Duration Of Blood Transfusion Research Articles

Analysis of how Serum Ferritin and the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) are correlated to Hepatic MRI T2* Findings in Children with Beta-Thalassemia Major

Background: Iron overload is a major complication in patients with beta-thalassemia major. Excessive iron accumulation leads to organ dysfunction. The regular assessment of iron is crucial to effectively manage iron overload in these patients. This study evaluated the correlation between serum ferritin levels, the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI), and hepatic MRI T2* findings in children with beta-thalassemia major. Materials and Methods: This retrospective analytical study was conducted at Shahid Sadoughi Hospital in Yazd in 2023. The research population comprised all the children under the age of 15 with beta-thalassemia major who had undergone multiple blood transfusions (at least ten units of blood). Results: The participants in this study were 70 children with beta-thalassemia major, including 35 males and 35 females. Their mean age was 3.52 ± 10.76 years. The mean relaxation time of liver MRI T2* was 4.42 ± 4.91 ms. The participants also had the APRI score of 0.55 ± 1.90, the aspartate aminotransferase (AST) level of 23.82 ± 36.29, and the serum ferritin level of 285.01 ± 3244.04 (ng/mL). Based on MRI T2* results, 30% of the patients had a severe liver iron overload, 27.1% had a moderate overload, 21.4% had a severe overload, 18.6% had a mild overload, and 2.9% had near-normal iron levels.The AST level demonstrated a significant association with the type of chelation treatment (P = 0.003). The duration of blood transfusion (in years) showed a strong positive correlation with the patients' age (Pearson's coefficient = 0.996). Conclusion: This study indicates the elevated serum ferritin levels and APRI scores in patients with beta-thalassemia major, most of whom have abnormal MRI T2* findings. However, no significant correlation was observed between the APRI score, serum ferritin level, and MRI T2* results.

Economic burden of beta-thalassaemia major receiving hypertransfusion therapy at a public hospital in Mumbai.

Background Treating beta-thalassaemia major may entail high costs with considerable out-of-pocket expenditure. Therefore, determination and valuation of the economic costs of a common haemoglobinopathy such as beta-thalassaemia major in India may provide insights to evolve policies for reduction or elimination of the disease. We estimated economic burden of beta-thalassaemia major in Mumbai in terms of cost to the family and the healthcare system. Methods This single-centre, prospective, cross-sectional, non-interventional study included children <12 years of age treated at the thalassaemia day care centre of a public hospital in Mumbai. The demographic data and treatment-related information was recorded. Cost of illness was studied from a societal perspective by the prevalence-based approach. Direct (medical and non-medical), indirect (loss of wages and loss of school days) and intangible costs (closed-ended iterative bidding) were calculated for each patient by interview. Results The total annual cost of treating 130 children with beta-thalassaemia major in Mumbai was ₹86 72 412 (US$ 127 535) or ₹66 710 (US$ 981) per patient per year and ₹12 82 30 412 (US$ 1 885 741) including intangible costs. Direct costs contributed to 94% of the cost of illness with chelation therapy (23%) and blood investigations (21%) being major contributors. Direct and indirect costs correlated significantly with duration of blood transfusion (p<0.05 and p=0.006, respectively), whereas indirect costs correlated with socioeconomic status (rho=0.25). Conclusion The majority (94%) of costs incurred by families for treatment of beta-thalassaemia major are direct costs, especially expenses for chelation and blood investigations. Even at subsidized rates, financial burden to the families from lower socioeconomic strata is likely to be considerable as these are out-of-pocket expenses. In consideration of the economic impact of treating beta-thalassaemia major in individual families, the healthcare system and society, it is prudent to promote and pursue long-term and short-term measures with urgent emphasis on prevention as a public health activity at the national level in India.

Health-related quality of life of parents of children with beta-thalassemia major attending a tertiary care institution in Eastern India

Context: Chronic diseases such as beta-thalassemia major among children impact their parents in various ways, as they face continuous stress and strain while striving to provide their children with a best possible care. Literature related to health-related quality of life (HRQoL) among parents of children with beta-thalassemia major are limited among Indian population. Aims: This study aimed to assess the HRQoL of parents of children with beta-thalassemia major attending a tertiary care institution in Eastern India and its various correlates. Settings and Design: This cross-sectional study was conducted at a tertiary care institution in Eastern India. Materials and Methods: A sample size of 192 was selected using the simple random sampling among parents with children suffering from beta-thalassemia major who fulfilled the inclusion criteria. Study participants were interviewed regarding different variables and their HRQoL, using a predesigned, pretested, and semi-structured schedule and the Short Form 36 Health survey, respectively, after obtaining ethical clearance from the Institutional Ethics Committee and informed consent from them. Statistical Analysis Used: Data were entered in MS Excel and analyzed using IBM SPSS 20.0 version (Armonk, NY: IBM Corp). Results: The mean HRQoL score was found to be 38.7 ± 11.3 with an interquartile range of 23–59.7. The Spearman's rho correlation matrix showed that HRQol of parents is weakly positively correlated with the educational status of the father of the child (r = 0.2), educational status of the mother of the child (r = 0.1), family history of thalassemia (r = 0.2), ongoing treatment (r = 0.1), and duration of blood transfusion (r = 0.2). Conclusions: Hence, we can conclude that HRQoL of parents of beta-thalassemia major children was correlated with the educational status of the father and mother, family history of thalassemia, ongoing treatment, and duration of blood transfusion.

Prevalence of HBV and HCV infection in beta-thalassemia major patients of Tabriz city, Iran

People with beta-thalassemia major are more likely to acquire blood-borne viral infections due to the need for frequent blood transfusions. Of these viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV) are of particular importance. In this study, the prevalence of HBV, HCV and their risk factors in beta-thalassemia major patients in East Azerbaijan province was investigated. The study was descriptive cross-sectional, and 116 beta-thalassemia major patients who received blood in Shahid Ghazi hospital and Children’s hospital in Tabriz city were studied. Data were collected by a questionnaire, and blood samples of patients in terms of serum markers HCV-Ab, HBsAg and HBs-Ab were analyzed by ELISA, and positive HCV-Ab results were confirmed by Real Time-PCR. Then using SPSS software version 22 and with the help of t-tests including Anova T-test, Man-Whitney U test, Independent sample t-test, chi-square and Fisher exact test, Statistical studies were performed. Of the 116 patients studied, no HBsAg positive cases were found. Four patients (3.4%) were positive for HCV-Ab, of which two patients (1.7%) became HCV-RNA positive after Real Time-PCR. There was a significant relationship between HCV-Ab positive and HCV-RNA positive (P = 0.000), blood transfusion intervals (P = 0.043), number of injected blood units (P = 0.001) and duration of blood transfusion (P = 0.006). The prevalence of HCV was lower in patients who started receiving blood after a blood donor screening program. HCV is less prevalent in thalassemia patients in East Azerbaijan province than in some studies in the country and various global statistics. After 1996, the prevalence of HCV in the thalassemia patient population has decreased significantly, and it seems that HCV infections since 1996 have been associated with various factors such as people’s jobs, position, behaviour in society, etc.

Impact of new chelating agents on ocular abnormalities in β-thalassemia major patients

Objectives The objectives of this study were to assess ocular changes in β-thalassemia major patients who have received multiple transfusions and different chelating agents. Patients and methods A cross-sectional study of 90 β-thalassemia major patients from age group 14 to 24 years were selected as case group, and 90 age-matched and sex-matched healthy participants were considered as a control group. Full medical history and thorough physical examinations were done to all patient groups. Ocular examination, including visual acuity, refraction testing, slit-lamp examination, funduscopy, tonometry, perimetry, tear-breakup time test, and color-vision testing, was performed for all the participants. We computed the frequency and duration of blood transfusion, the mean serum ferritin level, pretransfusion hemoglobin concentration, the type, duration, and daily dose of chelation therapy for thalassemia patients based on their records. Results All thalassemic patients were asymptomatic, but abnormal ocular findings [dry eye (13.3%), cataract (10%), retinal changes (16.7%), color-vision deficiency (3.33%), ocular hypertension (6.67%), and visual acuity (8.88%)] were seen in 58.9% of thalassemic group. The prevalence of ocular abnormalities in the control group was 19.4%, which was significantly lower than that in thalassemia patients (P=0.000). No significant correlation was found between ocular abnormalities and mean serum ferritin level (P=0.627) and mean hemoglobin concentration (P=0.143). A positive correlation between the number of blood transfusions with the presence of ocular abnormalities was found to be statistically significant (P=0.005). Recommendations As life expectancy for β-thalassemia patients extends, regular ophthalmologic evaluation to detect early changes in their ocular system is recommended.

Evaluation of glycemic abnormalities in children and adolescents with \u03b2-thalassemia major

BackgroundThe quality of life of B-thalassemia major (β-TM) patients has improved with the use of frequent blood transfusions. However, this leads to chronic iron overload with its sequelae, as prediabetes and diabetes mellitus. This study aimed to assess insulin resistance and glucose abnormalities in a sample of B-thalassemia major patients in Benha, Egypt.ResultsThis case-control study included 40 B-thalassemia major patients on regular blood transfusion and iron chelation. Their ages ranged from 8 to 16 years, and 30 normal age and sex-matched controls. Thorough clinical examination was performed including weight (kg), height (m), body mass index (BMI) (kg/m2), and liver and spleen size. Laboratory investigations were done in the form of complete blood count, liver enzymes, serum ferritin, fasting plasma insulin, and fasting, and 2 h postprandial plasma glucose. Insulin resistance (IR) was calculated using the Homeostasis Model Assessment of insulin resistance (HOMA-IR) index. Insulin resistance was found in 27.5% of thalassemic patients; 18.2% of them had diabetes, 72.7% were prediabetics (with impaired fasting glycemia), and 9.1% had normal fasting and 2 h postprandial plasma glucose level. Insulin resistance increased significantly with increased blood transfusion duration, serum ferritin, liver enzymes, fasting plasma insulin, fasting plasma glucose, and 2 h postprandial plasma glucose (ROC). The curve analysis showed that the duration of blood transfusion, serum ferritin, fasting plasma insulin, fasting, and 2 h postprandial plasma glucose could significantly predict insulin resistance at a certain cut-off point.ConclusionOur data show that HOMA-IR can be used to detect insulin resistance in β-TM patients on long-term blood transfusions, especially patients with high serum ferritin and impaired liver enzymes.

Health-related quality of life in children with hemoglobin E-?-thalassemia with special reference to iron overload

Background: Hemoglobin (Hb) E disease is the most common Hb variant in Southeast Asia. However, in India, it is prevalent in Eastern India and West Bengal, but relatively rare in rest of the country. Objective: The objective of the study was to study the quality of life (QOL) in Hb E/?-thalassemia children with special reference to iron overload. Materials and Methods: An analytical case–control study on Hb E/?-thalassemia children aged 8–12 years was conducted who were admitted in the thalassemia unit and outdoor basis from the departments of pediatric medicine and hematology. They were evaluated for a period of 1 year and the effect on the QOL was assessed with health-related QOL (HRQOL) score along with psychological assessment. Results: A total of 50 subjects were included in the study. The HRQOL was assessed by PedsQL 4.0 generic core scale along with parent proxy report and psychological assessment was done by childhood psychopathology measurement schedule score. It was found that QOL was significantly better when pre-transfusion Hb level was above 7 g/dl. Conclusion: We found that total summary QOL score was not statistically significant, but the physical domain of QOL score showed statistically significant better score when the duration of blood transfusion is less. Therapy should widen beyond drugs with adequate physical rehabilitation and emotional support.

Thyroid Function in Chronically Transfused Children with Beta Thalassemia Major: A Cross-Sectional Hospital Based Study.

Background Thalassemia is the most common genetic disorder worldwide. Use of iron chelators has improved survival but endocrine complications have become more frequent. The frequency of hypothyroidism in Beta Thalassemia Major (BTM) children ranges from 6 to 30 %. Thyroid dysfunction mainly occurs by gland infiltration, chronic tissue hypoxia, free radical injury, and organ siderosis. Objectives (a) To evaluate the thyroid function status in chronically transfused children with BTM, in the first and second decade of life and (b) to study the influence of factors like duration and amount of blood transfusions, serum ferritin level, and iron chelation therapy on thyroid function. Methodology BTM children, 3 years old and above, on regular blood transfusions with serum ferritin > 1500 mcg/l were included in the study. Thyroid function and ferritin assessment was done using ELISA kits. Autoimmune thyroiditis was ruled out by antithyroid peroxidase and antithyroglobulin antibody testing. Results A study population of 83 children consisted of 49 boys (59%) and 34 girls (41%). 4.8% of the children had evidence of subclinical hypothyroidism. Among them two belonged to the first decade and the other two to the second decade of life. Mean TSH, FT4, and ferritin values among children with thyroid dysfunction were 6.38 ± 0.83 mIU/ml, 1.08 ± 0.45 ng/dl, and 3983.0±1698.30 ng/ml, respectively. The severity of thyroid dysfunction was statistically significantly associated with higher serum TSH values in children in the second decade of life with a p value = 0.001. No other significant correlation was found between oral chelation, amount and duration of blood transfusion, or serum ferritin levels. Conclusion Subclinical hypothyroidism was the thyroid dysfunction observed in our study. Regular blood transfusions with adequate chelation may decrease incidence of thyroid dysfunction.

Zinc Status in Beta Thalassemia Major Patients.

Beta thalassemia is a common monogenic hereditary hemoglobinopathy which is associated with compound complications. Zinc deficiency, which is commonly observed in thalassemia patients, is also associated with multiple health complications. The objective of this study was to determine the zinc status and its effect on the growth and immune functions of young beta thalassemia major patients. The study included 40 patients in comparison with age- and sex-matched 30 healthy individuals as controls. The patients were interviewed for socio-demographic variables, and their medical histories were obtained from the hospital files. Serum concentrations of zinc and ferritin, height, and body mass indices (BMI) were calculated. Mean serum zinc level in beta thalassemia major patients was 44.7±24.2μg/dl whereas in the control group it was 63.3±30.3μg/dl. The mean serum zinc level is significantly low in beta thalassemia major patients with respect to the control group. The gender, age, duration of blood transfusion, blood transfusion volume, mean pretransfusion hemoglobin concentration, deferasirox dose, and serum ferritin level bear no relationship with serum zinc level of the beta thalassemia major patients. Zinc level showed no significant correlation with z-scores of stature, sitting height index, BMI, and frequency of recent infections of patients. Although zinc deficiency is common in beta thalassemia major patients, it was found to have no significant effect on physical growth and frequency of infections. Further studies are recommended to investigate zinc status of beta thalassemia major patients.

経皮的心肺補助装置装着後に合併した線溶亢進型播種性血管内凝固のため，抗凝固療法を回避して救命した肺血栓塞栓症の1例(A case of massive pulmonary embolism successfully resuscitated with veno–arterial extracorporeal membrane oxygenation without anticoagulation management due to complication of fibrinolytic phenotype disseminated intravascular coagulation)

75歳の女性。突然発症した呼吸困難を主訴に，当院に救急搬送された。来院時，循環虚脱および低酸素血症を認め，心臓超音波検査で左室の圧排を伴う右室の著しい拡大を認めた。来院15分後に，心肺停止状態となったため，心肺蘇生術を開始した。約2分後に自己心拍が再開したが，循環虚脱が継続したため，経皮的心肺補助装置（veno–arterial extracorporeal membrane oxygenation: VA–ECMO）を導入した。その後に行った肺動脈造影検査で，肺動脈の塞栓像を認め，肺血栓塞栓症と診断した。しかし，線溶亢進型の播種性血管内凝固（disseminated intravascular coagulation: DIC）を合併し，出血傾向を認めたため，抗凝固療法，血栓溶解療法は施行せず，輸血療法およびVA–ECMOを用いた循環呼吸管理を行った。第2病日に，出血傾向，循環呼吸動態が改善したため，VA–ECMOから離脱した。抗凝固療法は，VA–ECMO抜去部の止血が完了した第3病日から開始した。その後の経過は良好であり，第29病日に，神経学的後遺症もなく独歩退院した。心肺停止に至った重症肺血栓塞栓症に，線溶亢進型DICが合併し，急性期に抗凝固療法や血栓溶解療法が施行できない場合でも，出血傾向が改善するまでVA–ECMOによる循環呼吸管理を継続することで救命できる可能性がある。 A 75–year–old woman was admitted to our hospital because of sudden–onset dyspnea. She was in a state of obstructive shock and hypoxia and echocardiography showed right ventricular dilatation. Approximately 15min after arriving at the hospital, she experienced a cardiac arrest; we performed cardiopulmonary resuscitation, and spontaneous circulation restored in 2min. However, as obstructive shock was not resolved, we performed veno–arterial extracorporeal membrane oxygenation (VA–ECMO). Pulmonary angiography revealed pulmonary artery occlusions. Disseminated intravascular coagulation (DIC) was of the fibrinolytic phenotype; it was complicated with pulmonary embolism, and a bleeding tendency was noted. Therefore, blood transfusions were performed and hemodynamic support was provided with VA–ECMO and catecholamines, without anticoagulation and thrombolysis. The following day, her coagulopathy resolved and hemodynamic status recovered; VA–ECMO support was successfully removed. Anticoagulation was started on the 3rd hospital day, when bleeding at the VA–ECMO puncture site was confirmed to have stopped. The patient recovered and was discharged from the hospital on the 29th hospital day. DIC is sometimes complicated with pulmonary embolism in post–cardiac arrest patients. This case shows the possibility that continued hemodynamic and respiratory support with VA–ECMO until bleeding tendency resolves might aid in recovery of patients for whom anticoagulation and thrombolysis are contraindicated. 心肺停止（cardiopulmonary arrest: CPA）蘇生後は，播種性血管内凝固（disseminated intravascular coagulation: DIC）や 1, 2，胸骨圧迫による胸部外傷など 3, 4，出血性合併症を来す場合がある。今回我々は，線溶亢進型DICを合併した肺血栓塞栓症（pulmonary embolism: PE）症例を経験した。出血傾向のため，急性期に抗凝固療法や血栓溶解療法が施行できなかったが，DICが改善するまで経皮的心肺補助装置（veno–arterial extracorporeal membrane oxygenation: VA–ECMO）による循環呼吸管理を継続することで，救命できたため報告する。本症例報告の作成にあたり，個人情報保護法に基づき匿名化し，患者本人の同意を得た。 患 者：75歳の女性，身長145cm，体重42.7kg，body mass index 20.3 現病歴：未治療の下肢静脈瘤の既往はあるが，他の特記すべき既往歴，家族歴，常用薬はない。また，長期臥床や，安静を強いられる長距離移動などの病歴もない。来院当日の起床後，屋外で散歩中に突然，呼吸困難を自覚した後に転倒し，顔面を打撲した。その後，独歩で帰宅したが，患者が呼吸困難を訴えたため，家族が救急要請し当院に搬送された。 来院後経過：来院時，JCS 3–R，血圧94/60mmHg，心拍数104/分，呼吸数30/分，体温35.8℃，SpO2 92%（酸素リザーバーマスク10L/分 投与下）であった。胸部レントゲン写真では肺野に明らかな異常は認めなかったが，12誘導心電図検査ではV1–3誘導で，陰性T波を伴う完全右脚ブロックを（Fig. 1），心臓超音波検査では左室の圧排を伴う右室の著しい拡大を認めた。身体所見上は，呼吸音，心音に明らかな異常を認めなかったが，頸静脈の怒張を認めた。また，転倒時に受傷したと考えられる非活動性の出血を伴う口唇，口腔内の挫創，鼻出血を認めた。両側下肢には網目状静脈瘤を認めた。来院時の血液検査結果は，WBC 8,900/μL，Hb 9.6g/dL，PLT 8.2×104/μL，CK 48U/L，CKMB 18U/L，トロポニンI 0.090ng/mL，BNP 31.3pg/mL，APTT 62sec，PT–INR 1.43，fibrinogen 81mg/dL，D–dimer 114.9μg/mL，AT III 82%であった。 Electrocardiogram on admission. Electrocardiogram showing complete right branch block and a negative T wave in leads V1–3. 来院後，徐々に血圧が低下し，来院15分後にCPA状態（無脈性電気活動）となったため，心肺蘇生術を開始した。気管挿管し，アドレナリン1mgを投与したところ，約2分後に自己心拍が再開したが，循環虚脱が継続した。広範型PEを疑い，来院から43分後に透視下に右大腿動静脈からVA–ECMOを導入した（カテーテルサイズは脱血19.5Fr，送血13.5Fr，テルモ社キャピオックス®システムを使用，2,000回転で駆動開始）。その後，左大腿静脈アプローチで肺動脈造影を施行すると，右上葉動脈，中葉動脈，左肺尖動脈，肺舌動脈などが閉塞しており，PEと診断した（Fig. 2）。左右の肺動脈主幹部には血栓を認めず，VA–ECMO挿入後，循環動態が安定したため，直視下肺動脈血栓摘出術や，カテーテル的治療は不要と判断し，右内頸静脈から肺動脈カテーテルを留置し手技を終了した。しかし，来院から約2時間後より，顔面外傷部およびVA–ECMO，肺動脈カテーテル刺入部から止血困難な出血を認めるようになった。血液検査を再検したところ，Hb 5.6g/dLと貧血の進行およびD–dimer 264.5μg/dL，fibrinogen 50mg/dL未満，PT–INR 2.44，PLT 11.3×104/μLと凝固障害の悪化を認めた。線溶亢進型DICと診断し，顔面外傷部の縫合，鼻腔内へのガーゼタンポン挿入，カテーテル刺入部の圧迫および輸血療法を開始した。経過中，出血性合併症のため，VA–ECMO導入時を含め，抗凝固薬や血栓溶解薬は使用しなかった。VA–ECMO導入後に撮影したCT検査では，肋骨骨折，気胸，胸腹腔内出血などの胸骨圧迫による合併症は認めなかった。 Pulmonary artery angiography. Right upper lobe, middle segmental, left apical segmental, and lingular pulmonary artery branches are occluded with thrombi (arrowheads). Fig. 3aにD–dimer，fibrinogen，PLTの経時的変化および輸血療法の時間経過を示す。来院後16時間までに，赤血球濃厚液14単位，新鮮凍結血漿30単位，濃厚血小板20単位の輸血を行い，凝固障害は改善し，Hbは9.2g/dLまで上昇した。Fig. 3bにVA–ECMOの血液流量，肺動脈カテーテルで測定した心拍出量の経時的推移を示す。最大量ドブタミン5μg/kg/min，ノルアドレナリン0.1μg/kg/minを使用したが，抗凝固療法や血栓溶解療法を施行しなかったにも関わらず，心拍出量は徐々に上昇し，導入23時間後にVA–ECMOを離脱した。集中治療室に入室後に施行した超音波検査で，両側下肢深部静脈内に浮遊血栓を多数認めたため，下肢深部静脈血栓症がPEの原因と考え，VA–ECMO抜去後，回収可能型下大静脈フィルターを留置した。抗凝固療法は，出血傾向が消失し，VA–ECMO抜去部の止血が完了した第3病日から，未分画ヘパリンの持続投与を500単位/hrで開始し，APTTがコントロール値の1.5～2.5倍になるように調節した。 Clinical course of the patient. Fig. 3a shows the results of blood tests. Two–way arrow indicates the duration of blood transfusions. –●– D–dimer, –▲– Fibrinogen, –■– PLT Fig. 3b shows the hemodynamic status, and the two–way arrow shows the duration of catecholamine use. –●– CO, –▲– ECMO flow PLT: platelet count, CO: cardiac output, VA–ECMO: veno–arterial extracorporeal membrane oxygenation 第5病日に，人工呼吸器から離脱した。食事摂取量が安定した後，第12病日よりワルファリンの内服を3mg/日で開始した。下肢静脈血栓の消失した第14病日に，下大静脈フィルターを抜去した。未分画ヘパリンは，ワルファリンによる抗凝固効果が得られた第20病日まで継続した。その後の経過は良好であり，第29病日に独歩退院した。退院時のワルファリン服用量は3.5mg/日であり，PT–INRは1.61だった。 後日測定した，プロテインC活性はワルファリン3.5mg服用下で95%，プロテインS活性は90%，ループスアンチコアグラントは蛇毒法で1.29，抗カルジオリピン抗体（IgG）8U/mL以下，抗カルジオリピンβ2グリコプロテインI複合体抗体1.2U/mL以下，と正常範囲であり，先天的な血液凝固能亢進素因は認めなかった。本症例における下肢深部静脈血栓症の原因は，下肢静脈瘤による下肢血流停滞が原因と考え，永続的な抗凝固療法の継続を指示した。 「肺血栓塞栓症および深部静脈血栓症の診断，治療，予防に関するガイドライン」 5では，心肺蘇生を要する，あるいは高度なショックが遷延する広範型PEには，VA–ECMOによる循環呼吸補助を行ったうえで，血栓溶解療法，カテーテル的治療，外科的血栓摘出術などを行うことを推奨している。血栓溶解療法は，迅速な血栓溶解作用や血行動態改善作用に優れており，循環破綻を伴う重症PEの予後改善につながるとの報告 6があるが，出血性合併症のリスクがある 5, 6。 CPA蘇生後症例は，その心停止原因に関わらず，線溶亢進型DIC 1, 2や，胸骨圧迫による肋骨骨折，気胸，内胸動脈損傷などの合併報告 3, 4があり，出血性合併症のリスクが高い。とくに，extracorporeal cardiopulmonary resuscitation（ECPR）症例での出血性合併症の報告は多く，Iwashitaら 7は未分画ヘパリン3,000単位を投与したECPR 32症例のうち，3例（9%）に外科的処置や血管塞栓術を要する出血が合併したと報告している。また，Hashibaら 8は，ECPRを施行したPEによるCPA症例12例のうち，5例に血栓溶解療法を行ったところ，6例（50%）に出血性合併症を認めたと報告している。 CPA蘇生後症例に合併する線溶亢進型DICは，組織低灌流や虚血に伴い産生される内因性線溶物質が引き起こすと考えられており 1，心停止時間が長いほどその合併頻度は高くなる 2。本症例は心停止時間が約2分間と短時間であったにも関わらず，DICを合併した。広範型PEは心停止の有無に関わらず消耗性の凝固障害を合併することが知られている 9。本症例の来院時血液検査から算出した急性期DICスコアは6点であり，本症例は，来院時すでに，PEに伴う組織低灌流や虚血，あるいは凝固因子の消耗により，線溶亢進型DICが合併しており，VA–ECMO導入後も遷延したと考えた。 出血を伴う線溶亢進型DICに対しては，未分画ヘパリンの投与は禁忌であり，濃厚血小板，新鮮凍結血漿の補充が必要となる 10。しかしながら，DIC治療の根幹は基礎疾患，本症例でいえばPEの治療である 10。本症例は，出血性合併症のため抗凝固療法や血栓溶解療法などのPEの特異的治療が施行できず，VA–ECMOを用いた循環呼吸補助および合併したDICに対する輸血療法のみを施行したにも関わらず，入院翌日にはVA–ECMOから離脱できた。野村ら 11は，肺動脈近位部の血栓は，胸骨圧迫により破砕される可能性を報告している。本症例でも，肺動脈造影時に，肺動脈主幹部には血栓を認めず，上記機序による有効肺血管床の回復が血行動態の改善につながった可能性が考えられた。また，線溶亢進型DIC合併の過程で産生された内因性線溶物質が，自ら肺動脈内の血栓溶解に働きかけた可能性も示唆された。 VA–ECMO使用時には，ACTを180–200sec前後に維持するように抗凝固を行うことが推奨されている 12。本症例では，抗凝固薬を使用せずVA–ECMOを使用したが，回路トラブルは起こらなかった。今回用いたECMOは，テルモ社のキャピオックス®であり，血液流路面には，血液適合性ポリマーコーティングが施されている。同コーティングおよび患者が線溶亢進状態であったため，回路トラブルが起こらなかったと考えた。 なお，本症例では測定していないが，凝固活性化の指標となるTATや，線溶活性化の指標となるPICの測定は，DICの病態把握に有用であり 10，測定を考慮すべきであった。 線溶亢進型DICを合併した重症PE症例を経験した。CPAを合併したPEの診療の際には，胸骨圧迫に伴う胸部外傷や，線溶亢進型DICなどの出血性合併症に注意し，抗凝固療法や抗凝固療法の適応は，慎重に評価する必要がある。 本論文における利益相反はない。

Iron overload in beta thalassemia major patients

Aims: Beta thalassemia is the most common monogenic hereditary hemoglobin disorder, which poses a major health burden to Sri-Lanka. Regular transfusions of erythrocytes required for survival of these patients lead to inevitable iron overload, which is manifested, by elevated serum ferritin levels. Progressive deposition of iron leads to dysfunction and failure of the major organs. The aim of this study was to evaluate the iron overload of the beta thalassemia major patients in one of the thalassemia centres in Sri Lanka and to find its effect on growth status of the patients. Methods: The study included forty patients with confirmed diagnosis of beta thalassemia major, undergoing any chelation treatment. The mean age of the study group was 10.97±5.9 years with a range of 2–20 years. The patients were interviewed for the socio-demographic variables and their medical histories were obtained from the hospital files. Serum ferritin concentration, height and weight of the patients were measured and body mass index (BMI) was calculated. Results: The mean serum ferritin concentration was 2992.2±1575.35 ng/ml which showed a significant correlation with age and duration of blood transfusion. The mean z-score for height was -2.3±1.06 and 50% of the patients were stunted. The mean z-score for BMI was -1.32±1.28 and 35% of the patients were wasted. Both height and BMI had no significant correlation with iron overload of the patients. Conclusion: Iron overload and growth retardation were common in beta thalassemia major patients of the treatment center evaluated in this study in Sri Lanka. However, there was no significant relationship between physical growth and iron overload.

Liver Enzymes in Children with beta-Thalassemia Major: Correlation with Iron Overload and Viral Hepatitis

BACKGROUND:Beta Thalassemia is the most common chronic hemolytic anemia in Egypt (85.1%) with an estimated carrier rate of 9-10.2%. Injury to the liver, whether acute or chronic, eventually results in an increase in serum concentrations of Alanine transaminase (ALT) and Aspartate transaminase (AST).AIM:Evaluating the potentiating effect of iron overload & viral hepatitis infection on the liver enzymes.PATIENTS AND METHODS:Eighty (80) thalassemia major patients were studied with respect to liver enzymes, ferritin, transferrin saturation, HBsAg, anti-HCV antibody and HCV-PCR for anti-HCV positive patients.RESULTS:Fifty % of the patients were anti-HCV positive and 55% of them were HCV-PCR positive. Patients with elevated ALT and AST levels had significantly higher mean serum ferritin than those with normal levels. Anti-HCV positive patients had higher mean serum ferritin, serum ALT, AST and GGT levels and higher age and duration of blood transfusion than the negative group. HCV-PCR positive patients had higher mean serum ferritin and serum ALT and also higher age and duration of blood transfusion than the negative group.CONCLUSION:Iron overload is a main leading cause of elevated liver enzymes, and presence of HCV infection is significantly related to the increased iron overload.

Ocular abnormalities in multi-transfused beta-thalassemia patients

Aims:The aim of this study was to assess ocular changes in thalassemia patients who have received multiple transfusions and chelate binding therapy in order to avoid iron accumulation.Settings and Design:A cross-sectional study.Subjects and Methods:A total of 54 thalassemia major patients were selected as case group, and 54 age- and sex-matched healthy subjects were regarded as a control group. Ocular examination included visual acuity, refraction testing, slit lamp examination, funduscopy, tonometry, perimetry, tear break-up time test, and color vision testing were performed for all the participants. We computed the frequency and duration of blood transfusion, the mean serum ferritin level, pretransfusion hemoglobin concentration, and type, duration, and daily dose of chelation therapy for thalassemia patients based on their records.Statistical Analysis Used:All data analysis was performed using SPSS, version 19.Results:All the thalassemic patients were asymptomatic, but abnormal ocular findings (dry eye (33.3%), cataract (10.2%), retinal pigment epithelium degeneration (16.7%), color vision deficiency (3.7%), and visual field defects (33.7%)) were seen in 68.5% of thalassemic group. The prevalence of ocular abnormalities in normal group was 19.4%, which was significantly lower than that in thalassemia patients (P = 0.000). No significant correlation was found between ocular abnormalities and mean serum ferritin level (P = 0.627) and mean hemoglobin concentration (P = 0.143). Correlation of number of blood transfusion with the presence of ocular abnormalities was found to be statistically significant (P = 0.005).Conclusions:As life expectancy for beta-thalassemia patients extends, regular ophthalmological evaluation to detect early changes in their ocular system is recommended.

Prevalence of Helicobacter pylori infection among β-thalassemia major children with recurrent abdominal pain at Suez Canal University Hospital

Background Recurrent abdominal pain (RAP) is a common pediatric problem and it is also one the several gastrointestinal tract disturbances frequently seen in β-thalassemia major (β-TM) patients. Helicobacter pylori is known to be an etiological agent of chronic gastritis and peptic ulcer diseases, but its correlation with RAP is still under debate. Aim The aim of the study was to determine the prevalence of H. pylori infection among β-TM children with RAP. Patients and methods This study was cross-sectional in design. We recruited 48 β-TM cases (24 β-TM children who presented with RAP and 24 β-TM children who did not present with RAP), aged 5-18 years, and 48 age-matched and sex-matched controls (24 children who presented with RAP without any other apparent manifestations of disease and 24 healthy children who did not present with RAP). Children who presented with RAP fulfilled Apley's criteria for the diagnosis of RAP. All patients and controls had undergone serum H. pylori IgG evaluation by ELISA. Results The seroprevalence of H. pylori in β-TM patients who presented with RAP was more common than in controls who presented with RAP [14/24 (58.3%) vs. 7/24 (29.2%); P = 0.04]. Also, there was a statistically significantly higher seroprevalence of H. pylori among the total number of β-TM children than among the total number of control children [24/48 (50%) vs. 12/48 (25%)]. The mean duration of splenectomy was statistically significantly higher in total β-TM children who were H. pylori IgG positive than among total β-TM children who were H. pylori IgG negative. There was no significant difference between total H. pylori IgG-positive β-TM children and age, sex, duration of blood transfusion, duration of iron chelating agent, criteria of abdominal pain, and serum ferritin level. Conclusion There was a higher prevalence of H. pylori IgG in β-TM children with RAP than among control children with RAP, as well as among total β-TM children than among total control children. H. pylori IgG was detected more frequently in thalassemic patients with a longer duration of splenectomy.

The Correlation Of Hepatic Iron Loading Determined By Magnetic Resonance Image and Serum Ferritin In Patients With Beta-Thalassemia Intermedia

BackgroundCurrent practice of starting iron chelation when ferritin values reach 1,000 mcg/l has been given to patients with thalassemia disease. The body iron load in patients with thalassemia intemedia can be different from other severe thalassemia disease due to the increased intestinal iron absorption. ObjectiveThe correlation of hepatic iron loading determined by magnetic resonance image study (MRI) and various parameters was calculated. Materials and MethodsMRI study, using CRMtool to determine the myocardial and hepatic iron loading, was performed in pediatric patients with beta-thalassemia intermedia. The amount of blood transfusion and duration of iron chelation were recorded. The levels of serum ferritin as well as the transfusion-transmitted diseases were checked twice yearly. ResultsIn all, 40 patients (19 males, 23 females) manifested as beta-thalassemia intermedia were enrolled in the study. They included beta thalassemia/HbE disease (n=37) and beta thalassemia major (n=3) with the mean age of 14.9±3.6 years. Three patients with beta-thalassemia major behaved as beta-thalassemia intermedia since two patients carried the combination of beta-thalassemia0 and beta-thalassemia+ genes while another patient had an additional alpha-thalassemia gene. The remaining patients possessed the combination of beta-thalassemia genes at codon 41/42 (4 base pair deletion) and HbE gene at codon 26 (GAG>AAG). All patients received routine hepatitis B vaccination. None had positive serological testing for HBsAg, antiHCV or antiHIV. They required regular transfusion to maintain their pre-transfusion hematocrit at 24% starting at the mean age of 4.1±3.3 years with the mean duration of 10.1±4.6 years. Nineteen were splenectomized at the mean age of 8.0±3.1 years. They all received iron chelation of 10-12 hours of desferrioxamine subcutaneous injection, oral deferiprone ingestion or the combination of desferrioxamine and deferiprone starting at the mean age of 9.1±3.8 years with the mean duration of 6.2 ±4.3 years. At the mean age of 14.9±3.6 years, they underwent MRI study and revealed that the mean T2* of myocardium was 38.6±8.1 milliseconds (ms) and mean T2* of liver was 3.2±2.0 ms. Neither patients had myocardial iron loading while 36 patients had hepatic iron loading varying from severe degree of <1.4 ms (iron >10 mg/g dry weight, n=4), moderate degree of >1.4-2.7 ms (iron >5-10 mg/g dry weight, n=16) and mild degree of >2.7-6.3 ms (iron 2-5 mg/g dry weight, n=16). The results revealed no correlation of the hepatic T2* and the duration of blood transfusion (p=0.157), duration of iron chelation (p=0.071), total blood transfusion and total iron loading from transfusion (p=0.471) one-year blood transfusion and one-year iron loading from transfusion (p=0.321) except for the serum ferritin (p=0.001). The geographic mean of ferritin was 1584.9 mcg/l. The hepatic iron loading by MRI was shown in the equation of T2*(ms) = 4.663-0.001ferritin (mcg/l) (r=-0.503, p=0.001). Patients with serum ferritin ≥1,000 mcg/l risked hepatic iron loading (T2*<2.7 ms, iron 5-10 mcg/g dry weight) with an odds ratio of 5.07 (95% CI 1.09-23.44). Therefore, patients with beta-thalassemia intermedia were at risk of hepatic iron overloading if the initiation of iron chelation started at the serum ferritin of 1,000 mcg/l. ConclusionThe current practice of starting iron chelation when ferritin values reach 1,000 mcg/l risks hepatic iron loading in patients with beta-thalassemia intermedia. Advanced technology for evaluating hepatic iron loading is suggested. Thus, where MRI study is not feasible, serum ferritin can be used to estimate the hepatic T2*. Disclosures:No relevant conflicts of interest to declare.

Determination of serum protein desialylation status as an indicator of duration of transfusion therapy in individuals with thalassemia syndrome

In thalassemia patients blood transfusion is the mainstay of therapy. Blood transfusion is associated with oxidative stress. Oxidative stress has its influence on plasma proteins. The present study was carried out to explore the level of sialic acid content and oxidative changes in serum proteins of thalassemia subjects on regular blood transfusion. Blood was collected from thalassemia patients receiving long duration of blood transfusion and from newly diagnosed cases of thalassemia who never receive blood transfusion and from carriers or traits of thalassemia as control. The extent of carbonylation and desialylation of serum protein was estimated by dinitrophenylhydrazine and thiobarbuturic acid method respectively. The effects of in vitro treatment of serum protein H2O2 on the above mentioned parameters were observed. Carbonylation of serum protein was significantly higher and sialic acid content of serum protein significantly lower in thalassemia subjects on regular blood transfusion. A significant negative correlation exists between carbonylation and sialic acid content of serum protein. Enhanced desialylation and carbonylation of serum protein by in vitro H2O2 treatment suggest that oxidative stress can cause desialylation of serum proteins.

PULMONARY FUNCTION TEST IN TRANSFUSION-DEPENDENT β-THALASSEMIA PATIENTS

β-Thalassaemia is the most common hemoglobinopathies in our region with treatment of regular blood transfusion. Iron overload and hemosiderosis can cause organ involvement. Recent studies have focused on pulmonary involvement and pathophysiology of lung damage. The goal of this study was to investigate the pulmonary abnormalities in thalassemic patients in relation with sign and symptoms and iron overload. The authors studied pulmonary function test (PFT) at the Adult Thalassemia Clinic in Tehran. The history of blood transfusion, iron chelation, respiratory problems, and drug usage was taken. Physical examination, PFT, arterial blood gas (ABG), and chest X-ray (CXR) were done. In total, 139 patients were studied. The mean age was 21.1 years and mean duration of transfusion was 18 years. It was found that 133 patients (95.7%) did not have respiratory problems and only 6 (4.3%) had some respiratory complaints. In CXR, 100 patients (89.3%) had normal lung pattern and others (10.7%) had variable degrees of abnormal lung pattern. In ABG, mean of Po2 was 73.5% and mean of O2 saturation was 90.6%. In PFT, 101 patients (72.7%) had restrictive pattern, 35 (25.1%) had normal pattern, and 3 (2.2%) had combined pattern. According to vital capacity, the patients were placed in five categories: 54 patients (38.8%) normal, 37 (26.6%) mild, 35 (25.3%) moderate, 10 (7.2%) severe, and 3 (2.1%) extremely severe pulmonary deficit. There was no statistical significance between PFT results with all variables studied, except duration of blood transfusion, which may be considered a indirect effect of iron load (p =. 05, r =. 361). According to these results, restrictive pattern was the most common finding (72.7%) in PFT, while 95.7% of patients had no respiratory complaint, and in the chest X-ray group, 89.3% had normal pattern. The authors conclude that the lung may be considered a site for organ damage, and alteration of pulmonary function may be expected in transfusion-dependent patients in spite of no pulmonary symptoms or normal CXR. In recent years, because of new iron chelating drugs, doctors can expect thalassemic patients to have a long life-time and need to increase their quality of life. One way to do this is to evaluate the respiratory system by PFT to prevent the squeal of pulmonary disease.

Accuracy and efficacy of nuclear scintigraphy for the detection of gastrointestinal bleeding.

To determine the accuracy and cost-effectiveness of nuclear scintigraphy for the diagnosis and localization of gastrointestinal (GI) bleeding and to determine whether nuclear scintigraphy accurately predicts the results of angiography. Retrospective chart review. The following data were obtained from the medical records: age; diagnosis before scintigraphy; duration of bleeding; hemoglobin and hematocrit values; number and duration of blood transfusions; results of angiography and GI endoscopy; location of bleeding as determined by angiography, endoscopy, and nuclear scintigraphy; treatment received by patients; actual site of bleeding as documented in the medical record; and outcome of treatment. Community hospital in a city with a population of approximately 100,000 and a catchment area of approximately 500,000. One hundred fifty-five patients undergoing 161 nuclear scintigraphic examinations because of GI bleeding between January 1, 1989, and December 31, 1992. Diagnosis and location of GI bleeding as determined by nuclear scintigraphy and angiography and actual site of GI bleeding as confirmed by operative intervention or endoscopy. Of 114 scintigraphic examinations for which the diagnosis and localization of GI bleeding were definite, results were positive in 56 (49.1%); of these 56, a definite location of the bleeding was shown in 51 cases (91.1%), and the bleeding was localized to its exact site in 22 cases (19.3%). Of the scintigraphic examinations for which results were positive, results of angiograms were positive in 7 cases, which gives nuclear scintigraphy a 39% positive predictive value for angiography. The routine use of nuclear scintigraphy is neither accurate nor cost-effective for determining the site of GI bleeding in the community hospital.

Hormonal changes in thalassaemia major.

Patients with severe thalassaemia major suffer endocrine and other abnormalities before their eventual death from iron overload due to repeated blood transfusions. The endocrine status of 31 thalassaemic patients aged 2-5 to 23 years was investigated. Exact data were available on the rate and duration of blood transfusion in all of them and in many the liver iron concentration was also known. Although the patients were euthyroid, the mean serum thyroxine level was significantly lower, and the mean thyrotrophic hormone level significantly higher, compared with the values found in normal children. Forty oral glucose tolerance tests with simultaneous insulin levels were performed in 19 children, of whom 5 developed symptomatic diabetes and one had impaired tolerance. Previous tests on all 6 patients were available and some showed raised insulin levels possibly due to insulin resistance. 2 patients had clinical hypoparathyroidism and are described. The parathyroid hormone levels determined by radioimmunoassay in 25 patients were below the mean for the age group in all and outside the reference range in 16. Nonfasting plasma calcium levels were not reduced. Puberty was delayed in some patients. Concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measured in urine from 7 girls and 5 boys showed considerable variation. In the boys there was an overall tendency for FSH and LH excretion to be low with regard to age, but with respect to puberty rating FSH exretions were normal or low and LH normal or raised. The girls showed a tendency for LH but not FSH excretion to be raised in relation to puberty rating. The severity of the endocrine changes was related to the degree of iron loading and is discussed in relation to previous work in which the iron loading has rarely been accurately indicated nor parathyroid status assessed.