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Fulltext Antiphospholipid antibodies and stroke in the young--a study of three cases

Lee MK, Cheng HM, Ng SC, Menaka N, Tan CT, Wang F

Med J Malaysia, 1993 Sep;48(3):330-5.
PMID: 8183147

Cerebral infarction in the young is likely to be non-atheromatous. While in previous studies no cause has been found in 40% to 50% of patients, an increasing role for haemorheological factors is becoming apparent. Among these, an association between antiphospholipid antibodies (aPLs) and ischaemic cerebrovascular disease is now well-recognised. This entity has not been previously reported in Malaysian patients. In a study of 80 patients with stroke below the age of 50 years who were seen at the University Hospital, Kuala Lumpur, between January 1982 and May 1992, 3 patients with ischaemic cerebral infarction were found to have aPLs. aPLs was detected using ELISA method for anticardiolipin antibodies (aCLs), and presence of lupus anticoagulant (LA) was established by kaolin clotting time, thromboplastin inhibition test and platelet neutralisation procedure. Only 1 patient had active systemic lupus erythematous. Cerebrovascular events were recurrent in one of the 2 non-lupus patients. aPL-related stroke should be considered in young patients who have cerebral ischaemia occurring without obvious cause. More cases are likely to emerge in Malaysia with active screening.

Matched MeSH terms: Lupus Coagulation Inhibitor/analysis
Fulltext Apparent factor IX inhibitor

Jameela, S., Rozika, P., Rizalman, J., Phan, C.L., Visalachy, P., Chang, K.M.

Medicine & Health, 2011;6(2):126-130.
MyJurnal

The causes of an isolated prolonged activated partial thromboplastin time (APTT) with a normal prothrombin time (PT) are either a deficiency of clotting factors VIII, IX, XI or XII or the presence of an inhibitor. The inhibitor may be specific to an individual clotting factor or it may be a non-specific inhibitor like the lupus anticoagulant which has opposite therapeutic implications. We report a patient referred to our hospital for treatment that was previously diagnosed at another medical institution as an acquired factor IX inhibitor following an investigation for a prolonged APTT. On further testing this turned out to be a potent lupus anticoagulant which interfered with the phospholipid-dependent factor assays. The use of dilution studies, chromogenic assays and phospholipid neutralization can help differentiate these inhibitors. Great care must be taken in the interpretation of factor assays in the presence of lupus anticoagulant to avoid misdiagnosis and inappropriate treatment.

Matched MeSH terms: Lupus Coagulation Inhibitor
Comparative analysis of chromogenic vs clot.based one stage APTT assay for determination of factor VIII level

Baig MA, Swamy KB

Indian J Pathol Microbiol, 2021 1 13;64(1):123-127.
PMID: 33433421 DOI: 10.4103/IJPM.IJPM_900_19

Background: In the laboratory, factor VIII can be measured by three different methodologies, such as one-stage clotting assay, two-stage clotting assay, and chromogenic assay. These assays differ in ease of use, variety of reagents available, sensitivity to mild hemophilia A, and interference from lupus anticoagulants (LACs). Certain factor VIII gene mutations can cause discrepancy in results between one-stage activated partial thromboplastin time (APTT) and chromogenic assays.
Materials and Methods: The coagulometer for factor VIII assay is Sysmex CS-5100. All data were expressed as mean ± standard deviation (SD).
Results: A total of 135 cases were studied. Of these, 100 cases were of mild hemophilia A diagnosed by molecular genetics and, 15 cases were positive for LAC, which were confirmed by dilute Russell Viper venom test. Clot-based one-stage APTT assay showed 65% sensitivity and 80% specificity in diagnosing mild hemophilia A cases and out of 15 LAC cases, it showed false positivity in five cases. Chromogenic assay showed 85% sensitivity and 90% specificity in diagnosing mild hemophilia cases and was 100% specific in excluding LAC cases.
Conclusions: One-stage APTT assay is the most commonly used test for determining factor VIII levels but chromogenic assay are considered as the gold standard and recommended as the reference method by European Pharmacopoeia and ISTH subcommittee. Mild hemophilia A patients with missense mutations show discrepancy between the one-stage clot-based APTT assay and chromogenic assays for determination of factor VIII level and this can lead to misdiagnosis or misclassification of mild hemophilia A. Therefore, it is recommended that both the assays should be used in the evaluation of mild hemophilia cases.

Matched MeSH terms: Lupus Coagulation Inhibitor
Adverse pregnancy outcomes among multi-ethnic systemic lupus erythematosus patients in Malaysia

Shaharir SS, Maulana SA, Shahril NS, Mohd R, Mustafar R, Said MSM, et al.

Lupus, 2020 Sep;29(10):1305-1313.
PMID: 32660312 DOI: 10.1177/0961203320938871

BACKGROUND: Despite the improvement in the live birth rate among patients with systemic lupus erythematosus (SLE), they are still at an increased risk of adverse pregnancy outcomes (APOs).
OBJECTIVE: To determine the prevalence and factors associated with APOs in the multi-ethnic SLE populations in Malaysia.Methodology: This was a retrospective review of the consecutive SLE patients who attended the outpatient clinic in two major rheumatology centres from January 2016 until December 2019 with complete pre-pregnancy, antenatal and intra-partum records. APOs include pregnancy loss, prematurity, pre-eclampsia, intra-uterine growth restriction (IUGR) and maternal death. Univariate and multivariable logistic regression with generalised estimating equation (GEE) analyses were performed to determine the factors associated with APOs.
RESULTS: A total of 153 patients with 240 pregnancies were included and the majority of the patients were Malay (69.9%), followed by Chinese (24.2%) and Indian (5.9%). The prevalence of APOs was 61.7% with the commonest complication being prematurity (28.3%), followed by pregnancy loss (24.6%) and pre-eclampsia (21.8%). Logistic regression model-based GEE analysis revealed that the independent predictors of APOs were active haematological system during pregnancy, pre-pregnancy active disease, Indian patients and positive lupus anticoagulant. Hydroxychloroquine use was associated with lower APOs including pre-eclampsia, prematurity and IUGR in the univariate analyses but it was no longer significant in the GEE analysis.
CONCLUSION: The prevalence of APOs was high particularly among the Indian patients. Positive lupus anticoagulant and pre-pregnancy active disease were the factors strongly associated with APOs in our multi-ethnic cohort. Hydroxychloroquine may protect against APOs but further larger studies are needed to confirm this.

Matched MeSH terms: Lupus Coagulation Inhibitor