How I treat anticoagulant-refractory thrombotic antiphospholipid syndrome

The standard treatment of thrombotic antiphospholipid syndrome (APS) is lifelong oral anticoagulation with a vitamin K antagonist (VKA), generally warfarin. A minority of APS patients re-thrombose despite seemingly adequate anticoagulation. These patients are deemed anticoagulant-refractory. The management of anticoagulant-refractory APS is largely empirical and extrapolated from other clinically similar situations. Further options include increased VKA anticoagulation intensity or alternative antithrombotic strategies, including low-molecular-weight heparin, fondaparinux, the addition of antiplatelet therapy and consideration of vascular options. Anticoagulant-refractory thrombotic APS patients may have APS-associated thrombocytopenia, which necessitates balancing the risk of recurrent thrombosis versus bleeding, to achieve adequate anticoagulation. The multiple mechanisms involved in the generation of the thrombotic phenotype in APS suggest that anticoagulation alone may not control thrombosis. Thus, other modalities, including adjunctive treatment (hydroxychloroquine, statins and vitamin D) for APS-related thrombosis merit consideration, as well as immunomodulatory therapy and complement inhibition. APS patients may have coexistent systemic lupus erythematosus, which adds to the complexity of managing their thromboembolic disease. However, with attention to detail and judicious application of the limited data, it is possible to minimise the morbidity resulting from anticoagulant-refractory thrombotic APS. Multicentre studies are required to guide the sequence of interventions and their comparative efficacy in patients with anticoagulant-refractory thrombotic APS.

Prevention of Radial Artery Occlusions Following Coronary Procedures: Forward and Backward Steps in Improving Radial Artery Patency Rates

Radial artery (RA) occlusion (RAO) remains the Achilles heel of transradial coronary procedures. Although of silent nature, RAO is relatively frequent, results in graft shortage for future coronary artery bypass surgery, and may occur even after short-lasting, 5F coronary angiography (CAG). The most frequent predictors of RAO are RA size, body size, female gender, and periprocedural anticoagulation intensity. Methods to detect RAO are variable, of which the Barbeau test and ultrasonography have similar diagnostic accuracy. Data indicate that late RAO recanalization may occur. Meticulous handling of RA and the use of appropriate hemostatic devices and techniques along with sufficient heparin dose appear important measures to reduce RAO rates. Recent contradictory studies indicate that the decreasing incidence of RAO overtime is not as uniform as previously thought. In 2 meta-analyses, the benefit of higher over lower anticoagulation intensity became evident. As “it may all be appropriate anticoagulation” for a simplified approach against RAO, the results of an ongoing trial comparing 100 with 50 IU/kg body weight in transradial CAG are eagerly awaited.

Use of an On-X Prosthetic Valve In A 42-Year Old Female With Antiphospholipid Syndrome

Antiphospholipid syndrome is a rare autoimmune disease with a hypercoagulable state causing vascular thrombosis. We present the case of a 42-year old female who underwent mitral valve replacement with a mechanical valve 15 months ago. The postoperative course was uneventful, and echocardiography performed 14 months postoperatively showed good valve function. The patient developed sudden dyspnea 15 months postoperatively and was referred to our hospital. Echocardiography revealed mitral stenosis with stuck leaflets. Emergent re-mitral valve replacement was successfully performed using an On-X valve (On-X Life Technologies, Austin, TX, USA). The patient tested positive for antiphospholipid antibodies. Antiphospholipid syndrome should be considered when valve dysfunction occurs suddenly in relatively young female patients. The On-X valve may be considered as a therapeutic option in patients with antiphospholipid syndrome because of its low anticoagulation intensity.

Anticoagulation Therapy for Thrombotic Events in Paediatric Cancer Patients with Low Platelet Counts

Background Thrombocytopenia is common in children receiving cancer chemotherapy. In addition, children with cancer are also at increased risk of acute thrombotic events (TE). When these two complications occur simultaneously, TE management with anticoagulants (ACT) poses a unique challenge, as ACT use in thrombocytopenic patients increases their bleeding risk. Current guidelines provide only best practice recommendations on how to manage this treatment conundrum, and even these recommendations vary on optimal management due to the lack of evidence to guide treatment. To date, no systematic literature review summarizing the available paediatric data on treatment of TE in the presence of thrombocytopenia has been conducted. The aim of our systematic review was to summarize the data available to evaluate the safety of ACT for management of TE in paediatric oncology patients during periods of thrombocytopenia. Methods We systematically searched MEDLINE and EMBASE from the OVID platform from inception to April 15th 2016 for studies that included children aged less than 18 years with diagnosis of cancer complicated by an objectively confirmed TE, whose anticoagulation therapy was complicated by a period of thrombocytopenia (as defined by the study author). We included all study designs. Two authors (LB and AA) screened the data at title then full-text level to select eligible studies. Disputes were arbitrated by a third author (UA) until a consensus was reached. Our primary outcome was haemorrhagic complications, categorized as minor or major according to paediatric ISTH criteria. Bleeding episodes were divided according to anticoagulation intensity (age-appropriate, agent-specific full dose vs. half-dose, as per CHEST guidelines) and degree of thrombocytopenia (i.e. severe </=50 x109/L, moderate 51-99 x109/L, mild >/=100 x109/L). Our secondary outcome was the identification of platelet transfusion triggers according to degree of anticoagulation intensity. Results Our search yielded 244 articles, of which 13 were screened at a full text level. Four manuscripts were selected for inclusion, as follows: case report (n=1), case series (n=2), and prospective cohort study (n=1). Details of included studies are described inTable 1 and patient information in table 2. The studies included 39 patients with malignancies, of which the most common were acute lymphoblastic leukaemia (n=13), CNS malignancies (n=6), non-hodgkinlymphoma(n=4). All patients had venous TE. Type and regimen of ACT, and author definitions of thrombocytopenia and bleeding were variable. Thirty-five patients received low-molecular weight heparin (LMWH), of whom 33 received therapeutic dose, and no dose was recorded for two. Three patients received unfractionated heparin (UFH) with antithrombin(AT) supplementation; however, UFH wasstopped in periods of low platelet counts, and one received a reduced dose UFH. According to our definition, 36/39 (92.3%) experienced severe thrombocytopenia, 1 (2.6%) developed moderate thrombocytopenia, platelet count was not stated in 2(5.1%). Using the ISTH bleeding criteria, one patient (2.6%) developed major bleeding, and seven (17.9%) developed minor bleeding (n=2 intestinal bleeding, n=5 injection site/port bleeding). Only one study reported our secondary outcome, which used a platelet transfusion trigger of <40x109/L if receiving therapeutic LMWH and <20x109/L if receiving prophylactic LMWH. Given the heterogeneity, we were unable to statistically aggregate any data. Discussion The results of this systematic review highlight the paucity of high-quality data to assess the use and safety of ACT for TE in paediatric cancer patients during periods of thrombocytopenia. We identified only observational studies- one prospective and three retrospective in design. These studies included very few patients (total n=39), and had variable patients, disease and treatment-related factors. Evidence-based recommendations cannot be generated to guide an optimal ACT management in such situations. Further research using standardized definitions is needed to identify optimal strategies for treating thrombotic events during periods of thrombocytopenia. Such research will help on the development of evidence-based clinical practice guidelines to improve patient care. Disclosures Brandão: Boehringer Ingelheim: Consultancy.