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The article presents lists of forthcoming issues including "T-cell Lymphoblastic Lymphoma Presenting as an intra-muscular mass," by Z.-Y. Lim, S. Gupta, J. R. Salisbury, D. Elias, N. Venkatram, G. J. Mufti and A. Pagliuca, "Unusual Manifestations of Catastrophic Antiphospholipid Syndrome in the Abdomen," by D. C. L. Tan, A. H. L. Low, H. S. Ong, Y. C. Linn and J. Thumboo, "Towards Targeted Therapy for Infant Acute," by R. W. Stam, M. L. den Boer and R. Pieters, "Obtaining Consent for Chemotherapy," by J. Treleaven, J. O. Cullis, R. Maynard, E. Bishop, I. Ainsworth-Smith, A. Roques, A. Webb, J. Favre and D. Milligan and "cFLIP Expression Correlates with Tumour Progression and Patient Outcome in non Hodgkin Lymphomas of Low-Grade of Malignancy," by G. Valente, F. Manfroi, C. Peracchio, G. Nicotra, R. Castino, G. Nicosia, S. Kerim and C. Isidoro

The article offers information on antiphospholipid syndrome (APS) and APS management and investigation guidelines. It features a discussion for APS an acquired autoimmune condition which is diagnosed in thrombosis patients or with defined pregnancy morbidity. It discusses the paper published by Galli and colleagues regarding the relation of antiphospholipid antibodies (aPL) and thrombosis.

In late 2017, the Food and Drug Administration (FDA) approved CD19 CAR T-cell therapy for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. Since 2017, two anti-CD19 CAR T-cell therapy products, axicabtagene ciloleucel and tisagenlecleucel, have been approved by the FDA for the treatment of relapsed or refractory large B-cell lymphoma after the failure of two lines of systemic therapy (Nair & Neelapu, [15]). CAR T-cell therapy's potential for the treatment of autoimmune diseases such as APLS is based on its ability to specifically target the B cells that produce the autoantibodies causing these diseases. In conclusion, we report a patient with refractory DLBCL who was also undergoing lifelong anticoagulation therapy for APLS, and whose DLBCL and APLS remissions are likely attributable to CAR T-cell therapy. [Extracted from the article]

In all, 14 patients had isolated new onset deep venous thrombosis (DVT), eight patients had isolated pulmonary emboli (PE) and 4 patients had both DVT and PE upon study entry (Table 1). 1 TABLE Patient demographics. At the completion of 3 months of therapy, 63.6% (14 of 22) had a CR and 36.4% (8 of 22) had a PR with no patients having stable disease (Figure 1). Importantly, there were no patients who experienced a new VTE, which equates to 100% successful VTE secondary prophylaxis. [Extracted from the article]

Of the 26 patients with NPM1 + FLT3+ AML, 12 patients (48%) expressed HLA-DR and seven patients (27%) expressed CD34. Three patients (8%) developed primary graft failure, nine patients (24%) developed acute graft versus host disease (GVHD), 13 (35%) developed chronic GVHD, CMV reactivation was detected in 28 patients (75%).Two patients developed metastatic squamous cell carcinoma, both died 5.5 and 12 years post-alloHSCT, both had cGVHD of the mouth and none has received irradiation. Thirteen patients (20.3%) had VTE events at diagnosis of which 10 patients had DVT, and three patients had PE. Further filtering of these patients and those from MDT provided a list of recruited patients ( I n i = 10, at time of writing); this comprises seven patients from the Royal London Hospital, two patients from St Bartholomew's Hospital and one patient from Hammersmith Hospital. BSH23-EP13 UK healthcare professional experiences with intensive chemotherapies for AML: Survey of toler... Dr Priyanka Mehta 1, Dr Joe Cross 1, Ms Hayley Kuter 2, Dr Mariette Odabashian 2, Mr Emil... 1 University Hospitals of Bristol and Weston NHS Trust, Bristol, UK, 2 Jazz Pharmaceuticals,... B Background: b Patients with AML treated with intensive chemotherapy (IC) may experience a high symptom burden/prolonged hospitalisation; however, relative IC toxicities are difficult to gauge from patient experience as patients typically receive only one regimen. [Extracted from the article]

In the middle of March 2021, clinicians became aware of a syndrome that appeared to be linked to the AstraZeneca ChAdOx1 nCOV-19 vaccine. Patients were presenting with thrombosis, thrombocytopenia and very high D-dimer levels, much higher than would normally be expected in association with a new diagnosis of venous thrombosis. Whilst clinicians do need to remain vigilant for VITT, it is important that other causes of thrombocytopenia and high d-dimers, with or without thrombosis, such as malignancy or major vessel aneurysm, are not disregarded. [Extracted from the article]

Summary: Venous thromboembolism (VTE) is prevalent and impactful, with a risk of death, morbidity and recurrence. Post‐thrombotic syndrome (PTS) is a common consequence and associated with impaired quality of life (QoL). The ExACT study was a non‐blinded, prospective, multicentred randomised controlled trial comparing extended versus limited duration anticoagulation following a first unprovoked VTE (proximal deep vein thrombosis or pulmonary embolism). Adults were eligible if they had completed ≥3 months anticoagulation (remaining anticoagulated). The primary outcome was time to first recurrent VTE from randomisation. The secondary outcomes included PTS severity, bleeding, QoL and D‐dimers. Two‐hundred and eighty‐one patients were recruited, randomised and followed up for 24 months (mean age 63, male:female 2:1). There was a significant reduction in recurrent VTE for patients receiving extended anticoagulation [2·75 vs. 13·54 events/100 patient years, adjusted hazard ratio (aHR) 0·20 (95% confidence interval (CI): 0·09 to 0·46, P < 0·001)] with a non‐significant increase in major bleeding [3·54 vs. 1·18 events/100 patient years, aHR 2·99 (95% CI: 0·81–11·05, P = 0·10)]. Outcomes of PTS and QoL were no different between groups. D‐dimer results (on anticoagulation) did not predict VTE recurrence. In conclusion, extended anticoagulation reduced VTE recurrence but did not reduce PTS or improve QoL and was associated with a non‐significant increase in bleeding. Results also suggest very limited clinical utility of D‐dimer testing on anticoagulated patients. [ABSTRACT FROM AUTHOR]

The article looks at a research which focuses on complexity related to demonstration of an antiphospholipid antibody by the lupus anticoagulants (LA) assay in antiphospholipid syndrome (APS), an autoimmune disorder associated with hypercoagulability. Topics discussed include heparin neutralization for a prolonged partial thromboplastin time (PTT), coagulation testing characteristics and LA identification to culminate in less secondary testing and guide appropriate antithrombotic therapy.

The antiphospholipid syndrome ( APS) is an autoimmune disease characterized by the clinical features of recurrent thrombosis in the venous or arterial circulation and fetal losses. Antiphospholipid antibodies ( aPL), particularly against the phospholipid binding protein beta-2 glycoprotein I (β2 GPI), play an important role in APS pathological mechanisms. aPL can activate intracellular signal transduction in a β2 GPI-dependent manner to induce inflammatory responses, and promote hypercoagulable state and recurrent spontaneous abortion when β2 GPI is associated with the cell surface receptor. In vivo and in vitro studies show that Annexin A2 ( ANXA2) is the high affinity receptor that connects β2 GPI to the target cells. However, ANXA2 is not a transmembrane protein and lacks an intracellular signal transduction pathway. Growing evidences suggest that the transmembrane protein toll-like receptor 4 ( TLR4) might act as an 'adaptor' for intracellular signal transduction. This review focuses on the role of TLR4 and its signalling pathway in APS pathological mechanisms which will help us better understand the pathological processes of this syndrome. [ABSTRACT FROM AUTHOR]

Patients with immune thrombocytopenia ( ITP) paradoxically have an increased risk of thrombosis. The presence of antiphospholipid antibodies ( aPL) has been observed in a substantial proportion of ITP patients, but its clinical significance remains to be established. This study retrospectively investigated the prevalence and clinical significance of aPL in ITP patients and assessed the risk factors for thrombosis. One hundred and sixty-five subjects with ITP were included in the study and followed for a mean period of 63·4 months. Sixty-nine (41·6%) patients were positive for aPL at diagnosis, and their clinical characteristics and course of ITP were not different from those of aPL-negative patients. Twenty-one (12·7%) patients developed a thrombotic event during follow-up and the cumulative incidence rate ratio of aPL-positive to aPL-negative patients for thromboembolism was 3·15 [95% confidence interval ( CI) 1·21-8·17] after adjusting for confounding factors. Lupus anticoagulant and hypertension were identified by Cox regression analysis as independent risk factors for thrombosis [hazard ratio ( HR) 4·1, 95% CI 1·4-11·9, P = 0·009 and HR 5·6, 95% CI 1·9-15·8, P = 0·001, respectively]. Our results showed that a substantial proportion of ITP patients were aPL-positive, and that lupus anticoagulant and hypertension were independent risk factors for thrombosis. Detection of aPL can provide useful information for identifying patients at high-risk for developing thrombosis. [ABSTRACT FROM AUTHOR]

Recurrent pregnancy loss ( RPL) affects 1% pregnancies and is multi-factorial in origin. The role of the acquired thrombophilia antiphospholipid syndrome ( APS) as a common and potentially treatable cause of RPL is well established but this is less so for inherited thrombophilia. In obstetric APS the combination of aspirin and heparin has improved outcomes. By analogy, the use of low molecular weight heparin ( LMWH) has become commonplace in women with inherited thrombophilia and also those with unexplained miscarriage to help safeguard the pregnancy. This review will examine the pathophysiological role of thrombophilia in pregnancy loss, and the evidence for anticoagulant-based intervention. The limited data supporting the use of heparin for women with RPL and inherited thrombophilia suggests adoption of a more cautious and judicious approach in this setting. [ABSTRACT FROM AUTHOR]

The possibility of a genetic predisposition to develop antiphospholipid syndrome (APS) and to produce anticardiolipin antibodies and lupus anticoagulant has been addressed by family studies and population studies. Various studies suggest a familial occurrence of anticardiolipin antibodies and lupus anticoagulant, with or without clinical evidence of APS. This familial tendency could be genetically determined. Multiple human leucocyte antigen-DR or -DQ associations with antiphospholipid antibodies have been described. Genetic studies of a representative antigen, beta2-glycoprotein-I (β2GPI), have been carried-out and a particular valine247/leucine polymorphism could be a genetic risk for presenting anti-β2GPI antibodies and APS. Many other thrombosis-related genetic factors have been investigated in APS, but no additional risk for thrombosis has been indicated in affected patients. Although the mechanisms and pathophysiology of thrombosis in APS are highly heterogeneous and multifactorial, different genes and acquired factors seem to be involved. In this review, we will focus on those genetic variants that could contribute to the development of thrombosis in APS. [ABSTRACT FROM AUTHOR]

Autoantibodies to ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I motif, member 13) play an important role in the development of microthrombosis in thrombotic thrombocytopenic purpura (TTP). In severe cases of antiphospholipid syndrome (APS), microthrombosis can occur similar to that seen in TTP, suggesting possible mutual pathogenic factors. However, the role of ADAMTS13 in APS is unknown. We hypothesised that aberrations in ADAMTS13 may occur in APS and evaluated ADAMTS13 and von Willebrand factor (VWF) in 68 patients with antiphospholipid antibodies (aPA) including 52 with APS. Thirty-three (49%) had IgG anti-ADAMTS13 with 12 of these patients having reduced ADAMTS13 activity, suggesting neutralising antibodies. Low ADAMTS13 activity (median 34%) was demonstrated in 22/68 (33%), all with normal ADAMTS13 antigen levels consistent with dysfunctional ADAMTS13. Reduced ADAMTS13 activity was not secondary to elevated von Willebrand factor (VWF), or increased VWF secretion (normal VWF propeptide), although a reduced VWF clearance was noted in APS. Analysis found no associations between the ADAMTS13 abnormalities and any aPA profile or thrombotic/obstetric complications, although this study was not adequately powered to address clinical associations. Nevertheless, these findings highlight that ADAMTS13 autoantibodies and ADAMTS13 dysfunction can occur in APS, and although the clinical significance remains undetermined, ADAMTS13 dysfunction may be contributory to thrombogenesis in autoimmune conditions other than TTP. [ABSTRACT FROM AUTHOR]

Keywords: anticoagulants; antiphospholid antibodies; antiphospholipid; syndrome; lupus anticoagulant EN anticoagulants antiphospholid antibodies antiphospholipid syndrome lupus anticoagulant 210 211 2 04/15/20 20200415 NES 200415 Since the publication of the previous British Society for Haematology (BSH) guidelines on investigation and management of antiphospholipid syndrome (APS) the use of direct oral anticoagulants (DOACs) has been in constant increase, in particular in patients with venous thromboembolism. To obtain more information about APS patients continuing DOACs, an international registry is being launched under the auspices of the International Society on Thrombosis and Haemostasis (ISTH) and should indicate whether it is safe to continue DOACs in low-risk APS patients. Thus APS treatment in the future may be based on other drugs or treatment strategies: either new anticoagulant agents or combinations of anticoagulants with immunomodulation therapy (Erkan I et al., i [5]). [Extracted from the article]

Prothrombin is now accepted as one of the target antigens recognised by antiphospholipid (aPL) antibodies. However, it is not clear whether anti-prothrombin antibodies are pathogenic in vivo and if so, the possible mechanism(s) involved. Here, we examined the pathogenic effects of the IS6 monoclonal anti-prothrombin antibody isolated from a patient with Antiphospholipid Syndrome (APS). IS6 antibody was purified from hybridoma supernatant. Its pathogenic potentials were studied in an in vivo model of induced thrombosis. The expression of tissue factor (TF) and E-selectin on human umbilical vein endothelial cells (HUVEC) was determined by cyto-enzyme-linked immunosorbent assay. Transcription of TF mRNA was determined by quantitative real time-polymerase chain reaction (RT-PCR). In vivo, the thrombus size increased significantly when treated with IS6 compared with control-treated mice (5388 ± 1035 μm2 vs. 2845 ± 1711 μm2). In vitro, IS6 induced significant expression of TF and E-selectin on HUVEC, when compared with control preparation (3·1- and 5·1-fold increase compared with the control-treated cells). RT-PCR analysis of TF mRNA transcription showed a 2·5-fold increase of IS6-treated cells over the value obtained with control-treated cells. Taken together, these data show that IS6 monoclonal anti-prothrombin antibody promotes thrombosis and this is associated with TF and E-selectin expression. [ABSTRACT FROM AUTHOR]

The association between antiphospholipid antibodies and an increased risk of thrombosis in antiphospholipid syndrome (aPS) patients is probably caused by numerous mechanisms, including the effects of antibodies to phospholipid-binding proteins such as β2-glycoprotein I and prothrombin. In this study, we investigated the inhibition of tissue factor pathway inhibitor (TFPI) in 33 patients with primary antiphospholipid syndrome (PAPS). TFPI was measured in PAPS patients using an amidolytic assay, dependent on the generation of activated factor X (Fxa), and this was compared with 55 healthy subjects. Functional levels of TFPI (mean ± SD) were significantly lower in PAPS patients (0·89 ± 0·37 U/ml) than the control group (1·05 ± 0·15 U/ml) (P = 0·02). The difference was caused by a subset of five patients who had TFPI levels below the lower 99% confidence interval of the normal reference range, representing increased FXa generation in the assay system. IgG fractions were isolated from these five patients and five control subjects, then incorporated into normal plasma to measure FXa generation in the TFPI assay system. FXa generation was increased when polyclonal rabbit anti-human TFPI IgG (P < 0·0001) or PAPS IgG (P = 0·0001) were added to normal plasma, demonstrating inhibition of TFPI. The apparent anti-TFPI activity demonstrated in the five subjects with PAPS in this study may represent a significant new mechanism for thrombosis in patients with aPS, as it implies that increased tissue factor FVIIa-mediated thrombin generation might occur. [ABSTRACT FROM AUTHOR]