus older red blood cells. Methods We performed an updated systematic search in the CENTRAL, MEDLINE, EMBASE and CINAHL databases, from January 2015 to October 2016. RCTs of hospitalized patients of any age comparing transfusion of fresher versus older red blood cells were eligible. We used a random-effects model to calculate pooled risk ratios (RRs) with corresponding 95% confidence interval (CI). Results We identified 14 randomized trials that enrolled 26 374 participants. All-cause mortality occurred in 1219 of 9531 (12·8%) patients who received a transfusion of fresher red blood cells and 1810 of 16 843 (10·7%) in those who received older red blood cells (RR: 1·04, 95% CI: 0·98–1·12, P = 0·90, I2 = 0%, high certainty for ruling out benefit of fresh blood, moderate certainty for ruling out harm of fresh blood). In six studies, in-hospital death occurred in 691 of 7479 (9·2%) patients receiving fresher red cells and 1291 of 14 757 (8·8%) receiving older red cells (RR: 1·06, 95% CI: 0·97–1·15, P = 0·81, I2 = 0%, high certainty for ruling out benefit of fresh blood, moderate certainty for ruling out harm of fresh blood). Conclusion Transfusion of fresher red blood cells does not reduce overall or in-hospital mortality when compared with older red blood cells. Our results support the practice of transfusing patients with the oldest red blood cells available in the blood bank.

The Food and Drug Administration approval of ruxolitinib for treatment of myelofibrosis and polycythemia vera has changed the management of patients with myeloproliferative neoplasms. Yet the impact of this therapy on risk of thrombosis, a major cause of morbidity and mortality among these patients, remains unknown. The aim of this study was to evaluate the impact of ruxolitinib on the risk of thrombosis among patients with polycythemia vera or myelofibrosis. Following identification of randomized controlled trials comparing ruxolitinib to standard care or placebo, rates of thrombosis, including venous and arterial thrombosis, were analyzed using fixed effects models. Rates of thrombosis were significantly lower among patients treated with ruxolitinib [risk ratio 0.45, 95% confidence interval (CI) 0.23-0.88]. Subgroup analysis of venous and arterial thrombosis demonstrated similar risk ratios, which did not reach statistical significance (risk ratio 0.46, 95% CI 0.14-1.48 and RR 0.42, 95% CI 0.18-1.01, respectively). In conclusion, our analysis suggests that JAK2 inhibition with ruxolitinib decreases the risk of arterial and/or venous thrombosis in patients with polycythemia vera or myelofibrosis. These findings will require confirmation in a prospective study.

Background: A diagnosis of chronic myeloid leukemia (CML) is made on discovery of the presence of a Philadelphia (Ph) chromosome. The success of the treatment of this form of leukemia with tyrosine kinase inhibitor (TKI) is monitored by reduction of the Ph chromosome. Objective: To compare the role of conventional cytogenetic (CC) methods with a real time quantitative polymerase chain reaction (RQ-PCR) and fluorescence in situ hybridization (FISH) for diagnosis and treatment monitoring of CML patients. The secondary outcome was to analyze the treatment responses to TKI in CML patients. Materials and Methods: This was a retrospective study of CML patients who attended the Hematology clinic at Chiang Mai University Hospital from 2005-2010. Medical records were reviewed for demographic data, risk score, treatment response and the results of CC methods, FISH and RQ-PCR. Results: One hundred and twenty three cases were included in the study, 57.7% of whom were male with a mean age of 46.9 years. Most of the patients registered as intermediate to high risk on the Sokal score. At diagnosis, 121 patients were tested using the CC method and 118 (95.9%) were identified as positive. Five patients failed to be diagnosed by CC methods but were positive for BCR-ABL1 using the FISH method. Imatinib was the first-line treatment used in 120 patients (97.6%). In most patients (108 out of 122, 88.5%), a complete cytogenetic response (CCyR) was achieved after TKI therapy and in 86 patients (70.5%) CCyR was achieved long term by the CC method. Five out of the 35 analyzed patients in which CCyR was achieved by the CC method had a positive FISH result. Out of the 76 patients in which CCyR was achieved, RQ-PCR classified patients to only CCyR in 17 patients (22.4%) with a deeper major molecular response (MMR) in 4 patients (5.3%) and complete molecular response (CMR) in 55 patients (72.4%). In the case of initial therapy, CCyR was achieved in 95 patients (79.1%) who received imatinib and in both patients who received dasatinib (100%). For the second line treatment, nilotinib were used in 30 patients and in 19 of them (63.3%) CCyR was achieved. In half of the 6 patients (50%) who received dasatinib as second line or third line treatment CCyR was also achieved. Conclusions: CML patients had a good response to TKI treatment. FISH could be useful for diagnosis in cases where CC analysis failed to detect the Ph chromosome. RQ-PCR was helpful in detecting any residual disease and determining the depth of the treatment response at levels greater than the CC methods.

To study the clinical manifestations, outcomes, and survival of warm-type autoimmune hemolytic anemia (AIHA) patients.This study was a retrospective single-center study from 2002 to 2013. Clinical data of AIHA patients were reviewed and analyzed.One hundred and one patients were included, of whom 77% were female with a median age of 43 years. Primary AIHA was found in 61% of the patients. The secondary causes were systemic lupus erythematosus (SLE) (64%), solid malignancies (13%), lymphomas (10%), drugs (8%), and infections (5%). Most patients (96%) responded to steroids, which were not different between primary and secondary AIHA. Second-line treatments were required in 33 patients (33%). The indications were steroid dependence (58%), relapse (30%), and others (12%). The most common second-line treatment was cyclophosphamide (52%). The response rate for second-line treatments was 93%. Relapse occurred in 50 patients (50%) in which 58% occurred more than 3 years after diagnosis. The SLE patients relapsed and received second-line therapy more than the non-SLE group (P 0.001). At the median 53-month follow-up, the overall survival (OS) was 84%. The independent risk factors for OS were age more than 50 years and malignancy. Sepsis was the most common cause of death.AIHA has a good prognosis and long-term survival especially in young patients without malignancy. Most patients have responded initially to steroids and have a high response rate to second-line therapy. Carefully adjusted and rapid taper of immunosuppressant is necessary to avoid sepsis complications.

BACKGROUND The Patient Reported Outcomes Burdens and Experience (PROBE) study has developed and validated the PROBE questionnaire for assessing patient-reported outcomes in people with haemophilia and participants without bleeding disorders. OBJECTIVE To explore the regional variations in the international implementation of the PROBE questionnaire. METHODS Data were collected from participants in four regions (Western Pacific, South America, North America and Europe). Participants were able to choose English or translated versions of the PROBE questionnaire into their first language. We used analysis of variance methods and multivariable regression to determine the relative contribution of the variance explained by region controlling for haemophilia diagnosis, age group and levels of educations. We also explored interactions between region and the other components. RESULTS We used 862 questionnaires from 14 countries. Mean age of participants was 40.03 years (standard deviation 13.89), and 73.67% were male. After adjusting, region contributed 0.44%-7.98% of the variance component in subitem scores and 0.26% in the PROBE score. Years of education contributed 0.34% in the PROBE score. Age and haemophilia diagnosis contributed 3.42% and 22.42% of the PROBE score. CONCLUSIONS The results demonstrate that the PROBE questionnaire is valid to implement for assessing health status among patients with haemophilia and participants without bleeding disorders across regions.

Introduction Oral anticoagulation (OAC) is permanently discontinued in up to 50% of patients following a gastrointestinal (GI) bleed. A previous meta-analysis showed a reduced risk of thromboembolism and death, and a non-statistically significant increased risk of re-bleeding associated with resumption. We conducted an updated meta-analysis to determine the risks of recurrent GI bleeding, thromboembolism, and death in patients who resumed OAC compared to those who did not. Materials and methods We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials for new references from January 2014 to September 2017. Randomized controlled trials and observational studies involving adults with OAC-related GI bleeding were included. Risk of bias was assessed using the Cochrane Collaboration's ROBINS-I tool. Pooled relative risk (RR) ratios were calculated using a random-effects model. Results We identified 12 observational studies involving 3098 patients. There was an increased risk of recurrent GI bleeding (RR 1.91, 95% CI 1.47–2.48, I2 = 0%, 11 studies), and a reduced risk of thromboembolism (RR 0.30, 95% CI 0.13–0.68, I2 = 59.8%, 9 studies) and death (RR 0.51, 95% CI 0.38–0.70, I2 = 71.8%, 8 studies) in patients who resumed OAC compared to those who did not. Eleven studies were judged to be at serious risk of bias due to confounding. Conclusions Resuming OAC after OAC-related GI bleeding appears to be associated with an increase in recurrent GI bleeding, but a reduction in thromboembolism and death. Further prospective data are needed to identify patients for whom the net clinical benefit favours OAC resumption and the optimal timing of resumption.

Thalassemia patients have a high cell turnover rate due to chronic hemolysis and ineffective erythropoiesis; therefore, hyperuricemia is anticipated. This study aimed to identify the prevalence of hyperuricemia, gout and nephrolithiasis, conditions associated with serum uric acid (SUA), and urine uric acid excretion (UUA) in thalassemia patients. This was a cross-sectional study in patients aged 15 years or older at Chiang Mai University Hospital. All patients had blood and 24-h urine collection test. We enrolled 112 thalassemia patients in which 67.0% were female, 64.3% had beta thalassemia/Hb E, 76.8% were transfusion dependent, and 59.8% were post splenectomy. The median age was 29 (16-58) years. Mean SUA was 6.7 ± 2.0 mg/dl and hyperuricemia (SUA 6.8 mg/dl) was found in 47 cases (45.2%). Intact spleen (ORs 4.3, 95%CI 1.55-12.50, p = 0.01) and lower FEuric (ORs 2.08, 95%CI 1.35-3.33, p 0.01) were associated with hyperuricemia significantly. Seven (6.3%) had gouty arthritis and nine (8%) had microscopic hematuria, one case being confirmed nephrolithiasis. The mean UUA excretion was 981.3 ± 335.0 mg/day and UUA hyperexcretion ( 700 mg/24 h) was found in 83.3%. UUA hyperexcretion patients had renal hyperfiltration 46%, glomerular dysfunction 84%, and tubular dysfunction 7.7%. From our study, hyperuricemia was found in approximately 40% of thalassemia patients but gouty arthritis occurred only in few patients (6%). This may be explained by urinary uric hyperexcretion which is found in over 80%. The significant risk factors for hyperuricemia were intact spleen and lower fraction excretion of uric acid.

Background Dengue infection patients are presented with acute febrile illness. Clinical presentations may mimic other infections. The serology for definite diagnosis is costly and inaccessible in many hospitals. We sought to identify the clinical features and hematologic parameters from a complete blood count (CBC) which distinguish dengue infection from other causes. Methods This was a retrospective single center study from Chiang Mai University Hospital. All patients who presented with acute fever between September 2013 and July 2015 were included. The diagnosis of dengue infection must be confirmed by serology. The control groups were patients who presented with acute febrile illness without localizing signs. Clinical data and CBC results were reviewed and compared. The Chi-square test was used to compare categorical variables. The CBC parameters were analyzed using the linear mixed model. Results One hundred and fifty-four dengue and 146 control patients were included. Headache, nausea, loss of appetite and bleeding diathesis were significantly symptoms in dengue patients (p 1 on the first 5 days then reversed on day 6 to Day 9 but in non-dengue group, the ratio was always > 1. Conclusion We identified important clinical features and CBC parameters to differentiate dengue patients from other patients who had acute febrile illness from other causes. This identification could be done in local hospitals to give an accurate diagnosis, enabling further investigation to be tailored and treatment commenced earlier.

Establishment and analysis of mean platelet volume (MPV) may be helpful in the discrimination between underproduction or over-destruction of platelets as the causes of thrombocytopenia. The primary objective is to find the cut-off point of MPV for distinguishing causes of thrombocytopenia. The secondary objective is to validate the cut-off value of the MPV by using bone marrow examination. Thrombocytopenic patients were enrolled in a training set and a receiving operating characteristics (ROC) curve was plotted to obtain the cut-off value of MPV. A validation set of patients was recruited to validate the cut-off value. The training set included 240 patients. Half with with underproductive (n = 120) and half with over-destructive thrombocytopenia (n = 120). The best cut-off value of MPV was 8.8 fL. The validation set included 119 patients in total, again in 2 groups, those with underproductive (n = 84) and those with overdestructive thrombocytopenia (n = 35). The sensitivity, specificity, PPV and NPV when MPV ≥ 8.8 fL indicating over-destructive thrombocytopenia were 77%, 89%, 89% and 77%, respectively. MPV is useful for differentiating the cause of thrombocytopenia. The value of MPV ≥ 8.8 fL has acceptable sensitivity and specificity for diagnosis of over-destructive thrombocytopenia.

Cardiovascular complications are the most common cause of death among thalassemia patients in Thailand. In this study, we evaluated the prevalence of cardiac iron overload, cardiovascular complications and the associated risk factors. The information obtained will serve as a guidance for surveillance, prevention and early treatment of the complications. We conducted a cross sectional study of Thai patients with thalassemia attending Chiang Mai University Hospital, Thailand. Cardiac T2* magnetic resonance imaging (CMR T2*) was used to evaluate the myocardial iron deposition and echocardiography was used to evaluate the cardiac function and to identify pulmonary hypertension. Ninety-one patients were included in the study; 64% females with a median age of 31 (16-75) years. Of the total study subjects, 49% had homozygous β thalassemia, 32% had β thalassemia/Hb E disease, and 19% had Hb H disease. Half the participants were transfusion-dependent and 84% had received iron chelation. The CMR T2* showed cardiac iron overload in 10 patients (11%). The maximum ferritin level in the previous 3 years was higher among the patients with cardiac iron overload (6,310 ng/ml) than among the patients without cardiac iron overload (3,352 ng/ml) (p=0.001). Twenty-one patients (23%) had cardiovascular complications. Cardiomyopathy was seen in 8% of patients [17% in patients with transfusion-dependent thalassemia (TDT) and none in patients with non-transfusion-dependent thalassemia (NTDT)] and pulmonary hypertension in 15% of patients (14% in patients with TDT and 16% in patients with NTDT). TDT and cardiac iron overload were significantly associated with cardiomyopathy. No risk factors were found to be significantly associated with pulmonary hypertension. In summary, cardiac iron overload and cardiomyopathy are important complications in TDT while pulmonary hypertension is seen in both TDT and NTDT. Iron chelation and monitoring of serum ferritin level will prevent cardiac iron overload and cardiomyopathy. Interval monitoring with echocardiography will help with early identification of the cardiac complications.

Objectives The primary objective was to determine the prevalence of calreticulin (CALR) mutation in patients with non-JAK2V617F mutated essential thrombocythemia (ET). The secondary objectives were to evaluate the accuracy of CALR mutation analysis by high-resolution melting (HRM) analysis and real-time polymerase chain reaction (PCR) compared with DNA sequencing and to compare clinical characteristics of CALR mutated and JAK2V617F mutated ET. Methods This was a prospective cohort study involving ET patients registered at Chiang Mai University in the period September 2015-September 2017 who were aged more than 2 years, and did not harbor JAK2V617F mutation. The presence of CALR mutation was established by DNA sequencing, HRM, and real-time PCR for type 1 and type 2 mutation. Clinical data were compared with that from ET patients with mutated JAK2V617F. Results Twenty-eight patients were enrolled onto the study. CALR mutations were found in 10 patients (35.7%). Three patients had type 1 mutation, 5 patients had type 2 mutation, 1 patient had type 18 mutation, and 1 patients had novel mutations (c.1093 C-G, c.1098_1131 del, c.1135 G-A). HRM could differentiate between the types of mutation in complete agreement with DNA sequencing. Patients with a CALR mutation showed a significantly greater male predominance and had a higher platelet count when compared with 42 JAK2V617F patients. Discussion and conclusions The prevalence of CALR mutation in JAK2V617F-negative ET in this study is 35.7%. HRM is an effective method of detecting CALR mutation and is a more advantageous method of screening for CALR mutation.

Introduction Bleeding frequency is an important outcome commonly used in haemophilia studies. There is a variation in practice in how bleeding is measured and defined. Aim The primary objective of this study was to determine how investigators define and report bleeding outcome measures. Methods MEDLINE, EMBASE and the CENTRAL were searched from January 1990 to January 2014. We retrieved all published studies that included patients with haemophilia A or B and reported some measures of bleeding. Two reviewers independently performed title and abstract screening, full-text review and data abstraction of the identified studies. Results A total of 118 studies fulfilled the inclusion criteria. Study designs were randomized controlled trials (RCT; 14%), cohort (68%), cross-sectional (5%) and others design (11%). The median duration of follow-up (Q1, Q3) was 20 (7.9, 50) months. We found 10 different bleeding outcomes reported [absolute number of bleeding 60 (50.8%) studies, annualized bleeding rate 60 (50.8%) studies, bleed per month 10 (8.5%) studies and others 11 (9.3%) studies]. Of these, 32 (27%) studies reported only mean or median without dispersion and 33 (28%) studies did not report any measures of central tendency (dispersion). Conclusions There is substantial variation in definitions and measures of bleeding outcomes in the haemophilia literature. This creates difficulty and limitations in comparing the outcomes between studies and in performing meta-analysis. The haemophilia research community needs to develop a consensus on a clear definition of bleeding and how to address the limitations associated with variations in measures of bleeding between centres and studies.

Background Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by proliferation of one or more myeloid lineages. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical Philadelphia chromosome (Ph)-negative MPN that have a Janus Kinase 2 (JAK2) mutation, especially JAK2V617F in the majority of patients. The major complications of Ph-negative MPNs are thrombosis, hemorrhage, and leukemic transformation. Objective To study clinical manifestations including symptoms, signs, laboratory findings, and JAK2V617F mutations of Ph-negative MPN (PV, ET and PMF) as well as their complications. Materials and methods All Ph-negative MPN (PV, ET and PMF) patients who attended the Hematology Clinic at Maharaj Nakorn Chiang Mai Hospital from January, 1 2003 through December, 31 2013 were retrospectively reviewed for demographic data, clinical characteristics, complete blood count, JAK2V617F mutation analysis, treatment, and complications. Results One hundred and fifty seven patients were included in the study. They were classified as PV, ET and PMF for 68, 83 and 6 with median ages of 60, 61, and 68 years, respectively. JAK2V617F mutations were detected in 88%, 69%, and 100% of PV, ET and PMF patients. PV had the highest incidence of thrombosis (PV 29%, ET 14%, and PMF 0%) that occurred in both arterial and venous sites whereas PMF had the highest incidence of bleeding (PMF 17%, ET 11%, and PV 7%). During follow up, there was one ET patient that transformed to acute leukemia and five cases that developed thrombosis (three ET and two PV patients). No secondary myelofibrosis and death cases were encountered. Conclusions Ph-negative MPNs have various clinical manifestations. JAK2V617F mutations are present in the majority of PV, ET, and PMF patients. This study confirmed that thrombosis and bleeding are the most significant complications in patients with Ph-negative MPN.

Cytoreductive therapy, with or without low-dose aspirin, is the mainstay of thrombotic risk reduction in patients with essential thrombocythemia (ET), but the optimal choice of agent remains unclear. The aim of this study was to meta-analyze currently available data comparing anagrelide to hydroxyurea for reduction of rates of thrombosis, bleeding and death among patients with ET. A literature search for randomized, controlled trials comparing anagrelide to hydroxyurea among patients with ET revealed two published studies. Statistical analysis was performed using fixed effects meta-analysis. Rates of thrombosis were similar between patients treated with hydroxyurea vs anagrelide (RR 0.86, 95 % CI 0.64-1.16). Rates of major bleeding were lower in patients treated with hydroxyurea (RR 0.37, 95 % CI 0.18-0.75). Rates of progression to acute myeloid leukemia were not statistically different (RR 1.50, 95 % CI 0.43-5.29). The composite of thrombosis, major bleeding and death favored hydroxyurea (RR 0.78, 95 % CI 0.63-0.97). In conclusion, our analysis supports use of hydroxyurea as a first-line cytoreductive agent for patients with ET, based largely on decreased rates of major bleeding. Anagrelide appears to be equally effective for protection against thrombotic events and may be an appropriate alternative for patients who are intolerant of hydroxyurea.

Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies against factor VIII (FVIII). Spontaneous bleeding in the various sites and severity is the most common clinical presentation. Here, we report a 74-year-old Thai woman with HIV infection who presented with spontaneous ecchymoses. The laboratory revealed isolated activated partial thromboplastin time prolongation with low FVIII activity and a presence of FVIII inhibitor. She was diagnosed with acquired hemophilia A. Corticosteroid monotherapy was the treatment regimen for inhibitor eradication. We demonstrate the clinical course of the rare condition and review the relevant literature.

SummaryGastrointestinal (GI) bleeding commonly complicates anticoagulant therapy. We aimed to systematically review the published literature to determine the risk of thromboembolism, recurrent GI bleeding and mortality for patients on long-term anticoagulation who experience GI bleeding based on whether anticoagulation therapy was resumed. We performed a systematic review of phase III randomised controlled trials and cohort studies in patients with atrial fibrillation or venous thromboembolism who received oral anticoagulant. We searched MEDLINE, EMBASE and CENTRAL (from 1996-July 2014), conferences abstracts (from January 2006-July 2014) and www.clinicaltrials.gov (up to the last week of July 2014) with no language restriction. Two reviewers independently performed study selection, data extraction and study quality assessment. A total of three studies were included in the meta-analysis. The resumption of warfarin was associated with a significant reduction in thromboembolic events (hazard ratio [HR] 0.68, 95 % confidence interval [CI] 0.52 to 0.88, p < 0.004, I2=82 %). There was an increase in recurrent GI bleeding but not statistically significant for patients who restarted warfarin compared to those who did not (HR 1.20, 95 % CI 0.97 to 1.48, p = 0.10, I2 = 0 %). Resumption of warfarin was associated with significant reduction in mortality (HR 0.76, 95 % CI 0.66 to 0.88, p < 0.001, I2 = 87 %). This meta-analysis demonstrates that resumption of warfarin following interruption due to GI bleeding is associated with a reduction in thromboembolic events and mortality without a statistically significant increase in recurrent GI bleeding.Institution where the work was performed: McMaster University, Hamilton, Ontario, Canada.