ABSTRACT
Lupus anticoagulant-hypoprothrombinaemia syndrome (LAHPS) is a rare disorder caused by the presence of lupus anticoagulant (LA) and acquired prothrombin deficiency, which may present with severe haemorrhagic manifestations. LAHPS is usually associated with systemic lupus erythematosus (SLE), or infections and it is more frequent in the paediatric population and female gender. We describe a 42-year-old man with thrombotic antiphospholipid syndrome (APS) on chronic anticoagulation treatment with acenocoumarol who presented with spontaneous intracranial bleeding, prolongation of prothrombin time (PT), activated partial thromboplastin time (APTT) and low factor II levels (after optimal anticoagulation reversal) as a debut of SLE.
Subject(s)
Antiphospholipid Syndrome , Hypoprothrombinemias , Lupus Erythematosus, Systemic , Male , Child , Female , Humans , Adult , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Lupus Coagulation Inhibitor , Hypoprothrombinemias/complications , Hypoprothrombinemias/diagnosis , Lupus Erythematosus, Systemic/complications , Prothrombin , HemorrhageABSTRACT
The issue of how to identify newly diagnosed multiple myeloma (NDMM) patients requiring thromboprophylaxis remains unsolved. Several changes in thrombin generation (TG)-derived parameters have been described in multiple myeloma (MM) patients recently. Assessment of prothrombotic risk with a fully automated TG analyzer could reduce interlaboratory variability. Our objective was to determine whether ST-Genesia® could reveal a hypercoagulable state in NDMM compared to healthy controls. We conducted a multicenter observational study of NDMM requiring initial treatment to compare TG parameters obtained with ST-Genesia® analyzer and ST-ThromboScreen® reagent with a control group. Clinical data were obtained from medical records and blood samples were collected before initial anti-myeloma therapy. A thrombophilia panel was performed in all patients. Compared to age- and sex-matched controls (n = 83), NDMM patients (n = 83) had significantly higher peak height, higher velocity index, shorter time-to-peak and lower percentage of endogenous thrombin potential (ETP) inhibition after adding thrombomodulin (TM) (ETP%inh). NDMM on prophylactic low molecular weight heparin (LMWH) showed reduced both peak height and velocity index compared to NDMM who had not yet started VTE prophylaxis, similar to that of controls. Moreover, partial correction of ETP%inh was observed in MM patients on LMWH. The presence of a thrombophilia did not modify the TG phenotype. Untreated NDMM patients showed an enhanced TG, regardless of their thrombophilia status. They generate a higher peak of thrombin, take less time to produce it, and exhibit resistance to TM inhibition. Our findings suggest that standard prophylactic dose of LMWH may reduce TG at levels of healthy controls.
Subject(s)
Multiple Myeloma , Thrombophilia , Venous Thromboembolism , Humans , Thrombin , Multiple Myeloma/drug therapy , Anticoagulants/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Venous Thromboembolism/drug therapy , Thrombophilia/diagnosis , Thrombophilia/etiology , Thrombophilia/drug therapy , Blood Coagulation TestsABSTRACT
BACKGROUND: Lupus anticoagulant (LA) can be a cause of thrombosis and/or pregnancy morbidities, producing antiphospholipid syndrome (APS). An increase in thrombin generation (TG) is correlated with prothrombotic status. Several changes in TG-derived parameters have been reported in APS patients. OBJECTIVES: Evaluate whether the TG phenotype of APS can also be described in LA subjects without clinical manifestations of APS, and to investigate the possible influence of both LA potency and antiphospholipid (aPL) profile on it. RESULTS: TG was analyzed in 153 cases of LA and 41 healthy controls. We have observed prolongation of both lag time (3.7â¯min vs 2.32â¯min, pâ¯<â¯0.001) and time to peak (6.48â¯min vs 5.27â¯min, pâ¯<â¯0.001), increased peak height (221.7â¯nM vs 182.7â¯nM, pâ¯<â¯0.001), slightly higher ETP (221.7â¯nM·min vs 182.7â¯nM·min, pâ¯=â¯0.041), and higher velocity index (100.7â¯nM/min vs 74.53â¯nM/min, pâ¯=â¯0.001) in LA subjects compared to controls. After adding thrombomodulin (TM), ETP%inh was significantly lower in LA group (37.90% vs 59.90%, pâ¯<â¯0.001) showing resistance to TM/activated protein C (APC). Significant differences were found in lag time, time to peak and ETP%inh according to the potency and aPL profile. CONCLUSIONS: Previously described differences in TG-derived parameters in APS patients have been confirmed in incidental LA subjects: prolonged lag time and time to peak, slightly higher ETP, higher peak height, and less sensitivity to TM/APC. High LA potency and triple-positive aPL profile enhance differences in lag time, time to peak and, especially, increase APC resistance, but no effect in ETP was observed.
