Direct Oral Anticoagulants In Antiphospholipid Syndrome Research Articles

Clinical Characteristics and Anticoagulation Use in Antiphospholipid Syndrome: A Single-Center Retrospective Analysis

Background: Warfarin remains the anticoagulant of choice for patients with antiphospholipid syndrome (APLS). However, conflicting data exists regarding the role of direct oral anticoagulants (DOACs) as reasonable alternatives to warfarin, which has a less desirable side effect profile. In clinical practice, some patients start taking DOACs or aspirin before an official APLS diagnosis is confirmed and these patients may choose to continue a DOAC after an informed discussion with their hematologist. To gain a better understanding of anticoagulant use in APLS at our center, we conducted a retrospective study to assess the clinical characteristics of patients diagnosed with APLS. Methods: All patients with an ICD-10 code indicating APLS from January of 2020 to April of 2023 were included. Patient characteristics, relevant laboratory testing (lupus anticoagulant, beta-2 glycoprotein IgG/IgM, and anti-cardiolipin IgG/IgM), and treatment history were extracted from the electronic medical record. Patients were deemed to have single positivity if any one of the following were present: detectable lupus anticoagulant, elevated (defined as >40 GPL) beta-2 glycoprotein (B2GP) IgG or IgM, or elevated cardiolipin IgG or IgM both on initial and confirmatory testing (performed approximately 12 weeks later). Similarly, double positivity was defined as the presence of two of these biomarkers and triple positive was defined as the presence of three of these biomarkers. Initial laboratory testing results are included in Table 1. Statistical analysis was conducted using the SAS software (SAS Enterprise Guide 7.1) and the R Core Team (R 4.2.2). Continuous variables such as BMI and age were evaluated using the Wilcoxon rank-sum test, while categorical variables were assessed using Fisher's Exact Test and Chi-squared test. Results: Seventy-two patients were included in our analysis. Mean age and BMI were 56.3 ± 16.8 years and 32.3 ± 11.2, respectively. The majority of patients were female (69.4%) and white (83.8%). Approximately half of all patients had single positivity (64.4%) and more than half had detectable lupus anticoagulant (58.7%). Cardiolipin IgM was the most frequently (36.1%) elevated biomarker. Patient characteristics between the DOAC/aspirin and warfarin/enoxaparin cohorts were not significantly different; however, significantly more patients with single positivity received DOAC/Aspirin rather than warfarin/enoxaparin (77.8% vs.43.5%, p = 0.012). There was no statistically significant difference between the frequency of arterial complications in patients who took DOAC/Aspirin (4 events in 39 patients) versus those who took warfarin/enoxaparin (1 event in 33 patients), p = 0.366. The majority of arterial complications (4 of 5 events) occurred in patients with double and triple positivity. In addition, a logistical regression was performed regarding different characteristic effects on positivity level (single, double or triple laboratory positive), which found the presence of lupus anticoagulant had a significant association with higher likelihood of double/triple positivity (p = 0.048). Conclusion: This study provides potential reassurance for clinicians regarding the use of DOACs during the investigative phase of APLS and supports the continuation of DOAC therapy in patients, particularly those with single positivity, after careful evaluation and shared decision-making with patients. However, caution should be kept when considering DOAC use in patients with lupus anticoagulant, double, or triple positivity, due to concerning arterial events. Further large multi-center randomized clinical trials are necessary in the future to clarify the role of DOACs in APLS.

Recent Advances in Anticoagulant Treatment of Immune Thrombosis: A Focus on Direct Oral Anticoagulants in Heparin-Induced Thrombocytopenia and Anti-Phospholipid Syndrome.

For more than 10 years, direct oral anticoagulants (DOACs) have been increasingly prescribed for the prevention and treatment of thrombotic events. However, their use in immunothrombotic disorders, namely heparin-induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS), is still under investigation. The prothrombotic state resulting from the autoimmune mechanism, multicellular activation, and platelet count decrease, constitutes similarities between HIT and APS. Moreover, they both share the complexity of the biological diagnosis. Current treatment of HIT firstly relies on parenteral non-heparin therapies, but DOACs have been included in American and French guidelines for a few years, providing the advantage of limiting the need for treatment monitoring. In APS, vitamin K antagonists are conversely the main treatment (+/− anti-platelet agents), and the use of DOACs is either subject to precautionary recommendations or is not recommended in severe APS. While some randomized controlled trials have been conducted regarding the use of DOACs in APS, only retrospective studies have examined HIT. In addition, vaccine-induced immune thrombotic thrombocytopenia (VITT) is now a part of immunothrombotic disorders, and guidelines have been created concerning an anticoagulant strategy in this case. This literature review aims to summarize available data on HIT, APS, and VITT treatments and define the use of DOACs in therapeutic strategies.

HEAVILY CALCIFIED CLOTS IN A PATIENT WITH CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION PRESENTING WITH BACTEREMIA

SESSION TITLE: Medical Student/Resident Pulmonary Vascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Antiphospholipid syndrome (APLS) is an autoimmune disorder that can lead to thrombotic disease. Here, we present a challenging case of catastrophic antiphospholipid syndrome with calcified clots, and chronic thromboembolic pulmonary hypertension (CTEPH) presenting with persistent bacteremia. CASE PRESENTATION: A 23-year-old female patient with a history of diabetes mellitus, methamphetamine and intravenous drug use disorder presented to an outside hospital with dry cough, shortness of breath, pleuritic chest pain, chills, and fatigue for 2 weeks. Blood cultures upon admission grew methicillin sensitive staphylococcus aureus (MSSA). Other labs were notable for thrombocytopenia and acute kidney injury. CT scan of chest and abdomen without contrast showed a large clot in her left pulmonary artery, inferior vena cava (IVC) extending into the right atrium (RA) with impressive calcifications (Figure 1). Transesophageal echocardiography showed no vegetations but revealed a large atrial thrombus extending from IVC into a dilated RA, dilated right ventricle, moderate tricuspid regurgitation with calculated right ventricular systolic pressure 55mmHg. Ventilation perfusion (VQ) scan showed a diffuse left lung perfusion defect without matched ventilation defect. She was transferred to our hospital for further care, her work-up revealed positive dilute Russell's viper venom time (dRVVT), cardiolipin antibodies and beta2-glycoprotein antibodies suggesting triple positive antiphospholipid syndrome. She was treated with intravenous heparin, however, developed hemoptysis requiring multiple blood transfusions and intubation, thus bronchial artery embolization was performed. Furthermore, she developed ST elevation myocardial infarction and splenic infarcts which were managed medically with resumption of heparin and antiplatelet therapy. She was eventually discharged on coumadin after completing six weeks of cefazolin and rifampin. DISCUSSION: This case illustrates an unusual presentation and calcification pattern of chronic clot, possibly due to the underlying infection, in a patient with CTEPH secondary to APLS. Mainstay of treatment for CTEPH remains anticoagulation followed by evaluation for pulmonary thromboendarterectomy (PTE) which is the only definite treatment (1). However, patients must tolerate anticoagulation, be clear of any infection and demonstrate adherence to therapy to undergo surgery. Furthermore, coumadin with an INR goal of 2.5 to 3.5 is recommended over direct oral anticoagulants in APLS with thromboembolism (2). CONCLUSIONS: In conclusion, CTEPH is associated with high morbidity and mortality, mainly from right heart failure (3). High level of suspicion is required to diagnose and promptly treat this rare disease with atypical presentation. Reference #1: Fedullo P, Kerr KM, Kim NH, Auger WR. Chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med 2011; 183:1605. Reference #2: Pengo V, Denas G, Zoppellaro G, et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. 2018;132:1365–71. Reference #3: Hoeper MM, Mayer E, Simonneau G, Rubin LJ. Chronic thromboembolic pulmonary hypertension. Circulation 2006; 113:2011. DISCLOSURES: No relevant relationships by Timothy Fernandes, source=Web Response No relevant relationships by Abdurrahman Husain, source=Web Response No relevant relationships by Alexandra Rose, source=Web Response No relevant relationships by Qais Zawaydeh, source=Web Response

Treatment of thrombotic antiphospholipid syndrome in adults and children.

Antiphospholipid syndrome (APS), more common than once believed, is an autoimmune disease best known for its high risk of incident and recurrent thrombotic events. The approach to treatment potentially differs from treatment of thrombosis in the general population, and this article endeavors to review the latest updates on this topic. The epidemiology of APS is being increasingly elucidated by large population-based studies, with APS perhaps affecting as many as 1 in 2000 individuals. Vitamin K antagonists, aspirin, and heparinoids continue to have obvious roles in the management of patients with APS. There has recently been intensive study of direct oral anticoagulants in APS, with the most recent randomized studies raising concerns about their inferiority to vitamin K antagonists, at least in some subgroups. Other approaches to treating APS beyond anticoagulants and antiaggregants are also receiving increased attention in mechanistic and preclinical studies with an eye toward future roles in patients with refractory and/or microvascular disease. Pediatric APS is identified as an area in desperate need of additional prospective research. Progress continues to be made in pursuit of improving the lives of individuals afflicted with APS. The most important future directions would seem to involve leveraging modern molecular technologies in order to improve subphenotyping of antiphospholipid antibody-positive individuals. This will help personalize risk profiles and ideally define the optimal approach to therapy based on future risk, rather than past morbid events.

Antiphospholipid syndrome and direct oral anticoagulants: to the future and back again?

Antiphospholipid syndrome and direct oral anticoagulants: to the future and back again?