Hypertransfusion Therapy Research Articles

Unveiling Extramedullary Hematopoiesis: A Case Report Highlighting the Causes, Symptoms, and Management Strategies

Extramedullary hematopoiesis (EMH) serves as a compensatory mechanism in chronic hemolytic anemias, such as thalassemia, and can result in spinal cord compression. This case report highlights a 36-year-old woman with transfusion-dependent β-thalassemia (TDT) who presented with lower extremity motor deficiency, pelvic paresthesia, and bladder dysfunction. The patient had a history of lower back pain, bilateral lower limb weakness, and demonstrated poor compliance with iron chelation therapy. MRI findings indicated spinal cord compression attributable to extramedullary hematopoiesis. Due to the infeasibility of surgical intervention, the patient underwent hypertransfusion and iron chelation therapy. While neurological symptoms improved, urinary retention persisted. The patient continues to receive iron chelation treatment and undergo transfusions. Managing extramedullary hematopoiesis in thalassemia necessitates an individualized treatment approach.

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.

Epidemiological and Clinical Profile of Iraqi Patients with β-Thalassemia Major

Thalassemia is an autosomal recessive inherited blood disorder due to hemoglobin-production abnormalities. Over the past three decades, hyper-transfusion therapy in these patients has shown significant increase in life expectancy and quality of life. unfortunately, this type of therapy also increased the frequency of complications due to iron overload. The study aims to identify the Sociodemographic and clinical characteristics of patients with thalassemia, and to assess transfusion related complication among them. A descriptive, cross-sectional study was conducted in Thalassemia Center in Al-Najaf province in Iraq, during the period from the 1st of April to the 31st of August 2018. Data were collected through direct interview with patients/parents using a specially designed questionnaire form. A total of 175 transfusion dependent thalassemia major patients were included, the mean age 10. 5 years ranging from 5 m to 34years. Patients under 10 years of age represented the highest rate with Male: Female ratio 1.2:1. 60% were from rural area with high percentage of parental consanguinity (70%). The study documented the relationship between iron over load and appearance of complications. Development of preventive measures as genetic counseling, prenatal diagnosis, pre-marital screening are the best ways to decrease the incidence of disease, in addition to regular blood transfusion with optimum chelation therapy.

Severe hereditary spherocytosis and distal renal tubular acidosis associated with the total absence of band 3

AbstractAbsence of band 3, associated with the mutation Coimbra (V488M) in the homozygous state, caused severe hereditary spherocytosis in a young child. Although prenatal testing was made available to the parents, it was declined. Because the fetus stopped moving near term, an emergency cesarean section was performed and a severely anemic, hydropic female baby was delivered. She was resuscitated and initially kept alive with respiratory assistance and hypertransfusion therapy. Cord blood smears revealed erythroblastosis, poikilocytosis, and red cells with stalk-like elongations. Band 3 and protein 4.2 were absent; spectrin, ankyrin, and glycophorin A were significantly reduced. Renal tubular acidosis was detected by the age of 3 months. Nephrocalcinosis appeared soon thereafter. After 3 years of follow-up the child is doing reasonably well on a regimen that includes regular blood transfusions and daily bicarbonate supplements. The long-term prognosis remains uncertain given the potential for hematologic and renal complications.

Low Bone Mineral Density in Thalassemia Major: Sanjay Gandhi Post Graduate Institute Experience and a Brief Focus on Underlying Factors behind the Cause

Thalassemia major is a genetic disorder and blood transfusion is critical for survival in these patients. Over the course of the past three decades, hyper transfusion therapy in these patients has shown has dramatically extended life expectancy and improved quality of life. Unfortunately, this type of therapy also increased the incidence of complications due to iron overload. The aim of this study was to assess bone mineral density (BMD) in patients with β-thalassemia major and to determine their biochemical and hormonal profiles that may affect BMD. A cross- sectional study was carried out in Sanjay Gandhi—PGIMS, a tertiary care hospital over period of 3 years on all β-thalassemia major patients above 7 years receiving regular transfusion. Patients with transfusion dependent anaemia other than β thalassemia major were excluded. Physical examination, laboratory tests and bone density measurements were performed. Then, the data were analyzed. The total number of children over 7 years of age with β-thalassemia major receiving regular blood transfusions during the study period was 150. Mean hemoglobin was 7.8 ± 0.6 g/dL and the mean serum ferritin level 5295 ± 2736 ng/mL. Short stature was seen in 54.7% boys and 28.7% of girls. Prevalence of lumbar osteoporosis and osteopenia were 42.5% and 37.5%. Femoral osteoporosis and osteopenia were present in 32.5% and 55% of the patients. Impaired puberty, hypothyroidism, diabetes mellitus, hypoparathyroidism were observed in 26%, 18%, 7%, and 15%, of patients, respectively. Nearly 75% of patients had low bone mineral density. Bone mineral density was significantly associated with short stature (p = 0.002), hypogonadism (p = 0.006), hypoparathyroidism (p = 0.038), hypothyroidism (p = 0.044) and vitamin D deficiency (p &lt; 0.001). High prevalence of complications among our thalassemics signifies the importance of more detailed studies along with therapeutic interventions.

Hypertransfusion therapy in sickle cell disease in Nigeria.

Introduction. Hypertransfusion refers to chronic blood transfusion therapy aimed at ameliorating disease complications in various haemopathies particularly the haemoglobinopathies. In sickle cell disease, hypertransfusion is aimed at maintaining patient's haemoglobin level at 10 to 11 g/dL using haemoglobin AA blood and its resultant dilutional effect on sickle haemoglobin is sustained by intermittent long-term transfusions. Aim and Objective. This paper highlights hypertransfusion and its privileged position as a secondary measure in prevention and treatment of sickle cell disease, especially in the Nigerian context. Materials and Methods. Relevant literatures were searched on PubMed, Google Scholar and standard texts in haematology and transfusion medicine. Keywords used in the search are hypertransfusion, sickle cell disease, chronic transfusion, and Nigeria. Literatures gathered were reviewed, summarized, and presented in this paper. Result. Immense clinical benefit is associated with hypertransfusion therapy including prevention of stroke and amelioration of severe sickle cell disease especially in transplant ineligible patients. Careful patient selections, appropriate blood component, and prevention of transfusion hazards as well as oversight function of an experienced haematologist are pertinent to a successful hypertransfusion therapy. Conclusion. Improved knowledge of the benefits and practice of hypertransfusion will effectively translate into improved health status even among Nigerian sickle cell disease patients.

Primary Amenorrhea in a Thalassemia Major

ABSTRACT Background Thalassemia major is a severe type of hemolytic anemia. Hypertransfusion therapy in these patients can lead to iron overload and iron tissue toxicity leading to structural, metabolic and endocrine abnormalities. Case Report We hereby present a case of 16-year-old unmarried girl with thalassemia major presenting with primary amenorrhea and poorly developed secondary sexual characteristics. A thorough history, clinical examination, laboratory and radiological investigations were conducted. These tests confirmed the diagnosis of hypogonadotrophic hypogonadism. Patient was started on hormone replacement therapy. She is on regular follow-up and compliant with her treatment. Conclusion Timely recognition and management of hypertransfusion therapy in thalassemia major patients will have a favorable psychological outcome and improves the quality of life. How to cite this article Mishra VV, Choudhary S, Aggarwal RS, Ninama S, Dudhat A. Primary Amenorrhea in a Thalassemia Major. J South Asian Feder Obst Gynae 2014;6(2):114-115.

Effect of Hypertransfusion on Extramedullary Hematopoietic Compression Mass in Thalassemia Major: A Case Report

Hereby we report a patient with thalassemia major having extradural cord compression at T3-T9 levels due to a mass of extramedullary hematopoiesis (EMH) tissue, whose treatment was successful with hypertransfusion therapy alone. The patient was a 23-year-old man who had not received regular blood transfusion since two years before admission. He suffered from paraparesis with a history of progressive lower limb weakness for 2 months. MRI of the spinal cord demonstrated thoracic extramedullary hematopoietic mass causing spinal cord compression. The patient demonstrated a significant response to hypertransfusion and improvement in the neurologic status started a few days after treatment. Almost complete resolution of the mass was seen in spinal MRI one week after hypertransfusion. Hypertransfusion seems to be a useful method for treatment of spinal cord compression due to a hematopoietic mass. It may be used as the first line therapy.

Hematopoietic Stem Cell Transplantation for Thalassemia

Thalassemia is an autosomal recessive disorder associated with defective synthesis of the α- or β-chain of hemoglobin. For β-thalassemia major patients, therapeutic options are either monthly red cell transfusions and chelation therapy or allogeneic stem cell transplant. Patients undergoing transfusion therapy remain at risk for transmitted infections and iron overload with associated tissue damage. Stem cell transplant is the only curative approach and success is inversely correlated with the degree of iron overload and hepatic damage. Overall outcomes following stem cell transplant with a matched sibling donor are excellent with over 90% of low-risk children becoming transfusion free. Hypertransfusion therapy and aggressive chelation in addition to hydroxyurea, azathioprine and fludarabine is a new approach for high-risk patients to decrease graft rejection by suppressing endogenous erythropoiesis pretransplant. The use of unrelated donors and novel approaches such as gene therapy are under current investigation.

Intracranial extramedullary hematopoiesis in patients with thalassemia: a case report and review of the literature

Extramedullary hematopoiesis (EH) is a compensatory phenomenon that results in the production of blood cell precursors outside the marrow in patients with chronic hemolytic anemia and ineffective erythropoiesis. EH usually involves the liver, spleen, and lymph nodes. It can also be found at paravertebral, intrathoracic, or pelvic locations. Intracranial EH is a rare entity and often asymptomatic but can sometimes lead to symptomatic tumor-like masses. Treatment options are controversial and include hypertransfusion, surgical excision, radiotherapy, and hydroxyurea (HU). Successful treatment of an intracranial EH mass with HU and blood transfusions in a beta-thalassemia major patient was discussed along with a review of the published literature on intracranial EH in thalassemia. In our patient, the extramedullary hematopoietic mass in the interhemispheric fissure showed a marked improvement after 6 months of HU and hypertransfusion therapy. In the English literature, there are a few cases with intracranial EH and thalassemia, which were treated with different treatment modalities, with different outcomes. There is no standard treatment approach in patients with symptomatic EH. HU with hypertransfusion regimen is a reasonable first-choice modality in treating intracranial EH masses.

A case of hypophosphatemic osteomalacia secondary to deferasirox therapy

Patients with β-thalassemia major require iron-chelation therapy to avoid the complication of iron overload. Until recently, deferoxamine (DFO) was the major iron chelator used in patients requiring chronic hypertransfusion therapy, but DFO required continuous subcutaneous therapy. The availability of deferasirox (Exjade®), an orally active iron chelator, over the past 4 years represented a necessary alternative for patients requiring chelation therapy. However, there have been increasing reports of proximal renal tubular dysfunction and Fanconi syndrome associated with deferasirox in the literature. We report a case of hypophosphataemic osteomalacia secondary to deferasirox therapy.

Recurrent intrahepatic pigmented stones after liver transplantation in a patient with hemoglobin SC disease: Case report and review of the literature

Patients with hemoglobinopathies may have hepatic involvement, which if severe, can lead to chronic liver disease and a need for liver transplant. Here, we present a case of a 16-yr-old female adolescent who presented to our center with hemoglobin SC disease, obstructive jaundice because of pigmented intrahepatic biliary stones, and progressive liver disease. She underwent a successful liver transplant but a few years later, she developed recurrent cholangitis and graft dysfunction because of recurrent intrahepatic biliary stones. Recurrent formation of intrahepatic stones after liver transplant is a rare and severe complication in patients with hemoglobinopathies. We recommend hypertransfusion therapy and surveillance imaging studies after liver transplant for early detection and prevention of this complication.

Iron overload : A cause of primary amenorrhea

Primary amenorrhea i.e. absence of menses, resulting from hypogonadotropic hypogonadism occurs when the hypothalamus fails to secrete adequate amounts of gonadotropin releasing hormone (GnRH) or when a pituitary disorder is associated with inadequate production or release of pituitary gonadotropins [1]. Thalassemia major, a severe hemolytic anaemia due to a genetic defect in the synthesis of haemoglobin chain, can produce hypopituitarism. This hypopituitarism leads to hypogonadotropic hypogonadism, an endocrinopathy occurring secondary to iron overload [2]. The iron overload is a consequence of frequent blood transfusion, which is the most important treatment modality for thalassemia major. Other possible causes of hypogonadism in beta thalassemia major include liver disorders, chronic hypoxia, diabetes mellitus and zinc deficiency [3]. The anterior pituitary is especially sensitive to increased iron concentration which disrupts the hormonal secretion leading to hypogonadism, short stature and acquired hypothyroidism [4]. We present a case of primary amenorrhea in a thalassemie patient to highlight that hypertransfusion and regular chelation therapy may have allowed improved survival in patients with thalassemia major but despite medical advances, growth failure and hypogonadism remains a significant clinical problem in these patients in adolescence.

Intracranial mass in a patient with thalassaemia major

A 30-year-old man with thalassemia major was referred with headache. Neurological examination revealed no abnormalities and a diagnosis of ‘tension headache’ was made. An analgesic and an antidepressant were prescribed. After taking these medications for 3 months, his headache hadn’t improved so cranial magnetic resonance imaging (MRI) was done. This revealed a mass in the interhemispheric fissure measuring 4 · 5 · 11AE5 cm (Image). A biopsy of the lesion showed extramedullary haemopoiesis. The mass was considered unsuitable for surgery or radiotherapy. Hydroxycarbamide treatment in a dose of 1000 mg/day and hypertransfusion therapy were initiated.

Assessment of Renal Function in Transfused b-Thalassemia Patients Based on Cystatin C Measurements and Equations.

Cystatin C is a non-glycosylated protein that belongs to the cystatin superfamily of cysteine protease inhibitors. Its low molecular weight (13.3kDa) and positive charge at physiological pH levels facilitates its glomerular filtration and subsequently it is reabsorbed and almost completely catabolized in the proximal renal tubules. Therefore and due to its constant rate of production, its serum concentration is determined by the rate of glomerular filtration (GFR). Cystatin C production in the body is a stable process that is not influenced by renal conditions, increased protein catabolism or dietary factors. Moreover, in contrary to creatinine, it does not change with age or muscle mass. For these reasons, serum cystatin C has been suggested to be an ideal endogenous marker of GFR. Studies on the renal function of patients with transfusion-dependent β-thalassemia are sparse. These studies suggested that the renal abnormalities observed in β-thalassemia are due to proximal tubular dysfunction and postulated that their severity is related with the degree of anemia. They were less severe in patients on hypertransfusion and appropriate desferrioxamine therapy suggesting that the damage might be caused by both anemia and increased oxidation induced by excess iron deposition. None of these studies have demonstrated renal insufficiency as reflected by decreased GFR. This was probably due to the fact that all estimations were based on creatinine measurements. In this study we estimated GFR in 195 transfused patients with β-thalassemia major by measuring cystatin C and calculating GFR according to the recently proposed cystatin C-based prediction equation using only concentration in mg/L and a prepubertal factor:1GFR [mL/min/1.73m2] = 84.7 × cystatin C (mg/L)−1.68 × 1.38* (*if a child <14 years). We found that 136 patients had normal cystatin C levels (0.66–1.03mg/L) and GFR values (80–170mL/min/1.73m2), 36 patients had mild renal insufficiency (cystatin C levels: 1.04–1.22mg/L and GFR values: 60–79mL/min/1.73m2), 21 patients had moderate renal insufficiency (cystatin C levels: 1.23–1.72mg/L and GFR values: 34–59mL/min/1.73m2), while 2 patients had severe renal insufficiency with cystatin C levels >2.5mg/L and GFR values <20mL/min/1.73m2. We further determined plasma levels of Neutrophil gelatinase-associated lipocalin (NGAL) in 30 randomly selected patients. NGAL is a protein expressed on tubular cells of which the production is markedly increased in response to harmful stimuli, such as ischemia or toxicity. We found increased NGAL levels in 19 β-thalassemia patients (mean: 95.0±45.0mg/L compared to normal values of 51.2±11.8mg/L, p<0.0003). NGAL levels correlated significantly with cystatin C levels (r=0.740, p<0.0001), indicating that the renal impairment in these patients seems to be originated from tubular injury. The findings of this study indicate that renal insufficiency is present in a significant proportion of transfusion-dependent β-thalassemia patients. Further studies are warranted in order to identify predisposing factors that contribute to the renal damage in thalassemia and to establish appropriate guidelines for the evaluation and follow up of renal function in these patients. 1. Clin Chem 2005; 51:1420–143.

SUCCESSFUL TREATMENT OF SPINAL CORD COMPRESSION SECONDARY TO EXTRAMEDULLARY HEMATOPOIETIC MASS BY HYPERTRANSFUSION IN A PATIENT WITH THALASSEMIA MAJOR

A 15-year-old girl with thalassemia major who suffered from paraparesis with a history of progressive lower limb weakness for 2 years immigrated from mainland China to Hong Kong. She had not received regular blood transfusion since the age of 6 years after splenectomy. MRI of the spine showed thoracic spinal cord compression secondary to extramedullary hematopoietic mass. She made significant recovery with hypertransfusion therapy alone. MRI of the spine repeated 3 months later showed nearly complete resolution of the extramedullary hematopoietic mass.

Comparison of Oral and Subcutaneous Iron Chelation Therapies in the Prevention of Major Endocrinopathies in β-Thalassemia Major Patients

While hypertransfusion and subcutaneous iron chelation therapy have increased longevity of patients with β-thalassemia (thal) major, endocrinopathies have become more common and impair the quality of their lives. Additionally, subcutaneous iron chelation therapy is an uncomfortable experience and can prevent patients from regular compliance with iron chelation therapy. We compared the efficacy of oral deferiprone (L1) to subcutaneous desferrioxamine (DFO) chelation therapy for the prevention of major endocrinopathies (growth hormone insufficiency, diabetes mellitus and gonadal dysfunction) among patients with β-thal major to see if we could offer these patients an easier and more painless way to reduce their body iron load and related endocrine complications.

Growth of children with β-thalassemia major

Hypertransfusion and regular chelation therapy have allowed improved survival in patients with thalassemia major (TM). Despite medical advances, growth failure and hypogonadism remain significant clinical problems in these patients in adolescence. Disproportionate truncal shortening which is common especially among adolescents with thalassemia, is due to platyspondyly resulting from a combination of factors like hemosiderosis, desferrioxamine toxicity or deficiency of trace elements. Although growth hormone (GH) deficiency and GH neurosecretory dysfunction have been described in TM patients, most short TM patients have normal GH reserve. The low serum IGF-1 and IGFBP-3 concentrations in TM patients despite having normal GH reserve and serum GH binding protein levels suggest that a state of secondary GH insensitivity exists. The pubertal growth spurt may be impaired in TM patients going through spontaneous or induced puberty and may have a negative effect on final adult height. GH therapy in dosages ranging from 0.5-1.0 IU/kg/wk has resulted in a significant improvement in growth velocity in short TM children without any adverse effects on skeletal maturation, blood pressure, glucose tolerance and serum lipids. There is limited evidence that GH treatment can result in an improved final adult height in short TM children. Careful and regular clinical and biochemical monitoring should be preformed on these patients while they are treated with GH.

Low Bone Mass in Prepubertal Children with Thalassemia Major: Insights into the Pathogenesis of Low Bone Mass in Thalassemia

Low bone mass occurs frequently in the aging thalassemic population. However, limited information exists on bone mass in children with thalassemia major (TM) during their first decade of life. Spinal bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA) in 18 children (age 5.8 +/- 1.5 yr; M:F 8:10) with TM on hypertransfusion and iron chelation therapy. Serial BMD measurements were available for 11 of the 18 children. Weight and height z scores were 0.81 +/- 4.2 and -0.47 +/- 1.7 respectively. At the first BMD, four (22.2%) patients presented with BMD z scores less than -2.5, seven (38.8%) had BMD z scores between -1 and -2.5, while the remaining seven (38.8%) had normal BMDs (z score above -1). The mean decline of BMD z score was -0.38/year (p = ns). BMD z scores correlated with height z scores (p = 0.039), but not with liver enzymes, serum ferritin levels, or thalassemia genotypes. Low bone mass is present in most children with TM despite hypertransfusion and optimal chelation, adequate growth and lack of endocrine complications.

Renal tubular dysfunction in alpha-thalassemia.

Shortened red cell life span and excess iron cause functional and physiological abnormalities in various organ systems in thalassemia patients. In an earlier study, we showed that beta-thalassemia patients have a high prevalence of renal tubular abnormalities. The severity correlated with the degree of anemia, being least severe in patients on hypertransfusion and iron chelation therapy, suggesting that the damage might be caused by the anemia and increased oxidation induced by excess iron deposits. This study was designed to define the renal abnormalities associated with alpha-thalassemia and to correlate the renal findings with clinical parameters. Thirty-four pediatric patients (mean age 8.2+/-2.8 years) with Hb H disease or Hb H/Hb CS were studied. Ten patients (group 1) were splenectomized, with a mean duration post splenectomy of 3.5+/-1.4 years; 24 patients (group 2) had intact spleens. The results were compared with 15 normal children. Significantly higher levels of urine N-acetyl-beta- d-glycosaminidase, malondialdehyde (MDA), and beta(2)-microglobulin were found in both groups compared with normal children. An elevated urine protein/creatinine ratio was recorded in 60% of group 1 and 29% of group 2. Two patients (5.9%), 1 in each group, had generalized aminoaciduria. We found proximal tubular abnormalities in alpha-thalassemia patients. Increased oxidative stress, possibly iron induced, may play an important role, since urine MDA levels were significantly increased in both groups of patients.