Addendum to British Society for Haematology Guidelines on Investigation and Management of Antiphospholipid syndrome, 2012 (Br. J. Haematol. 2012; 157: 47–58): use of direct acting oral anticoagulants

We studied the efficacy and safety of humanized CAR-T therapy following intensive chemotherapy for refractory/relapsed (R/R) acute lymphoblastic leukaemia (B-ALL). Twenty-three patients with R/R B-ALL were pretreated with intensive chemotherapy (fludarabine combined with medium-dose cytarabine) 12 days before CAR-T therapy. Adverse events (AEs), curative effects, infection indicators and cytokine release syndrome (CRS) were monitored. Each of the 23 patients received a dose of 1·0 × 10⁶ cells/kg CAR-T cell infusion on day 0. After 14 days, 19 patients (82·61%) achieved complete response (CR) or CR with incomplete count recovery. No survival benefit was achieved with consolidative haematopoietic stem-cell transplantation (HSCT), with a median follow-up of 14·0 months (range, 1·5–21·0 months). The notable AEs were grade 1–2 CRS in 18 patients, while the other five patients were grade 3 CRS. No patients died of CRS. Only one patient died of respiratory failure due to cytomegalovirus infection 24 days after infusion. The proportion of leukaemic cells in bone marrow on infusion day and the peaks of IL-6, TNF-α and IL-8 levels were correlated with CRS levels. A lower disease burden was achieved by intensive lymphodepleting chemotherapy, and the subsequent CAR-T therapy had a high response and manageable toxicity. Trial registration: The patients were enrolled in a clinical trial of ChiCTR-ONN-16009862, and ChiCTR1800019622.     

Laboratory diagnosis of von Willebrand disorder. Current practice in the southern hemisphere

A survey of 44 laboratories was conducted to evaluate current testing proficiency in the diagnosis of von Willebrand disorder (vWD) and to assess recent changes in test practices. Laboratories performed their usual panel of tests for vWD and interpreted results for the likelihood of vWD and potential subtype. Samples were as follows: normal plasma; borderline normal or abnormal levels of von Willebrand factor (vWF) and factor VIII; type 3 vWD; type 2A vWD; and 2 samples from a healthy person, processed after handling at 22 degrees C and 4 degrees C, respectively. Interassay and within-method coefficients of variation were similar for all assays (approximately 15%-25%). Most laboratories reported test values consistent with expected findings and made correct interpretations, although discrepant results for 5% to 10% of responses are of concern. For the sample stored at 4 degrees C, all laboratories detected low or borderline levels of vWF and factor VIII coagulant, and no laboratory identified this sample as from a healthy person. In contrast, for the sample stored at 22 degrees C, most laboratories reported normal results. Compared with previous results, performance of some assays has declined while that of others has increased. Laboratories generally are proficient in tests for vWD, and transport of samples at 4 degrees C before processing may lead to false identification of vWD, suggesting that NCCLS guidelines should be reviewed.     

Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism in pregnancy and the postpartum period

Venous thromboembolism (VTE) in pregnancy and the postpartum is an important cause of maternal morbidity and mortality; yet, there are few robust data from clinical trials to inform an approach to diagnosis and management. Failure to investigate symptoms suggestive of pulmonary embolism (PE) is a consistent finding in maternal death enquiries, and clinical symptoms should not be relied on to exclude or diagnose VTE. In this consensus statement, we present our recommendations for the diagnosis and management of acute deep venous thrombosis (DVT) and PE. All women with suspected DVT in pregnancy should be investigated with whole leg compression ultrasonography. If the scan is negative and significant clinical suspicion remains, then further imaging for iliofemoral DVT maybe required. Imaging should be undertaken in all women with suspected PE, as the fetal radiation exposure with both ventilation/perfusion scans and CT pulmonary angiography is within safe limits. Low-molecular-weight heparin (LMWH) is the preferred therapy for acute VTE that occur during pregnancy. In observational cohort studies, using once-daily regimens appears adequate, in particular with the LMWH tinzaparin; however, pharmacokinetic data support twice-daily therapy with other LMWH and is recommended, at least initially, for PE or iliofemoral DVT in pregnancy. Treatment should continue for a minimum duration of six months, and until at least six weeks postpartum. Induction of labour or planned caesarean section maybe required to allow an appropriate transition to unfractionated heparin to avoid delivery in women in therapeutic doses of anticoagulation.