[Show abstract][Hide abstract] ABSTRACT: Primary Immune Thrombocytopenia (ITP) is an autoimmune disorder characterized by platelet counts < 100 x 10 9 /L. • There is limited available robust epidemiological and clinical data for ITP outside the United States and Europe. • Current treatment protocols lack uniformity. • Many existing guidelines are based on evidence from the USA and Europe-not necessarily reflecting best practice for populations in the Asia-Pacific, Middle-East and Latin America. To contrast and compare the International ITP Registry population with the Intercontinental Cooperative Immune Thrombocytopaenia Study Group Pediatric and Adult Intercontinental Registry on Chronic ITP (PARC-ITP Registry) adult population. The PARC-ITP Registry was selected as it represents a prospective cohort including newly diagnosed ITP patients, with a comparably sized adult cohort which is well established (>4 years) across the regions in which epidemiological data is already available 1. Clinical and laboratory data from the International ITP Registry were compared with clinical and laboratory data reported for adults enrolled in the PARC-ITP registry. To evaluate the differences between the two groups the two-sample test of proportion was used.
[Show abstract][Hide abstract] ABSTRACT: Prophylaxis with either intravenous (i.v.) factor VIII or IX is the gold standard of care for patients with severe hemophilia. A monoclonal antibody (concizumab) targeting tissue factor pathway inhibitor (TFPI) that can be administered subcutaneously (s.c.) has the potential to alter current concepts of prophylaxis in hemophilia.
To evaluate the safety, and describe the pharmacokinetics and pharmacodynamics of single-dose concizumab in healthy volunteers and patients with hemophilia A or B. Methods: In this first human dose, phase 1, multicenter, randomized, double-blind, placebo-controlled trial escalating single i.v. (0.5-9000 μg/kg) or s.c. (50-3000 μg/kg) doses of concizumab were administered to healthy volunteers (n = 28) and hemophilia patients (n = 24).
Concizumab had a favorable safety profile after single i.v. or s.c. administration. There were no serious adverse events and no anti-concizumab antibodies. No clinically relevant changes in platelets, prothrombin time, activated partial thromboplastin time, fibrinogen, or antithrombin were found. A dose-dependent procoagulant effect of concizumab was seen as increased levels of D-dimers and prothrombin fragment 1+2. Nonlinear pharmacokinetics of concizumab was observed due to target-mediated clearance. A maximum mean AUC0-∞ of 33 960 h*μg/mL and a maximum mean concentration of 247 μg/mL was measured at the highest dose.
Concizumab showed a favorable safety profile after i.v. or s.c. administration and nonlinear pharmacokinetics was observed due to target-mediated clearance. A concentration-dependent procoagulant effect of concizumab was observed supporting further study into the potential use of s.c. concizumab for hemophilia treatment. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Journal of Thrombosis and Haemostasis 01/2015; 13(5). DOI:10.1111/jth.12864 · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thrombosis is a common pathology underlying ischaemic heart disease, ischaemic stroke, and venous thromboembolism (VTE). The Global Burden of Disease Study 2010 (GBD 2010) documented that ischaemic heart disease and stroke collectively caused one in four deaths worldwide. GBD 2010 did not report data for VTE as a cause of death and disability. We performed a systematic review of the literature on the global disease burden due to VTE in low, middle and high income countries. Studies from Western Europe, North America, Australia, and Southern Latin America (Argentina) yielded consistent results with annual incidences ranging from 0.75 to 2.69 per 1,000 individuals in the population. The incidence increased to between 2 and 7 per 1,000 among those 70 years of age or more. Although the incidence is lower in individuals of Chinese and Korean ethnicity, their disease burden is not low because of population aging. VTE associated with hospitalisation was the leading cause of disability-adjusted-life-years (DALYs) lost in low and middle income countries, and second in high income countries, responsible for more DALYs lost than nosocomial pneumonia, catheter-related blood stream infections, and adverse drug events. VTE causes a major burden of disease across low, middle, and high income countries. More detailed data on the global burden of VTE should be obtained to inform policy and resource allocation in health systems, and to evaluate if improved utilisation of preventive measures will reduce the burden.
Thrombosis and Haemostasis 11/2014; 112(5):843-852. DOI:10.1160/TH14-08-0671 · 4.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Thrombosis is the common pathology underlying ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). The Global Burden of Disease Study 2010 (GBD 2010) documented that ischemic heart disease and stroke collectively caused 1 in 4 deaths worldwide. GBD 2010 did not report data for VTE as a cause of death and disability.
To review the literature on the global burden of disease caused by VTE.
Approach and results:
We performed a systematic review of the literature on the global disease burden because of VTE in low-, middle-, and high-income countries. Studies from Western Europe, North America, Australia, and Southern Latin America (Argentina) yielded consistent results with annual incidences ranging from 0.75 to 2.69 per 1000 individuals in the population. The incidence increased to between 2 and 7 per 1000 among those aged ≥70 years. Although the incidence is lower in individuals of Chinese and Korean ethnicity, their disease burden is not low because of population aging. VTE associated with hospitalization was the leading cause of disability-adjusted life-years lost in low- and middle-income countries, and second in high-income countries, responsible for more disability-adjusted life-years lost than nosocomial pneumonia, catheter-related blood stream infections, and adverse drug events.
VTE causes a major burden of disease across low-, middle-, and high-income countries. More detailed data on the global burden of VTE should be obtained to inform policy and resource allocation in health systems and to evaluate whether improved use of preventive measures will reduce the burden.
[Show abstract][Hide abstract] ABSTRACT: This multinational, randomized, single-blind trial (NCT01333111 [www.clinicaltrials.gov]) investigated safety and efficacy of nonacog beta pegol, a recombinant glycoPEGylated factor IX (FIX) with extended half-life, in 74 previously treated hemophilia B patients (FIX activity ≤2 IU/dL). Patients received prophylaxis for 52 weeks, randomized to 10 IU/kg or 40 IU/kg once weekly, or on-demand treatment for 28 weeks. No patients developed inhibitors and no safety concerns were identified. Three-hundred and forty-five bleeding episodes were treated with an estimated success rate of 92.2%. The median annualized bleeding rates (ABRs) were 1.04 in the 40 IU/kg prophylaxis arm, 2.93 in the 10 IU/kg prophylaxis arm, and 15.58 in the on-demand treatment arm. In the 40 IU/kg arm, 10 of 15 patients (66.7%) experienced no bleeding episodes into target joints, compared with 1 of 13 patients (7.7%) in the 10 IU/kg arm. Health-related quality of life (HR-QoL) assessed with the EQ-5D VAS score improved from median 75 to 90 in the 40 IU/kg prophylaxis arm. Nonacog beta pegol was well tolerated and efficacious for treatment of bleeding episodes, and associated with low ABRs in patients on prophylaxis. Once-weekly prophylaxis with 40 IU/kg resolved target joint bleeds in 66.7% of the affected patients and improved HR-QoL.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Heparin induced-thrombocytopenia (HIT) has been well recognized in Western countries. However, there are no data in the Thai population. We therefore investigated the prevalence of anti-platelet factor 4 (PF4)/heparin antibodies, HIT, and its thrombotic complications in Thai patients undergoing cardiac surgery using unfractionated heparin.
Materials and methods:
Seventy-three consecutive patients were prospectively enrolled in this study. Blood samples before operation and week 1, week 2, and week 3 after operation were collected from each patient for HIT antibody screening by enzyme-linked immunosorbent assay using IgG antibody specific to the PF4/heparin complex. Positive samples were further analyzed by (14)C-serotonin release assay. Complete blood count was performed daily during the first week, then weekly for 3 weeks.
No patient had detectable anti-PF4/heparin antibodies at baseline. Five patients sero-converted during the course of the study for anti-PF4/heparin IgG: 3 (4.1%) at week 1, 4 (5.5%) at week 2, and 5 (6.8%) at week 3 after surgery. However, none of these patients had anti-PF4/heparin antibodies that resulted in (14)C-serotonin release to be considered clinically significant antibodies. Post-operative thrombocytopenia after the operation was found in 35 patients (47.9%), but was not considered to be caused by HIT. Thromboembolic events occurred in 3 patients (4.1%) during follow up; however, none of these patients had positive PF4/heparin antibody tests.
Our study represents the first study to examine Thai patients exposed to heparin in the context of cardiac surgery. We found a lower prevalence of positive anti-PF4/heparin antibodies and clinical HIT than previously published studies.
Thrombosis Research 08/2014; 134(5). DOI:10.1016/j.thromres.2014.08.020 · 2.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by auto-antibody induced platelet (PLT)
destruction and reduced PLT production, leading to a low PLT count (< 100 x 109/L). The availability of robust epidemiological and
clinical data outside of Europe and the United States for ITP are very limited. Additionally, there is little uniformity in regards to the
treatment of ITP leaving physicians to make treatment decisions based on their experience and institutional protocols. The
International ITP-Registry is a prospective cohort study which seeks to collect real-world data on the epidemiological and clinical
data of adult ITP predominantly from the Asia-Pacific region.
Aims: The aims of the study are:
1. To compile an anonymous centralised database of demographic, ITP-specific, and co-morbid disease information on ITP
2. To collect data on the presentation and complications of the disease.
3. To document local treatment practices across multiple countries and regions and responses to treatments.
4. To develop and test a prognostic model for major bleeding among adult patients with ITP.
5. To identify factors that predict life-threatening bleeding.
Methods: Recruitment began in 2011. Patients ≥ 18 years old with a recent diagnosis of primary ITP (≤ 6 months since initial
diagnosis) are enrolled prospectively upon provision of informed consent. The primary data collected are: patient demographics,
laboratory investigations, co-morbidities, bleeding events, blood products used, interventional procedures, pharmacotherapeutic
agents administered, response to treatment and adverse events. Data is collected at baseline, after months 6 and 12 and then annually.
Results: As of 31 August 2013, 140 patients had been enrolled at 24 sites across 7 countries in the Asia-Pacific Region and Middle
East. At the time of data analysis, 80 patients had reached 6 month and annual follow-up time points with the remaining 60 patients
having been enrolled for less than six months from baseline data collection. Sixty per cent were female with a median age of 48 years
(range 18 – 96 years). Mean PLT count at baseline was 24 x 109/L (range 0 – 94 x 109/L). Haematology, coagulation and
biochemistry tests were within normal ranges.
Prior to enrolment 77 patients had bleeding events recorded. This decreased to 10 events in the follow-up period. Corticosteroids were
the most frequently used first-line treatment (59% of patients) achieving a partial (PR; ≥ 50 x 109/l but ≤ 100 x 109/l & 2 x pretreatment)
or complete (CR; ≥ 100 x 109/l & x 2 pre-treatment) PLT response (82%) and cessation of bleeding (100%) during the 6
month follow-up period. IVIg was also reported as a first line treatment in 14% of patients, achieving a PLT response in 47% and
cessation of bleeding in 82% treated. Second line therapies used included splenectomy (n = 3; PR = 1, CR = 2), TPO-receptor
agonists (n = 2; PR = 1, CR = 1). 22 patients received Immunotherapy, 14 had a PLT response.
Summary/Conclusion: Enrolled patients have a female predominance with median age of 48 years. Bleeding appears frequently at
diagnosis (36%) with symptoms abating with first line treatments. Corticosteroids are the most frequently used first line treatment
(59% of patients treated). Splenectomy appears uncommon and was performed in only 3 patients (14% of cohort) with
immunotherapies the most often used second line therapy. Data collection and analysis for this study is ongoing.
[Show abstract][Hide abstract] ABSTRACT: Blood coagulation activation is frequently found in patients with malaria. Clinically apparent bleeding or disseminated intravascular coagulation (DIC) is associated with very severe disease and a high mortality. Protein C, protein S, and antithrombin levels were found to be low in P. falciparum, but were normal in P. vivax infection. Plasma levels of plasminogen activator inhibitor-1 were high in cases of P. falciparum infection whereas tissue plasminogen activator levels were low. Elevated plasma levels of von Willebrand factor (vWF) and vWF propeptide, thrombomodulin, endothelial microparticles have been reported in P. falciparum-infected patients. It has been demonstrated that severe P. falciparum infection is associated with acute endothelial cell (EC) activation, abnormal circulating ultralarge vWF multimers, and a significant reduction in plasma ADAMTS13 function. These changes may result in intravascular platelet aggregation, thrombocytopenia, and microvascular disease. It has also been shown that P. falciparum-parasitized red blood cells (pRBCs) induce tissue factor (TF) expression in microvascular ECs in vitro. Recently, loss of endothelial protein C receptor (EPCR) localized to sites of cytoadherent pRBCs in cerebral malaria has been demonstrated. Severe malaria is associated with parasite binding to EPCR. The cornerstone of the treatment of coagulopathy in malaria is the use of effective anti-malarial agents. DIC with spontaneous systemic bleeding should be treated with screened blood products. Study in Thailand has shown that for patients who presented with parasitemia >30% and severe systemic complications such as acute renal failure and ARDS, survival was superior in the group who received exchange transfusion. The use of heparin is generally restricted to patients with DIC and extensive deposition of fibrin, as occurs with purpura fulminans or acral ischemia. Antiplatelet agents interfere with the protective effect of platelets against malaria and should be avoided.
Thrombosis Research 09/2013; 133(1). DOI:10.1016/j.thromres.2013.09.030 · 2.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Genetic and environmental factors interact in determining the risk of venous thromboembolism (VTE). The risk associated with the polymorphic variants G1691A of factor V (Factor V Leiden, FVL), G20210A of prothrombin (PT20210A) and C677T of methylentetrahydrofolate reductase (C677T MTHFR) genes has been investigated in many studies. We performed a pooled analysis of case-control and cohort studies investigating in adults the association between each variant and VTE, published on Pubmed, Embase or Google through January 2010. Authors of eligible papers, were invited to provide all available individual data for the pooling. The Odds Ratio (OR) for first VTE associated with each variant, individually and combined with the others, were calculated with a random effect model, in heterozygotes and homozygotes (dominant model for FVL and PT20210A; recessive for C677T MTHFR). We analysed 31 databases, including 11,239 cases and 21,521 controls. No significant association with VTE was found for homozygous C677T MTHFR (OR: 1.38; 95 % confidence intervals [CI]: 0.98-1.93), whereas the risk was increased in carriers of either heterozygous FVL or PT20210 (OR = 4.22; 95 % CI: 3.35-5.32; and OR = 2.79;95 % CI: 2.25-3.46, respectively), in double heterozygotes (OR = 3.42; 95 %CI 1.64-7.13), and in homozygous FVL or PT20210A (OR = 11.45; 95 %CI: 6.79-19.29; and OR: 6.74 (CI 95 % 2.19-20.72), respectively). The stratified analyses showed a stronger effect of FVL on individuals ≤ 45 years (p value for interaction = 0.036) and of PT20210A in women using oral contraceptives (p-value for interaction = 0.045). In this large pooled analysis, inclusive of large studies like MEGA, no effect was found for C677T MTHFR on VTE; FVL and PT20210A were confirmed to be moderate risk factors. Notably, double carriers of the two genetic variants produced an impact on VTE risk significantly increased but weaker than previously thought.
European Journal of Epidemiology 07/2013; 28(8). DOI:10.1007/s10654-013-9825-8 · 5.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: By guiding initial warfarin dose, pharmacogenetic (PGx) algorithms may improve the safety of warfarin initiation. However, once international normalised ratio (INR) response is known, the contribution of PGx to dose refinements is uncertain. This study sought to develop and validate clinical and PGx dosing algorithms for warfarin dose refinement on days 6-11 after therapy initiation. An international sample of 2,022 patients at 13 medical centres on three continents provided clinical, INR, and genetic data at treatment days 6-11 to predict therapeutic warfarin dose. Independent derivation and retrospective validation samples were composed by randomly dividing the population (80%/20%). Prior warfarin doses were weighted by their expected effect on S-warfarin concentrations using an exponential-decay pharmacokinetic model. The INR divided by that "effective" dose constituted a treatment response index . Treatment response index, age, amiodarone, body surface area, warfarin indication, and target INR were associated with dose in the derivation sample. A clinical algorithm based on these factors was remarkably accurate: in the retrospective validation cohort its R(2) was 61.2% and median absolute error (MAE) was 5.0 mg/week. Accuracy and safety was confirmed in a prospective cohort (N=43). CYP2C9 variants and VKORC1-1639 G→A were significant dose predictors in both the derivation and validation samples. In the retrospective validation cohort, the PGx algorithm had: R(2)= 69.1% (p<0.05 vs. clinical algorithm), MAE= 4.7 mg/week. In conclusion, a pharmacogenetic warfarin dose-refinement algorithm based on clinical, INR, and genetic factors can explain at least 69.1% of therapeutic warfarin dose variability after about one week of therapy.
Thrombosis and Haemostasis 12/2011; 107(2):232-40. DOI:10.1160/TH11-06-0388 · 4.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Venous thromboembolism (VTE) has been perceived for a long time to be less common in Asian populations, particularly in the Far East, than in Western populations. Generally, thromboprophylaxis is not implemented as frequently as it should be in high-risk patients. However, recent prospective studies undertaken in Asian countries have demonstrated higher rates of VTE after major surgery and in medical wards, approaching those observed in Western populations. Risk factors for VTE are not different in Asian patients from those of Western patients with the exception of thrombophilic mutations. Deficiencies of the natural anticoagulants (protein S, protein C, and antithrombin) are the predominant thrombophilias in Asia whereas factor V Leiden and prothrombin G20210A gene mutation are not found or rarely reported. Further large well-designed clinical studies are needed to evaluate the magnitude of the risk of VTE and the appropriate use of thromboprophylaxis in different clinical situations.
Thrombosis and Haemostasis 08/2011; 106(4):585-90. DOI:10.1160/TH11-03-0184 · 4.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Well-characterized genes that affect warfarin metabolism (cytochrome P450 (CYP) 2C9) and sensitivity (vitamin K epoxide reductase complex 1 (VKORC1)) explain one-third of the variability in therapeutic dose before the international normalized ratio (INR) is measured. To determine genotypic relevance after INR becomes available, we derived clinical and pharmacogenetic refinement algorithms on the basis of INR values (on day 4 or 5 of therapy), clinical factors, and genotype. After adjusting for INR, CYP2C9 and VKORC1 genotypes remained significant predictors (P < 0.001) of warfarin dose. The clinical algorithm had an R2 of 48% (median absolute error (MAE): 7.0 mg/week) and the pharmacogenetic algorithm had an R2 of 63% (MAE: 5.5 mg/week) in the derivation set (N = 969). In independent validation sets, the R2 was 26–43% with the clinical algorithm and 42–58% when genotype was added (P = 0.002). After several days of therapy, a pharmacogenetic algorithm estimates the therapeutic warfarin dose more accurately than one using clinical factors and INR response alone.
[Show abstract][Hide abstract] ABSTRACT: Hemophilia patients with inhibitors faced the constraint of inadequate treatment for several years before the era of recombinant factor VIIa (rFVII). Initially, rFVIIa was used in the compassionate-use programs. After a worldwide license was issued, more than 1.5 million doses were administered. Bleeding of joints and muscles was controlled effectively by means of an early home treatment program, with either a standard dose of 90 μg/kg every 2 to 3 hours for a few doses or a single dose of 270 μg/kg. For more serious bleeding episodes or minor surgery, an initial dose of 90 μg/kg was given every 2 hours for 24 to 48 hours followed by increased intervals of 3 to 6 hours according to the severity of bleeding and efficacy of bleeding control. In cases of major surgery such as orthopedic procedures, the same regimen can be applied except for a higher initial dose of 120 to 180 μg/kg. However, increasing the dose should be considered if there are unexpected bleeding complications since the half-life and clearance of rFVIIa differ between individuals. In addition, prophylaxis is administered to a small number of patients. Finally, the reported thromboembolic events found in hemophilia patients with inhibitors receiving rFVIIa are extremely low, much less than 1%.
Hematology Research and Reviews 03/2010; 1:37-48. DOI:10.2147/JBM.S6209
[Show abstract][Hide abstract] ABSTRACT: 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.
International Journal of Hematology 01/2008; 86(5):397-402. DOI:10.1532/IJH97.A20715 · 1.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Antibodies to beta(2)-glycoprotein I (anti-beta(2)-GPI) have been reported to have stronger association with clinical antiphospholipid syndrome (APS) than anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC). We investigated the sensitivity and specificity of ELISA for anti-beta(2)-GPI in Thai systemic lupus erythematosus (SLE) patients with clinical features of APS and compared the results with IgG/IgM aCL and LAC to find the test with the best association. The hospital records of 151 Thai SLE patients whose sera had been sent for either IgG/IgM anticardiolipin antibodies or lupus anticoagulant testing were reviewed. Sera of patients either without complete clinical records or those with APS-related manifestations other than vascular thrombosis and pregnancy morbidity (according to the international consensus statement on preliminary classification criteria for definite APS) were excluded. For the remaining subjects (112 patients), their sera were tested for anti-beta(2)-GPI antibody, IgG and IgM anticardiolipin, and lupus anticoagulant. The sensitivity and specificity of each method were compared by using the chi-square test. Among the 112 (74.2%) SLE patients in the study, 35 (31.3%) presented with preliminary clinical criteria for APS (i.e., vascular thrombosis and pregnancy morbidity) whereas 77 (68.7%) did not. The sensitivity and specificity of anti-beta(2)-GPI determination were 57.1 and 79.2%, respectively, whereas those of IgG aCL were 25.7 and 94.8%, of IgM aCL were 5.7 and 98.7%, and of LAC were 44.8 and 77.3%, respectively. The accuracy of the four tests showed similar association with clinical APS (accuracy of test = 72.3, 73.2, 69.6, and 68.3%, respectively). Concerning the sensitivity, specificity, and difficulty of the methods, the combination of anti-beta(2)-GPI and IgG aCL tests was the best for the diagnosis of APS in Thai SLE patients.
[Show abstract][Hide abstract] ABSTRACT: 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.
American Journal of Hematology 11/2007; 82(11):1001-4. DOI:10.1002/ajh.20945 · 3.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This is a retrospective study of 24 pediatric venous thromboembolism (VTE) patients with or without pulmonary embolism, conducted in Bangkok, Thailand, between 1981 and 2005. The incidence rate of VTE in Thai children was 3.9/10,000 hospital admissions per year. The median age was 11.7 years. Seventy-five percent of the patients had at least one associated medical condition accounting for the VTE; the two most common conditions, however, were infection and malignancy. Pulmonary embolism occurred in 29% of patients. Observed outcomes of VTE in this series included death (13%), postphlebitic syndrome (13%), and recurrence (26%). Genetic risk factors were explored in 19 patients, and no factor V Leiden or prothrombin 20210 mutations were detected. Protein C deficiency was found in 4 patients.
[Show abstract][Hide abstract] ABSTRACT: Intrathoracic extramedullary hematopoiesis is an unusual but well-described entity. The condition is typically found in patients who have chronic hemolytic anemias, especially thalassemia. We report a case of a 38-year-old man with underlying beta thalassemia/hemoglobin E who developed intrathoracic extramedullary hematopoiesis. The hematopoietic masses spontaneously ruptured, resulting in massive hemothorax. The condition was confirmed by video-assisted thoracoscopy and successfully treated with surgery, hydroxyurea, and radiation.
Respiratory care 04/2006; 51(3):272-6. · 1.84 Impact Factor