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Antiphosphatidylserine/prothrombin complex (aPS/PT) antibodies are recognized as a marker for antiphospholipid syndrome (APS). Dense and poorly lysable fibrin clots occur in thrombotic APS. Compact clots predict thromboembolism, but determinants of the unfavorable clot phenotype remain unknown in APS. We hypothesized that elevated aPS/PT antibodies determine unfavorable clot features.

Multiple myeloma (MM) is a rare malignancy, characterized by clonal proliferation of plasma cells, secreting monoclonal immunoglobulin. It is usually diagnosed based on histopathologic and immunophenotypic bone marrow examination. Abnormal results of screening coagulation tests, including prothrombin time, activated partial thromboplastin time and thrombin time, are commonly encountered in patients with plasma cell neoplasms. They do not, however, reflect bleeding tendency. We describe a 71-year-old patient who was accidentally diagnosed with multiple myeloma during coagulation diagnostics.

OBJECTIVE: To investigate the utility of receiver operating characteristic (ROC) analysis in determining the strength of association between various antiphospholipid and anti-protein cofactor antibodies (aPA) and thrombosis, pregnancy morbidity, and thrombocytopenia. METHODS: Clinical and laboratory variables were retrospectively studied in 204 patients: 160 with systemic lupus erythematosus (SLE), 22 with lupus-like syndrome (SLE-LS), and 22 with primary antiphospholipid syndrome (APS). Laboratory evaluation included detection of lupus anticoagulant (LAC) and measurement of IgG and IgM anticardiolipin (aCL), antiphosphatidylserine (aPS), antiphosphatidylinositol (aPI), anti-β2 glycoprotein I (aβ2GPI), and antiprothrombin (aPT) antibodies. ROC plot analysis was used to determine the clinical accuracy of aPA tests, and calculate cut-off values which best associate with clinical symptoms typical for APS. RESULTS: The LAC was associated with a history of thrombosis [odds ratio (OR): 3.04; 95% confidence interval (CI): 1.5-6.2] and even more strongly with recurrent fetal loss (OR: 8.7; 95%CI: 2.8-26.7). ROC plot analysis revealed that the most accurate test for thrombosis was aCL IgG (ROC-derived cutoff value > 17.2 GPL; OR: 3.69; 95% CI: 1.8-7.4), for recurrent fetal loss, aPI IgG [> 22.1 theoretical units (TU); OR: 6.21; 95%CI: 2.1-18.5], closely followed by aCL IgG and aβ2GPI IgG, and for thrombocytopenia aPS IgM (> 6.7 TU; OR: 1.9; 95%CI: 1.04-3.4). Among 182 autoimmune patients (SLE + SLE-LS), 6.6% presented clinical symptoms of APS without classic aPA (LAC and/or aCL), but with elevated levels of antibodies against other phospholipids, mainly aPI IgM. CONCLUSION: A laboratory that evaluates APS patients should establish its own threshold values for aPA tests. We suggest that ROC plot analysis is a valuable tool in establishing cutoff values. LAC and aCL determinations seem sufficient for the majority of laboratories. However, in specialized centers other tests should be available to detect those patients with clinical symptoms for APS but who are positive for antiphospholipid antibodies other than aCL and the LAC.

Rivaroxaban, a direct factor Xa inhibitor, affects laboratory clotting tests. We report here 10 venous thromboembolism patients with false-positive lupus anticoagulant during rivaroxaban therapy. Two dilute Russell Viper Venom time (dRVVT)-based integrated assays, HemosIL dRVVT Screen/HemosIL dRVVT Confirm (Instrumentation Laboratory, LA1/LA2 (Siemens, Germany) and LA1/LA2 (Siemens, Marburg, Germany), showed that the patients were lupus anticoagulant-positive. Antiphospholipid antibodies were negative except for one patient. Screening activated partial thromboplastin time-based assay PTT lupus anticoagulant was lupus anticoagulant-positive, whereas the confirmatory Staclot lupus anticoagulant (both Diagnostica Stago, France) was lupus anticoagulant-negative. Re-examination after discontinuation of rivaroxaban (>24 h) ruled out the presence of lupus anticoagulant. Our data indicate that to reliably evaluate lupus anticoagulant in patients on rivaroxaban, blood should be drawn 24 h after the last dose.

A 67-year-old woman with nephrotic syndrome as a complication of membranous glomerulonephritis associated with chronic active hepatitis B virus infection developed factor V inhibitor following emergency aortic aneurysm surgery followed by massive blood transfusions and haemodialysis. On the second postoperative day, prothrombin time and activated partial thromboplastin time increased and were unresponsive to fresh frozen plasma. Epistaxis and urethral bleeding were observed, followed by mucosal mouth bleeding. A very low factor V activity less than 5 was found and a factor V inhibitor was detected at 7.76 Bethesda Units. Treatment with corticosteroids was successful. In this patient, several conditions known to predispose to the generation of factor V inhibitor occurred simultaneously. Four months later, factor V inhibitor (225 Bethesda Units) recurred and the patient died of intracerebral haemorrhage.

Hereditary antithrombin (AT) deficiency is a rare autosomal disease. More than 200 mutations have been described in the AT gene leading to its deficiency. We describe here a case of type I AT deficiency in a 26-year-old Polish man who experienced proximal deep vein thrombosis and pulmonary embolism associated with a transient thrombotic risk factor, the right ankle trauma, despite the use of low-molecular-weight heparin prophylaxis. The family history was negative for venous thromboembolism. The AT activity was initially 47 and on repeated analysis 53, and the antigen level, 0.15gl. The analysis of AT gene revealed the presence at the heterozygous state of a substitution G more than T located at the first nucleotide 3′ of exon 3a (c.6241 G > T, Human Genome Variation Society numbering system). The substitution might be detrimental taking account for its position in a donor splice site. To the best of our knowledge this mutation has not been previously described, so it was named antithrombin Krakow II.