Assessment of Awareness, Prevalence and Treatment Trends of Thalassemia in NGO Sector, Sialkot, Pakistan

Introduction

The thalassemias are the set of hereditary hematologic disorders caused by the faults in the generation of one or more of the hemoglobin chains [1]. Thalassemias results from either the reduced synthesis or the complete absence of one or more of the globin chains that constitutes the hemoglobin (Hb) tetramers [2]. Thalassemias are among the most common inherited disorders occurring world- wide, with at least 60,000 individuals born affected every year [3]. Consanguineous marriages are very common in our traditions due to cultural reasons and the family system.

This results in increase in the disease burden with every passing day. Due to our cultural norms, people hesitate to opt for the premarital thalassemia screening even being aware of the nature of its inheritance, having thalassemia in the first cousins and regardless of the current legislations in Pakistan, necessitate pre-marital thalassemia screening for every couple [4]. Carriers of thalassemia mutations are asymptomatic. However, when both parents are carriers, for every pregnancy, there is a 25% chance of having a child with thalassemia, a 50% chance of having a child with thalassemia trait, and a 25% chance of having a normal child. When one parent is carrier, risk of child with thalassemia is 0%, and

50% chances of having a child with thalassemia trait. When one parent is patient and another is carrier, risk of child with thalassemia is 50%, and 50% chances of having a thalassemia carrier. When both parents have thalassemia minor, there is 50% chance of having a child with thalassemia major, 25% chances of having a child with thalassemia minor, and 25% chances of having a normal child [5]. Pakistan has a large population of over 150 million people with a normal carrier frequency of approximately 5.6% of β-thalassemia. Punjab is the largest province in the country with a population of over 50%. The incidence of β - thalassemia is alarming as the local capacity is very high (>81%) and the learning rate is low in South Punjab [6].

Treatment of thalassemia major includes regular RBC transfusions, iron chelation and management of secondary complications of iron excess. In some conditions, spleen removal may be obligatory. Bone marrow transplantation leftovers the only ultimate cure at this time available. Persons with thalassemia intermedia may need splenectomy, folic acid supplementation, treatment of extra medullary erythropoietic masses and leg ulcers, anticipation and therapy of thromboembolic events [7]. Good nutrition with sufficient vitamins and trace elements ingestion, all along with calcium and vitamin D supplementation, can increase bone density and avoid bone loss [8]. Desferroxamine has been found to be widely used in the treatment of thalassemia, restores toxins and prolongs life when used properly. However, the drug is a problem because it can be irritating when injected locally. After years of monitoring and monitoring patients, it is now clear that desferrioxamine can be toxic if given in high doses. There can be serious neurological consequences. Deferiprone, or L1, is the primary oral chelator now used in clinical trials worldwide. The purpose of these drugs as iron chelator is to burn down the residual stores of tumor tissue and, thus, to prevent iron organ disease from overload, another advantageous method which may be the removal of iron from the RBC membrane [9]. The decision for allogeneic marrow transplantation is generally considered appropriate only in patients with a complete HLA- donor (at least, 30- 40% of all patients). The decision to transfer patient to BMT is a frustrating issue with many ethical questions related to the length and quality of life of the transferred patient, compared to the patient being treated with BMT-supported care [10].

A closer examination of the problems of thalassemia patients treated with transplantation versus conventional treatment showed that the incidence of hypothyroidism, hypogonadism and cardiomyopathy was higher in patients treated with the convention method, while total sepsis and growth defects were higher in the transplanted patients. Iron overload should however be addressed in most BMT post patients, but can be treated with phlebotomy in patients with their hemoglobin level high enough to tolerate this type of treatment. Some patients may continue to require reduced doses of desferroxamine [7]. It is not possible to best treat the thalassemias with all its prevailing complications, unless stem cell transplant is carried out, which is uneconomical for the majority of population. So, the best way is to prevent the disease by educating people about prenatal and premarital screening [11].

Discussion

Thalassemia is the most common genetic disorder among the people of Pakistan. This is probably due to the lack of knowledge about the pre-marital and prenatal diagnosis of thalassemia. Majority (n=49; %=70) of the parents of patients suffering from thalassemia included in this study didn’t know about prenatal diagnosis. Results of this study are relatable to the study performed in Rahim Yar khan in 2016 which also shows that most of parents of thalassemia patients were unaware about the prenatal diagnosis [12].

Patients suffering from thalassemia major require frequent blood transfusion, which results in the accumulation of iron in various body organs leading to the damage of liver, heart, endocrine glands, and kidneys. Majority (n=62; %=88.5) of the participants involved in this study knew about the complication of iron overload. Results of this study are comparable to the study conducted in Peshawar in 2015 which depicts the high level of awareness among the parents about iron overload [13].

Life expectancy of patients of thalassemia has been increased in past few years due to the regular use of blood transfusion and iron chelation therapy. In developing countries, Government and various NGOs have provided the facilities for transfusions and iron chelation therapy free of cost for the patients who cannot afford this. This has increased the life expectancy of thalassemia patients in developing countries. In our study, (n=38; %=54.3) were aged more than 10 years. Results of this study are relatable to the study performed in London in 2009 which shows that life expectancy of thalassemia patients has increased above 10 years [14].

Thalassemia in majority of patients (n=52; %=74.2) had diagnosed within one year of age. Results of this study are relatable to the study conducted in Bangladesh in 2018 [15]. Majority of the patients (n=42; %=60) enrolled in this study were male, which depicts the greater prevalence of thalassemia in males as compared to females because parents give more attention to their male child and ready to spend more money on male child compared to female ones. Furthermore, investigations have shown that thalassemia is a single gene disorder inherited by the recessive mean of transmission. Results of this study are comparable to the study performed in India in 2015 [16]. Majority of patients (n=43; %=61.2) had hepatomegaly, patients (n=46; %=65.7) had splenomegaly, which means that hepatomegaly and splenomegaly are the major signs of thalassemia. These results are relatable to the study performed in Rawalpindi in 2004 [17]. In our study, majority of patients (n=52; %=74) had the symptoms of pallor, patients (n=43; %=61.4) had the symptoms of fever. Results of this study are relatable to the study performed in Bangladesh in 2018 [15]. Patients suffering from thalassemia major have the critical form of the disease and need chronic transfusion. A thalassemia inter-medium is the form of thalassemia featured by the less critical symptoms as compared to thalassemia major. Majority of the patients (n=60; %=85.7) were suffering from thalassemia major and only (n=10; %=14.3) were suffering from thalassemia intermedia. Results of this study are comparable to the study conducted in Jammu and Kashmir in 2014 [18].

Patients suffering from thalassemia have some severe transfusion related complications; most common among those is iron overload and infection. In our study, majority (n=69; %=98.5) of the patients had increased serum ferritin level. Results of this study are relatable to the study performed in Italy in 2017 [19]. Most common infection related to blood transfusion in thalassemia is hepatitis. In our study second most common complication reported is hepatitis, (n=43, %=61) patients were tested positive for hepatitis. Results of this study are comparable to the study performed in Islamabad, Pakistan in 2014 [20].

In our study, all cases were diagnosed by the hemoglobin electrophoresis (n=70; %=100). This assessment is related to the study performed in India in 2018 [21]. For the measurement of the occurrence and level of complications, all the patients (n=70; %=100) underwent CBC with differential and serum ferritin level assessment on routine basis. This result is relatable to the study performed in North America for the purpose of establishing the standard guidelines for the monitoring of the patients suffering from thalassemia [22].

Patients suffering from the thalassemia major require repeated blood transfusions. Blood transfusion may leads to the transfusion associated circulatory overload. This can be prevented by the use of diuretics before transfusion. Furosemide is the most effective diuretic used as a premedication in blood transfusion. In our study, all the patients (n=70; %=100) were receiving furosemide intravenously before transfusion. The result is consistent with the study conducted in Canada in 2013 [23]. Malnutrition is quite frequent in thalassemia patients. So, they regularly require dietary supplements to maintain their health. Most commonly prescribed dietary supplements according to our study were; folic acid (n=70; %=100), calcium (n=70; %=100), vitamin D (n=65; %=92.8). This result is relatable to the study performed in United States and Canada in 2012 [24]. Thalassemia patients receive iron chelation therapy in order to reduce the iron accumulation in body resulted from repeated blood transfusion. In our study most commonly used iron chelator was defesirox (n=59; %=84) and deferoxamine (n=15; %=21). These results are consistent with the results of the study conducted in Turkey [25].

In thalassemia, there is an increase destruction of RBCs which results in hypersplenism. Splenomegaly results in an increase in blood transfusion requirement. Physicians recommend the splenectomy when the need for blood transfusion exceeds 220mL RBCs/kg/y. In our study (n=10; %=14) patients had undergone through splenectomy. This result is comparable to the study performed in Iran in 2010 [26].

The ultimate treatment for thalassemia is stem cell transplant. This treatment is offered by the limited number of hospitals in Pakistan. The average cost for bone marrow transplant is unaffordable for the majority of our population. In our study only (n=1; %=1.4) patient had undergone through this treatment. This result is comparable to the study in Karachi, Pakistan [27].

Conclusion

Thalassemia is amongst the common genetic blood disorders. According to our study, awareness among the parents regarding thalassemia was insufficient. Hb- electrophoresis is used as conformational diagnostic tool for thalassemia. Treatment of thalassemia is associated with a lot of complications. To assess the complications, CBC, serum ferritin, LFT, RFT and serum calcium monitoring must be carried out regularly for all the patients. Patients suffering from thalassemia regularly require blood transfusion, which results in iron overload in body. Defesirox is the most commonly used iron chelator for treating iron overload. Ultimate treatment is stem cell transplant which is out of the reach of most of population. So, best way is to prevent thalassemia by enlightening the importance of pre-natal and pre-marital diagnosis of thalassemia.

Recommendations

Prime concentration should be laid towards the obviation of disease, which requires the enforcement by Government officials for premarital diagnosis. Proper campaign must be directed for educating the general public about the complexity of thalassemia.

Limitation of Study

Primary limitation of this study is that, it includes only one thalassemia patient who had undergone through the stem cell transplant, so this study does not provide a complete picture of the assessment of this treatment. This is due to the fact that this study is restricted in NGO sector of the single district, where majority of the patients can’t afford this expensive treatment.

Authors’ Contributions

Faiza Naeem proposed the idea of this project and designed the study. Hazima Tariq and Kainat performed the survey for data collection. Nimra Riasat, saba Zulfiqar and sidra mubarak compiled the data. Faiza Naeem analyzed the data. All authors equally contributed and wrote the manuscript. Faiza Naeem coordinated the project preparation of the final version of the manuscript.

Acknowledgment

The study was conducted by the Islam College of Pharmacy, Sialkot.