Detection of lupus anticoagulant in the era of direct oral anticoagulants.

Lupus anticoagulant (LAC) is an in vitro phenomenon determining a phospholipid-dependent elongation of clotting times. The presence of LAC associated with anticardiolipin (aCL) and anti-ß2 glycoprotein I (anti-ß2GPI) antibodies is strongly associated with thrombosis and pregnancy morbidity. Direct oral anticoagulants (DOACs) targeting thrombin and factor Xa are currently widely use to prevent and treat venous and arterial thromboembolism. Some concern has, however, been expressed about the possibility of false laboratory results during LAC assessment in patients taking these drugs. Several in vitro studies, spiking DOACs into normal plasma as well as ex vivo at peak levels in treated patients, led in false-positive LAC. The dilute Russell Viper Venom time is the assay that is most influenced by rivaroxaban, edoxaban, dabigatran and less by apixaban. Both screening and confirmatory tests have resulted equally prolonged for activated partial thromboplastin time and have not led to false-positive results, but this may depend on the type of reagent used for the test. Taipan/Ecarin snake venoms ratios, has been recommend by some investigators as they do not seem to be affected by rivaroxaban or edoxaban, but these tests are neither standardized nor generally available in clinical practice. In conclusion, for the time being it does not seem advisable to carry out LAC testing during anti-factor Xa and anti-factor IIa treatment because of the risk of false-positive results. Whenever needed in deciding the suspension of DOACs or in case of recurrent thrombosis, LAC determination should be carried out at trough better if DOAC concentration is known.

Fulminant phlegmasia cerulea dolens with concurrent cholangiocarcinoma and a lupus anticoagulant: a case report and review of the literature.

Phlegmasia cerulea dolens (PCD) is an aggressive and life-threatening form of venous thrombosis complicated by ischemic necrosis. Massive thrombosis extends to collateral veins resulting in venous congestion with fluid sequestration in the interstitium causing collapse of arterioles, which progresses to ischemia and, if severe, circulatory collapse and shock. The mortality rate for PCD is as high as 40%, especially when gangrene develops. PCD has been associated with acquired thrombophilias, including malignancy and antiphospholipid syndrome (APS). We present a unique case of a patient with PCD refractory to anticoagulant and thrombolytic therapy, whose fulminant course was attributed to concurrent cholangiocarcinoma and antiphospholipid antibodies identified by a positive lupus anticoagulant assay. This case highlights the importance of uncovering precipitating causes of thromboembolism, which may offer prognostic information and may necessitate therapy beyond anticoagulation and thrombolysis to reduce the morbidity of PCD. The current literature on PCD and APS, along with their associations with malignancy, is reviewed.

Expression of apoptosis in placenta of experimental antiphospholipid syndrome mouse.

PROBLEM: To study the histopathology and expression of apoptosis in placenta of pregnancy-complicated antiphospholipid syndrome (APS)-positive mouse models. METHOD OF STUDY: ICR mice were immunized with IgG isotype of human anticardiolipin (aCL) and/or lupus anticoagulant (LA). The pathological and apoptotic expression was studied in the placenta of positive APS mice and compared with respective control samples. RESULTS: Mice with passive immunization of human aCL and/or LA produced an increase in fetal resorption along with markedly induced thrombosis in the placenta associated with increased placental apoptosis. In addition, fewer mitotic cells, less trophoblast giant cell invasion, and more shrunken cells in the deciduas were seen. CONCLUSION: Our study showed the pathogenic role of aCL and LA in pregnancy complications.