Ho/01(P) incidence of iron deficiency in non anaemic children

HO/32(O) PARENTAL REACTIONS IN THALASSEMIA MAJOR PATIENTS

Gulgoona Jamal, Anupam Sachdeva, Ashum Gupta, Roma Kumar, VK Khanna, Vinita Jain, SP Yadav

Department of Pediatrics, Center for Child Health, Sir Ganga Ram Hospital

& Department of Psychology, University of Delhi, New Delhi
The relationship between psychology and medicine is often ambivalent. There is often misunderstanding between the disciplines about their role and responsibilities and by differences in patterns of communication, charting professional etiquette and approaches towards conceptualizing patient difficulties. The diagnosis of a chronic illness is accompanied by extraordinary stressors for the child and family that place them at risk for psychological difficulties associated with the disease and increase their vulnerability to non disease stressors. The present study investigated parents responses to the diagnosis of thalassemia major in their children and its treatment, their levels of emotional distress, their perceptions of the effects of the illness on family life, the support available to them, their unmet needs, the cognitive appraisal strategies employed and their ability to cope. Relationships between emotional distress and reported effects: support, unmet needs, cognitive reappraisal and ability to cope were investigated. 50 families were identified as eligible for the study and 40 families agreed to be interviewed. The eligibility criteria were that the child with Thalassemia was under 18 years old and living at home, the parents spoke enough English or Hindi to take part in interviews. All children in the study were receiving treatment. A performa was devised to collect information about the composition of the household and the family, amenities at home, health of family members, education and occupation of parents, age and educational status of the child with thalassemia. A semi structured interview was devised focusing on a number of areas, such as the time of diagnosis, how parents obtained the diagnosis, the way the diagnosis was communicated, their view of the information obtained, the effects of the illness on the parental employment and family’s financial position, changes in family relationships, partners relationship and social relationships brought about by the illness. Parental emotional distress was assessed using the Malaise Inventory. The diagnosis was communicated to 40% of parents when the child’s age was < 6months and 35% of parents when the childs age was <12 months. The doctor communicated the diagnosis in 95% of the cases. The majority were satisfied with the way in which they were told the diagnosis. The feelings at the time of diagnosis were disbelief (87.5%), depression (80%), anxiety (72.2%), guilt as to the genetic nature of the disease (17.5%) and relief by one mother who felt that knowing the disease makes it easier to cope. The employment was affected negatively in 60% of the cases especially for the mothers. 75% had financial problems because of the illness. 50% of the respondents felt that the child’s illness had no effects on the family, whereas 7.5% of respondents felt that the family relationship had become less close because of the illness. 42.5% felt that the family had become closer. 42.5% felt that there was no difference in the relationship. 15% mothers felt that the partner had become less close. 50% felt that the relationship had become closer. The comments indicated that these changes related to the quality and strength of the pre existing relationship. 60% of respondents felt that there was no change in their social relationships. 15% felt their relationships had become less close. Whereas, 25% of respondents reported that their social relationships had become closer. 67% of respondents reported to have emotional support. 32% of respondents felt that they had no one to talk to about their feelings. Majority felt that they trusted the doctor the most and turned to the doctor for emotional succor too. 60% felt that they needed counseling for themselves regarding their child’s illness. Thus a lot needs to be done to improve the psychological stress caused by chronic diseases in parents of the children.

HO/33(P) ASSESSMENT OF QUALITY OF LIFE IN THALASSEMIA MAJOR

Yadav S P, Arya SC, Kaul D, Raina A, Khanna V K, Sachdeva A,

Department of Pediatrics, Center for Child Health, Sir Ganga Ram Hospital, New Delhi,

Aim – Children with thalassemia major have good survival but little is known about their quality of life. We assessed Health Related Quality of Life in these children. Method – Quality of life was assessed of 26 children (average age 16 yr  5.5) with thalassemia major on regular blood transfusion, registered with Thalassemia unit at Sir Ganga Ram Hospital by using an 85-item Thalassemia Quality of life questionnaire. This questionnaire was developed by modifying Pediatric Cancer Quality of life scale developed by Varni et al covering five domains – disease and symptoms, physical, psychological, social and cognitive fields. Both desired and present quality of life assessed by patient’s response in each domain. Overall Quality of Life given as percentage of desired quality of life score.Result – Overall quality of life (QOL) was affected (<90%) in 88% of patients and severely affected (<70%) in only 15%of patients. QOL assessed in each domain showed that in disease and symptom domain 96% had QOL<90%, in physical domain 70% had QOL<90%, in psychological domain 81% had QOL<90%, in social domain 81% had QOL <90% and in cognitive domain 65% had QOL<90% Conclusions – QOL for each child was given as a summary score between 0% (worst QOL) and 100% (best possible QOL). Each child himself acted as a control for his best possible QOL i.e. desired at that point of life according to his understanding and development. This concept can be very useful for serial assessment of QOL of child with Thalassemia major and interventions can be done in various domains to improve QOL
HO/34(P) PULMONARY DYSFUNCTION IN BETA THALASSEMIA.

Amit Kandhari, Anupam Sachdeva, VK Khanna, Neeraj Jain, Subash C. Arya, Satya Yadav

Department of Pediatrics, Centre for Child Health, Sir Ganga Ram Hospital, Delhi


Thalassemia is one of the commonest hereditary hemolytic anemia. 3% to 17% of the population in Indian subcontinent carries beta thalassemia gene. Every year about 100,000 children are born with thalassemia major in the world. Out of these 8,000 to10, 000 are born in India. Survival of patients with thalassemia major has greatly improved during recent years, with the introduction of moderate –transfusion programs and chelation therapy with subcutaneous Desferal (deferrioxamine) and/or Kelfer (Deferiprone). The repeated transfusions in thalassemics lead to deposition of iron in different tissues, leading to damage and dysfunction of various systems. Iron deposition is also reported to exist in the lungs at autopsy. Although lung impairment in thalassemic patients has been reported in the 1980’s,yet it is one of the most under evaluated and functionally not well-characterized complication. Since there have been contradictory results reported in literature ranging from restrictive spirometric pattern to an obstructive one, and there is total paucity of data from India, this study was designed to find out the pulmonary function tests of the beta thalassemic patients attending our hospital.A total of 30 cases of beta thalassemia major who were attending the thalassemia clinic at Sir Ganga Ram Hospital were taken up for the study after a written informed consent. These patients were on moderate –transfusion regimen, maintaining a hemoglobin concentration of more than 9 gm %. Patients with asthma and cardiac disease were excluded. Pulmonary function tests done included Forced vital capacity (FCV), Forced expiratory volume in one second (FEV1), FEV1/FVC percent (FEV1 %) and peak expiratory flow rate (PEFR). Results were interpreted as obstructive, restrictive and normal pulmonary Function test (PFT). The data was analyzed using software SPSS version 10.We included three age groups in our study, with total 30 patients in all. Age group 6-10 yr had 9 patients (mean Serum ferritin 2301 ng/ml), 11-15 yr had 11 children (mean Serum ferritin 3315) and >15 yr had 11 children (mean Serum ferritin 5147 ng/ml) in the study. Mean age was 14.46 with standard deviation of 6.75 (mean ferritin was 3682 ng/ml). Overall out of 30 patients 13 had normal PFT and 17 had abnormal PFT (1 had obstructive PFT and 16 had restrictive PFT). In the age group of 6-10 years 7 had normal and 2 had abnormal PFT and in age group 11-15 yr 3 had normal and 6 had abnormal PFT and in age group >15 yr 3 had normal and 8 had abnormal PFT. Of 17 patients on chelation with Desferal alone 11 had normal and 6 had abnormal PFT. 6 patients were on Kelfer alone of which 1 had normal and 5 had abnormal PFT. Of 7 patients who were on both Desferal and Kelfer, 1 had normal and 6 had abnormal PFT. All patients on Kelfer or Kelfer + Desferal aged >10 years except one which may explain reason for increased number of abnormal results in this group. Critical age above which abnormal results were higher was 11.5 years. Mean Ferritin in patients with normal PFT was 2456 ng/ml and 4621 ng/ml for patients with abnormal PFT. (p value 0.037) We found a negative Pearson correlation between FVC (% of predicted) with increasing ferritin (p value 0.038). There was no difference detected between pre and post transfusion PFT results by using paired t test (p value 0.973).In conclusion the major pulmonary dysfunction in our study group is that of restrictive type. The abnormal PFT were found in older age group. FVC was negatively co-related with increasing ferritin level. The number of abnormal results was higher when the serum ferritin was > 4000 ng/ml and blood transfusion had no effect on the PFT.
HO/35(P) VER, BAER & NCV IN PATIENTS GIVEN HIGH DOSE METHOTREXATE

SP Yadav, A. Sachdeva, Vinita Jain, SC Arya, PK Pruthi, Suresh Gupta, Roma Kumar, LN Srivastava, Indu Jain

Department of Pediatrics, Center for Child Health, Sir Ganga Ram Hospital, New Delhi
HDMTX has been found to effective for CNS prophylaxis in children with ALL & NHL and to eliminate the need for cranial radiotherapy. It has been shown that methotrexate has very less toxicity as compared to radiotherapy. The study was done to determine the incidence of nervous system toxicity following HDMTX (in doses of 6-8g/sq.m) in Indian children treated for ALL & NHL. Methodolgy: VEP, BERA, NCV were done before starting HDMTX (Dose of 6-8 gm/mt²) as a part of UKALL XI protocol and then 3 & 6 months after last HDMTX and 1 year after stopping treatment. Data was analyzed using McNemar’s test for comparing the incidence of each individual clinically observed toxicity after three consecutive doses of methotrexate. Non-parametric test was applied to compare the methotrexate levels between the cases who developed toxicity and those who did not. Results: 49 children with ALL & NHL between the age group 0-18 years with mean age 5.8 years (range 2 to 13 years) were enrolled in the study. In our study group there were more boys than girls (Ratio was 1.8:1). Majority (80 %) of children enrolled had ALL rest had NHL Focal neurological deficit was observed in one patient. This child developed paraparesis after the third dose of high dose methotrexate (followed by intrathecal methotrexate. None of the patients showed a decrease in their VER, BAER after HDMTX infusion as well as on long term follow up. Only one patient who developed paraparesis had markedly decreased NCV in the lower limbs but no other deficit in the body. This child is now 6 years off treatment but has not recovered. Thus very rarely as an idiosyncratic reaction focal neurological deficits may be seen. This could be ascribed to the Intrathecal Methotrexate
HO/36(P) PREVALENCE OF HYPOGONADISM IN THALASSEMIA MAJOR PATIENTS – A SINGLE INSTITUTION EXPERIENCE

Archana Dayal Arya, Anupam Sachdeva, Satya Yadav, VK Khanna, Subhash C Arya.

Department of Pediatrics, Centre for Child Health, Sir Ganga Ram Hospital, New Delhi

Thalassemia is one of the commonest hereditary hemolytic anemia. The survival of thalassemics has improved significantly. The need for repeated transfusions in thalassemics, leads to deposition of iron in different tissues, which in turn leads to damage and dysfunction of various organs. If chelation is sub optimal, this can lead to delayed puberty/ arrested puberty or hypogonadism in these subjects. We need to address the quality of life issues in Thalassemics. Absence of sexual characteristics in girls till the age of 13 years and a testicular volume <4ml in boys till the age of 14 years is defined as delayed puberty. Arrested puberty is the non-progression of puberty for a period of 12 months and complete absence of puberty is known as hypogonadism. Hypogonadism also results in worsening of the bone mineral density, since sex steroids are also responsible for bone mineralization. Delayed puberty /hypogonadism is usually due to deposition of iron in the anterior pituitary gland since even moderate amount of iron deposition can affect this gland. Other factors that are responsible for delay in puberty are chronic anemia and delayed bone age. The gonads (testes in males and ovaries in females) are usually healthy with no significant iron deposition. All patients with Thalassemia major enrolled at our center are assessed for their pubertal status at every visit. The purpose of this study was to see the effect of beta thalassemia major on the onset and progression of puberty and its relation to chelation. A retrospective analysis of our case records of children and young adults between the age of 16 to 25 years was done. A diagnosis of hypogonadism was made on the basis of clinical assessment of puberty by a pediatric endocrinologist, levels of LH, FSH and testosterone in males and estradiol in females. Constitutional delay of puberty was ruled out before the laboratory evaluation.76 subjects in this group, of which 47 (62%) were males and 29 (38%) were females, had been assessed for their pubertal status at the Thalassemia endocrinology clinic. These patients were on moderate transfusion regimen, maintaining a hemoglobin concentration of 8- 9 gm %. Most were on chelation with desferrioxamine or deferiperone or both, but compliance was not good in many patients. Average serum ferritin levels were calculated by averaging the ferritin levels over the last 5 years. Puberty was staged according to Tanners stages of puberty. 39 of the 76 patients (51%) had normal onset of puberty i.e. before 13 years in females and 14 years in males. 28/47 (59.6%) males and 11/29 (37.9%) females had normal onset of puberty. Average mean serum ferritin for the group with normal puberty was 4127 ng/ml (976-7484ng/ml). 37 of the 76 (49%) patients had hypogonadism. 18/29 (62%) females and 19/47 (40.4%) males were affected. Mean S. ferritin for this group was 5234 ng/ml (Range 1248-10900). In conclusion 51% of our patients had hypogonadism, which did not correlate with the serum ferritin levels. It is possible that the anterior pituitary gland may be sensitive to lower ferritin levels. Age of onset of chelation and the effects of the 2 drugs used for chelation may indirectly affect puberty. These factors are currently being evaluated in our study subjects.
HO/37(O) BACK TO THE VEDAS – SUGGESTING COPING STRATEGIES FOR PARENTS OF CHILDREN SUFFERING FROM CANCERS

Anupam Sachdeva, Vinita Jain, SC Arya, PK Pruthi, Suresh Gupta, Prachi, SP Yadav

Department of Pediatrics, Centre for Child Health, Sir Ganga Ram Hospital, New Delhi

Objectives: Study was conducted to find out the thought processes and the coping mechanisms in the parents of children with cancer. Methodology: 50 families with recently diagnosed cancer within a month of diagnosis were included and a formal and informal interview technique was used. Results: As expected there was a lot of distress. The distress was compounded due to the belief that cancer is incurable. Majority had seen adult patients dying of cancer and they extrapolated this to their children. Some parents had a guilt complex that they had erred in taking care of their children. In the Indian context we could divide the parents into four distinct types. The predominantly emotional, and when we say emotional we mean they looked inwards. They settled down eventually with a leaning towards devotional or philosophical and treaded the pathway of Bhakti. The predominantly intellectual, was the one who explored the internet thought of all the possibilities, read the literature and talked to a lot of people, settled down after satisfying their quest for knowledge. They treaded the pathway of knowledge or Gyan. Balanced in both was the one who listened to the doctor and getting the information were interested in action or karma and took solace in the fact that lets do our duty and God will take care of the rest. Underdeveloped in both was the one who neither a seeker of knowledge nor interested in what was being done, left everything to the treating unit. They were not able to provide much support to the family or the kids. They are the ones who tread the pathway of compulsion or Hatha. We have devised methods to take care of all categories. Conclusions:Human beings can be divided into four categories and our support systems have to be resilient enough to provide support to all categories.

HO/38(P) ARE COAGULATION STUDIES DONE ON SAMPLES DRAWN THROUGH HEPARINISED INTRAVASCULAR LINES ACCURATE? A COMPARATIVE STUDY

D. Gupta, A Sachdev, K Chugh, Gurinder Pal Singh

Center for Child Health, Sir Ganga Ram Hospital New Delhi
Introduction: A large proportion of patients admitted to PICU need monitoring of their coagulation status. It would be advantageous to draw blood for these studies through intra-arterial and central venous lines, as that would avoid additional pricks to the sick child. However, doubt remains whether or not addition of heparin in the flush solution interferes with routine coagulation profile i.e. prothrombin time (PT) and activated partial thromboplastin time (aPTT ). Objectives: we designed a study to compare the results of prothrombin time ( PT) and activated partial thromboplastin time (aPTT) done on blood samples drawn from peripheral venous puncture , intra-arterial catheter and central venous line, which are being continuously flushed with heparin infusion at the rate of 2 units / hour. Methods: This prospective study was carried out in an 8-bedded PICU of a tertiary care teaching hospital.One hundred ten consecutive patients were enrolled in the study. There were 79 males. All the patients were sedated and had indwelling arterial catheter in radial artery and central venous line (femoral or subclavian). PT, and aPTT were tested from three separate blood samples, one each from peripheral vein, central venous line and arterial line. Five milliliters of blood from arterial and central line was withdrawn in a separate syringe to minimize heparin contamination in test sample. Results:Means of PT & aPTT taken from arterial port and venous puncture were compared. For Prothrombin time difference between means is 0.18 seconds with S.D of 3.6 with confidence limit of 0.5 to 0.86 (P value > 0.05). The arterial port and venous puncture samples for aPTT were analyzed by paired‘t’ test. Difference of mean was between 2-3 sec, confidence interval between –2.96 to –1.74. P-value is < 0.05 . Though P value is showing statistical significance but difference of 2 seconds from mean is clinically not relevant Samples drawn from central venous line and venous puncture were also compared. For Prothrombin time difference between means was 0.1216 sec with SD 3.59. Values were statistically not significant with P-value 0.723. For aPTT , the difference between means is less than 2 sec with P-value < 0.001 .Though P value is showing statistical significance but difference of 2 seconds from mean is clinically not relevant . Conclusion: Our results indicate that coagulation studies can be carried out on blood samples from a heparin flushed arterial line or central venous line and result co-relate well with those obtained from veni-puncture sample, provided sufficient blood volume is discarded to prevent heparin contamination.
HO/39(O) HIGH DOSE METHOTREXATE FOR CNS PROPHYLAXIS IN PEDIATRIC PATIENTS OF ALL & NHL HOW SAFE IS IT?

Indu Jain, Anupam Sachdeva, Vinita Jain, SC Arya, PK Pruthi, Suresh Gupta, Roma Kumar, LN Srivastava, SP Yadav

Department of Pediatrics, Centre for Child Health, Sir Ganga Ram Hospital, New Delhi
HDMTX has been found to greatly increase survival in children with ALL & NHL and to eliminate the need for cranial radiotherapy. Various studies have also shown that HDMTX is not very toxic. The study was done to determine the clinical toxicity following HDMTX (in doses of 6-8g/sq.m) in Indian children treated for ALL & NHL. Methodolgy: 49 cases of Acute Lymphocytic Leukemia (ALL) and Non-Hodgkin’s Lymphoma (NHL) in the age group 0-18 years were enrolled. Children were given 6-8gms/mt² along with hydration in 24 hours followed by intrathecal methotrexate and 12 hours latter with Folinic Acid rescue. Children below 3 years of age were given 8gms/mt² and children > 3 years of age were given 6gms/mt². Any clinical features of acute neurotoxicity (nausea, vomiting, seizures, features of raised intracranial pressure) or any bleeding tendency were noted. The presence or absence of mucositis was also noted. Along with this the renal parameters as well as hepatic parameters were also recorded. STATISTICAL ANALYSIS: Data was analyzed using McNemar’s test for comparing the incidence of each individual clinically observed toxicity after three consecutive doses of methotrexate. Results: 49 children with ALL & NHL between the age group 0-18 years with mean age 5.8 years (range 2 to 13 years) were enrolled in the study. In our study group there were more boys than girls (Ratio was 1.8:1). Majority (80 %) of children enrolled had ALL rest had NHL Each patient received 3 doses of HDMTX (followed by intrathecal methotrexate) with folinic acid rescue; one patient did not receive the third dose of high-dose methotrexate. Vomiting was most common symptom of toxicity. It was the maximum (49%) after the first dose with 12.5% after second dose and 39.7% after the third dose. Headache was a less common feature, seen in only 2% patients. The overall incidence was 0.7 %. Significant mucositis, WHO Grade III and IV, was seen in 44.8%, 36.7% and 31.2% of the cases after the first second and the third dose. Though the incidence of mucositis was the maximum (44.8 %) after the first dose as compared to the other doses, but the difference was not significant. First and second dose methotrexate had a higher frequency of toxicity 36.6% and 30% respectively. The overall incidence of hepatotoxicity was 25.5%. There were three cases, which had gone into non-oliguric renal failure (6.1%). All other patients had normal renal function tests. We also evaluated the children neurologically and one child had seizures and another developed paraparesis. The child who developed seizures died. Thus high dose methtrexate has a high incidence of transient abnormalities with involvement of the renal and the hepatic system but they are all more or less reversible.
HO/40(P) RELATION OF XMN-1 POLYMORPHISM AND FIVE COMMON INDIAN MUTATIONS OF THALASSAEMIA WITH PHENOTYPIC PRESENTATION IN -THALASSAEMIA :

Raina Aditya, Verma I.C., Saxena Renu, Kaul Dinesh, Khanna V.K., Sharma Juhi, Anupam Sachdeva

Department of Pediatrics, Center For Child Health, Sir Ganga Ram Hospital, New Delhi
Xmn-1 polymorphism is a known factor, which increases fetal hemoglobin production. Among,  thalassemics in India five mutations are common. Disease severity was assessed based on age of presentation, age when the first transfusion was received and the amount of blood transfused in ml/kg/year. Data was divided into three Xmn-1 categories, Xmn-1 +/+, Xmn-1 -/+, Xmn-1 -/-, intergroup correlation was made. Mutations were divided into 2 groups, (Group I) IVS 1-1 as one of its variables and (Group II) without IVS 1-1. They were correlated. In Xmn-1 +/+ category 66% were diagnosed after one year of age, in mutations (Group I) 54% had age of diagnosis after 1 year. 77.8% in Xmn-1 +/+ received their first blood transfusion after 1 year of age, in mutations (Group I) 64% received their first blood transfusion after 1 year of age. 66% patients in Xmn-1 +/+ category received blood <200ml/kg/year as against 72% in Xmn-1 -/- category. In mutations Group I 57% received blood transfusion <200 ml/kg/year as against 68% in Group II. It is concluded that the presence of Xmn-1 polymorphism and IVS 1-1 mutation leads to a milder phenotypic presentation causing a delay in onset of blood transfusions but dose not affect the amount of blood received/kg/year.