Anti-Phospholipid Antibodies in Women with Placenta-Mediated Complications Delivered at >34 Weeks of Gestation.

OBJECTIVE: To determine the prevalence of positive antiphospholipid (aPL) antibodies among pregnant women with placenta-mediated complications delivered at >340/7 weeks of gestation. METHODS: This was a single-center retrospective observational study conducted between 2017 and 2022. Inclusion criteria included pregnant or post-partum women, >18 years, diagnosed with any of the following placenta-mediated complications and delivered at >340/7 weeks of gestation: small-for-gestational-age neonate (SGA ≤ 5th percentile according to local birthweight charts), preeclampsia with severe features, and placental abruption. The primary outcome was the prevalence of positive aPL antibodies: Lupus anticoagulant, Anticardiolipin, or Anti-ß2glycoprotein1. RESULTS: Overall, 431 women met the inclusion criteria. Of them, 378(87.7%) had an SGA neonate, 30 had preeclampsia with severe features (7%), 23 had placental abruption (5.3%), and 21 patients had multiple diagnoses(4.9%). The prevalence of aPL antibodies in the cohort was 4.9% and was comparable between the three subgroups (SGA-3.9%; PET with severe features-3.3%; and placental abruption-13% (p = 0.17)). CONCLUSION: aPL antibodies prevalence in women with placenta-mediated complications > 34 weeks of gestation was 4.9%, with comparable prevalence rates among the three subgroups. Future prospective studies are needed to delineate the need for treatment in those who tested positive for aPL antibodies and do not meet Anti-Phospholipid Antibody Syndrome clinical criteria.

Clinical pharmacist led hospital-wide direct oral anticoagulant stewardship program.

INTRODUCTION: In the past decade, direct-acting oral anticoagulants (DOAC) have been introduced to medical practice for several indications, with a wide range of dosing regimens. As both over- and under-dosing might lead to life-threatening events, development of methods promoting safe and effective utilization of these agents is imperative. The Hadassah Clinical Pharmacy team initiated a hospital-wide program, for monitoring and promoting safe and effective prescription of DOAC during hospitalization. This study describes the types of drug related problems addressed and the program's performance in terms of consultation rates and physician acceptance. METHODS: Electronic medical records throughout the hospital were screened for DOAC orders. All DOAC orders were assessed by a clinical pharmacist for potentially-inappropriate prescribing. When potentially-inappropriate prescribing or a drug-related problem was identified, the clinical pharmacist provided consultation on management options. In specific cases, additional guidance was provided by coagulation and pharmacology specialists. Data on patient characteristics, clinical pharmacist consultations, and physician response was retrospectively retrieved for the first six months of 2017. Characteristics of patients with and without consultations were compared, consultations were categorized by the recommended management of the drug related problem, and physician acceptance rates were evaluated by category. RESULTS: During the evaluated period, 585 patients with DOAC orders were identified. Patients were evenly distributed by gender, and age averaged 78 years. Most patients received apixaban (75%) followed by rivaroxaban (14%) and dabigatran (11%), and most (63%) received "reduced dose" regimens. Clinical pharmacists provided 258 consultations for 210 patients, regarding anticoagulation management, such that more than one in three patients on DOAC had potentially inappropriate prescribing or drug related problems. Consultations included alerts regarding potentially inappropriate DOAC doses and recommendations to increase (29%) or decrease (5%) the dose, potentially inappropriate concomitant antiplatelet agents (20%), need for DOAC level monitoring (23%), and alerts regarding other drug related problems (23%). More than 70% of recommendations were accepted by the attending physician. CONCLUSION: Due to the complexity of DOAC management, potentially-inappropriate prescribing and drug related problems are common. Multidisciplinary collaborative projects including review and consultation by clinical pharmacists are an effective method of improving management of patients on DOAC. TRIAL REGISTRATION: Retrospectively registered at clinicaltrials.gov, NCT03527615 .

Management strategies of the interaction between direct oral anticoagulant and drug-metabolizing enzyme inducers.

Little is known regarding the management of direct oral anticoagulants (DOACs) in patients with enzyme-inducing drugs (EID). The use of EID may lead to sub-therapeutic concentrations of DOACs and to treatment failure. Thus, many patients on EIDs cannot benefit from the advantages of DOACs. This was a retrospective study, evaluating the management of hospitalized patients with DOACs. Characteristics of hospitalized patients with a prescription for DOACs, with and without EIDs, were summarized and evaluated, and management strategies addressing the potential interaction were documented, including the use of DOAC concentration monitoring. During the period evaluated, 1596 hospitalized patients with prescriptions for DOACs were identified. Most patients received apixaban (n = 1227, 77%), followed by rivaroxaban (240, 15%), and dabigatran (129, 8%). Twenty-two patients (1.4%) had concomitant EIDs. Demographic and clinical characteristics of hospitalized patients with DOACs were similar in those receiving EID and those not. Management strategies included stopping DOAC or EID (41%), and DOAC dose increase (14%). During management of these interactions, DOAC concentrations were measured for 11 of 22 patients and were below the 5th percentile of expected concentration for six of these patients. The management of patients with DOAC concentration measurement differed significantly from those without (p = 0.005), as they were much less likely to have one of the medications stopped and more often had the DOACs' dose increased. Among hospitalized patients with DOACs, EIDs are not rare. DOAC concentrations are often low in the presence of EIDs. DOAC concentration monitoring may be useful in settings requiring both DOAC and EIDs.

Managing Direct Oral Anticoagulants in Patients With Antiepileptic Medication.

Current guidance recommends avoiding concomitant use of direct-acting oral anticoagulants and enzyme-inducing antiepileptic drugs because of theoretical drug interactions potentially leading to subtherapeutic drug concentrations and treatment failure. We describe a case documenting a significant interaction between phenobarbital and rivaroxaban, and then apixaban. This case illustrates and supports the concerns regarding concomitant use of these medications. Additionally, in this case the interaction was managed with concentration-guided dosing of apixaban, suggesting this approach may represent a feasible strategy for managing patients requiring treatment with direct-acting oral anticoagulants and enzyme-inducing antiepileptic drugs.

Gender Differences in Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation: Systematic Review and Network Meta-analysis.

BACKGROUND: Studies indicate that women with atrial fibrillation (AF) are less likely to receive anticoagulants despite their higher risk of stroke compared with men. OBJECTIVE: To evaluate whether the efficacy and safety of direct oral anticoagulants (DOACs) differ in women with AF as compared with men. Our secondary aim was to examine gender differences regarding the safety and efficacy of specific DOACs. DATA SOURCES: MEDLINE, EMBASE, Cochrane, and ClinicalTrials.gov were searched through March 2017. STUDY SELECTION AND DATA EXTRACTION: Randomized clinical trials that reported on major bleeding and stroke with DOACs in women and men with AF were included. Meta-analysis and network meta-analysis was performed. DATA SYNTHESIS: Five trials met the inclusion criteria. Among 66 389 patients, 37.8% were women. Women treated with DOACs were at higher risk of stroke and systemic embolism compared with men (RR = 1.19; 95% CI = 1.04-1.35; I2 = 10%) but there was a significantly lower risk of major bleeding in women compared with men (RR = 0.86; 95% CI = 0.78-0.94; I2 = 0%). Network meta-analyses suggested differences between various DOACs in men and women. LIMITATIONS: Patient-level data enabling control for differences in baseline risk and head-to-head comparisons between DOACs were not available. Relevance to Patient Care and Clinical Practice: Undertreatment with DOACs among women cannot be justified. CONCLUSION: Women treated with DOACs had a lower rate of major bleeding and higher rate of stroke and systemic emboli compared with men. Further investigation of DOACs, including differences between the DOACs in specific populations is warranted.

Atypical presentations of thrombotic thrombocytopenic purpura: a diagnostic role for ADAMTS13.

Thrombotic thrombocytopenic purpura (TTP) is an acute, life threatening disease. Only a minority of patients expresses the complete clinical presentation and unusual manifestations can occur. Demonstration of low activity levels of ADAMTS13 (<5 %) is highly specific for the diagnosis of TTP. This study reports a series of five cases of TTP presenting with a thrombotic event and no hematological findings. Detailed chart reviews on these patients were conducted. We identified two patients whose first attack of TTP presented as a thrombotic episode without microangiopathic hemolytic anemia and thrombocytopenia, only to be diagnosed as TTP days later, after the appearance of hematological signs. We also describe three cases of classical TTP relapsing atypically as cerebrovascular accidents without hematological signs. Low levels of ADAMTS13 activity were detected and facilitated the diagnosis. The neurological manifestations disappeared concurrent with normalization of ADAMTS13 activity level after plasma exchange. This study underscores the importance of having a high clinical suspicion of TTP in cases of thrombosis even without hematological abnormalities in patients with previous attacks of TTP. In this clinical scenario, measurement of ADAMTS13 activity is important for diagnosis and early administration of treatment.

The role of N-acetylcysteine in the treatment of thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is an acute, thrombotic microangiopathy with a high mortality rate if left untreated. Plasma exchange (PEX) is the current standard of care. However, a significant number of patients are refractory to this treatment. N-acetylcysteine (NAC) was recently suggested as a potential therapeutic adjunct for patients with TTP. This study reports a series of three patients with TTP successfully treated with NAC in addition to standard therapy. Detailed chart reviews on these patients were conducted. We discuss clinical features, laboratory findings and management of three patients who presented with microangiopathic hemolytic anemia and thrombocytopenia. Anti-ADAMTS13 antibodies and low levels of ADAMTS13 were detected and confirmed the diagnosis of acquired TTP. Based upon their severe presentation or lack of response to initial treatment with PEX, corticosteroids and other immunosuppressive agents, NAC was added. Under this combined treatment, all three patients hada significant clinical improvement of symptoms with concurrent normalization of platelet count and ADAMTS13 activity level. This report highlights the potential therapeutic utility of NAC in the treatment of TTP. Randomized controlled studies will be required to better characterize the risk-to-benefit ratio of NAC in the treatment of TTP.