Diagnosis, management, and outcomes of venous thromboembolism in COVID-19 positive patients: a role for direct anticoagulants?

Coronavirus disease 2019 (COVID-19) has been associated with an increased risk of thromboembolic complications due to systemic coagulation activation. Little is known about the role of direct anticoagulants (DOACs) in COVID-19 related thrombosis. In this audit we sought to distinguish COVID-19 hospitalised patients with a diagnosis of venous thromboembolism (VTE) and record their outcomes over a period of 3 months (01/02/2020-30/04/2020). A total of 1583 patients were diagnosed with laboratory proven COVID-19 disease. Amongst them, 38 patients (0.82%) suffered VTE (median age 68 years, male/female: 20/18). VTE was the presenting symptom on admission in 71%. Pulmonary embolism was diagnosed in 92% of patients; 5 patients required intensive care and 3 underwent thrombolysis. 27 patients received initial treatment with unfractionated heparin/low molecular weight heparin (LMWH) while 10 were treated with direct anticoagulants (DOACs). After a median follow up of 25 days, 29 (76%) patients were alive while 5 were still hospitalised. Most patients (83%) were discharged on DOACs, no VTE recurrence or bleeding was recorded post-discharge. Our results suggest that direct anticoagulants could be a safe and effective treatment option in selected COVID-19 positive patients who have suffered venous thromboembolism.

Management of venous thromboembolism in patients experiencing direct oral anticoagulant treatment failure: a single-center review of practice and outcomes.

Direct oral anticoagulants (DOACs) have gained in popularity over vitamin K antagonists for the treatment of venous thromboembolism, however their efficacy is not routinely monitored. It is therefore a clinical challenge to know how to respond when treatment with DOACs fails, and there is little formal guidance on how to manage these patients. We sought to characterize VTE patients who experienced DOAC failure at our institution, and rationalize subsequent treatment strategies. We collated the details of 54 consecutive patients with suboptimal response or breakthrough thrombosis on a DOAC, from our large specialist-led thrombosis clinic. Initial treatment changes were recorded, as well as long-term anticoagulation therapy and treatment outcomes. On first recognition of DOAC failure, 69% of patients were temporarily switched to therapeutic-dose low molecular weight heparin; most of the remaining patients were treated with an alternative DOAC regimen. After a limited period of parenteral treatment, 84% of patients returned to oral anticoagulation, the majority of whom experienced no further treatment failures. By the end of follow-up, 72% of patients were either on long-term DOAC therapy or had completed treatment altogether. In the absence of evidence or guidelines, brief rescue of anticoagulation with parenteral therapy can be an effective strategy when treatment with a DOAC fails.

Caplacizumab for immune thrombotic thrombocytopenic purpura: real-world multicenter data.

Given the limited real-world data of caplacizumab, our multicenter real-world study was designed to assess the safety and efficacy of caplacizumab in immune thrombotic thrombocytopenic pupura (iTTP), compared to historic controls. We have studied 70 patients: 23 in the caplacizumab and 47 in the historic control group. Plasma exchange was applied in all episodes except for two patients that denied plasma exchange. Rituximab as first-line treatment was more common in the caplacizumab group compared to historic control. Caplacizumab (10 mg daily) was given at a median on day 7 (1-43) from initial diagnosis for 32 (6-47) dosages. In the caplacizumab group, a median of 12 (8-23) patients required plasma exchange sessions versus 14 (6-32) in the control group. Caplacizumab administration did not produce any grade 3 complications or major hemorrhagic events. After a median of 19.0 (2.6-320) months since the iTTP diagnosis, 5 deaths occurred (4 in the control group and 1 in the caplacizumab group, p = 0.310). Caplacizumab patients achieved early platelet normalization and ADAMTS13 activity normalization at the end of treatment. Relapse was observed only in 2/23 (9%) caplacizumab patients, compared to 29/47 (62%) historic controls (p < 0.001). Overall, caplacizumab is safe and effective in treating iTTP, including cases refractory to plasma exchange, re-administration, and cases without previous plasma exchange treatment. No major hemorrhagic events were observed. Cessation of dosing guided by ADAMTS13 has ensured a low relapse rate.

First case of near haploid philadelphia negative B-Cell acute lymphoblastic leukaemia relapsing as acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation.

Herein we present a female patient aged 61 with Philadelphia negative acute lymphoblastic leukaemia demonstrating near haploid karyotype and abnormal TP53 expression at diagnosis, who relapsed with lineage switch as Acute Monocytic Leukemia post allogeneic stem cell transplantation. Molecular analysis established that both neoplasms were derived from the same founder clone. The leukemic lineage switch phenomenon has recently re-attracted interest as mechanism of leukemic evasion post treatment with chimeric antigen receptor T-cells but there is paucity of data on its presence post allograft or following novel antibody treatments such as Inotuzumab Ozogamicin or Blinatumomab. Our proposition for cancer research is that near haploidy in ALL could be linked to leukemic stem cell plasticity evading stem cell transplantation and other immunotherapy approaches.