Cutaneous small vessel leukocytoclastic vasculitis (LCV) is isolated to the dependent areas of the skin. LCV can be induced by pharmaceutical drugs, and management requires abrupt discontinuation of the offending drug. Warfarin is a rare medication to cause LCV, with sparse literature to date. Here, we present a case of warfarin-induced LCV, complicated by a patient\'s comorbid left ventricular thrombus, and successful treatment with discontinuation of warfarin and replacement with a direct oral anticoagulant (apixaban).

Here, we describe a case of anaphylaxis secondary to rivaroxaban in a 61-year-old woman 24 hours after orthopedic surgery. 10-15 minutes after ingestion of rivaroxaban and nimesulide, the patient\'s palms started itching, her face and lips swelled, her face flushed, she developed shortness of breath and subsequently lost consciousness. Serum tryptase levels at the time of the anaphylactic reaction were elevated, with subsequent measurement one month later returning a value within the normal range. Dabigatran and meloxicam were identified as suitable alternative drugs by oral provocation at an allergy clinic. Even though rivaroxaban rarely causes serious allergic reactions, when prescribing it, it is important to analyze patients\' medical history for possible previously experienced drug-induced allergic reactions and to be aware of the risks of possible undesired drug interactions.

BACKGROUND: The clotting or hemostasis system is a meticulously regulated set of enzymatic reactions that occur in the blood and culminate in formation of a fibrin clot. The precisely calibrated signaling system that prevents or initiates clotting originates with the activated Factor Seven (FVIIa) complexed with tissue factor (TF) formed in the endothelium. Here we describe a rare inherited mutation in the FVII gene which is associated with pathological clotting.
METHODS: The 52-year-old patient, with European, Cherokee and African American origins, FS was identified as having low FVII (10%) prior to elective surgery for an umbilical hernia. He was given low doses of NovoSeven (therapeutic Factor VIIa) and had no unusual bleeding or clotting during the surgery. In fact, during his entire clinical course he had no unprovoked bleeding. Bleeding instances occurred with hemostatic stresses such as gastritis, kidney calculus, orthopedic surgery, or tooth extraction, and these were handled without factor replacement. On the other hand, FS sustained two unprovoked and life-threatening instances of pulmonary emboli, although he was not treated with NovoSeven at any time close to the events. Since 2020, he has been placed on a DOAC (Direct Oral Anticoagulant, producing Factor Xa inhibition) and has sustained no further clots.
UNASSIGNED: FS has a congenitally mutated FVII/FVIIa gene, which carries a R315W missense mutation in one allele and a mutated start codon (ATG to ACG) in the other allele, thus rendering the patient effectively homozygous for the missense FVII. Structure based comparisons with known crystal structures of TF-VIIa indicate that the patient\'s missense mutation is predicted to induce a conformational shift of the C170\'s loop due to crowding of the bulky tryptophan to a distorted \"out\" position (Fig. 1). This mobile loop likely forms new interactions with activation loop 3, stabilizing a more active conformation of the FVII and FVIIa protein. The mutant form of FVIIa may be better able to interact with TF, displaying a modified serine protease active site with enhanced activity for downstream substrates such as Factor X.
CONCLUSIONS: Factor VII can be considered the gatekeeper of the coagulation system. Here we describe an inherited mutation in which the gatekeeper function is altered. Instead of the expected bleeding manifestations resulting from a clotting factor deficiency, the patient FS suffered clotting episodes. The efficacy of the DOAC in treating and preventing clots in this unusual situation is due to its target site of inhibition (anti-Xa), which lies downstream of the site of action of FVIIa/TF.

The combination of oral anticoagulants (OAC) and dual antiplatelet therapy (DAPT) is the mainstay for the treatment of patients with atrial fibrillation (AF) presenting with acute coronary syndrome (ACS) and/or undergoing PCI. However, this treatment leads to a significant increase in risk of bleeding. In most cases, according to the most recent guidelines, triple antithrombotic therapy (TAT) consisting of OAC and DAPT, typically aspirin and clopidogrel, should be limited to one week after ACS and/or PCI (default strategy). On the other hand, in patients with a high ischemic risk (i.e., stent thrombosis) and without increased risk of bleeding, TAT should be continued for up to one month. Direct oral anticoagulants (DOAC) in triple or dual antithrombotic therapy (OAC and P2Y12 inhibitor) should be favored over vitamin K antagonists (VKA) because of their favorable risk/benefit profile. The choice of the duration of TAT (one week or one month) depends on a case-by-case evaluation of a whole series of hemorrhagic or ischemic risk factors for each patient. Likewise, the specific DOAC treatment should be selected according to the clinical characteristics of each patient. We propose a series of paradigmatic clinical cases to illustrate the decision-making work-up in clinical practice.

Direct oral anticoagulants (DOACs) are used to treat several conditions such as non-valvular atrial fibrillation, deep vein thrombosis, and pulmonary embolism. DOACs and other anticoagulants block crucial steps in the coagulation cascade and ultimately prevent clot formation. Generally, individuals initiated on an anticoagulant are predisposed to or have a propensity to form clots. Patients with hemophilia are given anticoagulants only in very rare cases. In this report, we discuss the case of a 75-year-old man with a history of atrial fibrillation managed on rivaroxaban; he presented to the emergency department with fatigue, easy bleeding, symptomatic anemia, and significantly elevated partial thromboplastin time (PTT) with an undiagnosed acquired factor VIII inhibitor. Reports of DOAC use and concomitant factor inhibitor autoimmunization, as seen in this case, are scarcely explored in the existing literature. While DOACs are popular anticoagulants, their variable effects on both prothrombin time (PT) and PTT make it difficult to detect superimposed bleeding disorders. In patients with severe anemia or significant elevations in PT or PTT, an expedited workup, including factor assays, may be a reasonable option as evidenced by this case.

UNASSIGNED: The use and utility of novel oral anticoagulants has been increasing in clinical practice due to their relatively lower incidence of side effects such as intracranial haemorrhage, particularly in the elderly, when compared with vitamin K antagonists. Rivaroxaban is a factor Xa and prothrombinase inhibitor indicated for stroke and venous thromboembolism prophylaxis in non-valvular atrial fibrillation as well as treatment of venous thromboembolism.
UNASSIGNED: A patient with history of paroxysmal atrial fibrillation on Rivaroxaban presented with generalized malaise, lightheadedness, and dizziness. The patient was found to be in profound cardiogenic shock despite unremarkable cardiac enzymes. Electrocardiogram revealed rate controlled atrial fibrillation and T-wave inversions in the inferolateral leads without associated electrical alternans. Bedside echocardiogram revealed a large pericardial effusion consistent with cardiac tamponade physiology. Following anticoagulation reversal, the patient underwent urgent pericardiocentesis yielding haemorrhagic fluid, with subsequent improvement in haemodynamic status. Despite the presence of retroperitoneal lymphadenopathy on previous computed tomography of the abdomen and concern for underlying malignant effusion secondary to lymphoma, cytology of the fluid revealed no evidence of malignant cells and follow-up flow cytometry and bone marrow biopsy were unremarkable.
UNASSIGNED: While hemopericardium is not listed as a known side effect of Rivaroxaban, previous cases of hemopericardium secondary to Rivaroxaban have been described in the literature secondary to pre-disposing risk factors including CYP450 drug interactions or cardiac device implantations. In this case, the patient experienced a spontaneous hemopericardium on Rivaroxaban without any previously elucidated risk factors or evidence of malignancy.

Direct oral anticoagulants, such as apixaban, are increasingly used in everyday practice in order to treat or prevent thromboembolic diseases. To date, there is no available data about apixaban pharmacokinetics in children, and no intoxication has previously been described.
A 23-month-old boy, with no medical history, was admitted to the emergency department 2 h after accidentally ingesting 40 mg apixaban and 0.75 mg digoxin. No adverse event was observed. Digoxin trough level was within therapeutic values. Apixaban blood concentration increased up to 1712 μg/L at H + 6 (1000-2750 μg/L using 2-5 mg/kg of apixaban in adults). The terminal half-life was 8.2 h (6-15 h in adults). The rapid elimination may explain the absence of bleeding despite high concentrations.
Despite an important intake of apixaban and a real disturbance in routine coagulation assays, no clinical sign of bleeding was observed, perhaps due to wide therapeutic range of apixaban. It may also be explained by its rapid elimination. Considering the high Cmax and a possible enteroenteric recycling, the use of activated charcoal should be considered in such situations in order to prevent eventual bleeding.

UNASSIGNED: Vitamin K antagonists (VKAs) have been regarded as the therapy of choice for intracardiac thrombosis for decades based mostly on observational data. The advent of direct oral anticoagulants (DOACs) has displaced VKAs as the first-line therapy for multiple thrombotic disorders but not for intracardiac thrombosis. Although limited, there is growing evidence that DOACs are effective for intracardiac thrombosis and some data suggest that thrombus resolution might be superior to that with warfarin.
UNASSIGNED: Here, we present a series of six patients with left atrial appendage thrombi were treated with a venous thromboembolic dose of DOACs with resolution within 2-6 months with no reported complications.
UNASSIGNED: This case series adds to the accumulating evidence supporting the efficacy of DOACs in the treatment of intracardiac thrombi.

A morbidly obese patient with history of deep vein thrombosis and pulmonary embolism was diagnosed with an acute left upper extremity deep vein thrombosis and started on rivaroxaban. Three months later, the patient returned with swelling in the right arm and was found to have a right brachial thrombosis. Anticoagulant therapy was switched to a low-molecular-weight heparin, and patient was discharged on enoxaparin along with an order to follow-up with a hematologist. Subanalyses from randomized controlled trials, pharmacokinetic/pharmacodynamic, and real-world studies suggest that rivaroxaban may be effective and safe in morbidly obese patients for primary and secondary prevention of venous thromboembolism. However, the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis does not recommend the use of direct-acting oral anticoagulants in this population. If used, drug levels should be monitored to guide the therapy. Due to the disparity in data to show efficacy and safety of rivaroxaban in morbidly obese subjects, the interpatient variability of rivaroxaban\'s effects in subjects, and the lack of defined therapeutic range for rivaroxaban drug concentration, rivaroxaban should be used cautiously in this population.

Post-marketing reporting of adverse drug events is essential for new medications, as pre-FDA approval studies lack sufficient subject numbers to detect signals for rare events. Prescriptions for the novel oral anticoagulant factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) have equaled or exceeded those for vitamin K antagonists in many clinical settings requiring chronic anticoagulation, and those of injectable heparins for deep vein thrombosis prophylaxis. We report the case of a 60-year-old woman followed for permanent atrial fibrillation who was prescribed apixaban. She rapidly developed worsening neurologic symptoms of imbalance and non-vertiginous dizziness preventing her from walking, headache, diplopia, and confusion/disorientation. Her symptoms began to resolve after stopping the drug, with return to baseline function within 72 h. Unbeknownst to her cardiology care team, the patient chose to re-challenge herself with apixaban at the same dose, producing identical symptoms and again total symptom resolution within 24 h of drug discontinuation. When seen by her physician, her physical examination was unchanged from her pre-treatment baseline. Symptoms did not recur when switched to rivaroxaban therapy.