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Fulltext Identification of hemoglobin AC heterozygote status in a Malay family: a decision between hemoglobin electrophoresis and high performance liquid chromotography

Rosline H, Roshan TM, Ahmed SA, Ilunihayati I

Southeast Asian J. Trop. Med. Public Health, 2007 May;38(3):543-5.
PMID: 17877232

Thalassemia is a common public health problem among Malays. Hemoglobin C (Hb C) is a hemoglobin beta variant resulting from a single base mutation at the 6th position of the beta-globin gene leading to the substitution of glycine for glutamic acid. Hb C is commonly detected in West Africans and in African American but has not been reported in Malaysia. It can be falsely diagnosed as HbE trait in the Malaysian Thalassemia Screening Program which utilizes cellulose acetate hemoglobin electrophoresis. This is the first reported case of Hb AC heterozygote status in a Malay family, with unusual splenomegaly in one of the family members.
Response rate of Malaysian blood donors with reactive screening test to transfusion medicine unit calls

Roshan TM, Rosline H, Ahmed SA, Rapiaah M, Khattak MN

Southeast Asian J. Trop. Med. Public Health, 2009 Nov;40(6):1315-21.
PMID: 20578467

Blood donors with reactive screening test results are requested to come in for counseling by letter and telephone call. It has been noticed many donors responded to neither the letters nor the telephone calls. We evaluated 589 cases with reactive screening test results (208 positive for hepatitis C, 209 for hepatitis B, 85 for VDRL and 87 for HIV). In the hepatitis C positive group 61 donors (29.3%) did not respond and 4.7% missed their follow-up appointment. Similarly low response rates were noted with the HBV (58.9%) and VDRL (67.1%) positive groups. Among HIV positive donors 46.0% failed to respond to multiple calls. We conclude that blood donors in Malaysia have a poor response to calls from the blood transfusion unit. A review of the effectiveness of the current deferral system and an increased public knowledge of transmissible infectious diseases may encourage blood donors to have a better response rate.
Blood pre-donation deferrals--a teaching hospital experience

Rabeya Y, Rapiaah M, Rosline H, Ahmed SA, Zaidah WA, Roshan TM

Southeast Asian J. Trop. Med. Public Health, 2008 May;39(3):571-4.
PMID: 18564700

Blood donor selection contributes to the safety of both the donor and the recipient. The objective of this study was to identify the number and causes of blood pre-donation deferrals at the Hospital Universiti Sains Malaysia (HUSM). A retrospective study was carried out to retrieve data regarding deferred blood donors at the HUSM in the year 2006. A total of 4,138 blood donors donated blood at the Transfusion Medicine Unit, of whom 231 were deferred or rejected as donors. The percentage of deferred donors was 5.6%. The main reason for deferral was a low hemoglobin (40.7%), with females constituting the majority of those deferred. This was followed by high blood pressure (29.4%) and male donors were predominant in this group. Medical illness caused 15.6% of donor deferrals. The majority of deferred donors were regular donors (64.1%). We recommend setting new hemoglobin criteria for donor deferral according to the reference range obtained for the particular population. Most of the other deferrals were preventable by proper health care education and awareness.
Trends in hepatitis B virus infection among blood donors in Kelantan, Malaysia: a retrospective study

Yousuf R, Rapiaah M, Ahmed SA, Rosline H, Salam A, Selamah S, et al.

Southeast Asian J. Trop. Med. Public Health, 2007 Nov;38(6):1070-4.
PMID: 18613548

The objective of this study was to determine the prevalence and trends in hepatitis B infection among blood donors attending the Transfusion Medicine Unit at the Hospital Universiti Sains Malaysia, Kelantan, Malaysia. A retrospective study was carried out by reviewing the results of HBsAg among blood donors for the years 2000 to 2004. During this period, 44,658 blood donors were studied. We noted that there was a significant difference in the prevalence of hepatitis B infection between regular and first time donors. There was also a decreasing trend noticed in both study groups. The mean prevalence was significantly different between first time (1.83%) and regular donors (0.45%) (p < 0.005). There is a need to improve public awareness programs to lower the incidence of hepatitis B infection in the general population and consequently first time blood donors. Future studies are also required to determine the trends and outcomes of these programs.
A study of serum ferritin levels among male blood donors in Hospital Universiti sains Malaysia

Norashikin J, Roshan TM, Rosline H, Zaidah AW, Suhair AA, Rapiaah M

Southeast Asian J. Trop. Med. Public Health, 2006 Mar;37(2):370-3.
PMID: 17125001

Iron deficiency is the commonest cause of anemia worldwide and healthy blood donors are estimated to lose about 236 mg of iron with each donation. The objective of this study was to determine the serum ferritin levels among first time and regular male blood donors, and also to correlate the serum ferritin levels with the number of donations and hemoglobin levels. Hemoglobin levels and serum ferritin were measured in three groups of donors divided into first time donors; (n = 92), donors with 2-4 donations (n = 41), and regular donors (n = 78). The mean hemoglobins in the first time donors, second group and regular blood donor group were 14.95 +/- 1.08, 15.12 +/- 1.44 and 15.56 +/- 1.48, respectively. The serum ferritin level were found to be significantly lower among the regular donors (62.0 +/- 39.78 ng/ml) compared to first time donors (90.7 +/- 66.63) and second group donors (114.12 +/- 66.97). The serum ferritin levels gradually decrease according to the number of donations and there was a significant correlation between frequency of donations and the serum ferritin level (r2 = 0.082). Significant correlation between the number of donations and hemoglobin level r2 = 0.061) was noted. However, there was no significant correlation between hemoglobin and serum ferritin levels (r2 = 0.015). Eleven percent of regular donors had depleted iron stores. This was not noted in donors who donated less than 5 times within 2 years.
Influence of the Angiotensin II type I receptor gene 1166A > C polymorphism on BP and aortic pulse wave velocity among Malays

Rehman A, Rasool AH, Naing L, Roshan TM, Rahman AR

Ann. Hum. Genet., 2007 Jan;71(Pt 1):86-95.
PMID: 17227479

Angiotensin II type 1 receptor (AGT1R) gene 1166A > C polymorphism has been shown to be associated with essential hypertension and aortic stiffness as measured by carotid femoral pulse wave velocity (PWV). This study was carried out to investigate the association of the 1166A > C polymorphism with blood pressure (BP) and PWV among Malay hypertensive and normotensive subjects. Two hundred and one hypertensive subjects without evidence of cardiovascular (CV) complications and 201 age- and sex-matched normotensive subjects were studied in a cross-sectional design. Blood pressures (BP) and PWV were measured, and 1166A > C genotype was determined by polymerase chain reaction followed by restriction enzyme digestion. The 1166C allele frequency was 7.96% and 7.73% among Malay hypertensive and normotensive subjects, respectively. There was no association of the 1166A > C polymorphism with BP in the hypertensive, normotensive or overall Malay populations. PWV was significantly higher among 1166C allele carriers as compared to non-carriers (10.52 +/- 1.82 vs. 10.15 +/- 1.80, p = 0.040) in the overall population, but not in the hypertensive and normotensive populations separately. In conclusion, the frequency of 1166C polymorphism is similar among Malay hypertensive and normotensive subjects. This polymorphism has no association with BP but may have an influence on PWV in Malays, which needs further investigation.
Effect of menopause on platelet activation markers determined by flow cytometry

Roshan TM, Normah J, Rehman A, Naing L

Am J Hematol, 2005 Dec;80(4):257-61.
PMID: 16315264

Pre-menopausal women have a lower risk of cardiovascular disease compared to post-menopausal women. Cardiovascular disease is more age dependent in women than in men. The association of platelet activation and cardiovascular thrombotic events is well established. Standardized techniques were used to evaluate platelet activation markers by flow cytometry, using 3-color analysis (CD 61PerCP, CD 62P, and PAC-1) in 49 post-menopausal (mean +/- SD age, 56.16 +/- 33.51 years) and 42 pre-menopausal (age, 39.38 +/- 7.07 years) women. Results of our study showed a significant increase in CD 62P in post-menopausal women as compared to the pre-menopausal group (2.66 +/- 4.26% vs. 0.52 +/- 2.71%, P < 0.001). Similarly, PAC-1 was significantly increased in post-menopausal women (21.54 +/- 2.48% vs. 3.70 +/- 2.31%, P < 0.001). Furthermore, there was a significant association of CD 62P with serum estradiol in both groups. PAC-1 was significantly associated with age in both groups. The results suggest the role of platelets in the increased incidence of thrombotic events and disease in post-menopausal women.
Factors influencing Hepatitis C virus sero-prevalence among blood donors in north west Pakistan

Khattak MN, Akhtar S, Mahmud S, Roshan TM

J Public Health Policy, 2008 Jul;29(2):207-25.
PMID: 18523475 DOI: 10.1057/jphp.2008.7

Hepatitis C virus infection is a major health problem worldwide. The current study estimated seroprevalence of Hepatitis C virus (HCV) and evaluated associated factors among volunteer blood donors of the Northwest Frontier Province (NWFP), Pakistan. Of 1,131 volunteer blood donors enrolled, 46 (4.1%) were positive for anti-HCV antibodies. Multivariate logistic regression analysis revealed that positive donors were more likely to be 27-32 years old or >32 years old, have had 1-2 injections or >2 injections in the past year, or 1-5 intravenous (IV) drips or >5 I/V drips in the past 5 years. Positive donors had a family history of jaundice and were more likely to have been shaved (facial and armpit) by barbers. There was high prevalence of anti-HCV antibodies among blood donors of the NWFP. Public awareness programs should target the identified risk factors to prevent HCV transmission. We highlight the weakness of the health care system for blood donation, as it does not offer any record management for donors.
Short-term estrogen replacement therapy reduces platelet marker levels in Malaysian postmenopausal women

Sheikh SA, Roshan TM, Khattak MN, Baig AA, Noor SJ, Hassan R, et al.

Menopause Int, 2011 Mar;17(1):6-10.
PMID: 21427417 DOI: 10.1258/mi.2011.011001

In healthy postmenopausal women (PMW) increased platelet activation has been associated with adverse cardiovascular events. There is much debate about the relationship between platelet function and serum estradiol level in PMW. This study assessed the effect of short-term oral estrogen replacement therapy (ERT) on platelet activation markers (CD62P and PAC-1) and its correlation with age and body mass index (BMI) among healthy PMW.
Hematological reference values of healthy Malaysian population

Roshan TM, Rosline H, Ahmed SA, Rapiaah M, Wan Zaidah A, Khattak MN

Int J Lab Hematol, 2009 Oct;31(5):505-12.
PMID: 18498389 DOI: 10.1111/j.1751-553X.2008.01068.x

Health and disease can only be distinguished by accurate and reliable reference values of a particular laboratory test. It is now a proven fact that there is considerable variation in hematology reference intervals depending on the demographic and preanalytical variables. There are evidences that values provided by manufacturers do not have appropriate application for all populations. Moreover, reference ranges provided by different laboratory manuals and books also do not solve this problem. We are presenting here normal reference ranges of Malaysian population. These values were determined by using Sysmex XE-2100 and ACL 9000 hematology and coagulation analyzers. Results from this study showed that there were considerable differences in the reference values from manufacturers, western population or laboratory manuals compared with those from the local population.
The prevalence of human cytomegalovirus seropositivity among blood donors at the Unit of Blood Transfusion Medicine, Hospital Universiti Sains Malaysia

Ahmed SA, Al-Joudi FS, Zaidah AW, Roshan TM, Rapiaah M, Abdullah YM, et al.

Southeast Asian J. Trop. Med. Public Health, 2006 Mar;37(2):294-6.
PMID: 17124989

Human cytomegalovirus (HCMV) is a species-specific DNA virus of the Herpetoviridae family. After a primary infection, HCMV persists in a latent form most probably in bone marrow progenitor cells or in peripheral blood monocytes. The virus can reactivate to result in shedding of the virus leading to virus dissemination and new infections. Immunocompromized patients are the ones most vulnerable to serious diseases occasionally acquired in blood transfusions. In a human population, HCMV seropositivity increases steadily with age to become approximately 100% in adults. This study was performed to detect seropositivity among regular blood donors in The Hospital of the Universiti Sains Malaysia, in the state of Kelantan. Using an enzyme immunoassay, it was found that 97.6% of blood donors were HCMV-positive. HCMV is highly prevalent and may be endemic in Kelantan. Hence, long-term strategies are required for the reduction of disease dissemination, and to prevent the exposure of immunocompromized patients to the virus.
Reduction in arterial stiffness with angiotensin II antagonism and converting enzyme inhibition. A comparative study among malay hypertensive subjects with a known genetic profile

Rehman A, Ismail SB, Naing L, Roshan TM, Abdul Rahman AR

Am J Hypertens, 2007 Feb;20(2):184-9.
PMID: 17261465 DOI: 10.1016/j.amjhyper.2006.07.015

BACKGROUND: Data comparing the effect of losartan and perindopril on aortic stiffness among hypertensive subjects without A(1166)C polymorphism was not available.
METHODS: The short-term and long-term effects of losartan (50 mg) and perindopril (4 mg) on aortic stiffness measured as carotid femoral pulse wave velocity (PWV) were compared in 39 middle-aged Malay subjects with mild-to-moderate hypertension in a 4-month, double-blind, randomized, controlled, parallel-design study.
RESULTS: Four-month treatment with both drugs showed a significant reduction in blood pressure (BP) (P < .005) and PWV (P < .05) as compared to the baseline. On the other hand 1-month treatment showed a significant reduction in BP only in perindopril group (P < .05) but not in the losartan group. There was no significant reduction in pulse pressure and PWV after 1 month treatment by both drugs. No significant difference was seen in reduction in BP after 1 month and 4 months treatment between the two drugs. Similarly no significant difference was seen in reduction in PWV between the two drugs after 1 month (P = .613) and 4 months (P = .521) of treatment. Reduction in PWV by losartan (r = 0.470) and perindopril (r = 0.457) correlated significantly only with reduction in DBP (P < .05) and remained significant even after controlling for reduction in DBP (P < .05). Reduction in PWV by both losartan and perindopril was independent of reduction in BP by these drugs.
CONCLUSIONS: These results showed that long-term treatment with losartan shows similar pressure independent reduction in PWV as perindopril among Malay hypertensive subjects with a homogenous "AA" genotype for angiotensin II type 1 receptor and may serve as a suitable alternative to perindopril.
Increased PAC-1 expression among patients with multiple myeloma on concurrent thalidomide and warfarin

Abdullah WZ, Roshan TM, Hussin A, Zain WS, Abdullah D

Blood Coagul Fibrinolysis, 2013 Dec;24(8):893-5.
PMID: 24030118 DOI: 10.1097/MBC.0b013e3283642ee2

Treatment with thalidomide is associated with vascular thrombosis. The effect of thalidomide on platelet activation is unclear, although the use of aspirin is justified for thromboprophylaxis. A study on platelet activation markers was done among multiple myeloma patients receiving thalidomide therapy with warfarin as thromboprophylaxis. Strict criteria and procedure were set to avoid misinterpretation of platelet activation other than due to the thalidomide's effect. Blood specimen pre and post thalidomide therapy were used for flow cytometric analysis. Platelet surface P-selectin, CD62P expression and PAC-1 (antibody that recognizes conformational change of the GPIIb/IIIa complex) were examined by using three-colour flowcytometer. Increased expression marker for PAC-1 was observed after 4 weeks of thalidomide treatment (P
Diffuse large B-cell lymphoma in Southeast Asian cohort: expression patterns of B-cell receptor (BCR) repertoire and its linkage with molecular subtypes and response to R-CHOP therapy

Masir N, Akhter A, Roshan TM, Florence CS, Abdul-Rahman F, Tumian NR, et al.

J Clin Pathol, 2019 Sep;72(9):630-635.
PMID: 31189540 DOI: 10.1136/jclinpath-2019-205837

AIMS: Heightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia.
METHODS: 79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS).
RESULTS: Activated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTKhigh/LYNhigh) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05).
CONCLUSIONS: Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.

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