Lupus anticoagulant associated with low grade B-cell lymphoma and IgM paraproteinaemia with lupus cofactor phenomenon on DRVVT and SCT assays - a possible novel association

Abstract Background Lupus anticoagulant (LA) is an in vitro phenomenon with prolongation of a phospholipid-dependent coagulation test which is not due to an inhibitor specific to a coagulation factor. Occasionally, addition of normal pooled plasma to patient plasma with lupus anticoagulant potentiat...

Full description

Saved in:
Bibliographic Details
Main Authors: Ting Hon Stanford Li, Pui Lun Yip, Hui Yiu Chan, Ho Kin Stephen Chan, Wai Shan Wong
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Thrombosis Journal
Subjects:
Online Access:https://doi.org/10.1186/s12959-024-00680-x
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849220610146697216
author Ting Hon Stanford Li
Pui Lun Yip
Hui Yiu Chan
Ho Kin Stephen Chan
Wai Shan Wong
author_facet Ting Hon Stanford Li
Pui Lun Yip
Hui Yiu Chan
Ho Kin Stephen Chan
Wai Shan Wong
author_sort Ting Hon Stanford Li
collection DOAJ
description Abstract Background Lupus anticoagulant (LA) is an in vitro phenomenon with prolongation of a phospholipid-dependent coagulation test which is not due to an inhibitor specific to a coagulation factor. Occasionally, addition of normal pooled plasma to patient plasma with lupus anticoagulant potentiates the inhibitory effect of lupus anticoagulant in the mixture, resulting in a paradoxical prolongation instead of shortening of clotting time. The phenomenon has been termed the “lupus cofactor effect”. Lupus anticoagulant are known to be associated with lymphoma and immunoglobulin M (IgM) paraproteinaemia. Cases of lymphoplasmacytic lymphoma with concomitant IgM paraproteinaemia and lupus anticoagulant demonstrating lupus cofactor phenomenon on activated partial thromboplastin time (APTT) assay has been reported previously. However, to our best knowledge, there were no reported cases of low grade B-cell lymphoma with positive LA results and lupus cofactor effect demonstrated on dilute Russell’s viper venom time (DRVVT) and/or silica clotting time (SCT) assays in the literature. Case presentation We report two cases of low grade B-cell lymphoma associated with monoclonal IgM paraprotein, high levels of anti-cardiolipin IgM antibody and presence of lupus anticoagulant with lupus cofactor phenomenon on DRVVT and/or SCT assay. Conclusions Our cases demonstrate a possible novel association between low grade B-cell lymphoma, IgM paraproteinaemia, high levels of anti-cardiolipin IgM antibody and the presence of lupus cofactor effect on DRVVT and SCT assays. The DRVVT assay in the first patient and SCT assay in second patient were falsely negative in the neat sample or less diluted sample, and the lupus anticoagulant activities were only revealed on dilution of samples with normal pooled plasma. This highlights the potential importance of dilution of samples with normal pooled plasma while evaluating the LA status of low grade B-cell lymphoma patients with a markedly prolonged APTT and/or prolonged PT by DRVVT and SCT assays, especially if there is concomitant IgM paraproteinaemia and a high level of anti-cardiolipin IgM antibody.
format Article
id doaj-art-de060efb93ee4f23bc560ee1c019f2be
institution Kabale University
issn 1477-9560
language English
publishDate 2024-12-01
publisher BMC
record_format Article
series Thrombosis Journal
spelling doaj-art-de060efb93ee4f23bc560ee1c019f2be2024-12-08T12:41:31ZengBMCThrombosis Journal1477-95602024-12-012211610.1186/s12959-024-00680-xLupus anticoagulant associated with low grade B-cell lymphoma and IgM paraproteinaemia with lupus cofactor phenomenon on DRVVT and SCT assays - a possible novel associationTing Hon Stanford Li0Pui Lun Yip1Hui Yiu Chan2Ho Kin Stephen Chan3Wai Shan Wong4Department of Pathology, Queen Elizabeth HospitalDepartment of Medicine, Queen Elizabeth HospitalDepartment of Pathology, Queen Elizabeth HospitalDepartment of Pathology, Queen Elizabeth HospitalDepartment of Pathology, Queen Elizabeth HospitalAbstract Background Lupus anticoagulant (LA) is an in vitro phenomenon with prolongation of a phospholipid-dependent coagulation test which is not due to an inhibitor specific to a coagulation factor. Occasionally, addition of normal pooled plasma to patient plasma with lupus anticoagulant potentiates the inhibitory effect of lupus anticoagulant in the mixture, resulting in a paradoxical prolongation instead of shortening of clotting time. The phenomenon has been termed the “lupus cofactor effect”. Lupus anticoagulant are known to be associated with lymphoma and immunoglobulin M (IgM) paraproteinaemia. Cases of lymphoplasmacytic lymphoma with concomitant IgM paraproteinaemia and lupus anticoagulant demonstrating lupus cofactor phenomenon on activated partial thromboplastin time (APTT) assay has been reported previously. However, to our best knowledge, there were no reported cases of low grade B-cell lymphoma with positive LA results and lupus cofactor effect demonstrated on dilute Russell’s viper venom time (DRVVT) and/or silica clotting time (SCT) assays in the literature. Case presentation We report two cases of low grade B-cell lymphoma associated with monoclonal IgM paraprotein, high levels of anti-cardiolipin IgM antibody and presence of lupus anticoagulant with lupus cofactor phenomenon on DRVVT and/or SCT assay. Conclusions Our cases demonstrate a possible novel association between low grade B-cell lymphoma, IgM paraproteinaemia, high levels of anti-cardiolipin IgM antibody and the presence of lupus cofactor effect on DRVVT and SCT assays. The DRVVT assay in the first patient and SCT assay in second patient were falsely negative in the neat sample or less diluted sample, and the lupus anticoagulant activities were only revealed on dilution of samples with normal pooled plasma. This highlights the potential importance of dilution of samples with normal pooled plasma while evaluating the LA status of low grade B-cell lymphoma patients with a markedly prolonged APTT and/or prolonged PT by DRVVT and SCT assays, especially if there is concomitant IgM paraproteinaemia and a high level of anti-cardiolipin IgM antibody.https://doi.org/10.1186/s12959-024-00680-xLupus anticoagulantLupus cofactor effectLow grade B-cell lymphomaIgM paraproteinaemia
spellingShingle Ting Hon Stanford Li
Pui Lun Yip
Hui Yiu Chan
Ho Kin Stephen Chan
Wai Shan Wong
Lupus anticoagulant associated with low grade B-cell lymphoma and IgM paraproteinaemia with lupus cofactor phenomenon on DRVVT and SCT assays - a possible novel association
Thrombosis Journal
Lupus anticoagulant
Lupus cofactor effect
Low grade B-cell lymphoma
IgM paraproteinaemia
title Lupus anticoagulant associated with low grade B-cell lymphoma and IgM paraproteinaemia with lupus cofactor phenomenon on DRVVT and SCT assays - a possible novel association
title_full Lupus anticoagulant associated with low grade B-cell lymphoma and IgM paraproteinaemia with lupus cofactor phenomenon on DRVVT and SCT assays - a possible novel association
title_fullStr Lupus anticoagulant associated with low grade B-cell lymphoma and IgM paraproteinaemia with lupus cofactor phenomenon on DRVVT and SCT assays - a possible novel association
title_full_unstemmed Lupus anticoagulant associated with low grade B-cell lymphoma and IgM paraproteinaemia with lupus cofactor phenomenon on DRVVT and SCT assays - a possible novel association
title_short Lupus anticoagulant associated with low grade B-cell lymphoma and IgM paraproteinaemia with lupus cofactor phenomenon on DRVVT and SCT assays - a possible novel association
title_sort lupus anticoagulant associated with low grade b cell lymphoma and igm paraproteinaemia with lupus cofactor phenomenon on drvvt and sct assays a possible novel association
topic Lupus anticoagulant
Lupus cofactor effect
Low grade B-cell lymphoma
IgM paraproteinaemia
url https://doi.org/10.1186/s12959-024-00680-x
work_keys_str_mv AT tinghonstanfordli lupusanticoagulantassociatedwithlowgradebcelllymphomaandigmparaproteinaemiawithlupuscofactorphenomenonondrvvtandsctassaysapossiblenovelassociation
AT puilunyip lupusanticoagulantassociatedwithlowgradebcelllymphomaandigmparaproteinaemiawithlupuscofactorphenomenonondrvvtandsctassaysapossiblenovelassociation
AT huiyiuchan lupusanticoagulantassociatedwithlowgradebcelllymphomaandigmparaproteinaemiawithlupuscofactorphenomenonondrvvtandsctassaysapossiblenovelassociation
AT hokinstephenchan lupusanticoagulantassociatedwithlowgradebcelllymphomaandigmparaproteinaemiawithlupuscofactorphenomenonondrvvtandsctassaysapossiblenovelassociation
AT waishanwong lupusanticoagulantassociatedwithlowgradebcelllymphomaandigmparaproteinaemiawithlupuscofactorphenomenonondrvvtandsctassaysapossiblenovelassociation