Li Ting Hon Stanford, Yip Pui Lun, Chan Hui Yiu, Chan Ho Kin Stephen, Wong Wai Shan
Department of Pathology, Queen Elizabeth Hospital, Block M, 30 Gascoigne Road, Kowloon, Hong Kong.
Department of Medicine, Queen Elizabeth Hospital, Kowloon, Hong Kong.
Thromb J. 2024 Dec 5;22(1):109. doi: 10.1186/s12959-024-00680-x.
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.
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.
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.
狼疮抗凝物（LA）是一种体外现象，表现为磷脂依赖的凝血试验延长，这并非由于针对凝血因子的特异性抑制剂所致。偶尔，向含有狼疮抗凝物的患者血浆中加入正常混合血浆会增强狼疮抗凝物在混合物中的抑制作用，导致凝血时间反常延长而非缩短。这种现象被称为“狼疮辅助因子效应”。已知狼疮抗凝物与淋巴瘤和免疫球蛋白M（IgM）副蛋白血症有关。先前已有报道伴有IgM副蛋白血症和狼疮抗凝物的淋巴浆细胞淋巴瘤病例，其在活化部分凝血活酶时间（APTT）试验中表现出狼疮辅助因子现象。然而，据我们所知，文献中尚无关于低级别B细胞淋巴瘤LA结果为阳性且在稀释蝰蛇毒时间（DRVVT）和/或硅土凝血时间（SCT）试验中表现出狼疮辅助因子效应的报道。
我们报告了两例低级别B细胞淋巴瘤病例，其与单克隆IgM副蛋白、高水平抗心磷脂IgM抗体相关，并在DRVVT和/或SCT试验中存在具有狼疮辅助因子现象的狼疮抗凝物。
我们的病例表明低级别B细胞淋巴瘤、IgM副蛋白血症、高水平抗心磷脂IgM抗体与DRVVT和SCT试验中狼疮辅助因子效应的存在之间可能存在新的关联。首例患者的DRVVT试验和第二例患者的SCT试验在纯样本或稀释度较低的样本中出现假阴性，狼疮抗凝物活性仅在加入正常混合血浆稀释样本后才显现。这突出了在通过DRVVT和SCT试验评估APTT明显延长和/或PT延长的低级别B细胞淋巴瘤患者的LA状态时，尤其是伴有IgM副蛋白血症和高水平抗心磷脂IgM抗体时，用正常混合血浆稀释样本的潜在重要性。
