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Elucidation of clinical and laboratory features, comorbidity risks, treatment options and molecular pathophysiology of antiphospholipid syndrome (APS) patients

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by the presence of circulating antiphospholipid antibodies (aPLs) such as lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2-glycoprotein I (β2-GPI) antibodies to phospholipid binding proteins. Although the di...

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Main Author: Islam, Md Asiful
Format: Thesis
Language:English
Published: 2018
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RC Internal medicine
Online Access:http://eprints.usm.my/45830/1/Dr.%20Asiful%20Islam-24%20pages.pdf
http://eprints.usm.my/45830/
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spelling my.usm.eprints.45830 http://eprints.usm.my/45830/ Elucidation of clinical and laboratory features, comorbidity risks, treatment options and molecular pathophysiology of antiphospholipid syndrome (APS) patients Islam, Md Asiful RC Internal medicine Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by the presence of circulating antiphospholipid antibodies (aPLs) such as lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2-glycoprotein I (β2-GPI) antibodies to phospholipid binding proteins. Although the disease has been in existence for approximately 35 years, the diagnostic criteria, risk factors, pathogenesis, genetic aspects, treatment strategies are poorly understood and have yet to be fully developed. In this study, the clinical and laboratory features, genetic risk factors, comorbidity risks, molecular pathophysiology and optimal treatment strategy of APS patients are explored. Human peripheral blood mononuclear cell (PBMC)-derived high-quality and integrity RNA extraction and purification method was optimised (centrifugal speed: 14000 rpm + spin time: 75 seconds + DNase treatment + Ribolock RNase inhibitor + RNA clean-up) which could be used to send APS patients’ RNA for RNA-Seq. In quest of APS patients, two studies were conducted. Firstly, on a familial primary APS cases from Sarawak, Malaysia, patients however became seronegative following long warfarin therapy. Another one with APS subjects from Hospital Universiti Sains Malaysia (HUSM) were retrospectively investigated by exploring the clinical, laboratory and treatment strategies. High occurrence of pregnancy morbidity, as well as some unusual clinical features such as persistent dysfunction of liver and kidneys; menorrhagia and ovarian cyst were observed. The use of medium-intensity warfarin was successful in preventing thrombosis recurrence. Additionally, since theHUSM patients were unwilling to participate in this study, we were unable to send the RNA samples for RNA-Seq to BGI. A systematic review with bioinformatic analyses was conducted to identify the genetic risk factors in thrombotic APS subjects where 16 genes were significantly associated with thrombosis affecting mostly the blood coagulation pathway and the immune system related to APS. Overall, three systematic reviews and meta-analyses were conducted to determine the influence of aPLs in patients with migraine, epilepsy and dementia without autoimmune disease as compared to controls, where aPLs were significantly comorbid with the said manifestations. Therefore, the neurologic features were early clinical manifestations before the development of full-blown APS. A single Cochrane systematic review was developed to explore the optimum treatment strategy for thrombotic APS subjects, where, moderate-intensity warfarin was superior than high-intensity warfarin. Overall, a comprehensive study exploring the clinical and laboratory features, genetic risk factors, comorbidity risks, molecular pathophysiology and optimal treatment strategy of APS patients was successfully established. 2018-10 Thesis NonPeerReviewed application/pdf en http://eprints.usm.my/45830/1/Dr.%20Asiful%20Islam-24%20pages.pdf Islam, Md Asiful (2018) Elucidation of clinical and laboratory features, comorbidity risks, treatment options and molecular pathophysiology of antiphospholipid syndrome (APS) patients. Masters thesis, Universiti Sains Malaysia.
institution Universiti Sains Malaysia
building Hamzah Sendut Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Sains Malaysia
content_source USM Institutional Repository
url_provider http://eprints.usm.my/
language English
topic RC Internal medicine
spellingShingle RC Internal medicine
Islam, Md Asiful
Elucidation of clinical and laboratory features, comorbidity risks, treatment options and molecular pathophysiology of antiphospholipid syndrome (APS) patients
description Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by the presence of circulating antiphospholipid antibodies (aPLs) such as lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2-glycoprotein I (β2-GPI) antibodies to phospholipid binding proteins. Although the disease has been in existence for approximately 35 years, the diagnostic criteria, risk factors, pathogenesis, genetic aspects, treatment strategies are poorly understood and have yet to be fully developed. In this study, the clinical and laboratory features, genetic risk factors, comorbidity risks, molecular pathophysiology and optimal treatment strategy of APS patients are explored. Human peripheral blood mononuclear cell (PBMC)-derived high-quality and integrity RNA extraction and purification method was optimised (centrifugal speed: 14000 rpm + spin time: 75 seconds + DNase treatment + Ribolock RNase inhibitor + RNA clean-up) which could be used to send APS patients’ RNA for RNA-Seq. In quest of APS patients, two studies were conducted. Firstly, on a familial primary APS cases from Sarawak, Malaysia, patients however became seronegative following long warfarin therapy. Another one with APS subjects from Hospital Universiti Sains Malaysia (HUSM) were retrospectively investigated by exploring the clinical, laboratory and treatment strategies. High occurrence of pregnancy morbidity, as well as some unusual clinical features such as persistent dysfunction of liver and kidneys; menorrhagia and ovarian cyst were observed. The use of medium-intensity warfarin was successful in preventing thrombosis recurrence. Additionally, since theHUSM patients were unwilling to participate in this study, we were unable to send the RNA samples for RNA-Seq to BGI. A systematic review with bioinformatic analyses was conducted to identify the genetic risk factors in thrombotic APS subjects where 16 genes were significantly associated with thrombosis affecting mostly the blood coagulation pathway and the immune system related to APS. Overall, three systematic reviews and meta-analyses were conducted to determine the influence of aPLs in patients with migraine, epilepsy and dementia without autoimmune disease as compared to controls, where aPLs were significantly comorbid with the said manifestations. Therefore, the neurologic features were early clinical manifestations before the development of full-blown APS. A single Cochrane systematic review was developed to explore the optimum treatment strategy for thrombotic APS subjects, where, moderate-intensity warfarin was superior than high-intensity warfarin. Overall, a comprehensive study exploring the clinical and laboratory features, genetic risk factors, comorbidity risks, molecular pathophysiology and optimal treatment strategy of APS patients was successfully established.
format Thesis
author Islam, Md Asiful
author_facet Islam, Md Asiful
author_sort Islam, Md Asiful
title Elucidation of clinical and laboratory features, comorbidity risks, treatment options and molecular pathophysiology of antiphospholipid syndrome (APS) patients
title_short Elucidation of clinical and laboratory features, comorbidity risks, treatment options and molecular pathophysiology of antiphospholipid syndrome (APS) patients
title_full Elucidation of clinical and laboratory features, comorbidity risks, treatment options and molecular pathophysiology of antiphospholipid syndrome (APS) patients
title_fullStr Elucidation of clinical and laboratory features, comorbidity risks, treatment options and molecular pathophysiology of antiphospholipid syndrome (APS) patients
title_full_unstemmed Elucidation of clinical and laboratory features, comorbidity risks, treatment options and molecular pathophysiology of antiphospholipid syndrome (APS) patients
title_sort elucidation of clinical and laboratory features, comorbidity risks, treatment options and molecular pathophysiology of antiphospholipid syndrome (aps) patients
publishDate 2018
url http://eprints.usm.my/45830/1/Dr.%20Asiful%20Islam-24%20pages.pdf
http://eprints.usm.my/45830/
_version_ 1657488774669533184
score 13.211869

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