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To find the prevalence and risk factors of pulmonary hypertension (PHT) in adult patients with hemoglobin E/β-thalassemia disease (E/β-Thal).One hundred and ten clinically stable E/β-Thal outpatients, sixty-one of whom had undergone splenectomy, were prospectively studied using their clinical profiles, selected blood tests, chest roentgenogram, and transthoracic echocardiogram. Based on the pulmonary artery systolic pressure (PASP) values estimated by the echocardiogram of ≥36 mmHg, they were dichotomized into those with (PHT+) and without (PHT-) PHT.PHT was found in 41 (37.3%) patients without gender preponderance. It was not due to the left heart and was not severe (PASP = 46.3 ± 10.4 mmHg). PASP was higher in splenectomized patients (48.0 ± 11 vs. 40.3 ± 4.7 mmHg (P = 0.004)). PHT was found in 32 of 61 (52.5%) splenectomized patients, mostly (53%) in the second decade, and rarely (6.3%) during the first 5 yr after splenectomy. PHT+ patients had more hemolysis (P = 0.001-0.04 depending on the parameters), more asplenic cases (P 0.001), and higher serum soluble vascular cell adhesion molecule-1 (sVCAM-1) and high-sensitivity C-reactive protein levels (P = 0.004 and 0.008, respectively). Strong risk factors by univariate analysis were serum sVCAM-1 levels ≥1600 ng/mL, serum cell-free Hb ≥ 3 mg/dL, asplenia, and amount of NRBCs/100 WBCs40.Prevalence of PHT in E/β-Thal patients was 37.3% without gender preponderance. Those with severe hemolysis and asplenia invariably had severer PHT. Strong risk factors were asplenia and associated markedly elevated values of sVCAM-1, cell-free Hb, and NRBCs in blood.

Therapy related myelodysplastic syndrome (t-MDS) and secondary acute myeloid leukemia (AML) are seriously late complications of the use of alkylating agents, topoisomerase II inhibitors, and other ...

Four patients with acquired amegakaryocytic thrombocytopenic purpura, who had failed corticosteroids, intravenous immunoglobulin and cyclophosphamide therapy, were treated with antithymocyte globulin, followed by cyclosporin. Three patients achieved complete remission in 28-178 days and the response duration was 16-60 months from the beginning of treatment. One patient achieved a partial response for 2 months followed by myelodysplastic syndrome 5 months later. He died in 9 months due to intracerebral bleeding. Marrow cytogenetics showed 47, XY, +21.

Venous thromboembolism (VTE) has been reported to be less common among Thais than Caucasians. Whether this observation reflects genetic or environmental factors, or both, is uncertain. To identify genetic and acquired risk factors of Thai patients with VTE, we enrolled in the study 105 consecutive Thai patients (34 men, 71 women) who had an objectively confirmed history of VTE. A complete clinical summary was obtained from each patient, with emphasis on personal and family history of VTE, as well as circumstantial vascular risk factors (surgery, immobilization, pregnancy, postpartum condition, trauma, oral contraceptive use, and malignancy). Of the 105 patients, 19% were found to have a malignancy. The mean age at the time of the first thrombotic episode was 52.1 years (range, 29-76 years), compared with 42.6 years (range, 17-82 years) for the patients without malignancy. Of the 85 patients without malignancy, 12.3% had protein S deficiency, 8.9% had protein C deficiency, 4.7% had antithrombin deficiency, 10.4% had antiphospholipid antibody, 30.4% had an elevated factor VIII level, 26.8% had an elevated factor XI level, 5.3% had hyperhomocysteinemia, and 16.5% were on oral contraceptives before the thrombotic episode. Factor V Leiden, the G20210A prothrombin gene mutation, and homozygosity for the C677T methylenetetrahydrofolate reductase (MTHFR) gene variant were not found. The VTE in 7.1% of the patients was considered to be secondary to recent surgery, trauma, and/or immobilization. Compared with studies of Caucasian patients, there were significant differences in the risk factors for VTE, with protein S deficiency and protein C deficiency being more common in the Thai patients. In contrast, factor V Leiden, the G20210A prothrombin gene mutation, and the C677T MTHFR gene mutation are not genetic risk factors among Thai patients with VTE. Malignancy and the use of oral contraceptives were the most common acquired risk factors for VTE in the Thai patients.

Increased frequency of thrombosis has been observed in patients with hemoglobin E/beta-thalassemia (Hb E/beta-thal) disease, particularly those who have previously been splenectomized. We compared various hemostatic and thrombotic markers in blood from 15 Hb E/beta-thal patients who were not splenectomized (NS), 15 who had been splenectomized (S), and 15 normal controls (NC). Levels of plasma thrombin-antithrombin, beta2 thromboglobulin, C-reactive protein, tissue plasminogen activator antigen were significantly higher in the S group than in either the NS or the NC groups, and levels of prothrombin fragment 1.2 were significantly higher in the S than in the NC group. Levels of plasminogen activator inhibitor-1 antigen were significantly higher in the S than in the NS group. Levels of protein C, protein S, antithrombin, and fibrinogen were significantly lower in the S and NS groups than in the NC group. Plasma lipoprotein(a) levels in the S and NS groups were not statistically different from NC. Our findings indicated that there is evidence of chronic low-grade coagulation and platelet activation, chronic low-grade inflammation, endothelial cell injury, impaired fibrinolysis, and decreased naturally occurring anticoagulants in splenectomized Hb E/beta-thal patients. These changes may account for the increased risk of thrombosis in these patients.

Our aim was to study the cause and describe the clinical features of pulmonary arterial hypertension (PHT) in splenectomized beta-thalassemia (beta-Thal) patients. Ten splenectomized beta-Thal patients with systolic pulmonary artery (PA) pressure >30 mm Hg were evaluated by echocardiography, right-heart catheterization, and pulmonary angiography. Five of these patients later underwent hemodynamic studies. Echocardiography and pulmonary angiography on the 10 patients showed normal values of left ventricular systolic function and no findings of acute or chronic pulmonary embolism. Hemodynamic evaluation showed very high PA pressures associated with markedly increased pulmonary vascular resistance indices (PVRIs). Hematological evaluation of the 10 patients showed marked anemia, markedly increased numbers of nucleated red blood cells (nRBCs), and serum ferritin. Mean platelet count, plasma beta2 thromboglobulin, and thrombin-antithrombin III complex levels were significantly increased. It was concluded that PHT can be found in splenectomized beta-Thal patients. Features associated with PHT were female sex, hemoglobin E/beta-Thal, status many years postsplenectomy, marked anemia, markedly increased nRBC count, thrombocytosis, and very high serum ferritin levels. PHT was not due to pulmonary emboli. Our findings suggested that severe PHT was due to increased PVRI from thrombotic pulmonary arteriopathy, likely from chronic low-grade hypercoagulability and platelet activation after splenectomy.

Small pulmonary arterial thromboses can occur following splenectomy of patients with haemoglobin E/beta-thalassaemia (Hb E/beta-thal). We compared plasma markers of coagulation activation in vivo and red blood cell (RBC) markers of procoagulant activity in 15 Hb E/beta-thal patients who were not splenectomized (NS), 15 who had been splenectomized (S), and 15 normal controls (NC). Levels of plasma thrombin-antithrombin III complex (TAT) were significantly higher in the S group than in either the NS or the NC groups, and levels of prothrombin fragment 1.2 (F 1.2) were significantly higher in the S than in the NC group. Diluted Russell's viper venom clotting times were significantly shorter when RBCs from group S patients were added to the assay compared with RBCs from the NC group. Phosphatidylserine (PS) expression (% of annexin V-positive RBCs) on the outer leaflet of RBC membrane of both 'larger'- and 'smaller'-sized RBCs was significantly higher for the S than the NC group. The RBC PS expression of the S and the NS groups, respectively, accounted for 25 x 3% (P = 0 x 174) and 6.3% (P = 0 x 675) of the variation in plasma TAT levels. Our findings indicated that, when compared with NC, splenectomized patients with Hb E/beta-thal were in a chronic low-grade hypercoagulable state associated with increased numbers of circulating PS exposed RBCs. This condition may have a role in the risk of these patients for pulmonary arterial thromboses.

We investigated the prevalence of a genetic variation in the factor V gene (G1691A Leiden mutation) and the prothrombin gene (G20210A) using polymerase chain reaction techniques in samples from 500 normal Thai population and among 50 unselected Thai patients with an objectively confirmed history of deep venous thrombosis. The prevalence of factor V Leiden and the prothrombin G20210A gene mutation in a group of 500 healthy controls was 0.2% in both groups (allele frequency of 0.1%). Of the 50 adult patients studied, none was a carrier of factor V Leiden or the prothrombin G20210A gene mutation. Our findings confirm that the prevalence of factor V Leiden and prothrombin G20210A gene mutation is lower among Asians than Caucasians and that the distribution of factor V Leiden is similar to that of the prothrombin G20210A variant. The low prevalence of these two mutations can, at least in part, account for the lower frequency of deep venous thrombosis reported in the Thai population. Screening for factor V Leiden and prothrombin gene mutation is of limited benefit and may not be cost-effective in Thai patients with the first episode of deep venous thrombosis.

The relationship between asplenia and thrombophilia in β-thalassemia disease patients is not yet completely understood. One hundred and ten adult hemoglobin (Hb) E/β-thalassemia (E/β-Thal) disease outpatients, dichotomized according to the presence or absence of the spleen, were prospectively studied for evidence of intravascular hemolysis (IVH) and vascular endothelial cell (EC) activation. Biomarkers of IVH (serum cell-free Hb), EC [soluble E-selectin (sE-selectin) and soluble vascular cell adhesion molecule 1 (sVCAM-1)], platelet and EC [soluble P-selectin (sP-selectin)], inflammation [high-sensitivity C-reactive protein (hs-CRP)], and coagulation [thrombin-antithrombin complexes (TAT)] activation, as well as other selected blood tests were determined. The 61 splenectomized patients had a more severe hemolytic disease and higher levels of cell-free Hb and ferritin (p = 0.003), sE-selectin, sP-selectin, hs-CRP, and TAT (p < 0.05). However, serum levels of sVCAM-1 were not different between the two groups. The findings suggested IVH and EC activation. Together with chronic iron overload and chronic low-grade inflammation activation, the findings extend our understanding of the mechanism of thrombophilia in splenectomized E/β-Thal disease patients.

Aged or abnormal red blood cells with exposed phosphatidylserine (PSRBCs) are cleared from the circulation by splenic macrophages. In asplenic patients, other mononuclear phagocytic cells in tissues and in circulation may function in this capacity. To better understand these changes and the relationship among splenic status, PS-RBCs, blood monocytes, and serum tumor necrosis factor (TNF-α), a product of mononuclear phagocyte activation, patients with hemoglobin E/β-thalassemia (E/β-Thal) were studied. Whole blood of 20 nonsplenectomized, 20 splenectomized E/β-Thal patients, and 20 healthy subjects was assayed for PS-RBCs; for monocytes, activated monocytes, and monocyte response to lipopolysaccharide stimulation; and serum was assayed for TNF-α. Asplenic E/β-Thal patients had significantly increased (P < 0.05) amounts of PS-RBCs, monocytes, activated monocytes, and levels of serum TNF-α. The amount of PS-RBCs correlated with levels of serum TNF-α, but the amount of activated monocytes did not correlate with either the amount of PS-RBCs or levels of serum TNF-α. Monocyte response to lipopolysaccharide stimulation in asplenic patients was not as efficient as in the other patients or in normals (77 vs. 404, and 304 folds increment, respectively). The results suggest that splenectomy in E/β-Thal patients led to an increased amount of PSRBCs and activation in the mononuclear phagocytic system.

Background Thalidomide based regimen is an effective and well tolerated therapy in multiple myeloma (MM) patients, however, there were a small number of studies written about the results of thalidomide therapy in non-transplant MM patients. We therefore conducted a retrospective study of 42 consecutive patients with newly diagnosed and relapsed/refractory MM treated with thalidomide- based induction regimens followed by thalidomide maintenance therapy. Results Induction regimens with thalidomide and dexamethasone, and the oral combination of melphalan, prednisolone and thalidomide were administrated in 22 and 16 patients, respectively. The remaining 4 patients received other thalidomide- containing regimens. Twenty-nine patients received thalidomide as a salvage regimen. Twenty-three out of 26 patients achieving complete remission (CR) and very good partial remission (VGPR) received thalidomide maintenance. Of the 41 evaluable patients, median time of treatment was 21 months (3- 45 months), ORR was 92.7% with a 63.4% CR/VGPR. With a median follow up of 23 months, 3-year- PFS and 3-year-OS were 58.6 and 72.6%, respectively. Median time to progression was 42 months. While 3-year-PFS and 3-year-OS in non-transplant patients receiving thalidomide maintenance therapy were 67 and 80%, respectively. Conclusions Prolonged thalidomide therapy enhanced survival rate and less frequently developed serious toxicity in non-transplant multiple myeloma patients.

Acute myeloid leukemia (AML) is the heterogeneous disease. As per previous reports, there are some differences in clinical features and cytogenetic biomarkers of AML among different ethnic backgrounds. Therefore, we conducted a retrospective study to analyze clinical outcomes and predictive factors of Thai AML patients receiving chemotherapy treatment.The authors performed a retrospective analysis of 106 adults with newly diagnosed de novo AML at Ramathibodi Hospital between 2003 and 2007. Of 101 patients with non- M3 subtype, the patients received induction and consolidation chemotherapy with anthracyclin plus cytarabine based regimens (3 + 7). All patients achieving complete remission (CR) were treated with intensive chemotherapy using intermediate dose cytarabine plus anthracyclin based protocol. All patients with M3 subtype, the induction chemotherapy consisted of a combination of all-trans retinoic acid (ATRA) and anthracyclin. All patients achieving complete remission (CR) were treated with three courses of mitoxantrone as consolidation chemotherapy, followed by maintenance chemotherapy with methotrexate, etoposide and ATRA.Of the 106 patients, median age was 43.5 years (15-73 years) and 19 (17.9%) were older than 60 years. Fifty-six patients (52.8%) were female. Common subtypes were M4 (28.3%), M1 (26.4%) and M2 (20.8%). Of the 95 patients who were performed with cytogenetic analysis, 55 (58%) had abnormal karyotype. AML with recurrent cytogenetic translocations, complex chromosome, trisomy 8, polyploidy, del 5q and del 7q were found in 16.8, 6.3, 5.3, 5.3, 2.1 and 3.2%, respectively. Most patients (70.5%) had intermediate-risk cytogenesis. Eighty patients (75.5%) were treated with idarubicin and cytarabine induction regimen. Of the 96 evaluable patients, 60 (62.5%) achieved complete remission (CR), 38 (39.6%) with the first course of chemotherapy. Median time to CR was 54 days (25-168 days). The CR rate was 78.6% for the good-risk cytogenetic group, 67.2% for the intermediate- risk cytogenetic group, and 37.5% for the poor-risk cytogenetic group. Median follow-up time was 10.4 months, 5-year-DFS and 5-year-OS were 41 and 22.2%, respectively. Patients with poor-risk cytogenetic factors had significantly lower CR rate (p = 0.021). The CR status significantly predicted OS (p0.001).The overall complete remission rate of Thai AML patients is in 60%. Only a small proportion of the presented patients have long-term DFS and OS, the significant factor for predicting survival of Thai AML patients is the complete remission status. Poor-risk cytogenetic factors are associated with poor treatment outcomes.

The mechanism of anemia in severe falciparum malaria is still not completely understood. The purpose of this study was to determine whether apoptosis in the erythroid lineage causes anemia in falciparum malaria. Bone marrow aspirated from 8 severe falciparum malaria patients, 3 normal volunteers and 5 retrospective normal bone marrow smears were investigated. By light microscopic study, 5 of 8 hyperparasitemic patients had hypocellular bone marrows and erythroid hypoplasia, whereas the other 3 patients had normal cellularity. The mean myeloid : erythroid ratio of these 5 patients was significantly (por = 0.05) higher than normal. Apoptosis of bone marrow nucleated cells (BMNC) could be determined from the exposure of phosphatidylserine (PS) on the cell membrane but not DNA fragmentation (180-250 bp) or ultrastructural morphology. The percentages of apoptotic BMNC and apoptotic erythroid cells in bone marrow from each patient and controls varied from low to high, and were not associated with parasitemia. This study suggests that destruction of erythroid lineage, particularly through apoptosis regulation, cannot solely account for anemia in falciparum malaria.

Chronic transfusion of packed red blood cells, in addition to other ongoing treatment with warfarin, acetyl salicylic acid, desferrioxamine, and other supportive measures, was given to a splenectomized hemoglobin E/β-thalassemia woman with pulmonary arterial hypertension (PHT). Serial measurements of plasma thrombin-antithrombin III complex (TAT) levels and right-sided cardiac catheterization were used to monitor changes after treatment. Reduction of plasma TAT levels from 7.5 to 3.8 μg/L (normal, 3 ± 2.4 μg/L), pulmonary vascular resistance (PVR) from 553.8 to 238.6 dyne.sec.cm-5 (normal, 67 ± 30 dyne.sec.cm-5), and mean pulmonary arterial pressure from 51 to 32 mm Hg (normal, 9 to 19 mm Hg) occurred in tandem. Normalization of blood hypercoagulability as reflected in plasma TAT level by chronic blood transfusion was the likely basis for improvement of increased PVR, being secondary to thrombotic pulmonary arteriopathy and subsequently PHT. (Blood. 2004;103: 2844-2846)

Small pulmonary arterial thromboses can occur following splenectomy of patients with haemoglobin E/beta-thalassaemia (Hb E/beta-thal). We compared plasma markers of coagulation activation in vivo and red blood cell (RBC) markers of procoagulant activity in 15 Hb E/beta-thal patients who were not splenectomized (NS), 15 who had been splenectomized (S), and 15 normal controls (NC). Levels of plasma thrombin-antithrombin III complex (TAT) were significantly higher in the S group than in either the NS or the NC groups, and levels of prothrombin fragment 1.2 (F 1.2) were significantly higher in the S than in the NC group. Diluted Russell's viper venom clotting times were significantly shorter when RBCs from group S patients were added to the assay compared with RBCs from the NC group. Phosphatidylserine (PS) expression (% of annexin V-positive RBCs) on the outer leaflet of RBC membrane of both 'larger'- and 'smaller'-sized RBCs was significantly higher for the S than the NC group. The RBC PS expression of the S and the NS groups, respectively, accounted for 25 x 3% (P = 0 x 174) and 6.3% (P = 0 x 675) of the variation in plasma TAT levels. Our findings indicated that, when compared with NC, splenectomized patients with Hb E/beta-thal were in a chronic low-grade hypercoagulable state associated with increased numbers of circulating PS exposed RBCs. This condition may have a role in the risk of these patients for pulmonary arterial thromboses.

Background Hydroxyurea at a relatively low dose is frequently prescribed to induce hemoglobin F production in patients with sickle cell and β-thalassemia diseases because of its good efficacy and safety profiles. However, a potentially fatal gastrointestinal ulceration was recently found and herein reported. Case presentation A thirty-seven-year-old man with transfusion dependent hemoglobin E/β-thalassemia disease was treated with hydroxyurea to induce hemoglobin F production since 2007 without incident. From 2008 to April 2010, episodes of hematochezia, mucous diarrhea and epigastric pain intermittently manifested. Four colonoscopies done during the period repeatedly showed ulcerative lesions from the terminal ileum to the ascending colon with a non-specific histo-pathologic finding. Subsequently, ulcerative lesions also developed at the pharynx, histo-pathologic findings of which were not different from those in the colon. These ulcerative lesions resolved within a month after discontinuing hydroxyurea in April 2010 and have not recurred since. Conclusion The findings suggested role of hydroxyurea in the pathogenesis of these ulcers, and that it must be immediately discontinued to prevent further damage to the digestive mucosa.

Introduction Pulmonary hypertension (PHT) associated with thalassemia hemoglobinopathy is now an accepted clinical entity. Due to a high prevalence of thalassemia hemoglobinpathy worldwide, it is the most common entity of PHT. Despite the commonness, its pathogenesis is not yet completely understood. Although asplenia is a known risk factor, PHT does not develop in all splenectomized patients. The present study was therefore done to search for other associated features. Patients and Methods Sixty-one clinically stable splenectomized hemoglobin E/β-thalassemia disease (E/β-Thal) adult outpatients, on no medication aside from folic acid and who received no blood transfusion in the preceding 4 weeks, were prospectively studied. All gave written informed consent, and study protocol was approved by the institution ethics committee on studies in humans (#0774/2548). Transthoracic echocardiogram was used to evaluate cardiac function and to estimate pulmonary artery systolic pressure (PASP). PHT was defined as an estimated PASP ≥36 mmHg. Clinical features and laboratory data were dichotomized according to the presence (PHT+) or absence (PHT-) of PHT, and statistical analysis was done by STATA version 10 (Stata Corp, Texas), considering a P value

The effect of splenectomy on pulmonary function test (PFT) and pulmonary hypertension (PH) in thalassemia remains unclear. We aimed to investigate PFT and their association with PH in patients with hemoglobin E/β-thalassemia stratified by their splenic status. Thirteen splenectomized patients (SP) and 12 non-splenectomized patients (NSP) were compared regarding to the PFT abnormalities and PH (mean pulmonary artery pressure from right-heart catheterization ≥25 mmHg or estimated systolic pulmonary artery pressure from echocardiography ≥40 mmHg). Eleven (84%) SP and 9 (75%) NSP had restrictive impairment (RI). Of these, more patients having severe RI in SP than in NSP (8 vs 2, P=0.035). FVC and PaO2 were lower in SP than in NSP (66±15% vs 77±12%, P=0.043, and 79.38±1.6 mmHg vs 98.83±6.2 mmHg, Pvs 64±15%, P=0.036). Seven (54%) SP who developed PH had a longer time interval between splenectomy and the onset of PH than those who did not (17±4.9 years vs 9.8±6.1 years, P=0.04). In conclusion, greater severity of extrapulmonary restrictive impairment and hypoxemia were more common in SP. These patients developed PH as a late complication unrelated to hypoxemia and PFT parameters. 因脾脏切除而对肺功能测试(PFT)以及地中海贫血症中肺动脉高压 (PH)情况造成的影响，尚不明确。我们旨在通过对血红蛋白E/β-地中海贫血症的患者进行脾脏位置的分级来探查肺功能测试(PFT)和肺动脉高压 (PH)之间的相关性。十三位脾切除患者(SP)和十二位未切除脾脏的患者(NSP)参与了有关肺功能测试(PFT)和肺动脉高压 (PH)(肺动脉高压是指从右心房导管术测量的肺动脉平均压力≥25 mmHg或者由超声心动图所估计的收缩期的肺动脉平均压力≥40 mmHg)的对比检查。十一位脾切除患者(SP)(84%)和九位未切除脾脏的患者(NSP)(75%)显现出了限制性的障碍 (RI)。毫无疑问，脾切除患者(SP)对于未切除脾脏的患者(NSP)表现出了更严重的限制性障碍(RI)(8 比2, P=0.035)。脾切除患者(SP)比未切除脾脏的患者(NSP)表现出更低的肺活量最大值及动脉氧分压值(相对应地，66±15% 比77±12%, P=0.043, 79.38±1.6 mmHg 比98.83±6.2 mmHg, P

Abstract 2156 Introduction: Clinically significant pulmonary arterial hypertension (PAH) has been reported in splenectomized hemoglobin E/β-Thalassemia patients. Like primary PAH, the underlying basis is hypercoagulability related thrombotic pulmonary arteriopathy, which results in an increased pulmonary vascular resistance. In the non-splenectomized counterparts with no clear evidence of hypercoagulability only mild PAH is found. To evaluate role of splenomegaly and the accompanying increased blood volume in the pathogenesis of PAH in this group of patients, we studied the relationship between spleen volume and PA pressure. Patients and Methods: Nineteen clinically stable hemoglobin E/β-Thalassemia outpatients, on no medication aside from folic acid and who received no blood transfusion in the preceding 4 weeks were first analyzed in this ongoing study. All gave written informed consent, and study protocol was approved by the institution ethics committee on studies in humans (ID 07–53-01). PA pressure (PAP) was estimated by a single echocardiologist (T.Y.) using Philips iE33 echocardiographic system with a S5 probe (Philips Medical Systems, Andover, MA). Spleen volume was determined by CT scan with non-contrast, 320-slice, 3 mm axial cut (Aquilion one, Toshiba, Japan). Statistical analysis of clinical and laboratory data was done by SPSS version 18 (SPSS Inc, Chicago, Ill), considering a P value Conclusions: Non-splenectomized patients with hemoglobin E/β-Thalassemia have elevated PAP in proportion to spleen size, likely secondary to elevated blood volume. This situation is distinct from the pathologic PAH that results from increased pulmonary vascular resistance in splenectomized patients. Disclosures: No relevant conflicts of interest to declare.

Abstract 2014 Poster Board I-1036 Introduction: Clinical manifestations of blood hypercoagulability, such as pulmonary arterial hypertension (PAH) and ischemic stroke, are well known in patients with thalassemia. We herein present evidence that the hypercoagulable state in β-Thalassemia disease patients is to a significant extent the result of prior splenectomy. Patients and Methods: One hundred and ten clinically stable hemoglobin E/β-Thalassemia outpatients, on no medication aside from folic acid and who received no blood transfusion in the preceding 4 weeks were studied. All gave written informed consent, and study protocol was approved by the institution ethics committee on studies in humans (#0774/2548). Echocardiogram was used to estimate systolic PA pressure (SPAP). Clinical features and laboratory data were stratified according to the presence or absence of the spleen, and statistical analysis was done by STATA version 10 (Stata Corp, Texas), considering a P value Results: Of the 110 patients, 61 were asplenic and females comprised 51% in both groups. Selected statistically significant results are shown in the table . Results Asplenic (61 Patients) Non-splenectomized (49 Patients) P value Age at 1st transfusion (median) 4.7 years 17 years Total transfusions (median) 35 units PRBC 13 units PRBC 0.005 Systolic pulmonary artery pressure 37.1 +/- 14.6 mm Hg 28.8 +/- 7.6 mm Hg Cardiomegaly 50.9% 27.3% 0.013 Extramedullary hematopoiesis 50.9% 27.3% 0.013 RBC count 3.19 +/- 0.57 × 106/μL 3.87 +/- 1.09 × 106/μL Corrected reticulocyte count (median) 5.2% 1.4% Nucleated RBC (median) 581/100 WBCs 5/100 WBCs Corrected WBC count 9.72 +/- 4.2 × 103/μL 6.71 +/- 2.3 × 103/μL Platelet count 726 +/- 215 × 103/μL 243 +/- 115 × 103/μL Serum ferritin (median) 1,892 ng/mL 1,050 ng/mL 0.001 ALT (median) 65.5 u/L 44.5 u/L 0.004 AST (median) 64 u/L 36 u/L 0.001 Free hemoglobin (median) 4.2 mg/dL 2.5 mg/dL 0.001 C-reactive protein (high sens) (median) 2.7 mg/L 1.2 mg/L 0.012 Thrombin-antithrombin complexes 3.5 μg/L 1.1 μg/L Soluble P-selectin 113.4 +/- 31.2 ng/mL 56.4 +/- 32.1 ng/mL Soluble E-selectin 43.3 +/- 21.5 ng/mL 29.5 +/- 18.4 ng/mL 0.003 Conclusions: In comparison with non-splenectomized hemoglobin E/β-Thalassemia patients, asplenic ones have higher SPAP, more severe hemolysis, more liver impairment and chronic iron overload, significant chronic low grade inflammation, and evidence of coagulation activation. Splenectomy should be more judiciously applied than heretofore, and if performed, measures to blunt or prevent a subsequent hypercoagulable and inflammatory state, which could lead to PAH should be initiated. Disclosures: No relevant conflicts of interest to declare.

2015 Poster Board I-1037 Introduction: Pulmonary arterial hypertension (PAH) associated with thalassemia (Thal) hemoglobinopathy is now an accepted clinical entity. Most of the reports are in sickle cell disease and splenectomized β-Thal patients. Once manifested, it connotes poor prognosis. We herein present its prevalence and predictors in hemoglobin E/β-Thal (E/β-Thal) patients. Patients and Methods: One hundred and ten clinically stable E/β-Thal outpatients, on no medication aside from folic acid and who received no blood transfusion in the preceding 4 weeks were studied. All gave written informed consent, and study protocol was approved by the institution ethics committee on studies in humans (#0774/2548). Echocardiogram was used to estimate systolic PA pressure (SPAP). PAH was defined as an estimated SPAP ≥36 mmHg. Clinical features and laboratory data were stratified according to the presence or absence of PAH, and statistical analysis was done by STATA version 10 (Stata Corp, Texas), considering a P value

Human factor VIII was purified from cryoprecipitate and subjected to enzymatic degradation with plasmin, trypsin, chymotrypsin, and thrombin. The reactions were monitored by sodium dodecyl sulfate (SDS)-Polyacrylamide gel electrophoresis and by measurement of four biologic properties, namely, procoagulant activity, ristocetin cofactor activity, precipitation by heterologous antibody, and neutralization of a human factor VIII inhibitor. The electrophoretic patterns of reduced digests showed a reproducible sequence of degradation of the 215,000 molecular weight subunit by plasmin, trypsin, and chymotrypsin, each with well-defined intermediate and enzyme-resistant chain remnants. There were striking similarities in the sizes of several intermediate chain remnants produced by these three enzymes, suggesting the presence of regions on the factor VIII molecule that are especially susceptible to enzymatic degradation, but each enzyme also produced distinctive proteolytic derivatives. The most obvious differences included (1) a single-chained 40,000 molecular weight remnant cleaved by plasmin and trypsin which was either absent or degraded in chymotryptic digests, (2) large intermediate chain remnants of 176,000 and 157,000 molecular weight which were produced only by trypsin, and (3) differences in size and content of nonreduced fragments in the final digests. Thrombin caused no detectable change in electrophoretic patterns. The immunoprecipitation reaction was sensitive to minor degrees of proteolytic cleavage, showing a marked increase in rocket size even when the SDS-treated subunit chains showed virtually no change in electrophoretic mobility. Procoagulant and inhibitor neutralizing activities were rapidly destroyed by trypsin and plasmin, but this destruction did not correlate with specific changes in electrophoretic patterns. Both thrombin and chymotrypsin caused an increase in procoagulant activity prior to destruction of activity; changes in this property were therefore unrelated to changes in the protein visualized by gel electrophoresis. Ristocetin cofactor activity was considerably more resistant to plasmin than to trypsin or chymotrypsin, and roughly paralleled the persistence of highly aggregated forms in the digests.

The first two cases of Penicillium marneffei infection in humans were reported in 1959 and 1973. There had been no additional clinical reports of penicilliosis marneffei, until the five new cases of human infection described in this paper, the first from Thailand. The patients, three of whom died, came from various parts of the country. Their common clinical manifestations were fever and generalized lymphadenopathy, with multiple soft tissue, bone, joint and pulmonary involvement. Pericarditis with effusion was also seen. The diagnosis was established by isolating and identifying a dimorphic Penicillium species that produced a soluble red pigment in its mycelial form. The histopathologic features of the lymph nodes and bone marrow were similar to those of histoplasmosis capsulati. However, the yeast-like tissue form of P. marneffei divides by fission; that of Histoplasma capsulatum by budding. Treatment with amphotericin B was effective when this antifungal antibiotic was administered early in the course of the disease.

Neoplastic disease is quite rare in an XYY syndrome. We report the fifth known case, who suffered from acute nonlymphocytic leukemia (ANLL). Cytogenetic study of his bone marrow revealed a new chromosomal translocation (1;3)(q36;q21), which has only recently been described in patients with myelodysplastic syndrome.

Pythium infection (pythiosis) in humans has not previously been described, even in areas endemic for animal pythiosis. We report five patients with a unique presentation of fungal arteritis. The medium- to large-sized arteries were involved, and in some cases this involvement led to gangrene of the limbs, aneurysm formation, and ultimately fatal arterial leakage. All five patients were farmers. All patients, with the possible exception of one who had hemoglobin typing performed after receiving a blood transfusion, had thalassemia hemoglobinopathy syndrome. Fungal isolation was difficult. Amphotericin B treatment seemed to be ineffective. Radical surgical removal of infected tissues and oral administration of a saturated solution of potassium iodide are proposed therapy. In the tropics, where Pythium is ubiquitous, one should actively look for this fungal infection in patients with unexplained arterial occlusion, especially in the case of patients with thalassemia hemoglobinopathy syndrome.

An anti B autoantibody was found during a routine cross-matching of the blood of two patients who presented with fever and hemolytic anemia. It appeared transiently and was shown to be IgM- and cold-reacting. The patients had an excellent response to a short course of corticosteroid treatment.

The pharmacokinetics of amikacin in 10 patients with hematologic malignancies and 1 patient with aplastic anemia were investigated. At an administered dose of 7 mg/kg of body weight, a volume of distribution of 0.4 liters/kg, an elimination half-life of 3.0 h, and a total body clearance of 2.1 ml/min per kg, amikacin achieved a peak level in blood of 21 micrograms/ml. Results of the study revealed that there was a marked increase in volume of distribution of amikacin in these patients compared with normal.

• A pilot study was done during April 1984 through June 1986 to determine the incidence of postoperative deep vein thrombosis (DVT) among 50 Thai patients who underwent hip surgery, which mainly consisted of total hip replacement (19 patients) and repair of hip fracture (29 patients). Most patients were in the sixth to seventh decade of life, and the male-to-female ratio was 32:18. Most patients were of normal or low weight, few had known risk factors for DVT, and all but three had general anesthesia. Venography performed on the operated on legs on the seventh to tenth postoperative days showed that only two patients had DVT, one in the calf and another in the calf and thigh veins. The low incidence of DVT in the Thai population even after such extensive surgery, which is associated with a high (40% to 70%) frequency of DVT in the Western world, suggests that routine prophylactic anticoagulant measures are not presently needed in this country. ( Arch Intern Med 1988;148:1349-1353)