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Prothrombotic markers in Thalassemia major patients: A paradigm shift

Sultan S, Irfan SM, Zaidi SM

Med J Malaysia, 2018 08;73(4):185-189.
PMID: 30121679

BACKGROUND: It is being increasingly recognised that thalassemia major patients, like intermedia, have increased propensity for thromboembolism. Deficiency of natural anticoagulants is more recently defined finding contributing to the hypercoagulable state. The aim this study is to determine natural anticoagulants levels and their correlation with maternal characteristics, haematological and biochemical markers.
METHODS: This is a prospective case-control study. We registered 80 patients and 60 healthy controls from Jan 2009 to Dec 2013. Complete blood counts, prothrombin time, activated partial thromboplastin time, protein C, protein S, antithrombin, serum ferritin, liver enzymes; HbsAg and Anti- HCV were evaluated.
RESULT: There were 42 males and 38 females with mean age of 12.30±5.50 years. The mean protein C, protein S and antithrombin in patients and control were 58.25±22.5 versus 110.67±22.60, 67.90±19.58 versus 98.70±21.54 and 89.73±18.09 versus 104.0±10.98 (p<0.001) respectively. Protein C was predominantly deficient in 65% followed by protein S and antithrombin in 35% and 20% respectively. Protein C deficiency divulged positive correlation with protein S deficiency (p = 0.035) and antithrombin deficiency with hemoglobin of ≤8gm% (p<0.0025). No significant correlation of prothrombotic markers was established with maternal characteristics, hepatic dysfunction, hepatitis and serum ferritin.
CONCLUSION: Substantial decrement in prothrombotic markers, primarily protein C, may be implicated in elevated thrombosis; however follow-up data is required to establish definitive thromboembolic events.
Primary versus secondary immune thrombocytopenia in adults; a comparative analysis of clinical and laboratory attributes in newly diagnosed patients in Southern Pakistan

Sultan S, Ahmed SI, Murad S, Irfan SM

Med J Malaysia, 2016 10;71(5):269-274.
PMID: 28064294

BACKGROUND: Immune thrombocytopenic purpura (ITP) is a hemorrhagic diathesis, characterized by platelets destruction alongside impaired production. Patients from Asian regions often exhibit distinctive characteristics in comparison to the western patients. We accomplished this study to evaluate the prevalence of primary versus secondary ITP along with the comparative analysis between them. The secondary objective was to determine the etiological spectrum of secondary ITP.
METHODS: We illustrate the results of a large cohort of newly diagnosed adults ITP from southern Pakistan. The study extended from January 2009-December 2013. Complete blood counts, HbsAg, Anti-HCV, ANA, stool for Helicobacterpylori were done on all. HIV, TSH, anti-dsDNA, RA factor, APLA and direct coombs test were evaluated in cases where indicated.
RESULTS: A total of 417 patients were included with a mean age of 40.95±14.82 years. Primarily disease was observed in the 3rd decade of life. Male to female ratio was 1:1.5. Mean platelets count was 46.21±27.45x109/l. At diagnosis 43.16% (n=180) patients had hemorrhagic manifestations whilst 56.8% (n=237) were asymptomatic. None of the patient presented with visceral, retropharyngeal or intracranial bleed. The prevalence of secondary ITP was substantially higher (64.8%) as compared to primary ITP (35.2%). Secondary ITP was predominantly seen in HCV reactive patients (24.4%) followed by helicobacter-pylori infection (11%). Nevertheless 16.4% patients had underlying autoimmune disorders. Providentially no study subject was found to be HIV reactive.
CONCLUSIONS: Our study revealed predominance of secondary ITP. However bleeding manifestations and degree of thrombocytopenia were high in primary-ITP. Infectious etiology followed by autoimmune disorders is mainly implicated for secondary ITP in our setting.
Fulltext Efficacy of helicobacter pylori eradication as an upfront treatment of secondary immune thrombocytopenia: an experience from Pakistan

Sultan S, Irfan SM, Kaker J, Hasan M

Med J Malaysia, 2016 04;71(2):53-6.
PMID: 27326941

BACKGROUND: The effect of Helicobacter-pylori eradication therapy on the platelet counts in patients with immune thrombocytopenia is still debatable. The aim of this study was to assess the response rates of standard triple eradication therapy in secondary immune thrombocytopenia with Helicobacter pylori infection.

METHODS: From January 2012 to December 2013, 197 patients were diagnosed to have immune thrombocytopenia, out of which 22(11.1%) patients infected with Helicobacter- Pylorus were enrolled in this study. Helicobacter-Pylori infection was documented by Helicobacter-pylori stool antigen enzyme immunoassay method. All positive patients were put on triple eradication therapy. The responses rates to treatment were defined as per International Working Group on ITP.

RESULTS: Mean age of patients was 43.18±12.5 years. There were 10(45.5%) males and 12 (54.5%) females. Of the 22 patients, 7(31.8%) exhibited a complete response (CR) to Hpylori eradication therapy; 10(45.4%) attained a response; and 5(22.7%) had no response. Mean base line platelet counts were 53.36±24.5x109/l, while platelet counts at 4 week following eradication was 80.86±51.0x109/l (P=0.003). The predictive factor of response following eradication therapy was baseline platelet counts. Virtually all responders had baseline platelet counts >30x109/l and all non-responders had <30x109/l of platelet counts.

CONCLUSIONS: Though the prevalence of H-pylori is low, this study confirmed the efficacy of eradication in increasing the platelet counts in H-pylori positive patients with ITP. It is an important measure in short time, safe and very cost effective to achieve platelets increment. We endorse the routine detection and eradication treatment of H-pylori infective ITP patients.
Multiplex real-time RT-PCR assay for transfusion transmitted viruses in sero-negative allogeneic blood donors: an experience from Southern Pakistan

Sultan S, Nasir MI, Rafiq S, Baig MA, Akbani S, Irfan SM

Malays J Pathol, 2017 Aug;39(2):149-154.
PMID: 28866696

BACKGROUND: Blood transfusion safety commences with healthy donor recruitment. The threat of transfusion transmitted infections is greatly minimized by serological tools but not entirely eliminated. Recently, nucleic-acid testing for blood donor screening has virtually eliminated this jeopardy.
METHODS: This prospective study was conducted from February 2015 to February 2016. Samples from seronegative donors were run on multiplex assay (Cobas, S-201 system platform, Roche) in a batch of six [MP-NAT]. In case of reactive pool, tests were run on every individual sample [IDNAT].
RESULTS: Of 16957 donors, 16836 (99.2%) were replacement donors and the remaining 121 (0.7%) were voluntary donors, with a mean age of 29.09 ± 7.04 years. After serologic screening of all 16957 donors, 955 (5.6%) were found to be reactive; 291(1.71%) were reactive for hepatitis-B surface antigen, 361 (2.12%) for antibody to hepatitis C virus (anti-HCV), 14 (0.08%) for antibody to human immunodeficiency virus, 287 (1.69%) for syphilis and 2 (0.01%) for malaria. 14 (0.08%) NAT reactive donors were identified after testing the 16002 seronegative donors, with an overall NAT yield of one reactivity out of 1143 blood donations; 10 donors for HBV-DNA (HBV NAT yield-1:1600) and remaining 4 for HCV-RNA (HCV-NAT yield-1:4000). None were HIV positive.
CONCLUSION: NAT has improved the safety attributes in blood products. Although the positivity rate for NAT testing is low but in view of the high prevalence of transfusion transmitted infections in our country, we recommend the parallel use of both serology and NAT screening of all donated blood.