Year : 2010 | Volume
: 53 | Issue : 1 | Page : 50--53
Clinical audit of inherited bleeding disorders in a developing country
Raihan Sajid1, Safoorah Khalid1, Nazish Mazari2, Waleed Bin Azhar2, Mohammad Khurshid1,
1 Department of Pathology and Microbiology, Aga Khan University, Stadium Road, Karachi 74800, Pakistan
2 Fatimid Foundation, Pakistan
Section of Hematology, Department of Pathology and Microbiology, The Aga Khan University, Stadium Road, Karachi - 74800
Objective: We did a clinical audit to determine the status of coagulation disorders in a hemophilia care center in Pakistan. Setting: Fatimid foundation blood bank and hematological diseases center, Lahore. Study Design: This is a retrospective descriptive study. Materials and Methods: All patients registered at Lahore center were included. Data was collected using a questionnaire including age, gender, diagnosis, hepatitis and human immune deficiency virus (HIV) status, number of episodes of bleeding, most common site of bleeding, severity of disorder and number of transfusions required to treat the episode. Results: During the study period, a total of 923 registered patients were reviewed at Lahore center and of these, 408 patients (44.2%) were on regular follow-up. Inherited bleeding disorders identified in these patients included hemophilia A, hemophilia B, vWD, factor VII deficiency, factor V deficiency, factor X deficiency, dysfibrinogenemia, afibrinogenemia, factor XIII deficiency; and platelet function defects. Median age was 17 years with a range of three to 57 years. Median age at diagnosis was one year. There were 329 (80.6%) males and 79 (19.3%) females. The products used in these patients included factor VIII concentrate, fresh frozen plasma, cryoprecipitate, cryosupernatant and platelets. Testing for transmission of viral infections was also done in these patients and one patient (0.2%) was found hepatitis B positive, six patients (1.4%) were hepatitis C positive and two patients (0.49%) were HIV positive. Conclusion: Hemophilia A, hemophilia B and vWD are the commonly encountered inherited bleeding disorders in our patients followed by other recessively transmitted disorders with a median age of 17 years and male to female ratio of 4: 1. Most of the patients utilized services available at Fatimid foundation with good clinical results. In Pakistan, non-governmental organizations (NGOs) are trying their best for providing optimal treatment to patients with inherited bleeding disorders. There is a need for government participation to improve the availability of current hemophilia care services.
|How to cite this article:|
Sajid R, Khalid S, Mazari N, Azhar WB, Khurshid M. Clinical audit of inherited bleeding disorders in a developing country.Indian J Pathol Microbiol 2010;53:50-53
|How to cite this URL:|
Sajid R, Khalid S, Mazari N, Azhar WB, Khurshid M. Clinical audit of inherited bleeding disorders in a developing country. Indian J Pathol Microbiol [serial online] 2010 [cited 2021 Jan 22 ];53:50-53
Available from: https://www.ijpmonline.org/text.asp?2010/53/1/50/59183
Inherited bleeding disorders lead to a lifelong bleeding tendency. Diagnosis, frequently made in childhood, is based on clinical presentation of bleeding and family history together with the laboratory tests. Hemophilia A and B are the most frequent of these disorders. Together with von Willebrand's disease (vWD), these X-linked disorders comprise of 95 to 97% of all inherited bleeding disorders.  The remaining defects, generally transmitted as autosomal recessive traits in both sexes are rare with low prevalence rate.  However, in countries where consanguineous marriages are relatively common, these autosomal recessive disorders occur more frequently in homozygosity.  The reported incidence of these coagulation factor deficiencies is shown in [Table 1]. 
These inherited bleeding disorders occur in mild, moderate and severe forms depending upon the plasma factor levels of 6-30%, one to five per cent and less than one per cent respectively. While some patients may only have mild bruising or bleeding following trauma, others with severe deficiency may exhibit intracranial hemorrhages and hemarthroses.  With the exception of vWD, these disorders produce similar signs and symptoms, regardless of the particular factor that is lacking.
From 1970 to the early 1980s, mortality among people with hemophilia has declined substantially due to the availability of improved hemophilia management centers and clotting factor concentrates in the United States and Europe. , However, this significantly increased the incidence of human immune deficiency virus (HIV) and hepatitis in treated hemophiliacs. This led to the production of safer plasma concentrates of coagulation factors. And finally, in the past few years, somatic gene therapy has produced promising results in patients with hemophilia.
Despite advances in the diagnosis and management of these inherited bleeding disorders, the natural history and clinical spectrum of these disorders are not well established in our population. However, the incidence of these disorders is expected to be higher because of the traditional trends of consanguineous marriages in our country. Punjab (Pakistan) is estimated to have 5200 males affected by hemophilia A and approximately 1000 to 1300 cases of hemophilia B.  Therefore, the total estimate for Pakistan is approximately 10,000 cases of hemophilia A and 2000 cases of hemophilia B.
Since inherited bleeding disorders are a big problem in our country and very limited reports on these disorders are available, we did a clinical audit to determine the status of these disorders registered at Lahore center of Fatimid foundation blood bank and hematological services over a period of one year.
Materials and Methods
A retrospective descriptive study was conducted at Fatimid foundation blood bank and hematological services center at Lahore over a period of one year (January 1, 2006 to December 31, 2006). All the patients registered were included in the study. The data was collected using a questionnaire including age, gender, diagnosis, hepatitis B, C and HIV status, number of episodes of bleeding, severity of disorder and number of transfusions required to treat the episode. The severity of the disease was based on plasma factor levels and the clinical manifestations of the disease; and divided into severe (less than one per cent of normal activity), moderate (one to five per cent of normal activity) and mild (6-30% of normal activity).
All the data was collected and entered into SPSS version 15.0 for analysis.
A total of 923 patients had registered; 408 (44.2%) of them were in regular follow-up and further reviewed. Inherited bleeding disorders identified in these patients included hemophilia A, hemophilia B, vWD, factor VII deficiency, factor V deficiency, factor X deficiency, dysfibrinogenemia, afibrinogenemia, factor XIII deficiency; and platelet function defects. [Table 2] shows the break-up of these patients. The median age was 17 years with a range of three to 57 years. Median age at diagnosis was one year. Among these 408 patients, 329 (80.6%) were males and 79 (19.3%) were females.
History of inherited bleeding disorders in family was positive in 196 (48%) patients and negative in 108 (26.5%) cases. Family history was not available in 104 (25.5%) patients.
In patients with hemophilia A, knee joint was the most commonly involved joint (48%) and in 36% of cases, more than one joint was involved [Table 3]. Regarding disease severity, 61 patients (14.9%) had severe disease, 185 (45.3%) had moderate disease and mild disease was seen in 162 patients (39.7%). [Table 4] shows the severity of disease in various inherited bleeding disorders. In 105 patients (49.5%), up to three bleeding episodes were experienced during the study period. Four to eight episodes were noticed in 90 patients (42.5%) and nine to 12 episodes in 13 patients (6.1%). More than 12 episodes were observed in four patients (1.9%). Thirty five patients (8.5%) with hemophilia A and three (1%) with hemophilia B were found to have some disability.
Hepatitis B, C and HIV status of patients were also determined and one patient (0.2%) was found hepatitis B positive, six patients (1.4%) hepatitis C positive and two (0.49%) HIV positive.
The products used in these patients included factor VIII concentrate, fresh frozen plasma, cryoprecipitate, cryosupernatant and platelets. [Table 5] shows the number of these products transfused in the year 2006 at the Lahore center. Fresh frozen plasma was the most commonly used product and the response to plasma transfusion was assessed by the number of transfusions required to stop bleeding [Table 6].
Hemophilia can be referred to as a disorder that causes joint damage leading to limitation in conducting daily activities and changes in social functioning. In developed countries, hemophiliacs have a quality of life very similar to that seen in general population due to the provision of safety factor concentrates and a multidisciplinary comprehensive care approach. In the opinion of the author, in developing countries like Pakistan, hemophiliacs are not treated with safe products and appropriate quantities of the products because of cost related issues. So the lack of adequate treatment can result in pain, arthropathy and disability. It is estimated that only 25% of all hemophiliacs around the world receive adequate treatment and most of them die before the age of 20.  Despite financial limitations, some developing countries like Chile, Iran, Venezuela and Vietnam are optimizing their resources for hemophilia care. ,,,
Pakistan is a country with a high prevalence of inherited bleeding disorders and the reason for this is the tradition of consanguineous marriages which is responsible for common inheritance of autosomal recessive disorders. However, data available is very limited and does not exactly define the burden of these disorders in our community. , We retrospectively reviewed cases with inherited bleeding disorders registered at Fatimid foundation to evaluate the current diagnostic, therapeutic and transfusion facilities that are available for these patients in Pakistan.
The common inherited bleeding disorders identified in our population include hemophilia A, hemophilia B and vWD; majority of the patients have mild to moderately severe disease. This is in accordance with data from other studies. ,,
Degenerative joint diseases leading to disability were noted in 8.5% of our patients in contrast to a fairly high rate observed in China  and Iran.  This is surely an under reported figure as the patients usually present late to the hemophilia centers when already too much damage has occurred. The number of patients will also increase if radiography is included in the investigation of hemarthrosis. Moreover, data from all over the country is not available.
Transfusion transmitted diseases are one of the most important complications seen in patients with inherited bleeding disorders. ,, Fortunately, the incidence of these diseases has not been found to be very significant in our study. Prevention of these diseases is a major responsibility of hemophilia care services through the provision of properly screened products. This can also be reduced by the use of recombinant factor concentrates but these are very expensive and in majority of cases are beyond the reach of our patients. So we follow a more stringent policy of proper donor selection and, universal HCV and HIV screening to abolish the transmission of viral diseases in patients with these disorders.
In Pakistan, there are many problems which have resulted in under diagnosis and under treatment of patients with these disorders. There is no nationally funded hemophilia care service. Diagnostic and therapeutic services to these patients are delivered through the efforts of NGOs and they have no governmental support. Contact between the organization and the patients and their family is infrequent and only occurs in case of medical emergencies. A large number of patients with inherited bleeding disorders remain undiagnosed because of the limitation of coagulation laboratories and lack of awareness among healthcare professionals and family members and so the figures presented in this study do not reflect the actual burden of these crippling disorders in our community. Also, we do not have any proper data collection and storage system. If upgraded to user friendly software, data entry could be undertaken by the hemophilia organizations and a hemophilia registry can then be maintained at the national level. Government should provide resources for the diagnosis and management of these patients so that more and more patients benefit from hemophilia services all over the country.
The common inherited coagulopathies observed in our population include hemophilia A, hemophilia B and vWD followed by other recessively transmitted disorders. Most of the patients utilize services available at Fatimid Foundation with good clinical results and this confirms the positive impact of the establishment of hemophilia care services. There is a need to create awareness about these disorders among general practitioners as well as families so that patients are referred early to the hemophilia centers.
Despite efforts made so far to improve the quality of life of these patients, in the developing world, there is still much more to be done. Governmental participation is essential. It is also necessary to establish multidisciplinary teams for providing the optimal care to the patients. Limited resources are a barrier to the hemophilia care services, however even with limited budget; numerous beneficial effects can be achieved.
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