Weerasak Nawarawong

Splenectomy: a strong risk factor for pulmonary hypertension in patients with thalassaemia

Objective: To determine the association between splenectomy and pulmonary hypertension in patients with thalassaemia with anaemia. Design: Prospective cross-sectional study. Methods: 68 patients with thalassaemia, who had a haemoglobin concentration of less than 100 g/l, were recruited into this study. Echocardiography was performed before clinical data were reviewed. Pulmonary artery pressure was estimated by measuring the systolic transtricuspid pressure gradient from tricuspid regurgitation and adding it to the right atrial pressure, which was estimated by the response of the inferior vena cava to inspiration. Pulmonary hypertension was defined as systolic pulmonary artery pressure > 35 mm Hg. History of splenectomy and other clinical data were compared between patients with and without pulmonary hypertension. Results: 29 patients had pulmonary hypertension and 39 did not. Patients with pulmonary hypertension had significantly more nucleated red blood cells and higher platelet counts, and a higher prevalence of splenectomy (75.8% v 25.6%, odds ratio 9.1, 95% confidence interval 3.0 to 27.7). In multivariate analysis, splenectomy was the only factor significantly related to pulmonary hypertension. Conclusion: Splenectomy is a strong risk factor for pulmonary hypertension in patients with thalassaemia.

Clinical profiles of multiple myeloma in Asia—An Asian Myeloma Network study

The incidence of multiple myeloma (MM) is known to be variable according to ethnicity. However, the differences in clinical characteristics between ethnic groups are not well‐defined. In Asian countries, although the incidence of MM has been lower than that of Western countries, there is growing evidence that MM is increasing rapidly. The Asian Myeloma Network decided to initiate the first multinational project to describe the clinical characteristics of MM and the clinical practices in Asia. Data were retrospectively collected from 23 centers in 7 countries and regions. The clinical characteristics at diagnosis, survival rates and initial treatment of 3,405 symptomatic MM patients were described. Median age was 62 years (range, 19–106), with 55.6% of being male. Median overall survival (OS) was 47 months (95% CI 44.0–50.0). Stem cell transplantation was performed in 666 patients who showed better survival rates (79 vs. 41 months, P < 0.001). The first‐line treatments of 2,970 patients were analyzed. The overall response rate was 71% including very good partial response or better in 31% of the 2,660 patients those were able to be evaluated. New drugs including bortezomib, thalidomide, and lenalidomide were used in 36% of 2,970 patients and affected OS when used as a first‐line treatment. Am. J. Hematol. 89:751–756, 2014.

Management of multiple myeloma in Asia: resource-stratified guidelines

Treatment of multiple myeloma has undergone substantial developments in the past 10 years. The introduction of novel drugs has changed the treatment of the disease and substantially improved survival outcomes. Clinical practice guidelines based on evidence have been developed to provide recommendations on standard treatment approaches. However, the guidelines do not take into account resource limitations encountered by developing countries. The huge disparities in economy, health-care infrastructure, and access to novel drugs in Asian countries hinder the delivery of optimum care to every patient with multiple myeloma in Asia. In this Review we outline the guidelines that correspond with different levels of health-care resources and expertise, with the aim to unify diagnostic and therapeutic guidelines and help with the design of future studies in Asia.

The rate of fibrinopeptide B release modulates the rate of clot formation: a study with an acquired inhibitor to fibrinopeptide B release

Summary An asymptomatic 50‐year‐old male with a gamma globulin paraprotein was found to have prolonged prothrombin time, activated partial thromboplastin time, and thrombin time but a normal reptilase time. The prolonged clotting times were not the result of a factor deficiency because they were not corrected by the addition of normal plasma. Instead, this patient had an antibody that delayed thrombin‐mediated fibrinopeptide B release thereby producing an apparent dysfibrinogenaemia. His isolated IgG prolonged the thrombin clotting time of both normal plasma and fibrinogen. Precincubation of his IgG with fibrinopeptide B, but not with fibrinopeptide A or thrombin, decreased its ability to prolong the thrombin clotting time. The patients purified IgG but not control IgG delayed thrombin‐mediated fibrinopeptide B release from fibrinogen without affecting the release of fibrinopeptide A. These studies define a novel, clinically silent dysfibrinogenaemia due to an antibody that delays thrombin‐mediated fibrinopeptide B release from fibrinogen thereby markedly prolonging the clotting times.

Inferior progression-free survival for Thai patients with diffuse large B-cell lymphoma treated under Universal Coverage Scheme: the impact of rituximab inaccessability

The impact of health insurance with inequitable rituximab coverage on the survival of patients with diffuse large B-cell lymphoma (DLBCL) has never been reported. We conducted a nationwide multicenter analysis on the outcome of 553 adult patients consecutively diagnosed with DLBCL between July 2003 and June 2006, in whom treatment cost was reimbursed under the Civil Servant Medical Benefit Scheme (CSMBS) (n =201) or the Universal Coverage Scheme (UCS) (n =352). The international prognostic index was comparable between the two payment groups. Rituximab-based therapy was administered in 45.3% and 3.1% of CSMBS and UCS patients, respectively (p <0.001). With a median follow-up of 24.6 months, the 6-year progression-free survival (PFS) was superior for CSMBS patients (34.2 vs. 23.2%, p =0.005). “Not treated with rituximab-based therapy” was the strongest adverse prognostic feature indicating a short PFS (hazard ratio 2.1, p <0.001). It is concluded that lack of access to rituximab is the principal factor accounting for the inferior PFS observed in Thai patients with DLBCL who are treated under the UCS.

Benefits of chronic blood transfusion in hemoglobin E/β thalassemia with pulmonary arterial hypertension

Objective The aim of the research reported here was to compare pulmonary artery systolic pressure (PASP) and 6-minute walk distance after 1 year of follow-up in hemoglobin E/β thalassemia (E/β-Thal) with pulmonary arterial hypertension (PAH) patients who received chronic blood transfusions versus those who received occasional transfusions. Methods A nonrandomized clinical trial was conducted at the Hematological Outpatient Clinic of Chiang Rai Hospital, Thailand. All adult cases of E/β-Thal with PAH (defined as PASP >35 mmHg by Doppler echocardiography) were evaluated and followed for the next 12 months. The patients were classified into two groups by patient preference. Group 1 patients received chronic blood transfusions – one to two units of leukocyte-poor packed red cells every 2–4 weeks – over 1 year to maintain pre-transfusion hemoglobin levels of ≥7.0 g/dL. Group 2 patients received occasional transfusions over the course of 1 year, with more than 4 weeks between transfusions. All patients were treated with iron chelation when serum ferritin levels were ≥1,000 μg/dL. PASP and the 6-minute walk distance were evaluated at baseline and at 6 and 12 months. Propensity score adjustment was used to control for confounding by indication and contraindication. Multivariable regression analysis was used to evaluate the effects of chronic blood transfusion. Results There were 16 (53.3%) patients in Group 1 and 14 (46.7%) in Group 2. At 12 months, patients in Group 1 had a greater reduction in PASP than those in Group 1 (adjusted mean difference, −16.83; 95% confidence interval, −26.35 to −7.32; P=0.001). The 6-minute walk distance at 12 months in Group 1 patients was greater than that in Group 2 patients (adjusted mean difference, 46.55; 95% confidence interval, 18.08 to 75.02; P=0.001). Conclusion This study found evidence that chronic blood transfusions may have beneficial effects in PAH in thalassemia patients over 1 year.

Younger age at presentation of acquired haemophilia A in Asian countries: a single‐centre study and systematic review

Acquired haemophilia A is a rare bleeding disorder caused by autoantibodies against factor VIII (FVIII). There is a scarcity of acquired haemophilia A studies from Asian countries. The aim of this study was to evaluate clinical characteristics and outcomes of acquired haemophilia A among Asian populations. Data were collected from a retrospective case series and combined with a systematic review. The case series included all patients with acquired haemophilia A from 1999 to 2012 at Chiang Mai University Hospital. The systematic review searched MEDLINE and EMBASE databases for relevant keywords. A total of 111 patients were reviewed in this study (including 26 patients from the present series). There were 56 male (50.5%) and 55 female (49.5%) patients. We compared the demographic data with ECAH2 and UKHCDO studies. The weighted mean (SD) age at diagnosis was 58.10 (16.96) years compared with 75.70 (14.47) years in the European series (absolute difference 17.6 years, 95% confidence interval [CI] 14.20–20.99, P = 0.025). The mean (SD) FVIII activity was 2.97 (3.81) IU dL−1 and the mean (SD) FVIII inhibitor titre was 26.35 (399.16) BU mL−1. Fifty‐six per cent of the patients underwent immunosuppression with steroids alone. The pool complete remission rate was comparable to the European studies, at 67.2% vs. 66.6% respectively (absolute difference 0.7, 95% CI 0.18 to 1.22, P = 0.99). This study reveals a novel finding of younger age at diagnosis of acquired haemophilia A among Asian patients.

Modification of Solid Phase Red Cell Adherence Assay for the Detection of Platelet Antibodies in Patients With Thrombocytopenia

Platelet refractoriness is caused by HLA antibodies and platelet-specific antibodies. Current methods used to detect antiplatelet antibodies have limitations. Solid phase red cell adherence (SPRCA) lacks sensitivity and requires a second assay using chloroquine-treated intact platelets to specify the response due to anti-HLA. We modified SPRCA by using 2 types of antihuman platelet antibodies with different specificities toward platelet lysate and tested samples from 361 patients (69 with unexplained thrombocytopenia and 292 with poor response to platelet transfusions not explicable by alloimmunization or the clinical situation) and 50 from healthy volunteers. Our method compared favorably with platelet suspension direct immunofluorescence. All samples from healthy volunteers were negative; of the samples from the patient population, 240 were positive (147 samples had only antiplatelet and 3 samples had only anti-HLA antibodies). This modified technique had a sensitivity of 98% and a specificity of 91%.

Recent advances in the management of multiple myeloma: clinical impact based on resource-stratification. Consensus statement of the Asian Myeloma Network at the 16th international myeloma workshop

Abstract Predicated on our improved understanding of the disease biology, we have seen remarkable advances in the management of multiple myeloma over the past few years. Recently approved drugs have radically transformed the treatment paradigm and improved survivals of myeloma patients. The progress has necessitated revision of the diagnostic criteria, risk-stratification and response definition. The huge disparities in economy, healthcare infrastructure and access to novel drugs among different Asian countries will hinder the delivery of optimum myeloma care to patients managed in resource-constrained environments. In the light of the tremendous recent changes and evolution in myeloma management, it is timely that the resource-stratified guidelines from the Asian Myeloma Network be revised to provide updated recommendations for Asia physicians practicing under various healthcare reimbursement systems. This review will highlight the most recent advances and our recommendations on how they could be integrated in both resource-abundant and resource-constrained facilities.

Hypercoagulable state as demonstrated by thromboelastometry in hemoglobin E/beta-thalassemia patients: Association with clinical severity and splenectomy status

INTRODUCTION Patients with hemoglobin E/beta-thalassemia disease (E/β) are at risk of thromboembolism. Rotational thromboelastometry (ROTEM®) can be used to determine a hypercoagulable state. The objective was to describe the hemostatic and thromboelastometric changes in pediatric patients with E/β with different clinical severity, in comparison with healthy children as controls. MATERIALS AND METHODS Fifty-three pediatric patients with E/β and 21 healthy children were enrolled. The clinical severity of E/β was categorized by using the clinical severity scores. All subjects were tested for complete blood count, protein C activity (PC), total protein S (PS), antithrombin (AT), D-dimer and fibrinogen (Fib) levels and thromboelastometry, measured by ROTEM®. RESULTS The levels of PC (65.7 vs 118.5%), PS (46.8 vs 78.4%), AT (95.7 vs 105.7%) and Fib (217 vs 294 mg/dL) were significantly lower, and the platelet count (PLT) was significantly higher in the patient group than the controls. The maximum clot firmness (MCF) of patients with moderate disease who were previously splenectomized (seven patients) and patients with severe disease (nine patients) were higher than patients who had intact spleen with moderate disease, patients with mild disease and controls (P<0.05). Only PLT had significant correlation with MCF (P<0.05). CONCLUSIONS Hypercoagulable state was demonstrated by ROTEM® in patients with E/β with severe disease and who were previously splenectomized. The hypercoagulable state was associated with the higher numbers of PLT rather than the decrease of PC, PS, and AT.