Heparin-Induced Thrombocytopenia After Revascularization of Gustilo-Anderson Type IIIC Open Lower Leg Fracture: A Case Report of Subsequent Ischemic Limb Salvage Failure.

BACKGROUND Heparin-induced thrombocytopenia (HIT) is a disease in which the immune response elicited by heparin results in a state of hypercoagulability and platelet activation, leading to thrombocytopenia and thromboembolism. Gustilo-Anderson type IIIC open fractures of the extremities are defined as open fractures presenting with arterial injuries that require repair and result in treatment challenges and complications. The diagnosis of HIT can be difficult in patients with severe trauma with consumptive thrombocytopenia associated with heavy bleeding and the use of heparin after vascular anastomosis. CASE REPORT A 48-year-old man was injured in a car accident, pinching his right lower leg and sustaining a Gustilo-Anderson type IIIc open fracture, for which he underwent emergency revascularization surgery. Heparin was administered continuously immediately after the surgery. On postoperative day 9, ischemic changes were observed in the right foot, and we performed suture re-anastomosis; however, the blood circulation in the right lower leg did not resume, and right lower leg amputation was performed due to ischemic necrosis with the onset of HIT. Postoperatively, the patient was switched to edoxaban after the recovery of his platelet count. Thereafter, the patient experienced no new thrombus occlusion or wound trouble, and was able to walk on a prosthetic leg and return to daily life. CONCLUSIONS It is important to consider the possibility of HIT as soon as thrombocytopenia appears in patients with Gustilo-Anderson type IIIC open fracture who are receiving heparin after vascular anastomosis, as a delayed diagnosis of HIT can make it difficult to save the limb.

New Score Models for Predicting Bleeding and Ischemic of Ticagrelor Therapy in Patients with Diabetes Mellitus.

PURPOSE: Ticagrelor is an antiplatelet drug, and its use increases the risk of bleeding. Coronary artery disease is significantly influenced by the widespread occurrence of diabetes mellitus. In order to decrease the incidence of clinical adverse events, a novel bleeding and thrombosis score is developed in this research. METHODS: We conducted a retrospective analysis of patient data from two medical centers who were diagnosed with diabetes mellitus and treated with ticagrelor. We gathered information on every patient from the electronic database of the hospital and follow-up. The collected data were statistically analyzed to obtain risk factors for bleeding and ischemic events. RESULTS: A total of 851 patients with diabetes mellitus who have been administered ticagrelor are included in our investigation. A total of 76 patients have bleeding events and 80 patients have ischemic events. The analysis of multiple variables indicates that characteristics like the age of >65, having a previous occurrence of bleeding, experiencing anemia, using aspirin, and taking atorvastatin are linked to a higher likelihood of bleeding. Additionally, the age of >65, smoking, having a history of blood clots, and having a BMI ≥ 30 are found to increase the risk of ischemia. CONCLUSION: The A4B score established in this study was better than the HAS-BLED score，and the same is true for the ABST score to the CHA2DS-VASc score. This new risk assessment model can potentially detect patients who are at high risk for bleeding and ischemic events. For high-risk patients, the dose of ticagrelor can be adjusted appropriately or the medication can be adjusted.(2023-09-11, ChiCTR2300075627).

Ischemic and Inflammatory Ocular Adverse Events Following Different Types of Vaccination for COVID-19 and Their Incidence Analysis.

PURPOSE: To evaluate the ocular adverse event (OAE) and the incidence rate that can occur after the COVID-19 vaccination. METHODS: Patients who visited with an ophthalmologic diagnosis within a month of COVID-19 vaccination were retrospectively analyzed. OAEs were categorized as ischemia and inflammation by their presumed pathogenesis and were compared by types of vaccine: messenger RNA (mRNA) and viral vector vaccine. The crude incidence rate was calculated using data from the Korea Disease Control and Prevention Agency. RESULTS: Twenty-four patients with OAEs after COVID-19 vaccination were reviewed: 10 patients after mRNA and 14 after viral vector vaccine. Retinal vein occlusion (nine patients) and paralytic strabismus (four patients) were the leading diagnoses. Ischemic OAE was likely to occur after viral vector vaccines, while inflammatory OAE was closely related to mRNA vaccine (p = 0.017). The overall incidence rate of OAE was 5.8 cases per million doses: 11.5 per million doses in viral vector vaccine and 3.4 per million doses in mRNA vaccine. CONCLUSIONS: OAEs can be observed shortly after the COVID-19 vaccination, and their category was different based on the types of vaccine. The information and incidence of OAE based on the type of vaccine can help monitor patients who were administered the COVID-19 vaccine.

Ticagrelor Versus Clopidogrel in Acute Large-Vessel Ischemic Stroke: A Randomized Controlled Single-Blinded Trial.

BACKGROUND: Large-vessel ischemic stroke represents about 25-40% of all ischemic strokes. Few clinical trials compared ticagrelor versus clopidogrel in ischemic stroke patients; all these studies included only patients with a transient ischemic attack or minor stroke; moreover, none of these studies included patients from North Africa. OBJECTIVES: We aimed to compare ticagrelor versus clopidogrel in the first-ever large-vessel occlusion (LVO) acute ischemic stroke in Egypt. METHODS: Our trial involved 580 first-ever LVO ischemic stroke patients who were randomly assigned to administer loading and maintenance doses of ticagrelor or clopidogrel. Screening, randomization, and start of treatment occurred during the first 24 hours of the stroke. RESULTS: 580 patients were included in the intention-to-treat analysis. Thirty patients in the ticagrelor group and 49 patients in the clopidogrel group experienced a new ischemic or hemorrhagic stroke at 90 days (hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.38-0.98; p-value = 0.04), 36 patients in the ticagrelor group, and 57 in the clopidogrel group experienced composite of a new stroke, myocardial infarction, or death due to vascular insults (HR 0.56; 95% CI 0.37-0.87; p = 0.009). Patients who received ticagrelor had better clinical outcomes regarding National Institutes of Health Stroke Scale (NIHSS) reduction and a favorable modified Rankin scale (mRS) score. There were no differences between ticagrelor and clopidogrel regarding hemorrhagic and non-hemorrhagic complications. CONCLUSION: Patients with acute large-vessel ischemic stroke who received ticagrelor within the first 24 hours after ischemic stroke had better clinical outcomes based on recurrent stroke rates, NIHSS reduction, and favorable mRS rates compared with those who received clopidogrel. There were no differences between ticagrelor and clopidogrel regarding hemorrhagic and non-hemorrhagic complications. TRIAL REGISTRATION: Clinical trials.gov (NCT06120725).

Cocaine-related ischemic priapism. Systematic review and presentation of a single center series.

INTRODUCTION: Ischemic priapism is a medical emergency that, if not treated, could lead to permanent erectile dysfunction. The association between cocaine and priapism is well-known; however, data on patient characteristics, treatment, and outcomes is missing. This work aimed to answer the research question: What are the characteristics, management strategies, and erectile prognosis of patients consuming cocaine and presenting with priapism? METHODS: We conducted a systematic review according to PRISMA guidelines and described our case series. RESULTS: Eight studies were selected for qualitative synthesis, presenting information on ten patients. In our case series, we showed information regarding four patients. From the systematic review, the mean presentation time was 42.6 h, and the mean number of procedures to solve priapism was 2,4; in our case series was 42.75 h and 2, respectively. CONCLUSION: Cocaine-related priapism might present with a delayed diagnosis, need more procedures to be managed, and have a worse prognosis. More extensive and prospective studies are required.

Abbreviated or Standard Dual Antiplatelet Therapy by Sex in Patients at High Bleeding Risk: A Prespecified Secondary Analysis of a Randomized Clinical Trial.

Importance: Abbreviated dual antiplatelet therapy (DAPT) reduces bleeding with no increase in ischemic events in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI). Objectives: To evaluate the association of sex with the comparative effectiveness of abbreviated vs standard DAPT in patients with HBR. Design, Setting, and Patients: This prespecified subgroup comparative effectiveness analysis followed the Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated vs Standard DAPT Regimen (MASTER DAPT) trial, a multicenter, randomized, open-label clinical trial conducted at 140 sites in 30 countries and performed from February 28, 2017, to December 5, 2019. A total of 4579 patients with HBR were randomized at 1 month after PCI to abbreviated or standard DAPT. Data were analyzed from July 1 to October 31, 2022. Interventions: Abbreviated (immediate DAPT discontinuation, followed by single APT for ≥6 months) or standard (DAPT for ≥2 additional months, followed by single APT for 11 months) treatment groups. Main Outcomes and Measures: One-year net adverse clinical events (NACEs) (a composite of death due to any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (MACCEs) (a composite of death due to any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding (MCB). Results: Of the 4579 patients included in the analysis, 1408 (30.7%) were women and 3171 (69.3%) were men (mean [SD] age, 76.0 [8.7] years). Ischemic and bleeding events were similar between sexes. Abbreviated DAPT was associated with comparable NACE rates in men (hazard ratio [HR], 0.97 [95% CI, 0.75-1.24]) and women (HR, 0.87 [95% CI, 0.60-1.26]; P = .65 for interaction). There was evidence of heterogeneity of treatment effect by sex for MACCEs, with a trend toward benefit in women (HR, 0.68 [95% CI, 0.44-1.05]) but not in men (HR, 1.17 [95% CI, 0.88-1.55]; P = .04 for interaction). There was no significant interaction for MCB across sex, although the benefit with abbreviated DAPT was relatively greater in men (HR, 0.65 [95% CI, 0.50-0.84]) than in women (HR, 0.77 [95% CI, 0.53-1.12]; P = .46 for interaction). Results remained consistent in patients with acute coronary syndrome and/or complex PCI. Conclusions and Relevance: These findings suggest that women with HBR did not experience higher rates of ischemic or bleeding events compared with men and may derive particular benefit from abbreviated compared with standard DAPT owing to these numerically lower rates of events. Trial Registration: ClinicalTrials.gov Identifier: NCT03023020.

Regulation of Dihydropyrimidinase-like 3 Gene Expression by MicroRNAs in PC12 Cells with Induced Ischaemia and Hypothermia.

Although hypothermic treatment has been reported to have some beneficial effects on ischaemia at the clinical level, the mechanism of ischaemia suppression by hypothermia remains unclear due to a lack of mechanism understanding and insufficient data. The aim of this study was to isolate and characterize microRNAs specifically expressed in ischaemia-hypothermia for the dihydropyrimidinase-like 3 (Dpysl3) gene. PC12 cells were induced with CoCl2 for chemical ischaemia and incubated at 32 ℃ for hypothermia. In ischaemia-hypothermia, four types of microRNAs (miR-106b-5p, miR-194-5p, miR-326-5p, and miR-497-5p) were highly related to the Dpysl3 gene based on exosomal microRNA analysis. Dpysl3 gene expression was up-regulated by miR-497-5p but down-regulated by miR-106b-5p, miR-194-5p and miR-326-5p. Our results suggest that these four microRNAs are involved in the regulation of Dpysl3 gene expression. These findings provide valuable clues that exosomal microRNAs could be used as therapeutic targets for effective treatment of ischaemia.

Who may benefit from low-dose rivaroxaban plus aspirin? Practical implications for outpatients with cardiovascular disease.

Despite availability of effective preventive therapies based on guidelines, patients with vascular diseases continue to be at a high risk for recurrent ischemic events. Therefore, novel therapeutic strategies are required to further reduce the residual risk present in these patients. Platelet aggregation and fibrin organization are involved in arterial thrombosis. Rivaroxaban is capable of targeting both processes and has a synergistic effect when used in combination with acetylsalicylic acid (ASA), providing the so­called dual pathway inhibition (DPI). The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial showed that the DPI (a combination of rivaroxaban at 2.5 mg twice daily [vascular dose] and ASA at 100 mg once daily) reduced cardiovascular death, stroke, or myocardial infarction by 24% in patients with chronic coronary artery disease (CAD) and peripheral artery disease (PAD). Subsequently, the VOYAGER PAD (Vascular Outcomes Study of ASA Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) trial confirmed the effectiveness of the vascular dose of rivaroxaban in patients with PAD after lower­extremity revascularization, as compared with ASA alone. Therefore, DPI is recommended in the patients with CAD (+/- PAD) or symptomatic PAD at a high risk of ischemia. The purpose of this review is to examine the clinical benefits and practical implications of DPI in the CAD and PAD patients.

Aortic thrombosis and acute limb ischemia after ChAdOx1 nCov-19 (Oxford-AstraZeneca) vaccination: a case of vaccine-induced thrombocytopenia and thrombosis (VITT).

INTRODUCTION: Vaccine-induced thrombocytopenia and thrombosis (VITT) is a rare but devastating adverse event associated with the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) adenoviral vaccine against the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2). METHODS: A 49-year-old man presented to the emergency department with acute right limb ischemia (Rutherford IIB) nine days after his ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccination. CT angiography revealed significant aortic thrombosis and right femoral artery occlusion. Severe thrombocytopenia (platelet count of 23 × 103/µL), promptly elevated D-dimers (37937 ng/mL) and a reduced fibrinogen level (176 mg/dL) were remarkable. ELISA testing for anti-PF4 antibodies confirmed the diagnosis of VITT. RESULTS: An emergency revascularization of the right leg was provided via thrombectomy. High-dose intravenous immunoglobulins were administered whereafter the platelet count restored gradually. Therapeutic anticoagulation was progressively started. The postoperative course was uneventful and follow-up imaging after four weeks showed an almost complete resolution of the significant aortic thrombosis. CONCLUSION: Early recognition and appropriate counseling of VITT is advocated to pursue a good clinical outcome. Our patient presenting with severe aortic thrombosis and acute limb ischemia was successfully treated by a vascular thrombectomy along with intravenous immunoglobulins and anticoagulation therapy as the mainstay therapy.

PARACENTRAL ACUTE MIDDLE MACULOPATHY AND OCULAR ISCHEMIC SYNDROME AFTER INTRANASAL STEROID INJECTION: A CASE REPORT AND REVIEW OF THE LITERATURE.

PURPOSE: To describe a case of paracentral acute middle maculopathy and ocular ischemic syndrome after intranasal steroid injection. METHODS: Case report. RESULTS: Following an intranasal steroid injection, the patient experienced an episode of amaurosis fugax in her right eye lasting several minutes. Afterward, her visual acuity returned to baseline, but she noted a persistent central scotoma. Optical coherence tomography demonstrated paracentral acute middle maculopathy and fluorescein angiography showed staining and leakage to peripheral vessels concerning for diffuse ischemia. CONCLUSION: Steroid injections to the face and nasopharynx may result in ischemic and vaso-occlusive events in the retina. Ophthalmologists and other physicians performing these procedures need to be aware of this potential adverse outcome.

Patterns of Filler-Induced Facial Skin Ischemia: A Systematic Review of 243 Cases and Introduction of the FOEM Scoring System and Grading Scale.

BACKGROUND: The incidence of facial skin necrosis has increased considerably because of the growth in the popularity of dermal fillers. This study describes the patterns and severity of facial skin ischemia, along with associated neuro-ophthalmologic injuries, in the published literature through the introduction of the facial artery, ophthalmic artery, distal external carotid artery, internal maxillary artery (FOEM) facial angiosome scoring system and grading scale. METHODS: A systematic review of all photographic cases of facial skin ischemia attributable to vascular occlusion with dermal fillers and injectable materials was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: A total of 243 cases were identified, with 738 digital clinical photographs retrieved. The facial artery (58% of cases) and ophthalmic artery (48% of cases) angiosomes were most commonly affected. The frontonasal and angulonasal territories were the most common facial skin segments injured by filler-induced vascular occlusion. Cutaneous involvement of the ophthalmic angiosome was significantly associated with neuro-ophthalmologic complications [vision loss, 39% versus 0.8% ( P = 0.00001); stroke, 8% versus 0.8% ( P = 0.0085)]. Injuries with greater cutaneous surface area or cross-angiosome involvement were associated with a higher incidence of severe visual deficits and bilateral stroke. CONCLUSIONS: Facial skin necrosis attributable to vascular occlusion is a rapidly growing problem that has remained poorly characterized in the literature. This study provides the largest descriptive analysis of published photographic reports of skin ischemia to date and proposes a novel scoring system and grading classification to aid in future reporting.

Patient selection for long-term secondary prevention with ticagrelor: insights from PEGASUS-TIMI 54.

AIM: In patients with prior myocardial infarction (MI) on aspirin, the addition of ticagrelor reduces ischaemic risk but increases bleeding risk. The simultaneous assessment of baseline ischaemic and bleeding risk may assist clinicians in selecting patients who are most likely to have a favourable risk/benefit profile with long-term ticagrelor. METHODS AND RESULTS: PEGASUS-TIMI 54 randomized 21 162 prior MI patients, 13 956 of which to the approved 60 mg dose or placebo and who had all necessary data. The primary efficacy endpoint was cardiovascular death, MI, or stroke, and the primary safety outcome was TIMI major bleeding; differences in Kaplan-Meier event rates at 3 years are presented. Post-hoc subgroups based on predictors of bleeding and ischaemic risk were merged into a selection algorithm. Patients were divided into four groups: those with a bleeding predictor (n = 2721, 19%) and then those without a bleeding predictor and either 0-1 ischaemic risk factor (IRF; n = 3004, 22%), 2 IRF (n = 4903, 35%), or ≥3 IRF (n = 3328, 24%). In patients at high bleeding risk, ticagrelor increased bleeding [absolute risk difference (ARD) +2.3%, 95% confidence interval (CI) 0.6, 3.9] and did not reduce the primary efficacy endpoint (ARD +0.08%, 95% CI -2.4 to 2.5). In patients at low bleeding risk, the ARDs in the primary efficacy endpoint with ticagrelor were -0.5% (-2.2, 1.3), -1.5% (-3.1, 0.02), and -2.6% (-5.0, -0.24, P = 0.03) in those with ≤1, 2, and 3 risk factors, respectively (P = 0.076 for trend across groups). There were significant trends for greater absolute risk reductions for cardiovascular death (P-trend 0.018), all-cause mortality (P-trend 0.027), and net outcomes (P-trend 0.037) with ticagrelor across these risk groups. CONCLUSION: In a post-hoc exploratory analysis of patients with prior MI, long-term ticagrelor therapy appears to be best suited for those with prior MI with multiple IRFs at low bleeding risk. CLINICAL TRIAL REGISTRATION: NCT01225562 ClinicalTrials.gov.

Case report: Non-occlusive mesenteric ischemia in the setting of sildenafil use.

Acute mesenteric ischemia (AMI) is a condition that results from a sudden decline in blood flow through the mesenteric vessels that has a high morbidity and mortality. Non-occlusive AMI often presents in critically ill, hypotensive patients that suffer from decreased organ perfusion. Here we describe a case of non-occlusive acute mesenteric ischemia in the setting of transient hypotension precipitated by sildenafil. The patient required rapid fluid resuscitation in the emergency department. He did not require surgical intervention and was able to be discharged home with resolution of symptoms after a 7-day inpatient stay.

Ischemic and hemorrhagic abdominal complications in COVID-19 patients: experience from the first Italian wave.

PURPOSE: To report ischemic and haemorrhagic abdominal complications in a series of COVID-19 patients. To correlate these complications with lung involvement, laboratory tests, comorbidities, and anticoagulant treatment. METHODS: We retrospectively included 30 COVID-19 patients who undergone abdomen CECT for abdominal pain, between March 16 and May 19, 2020. Ischemic and haemorrhagic complications were compared with lung involvement (early, progressive, peak or absorption stage), blood coagulation values, anticoagulant therapy, comorbidities, and presence of pulmonary embolism (PE). RESULTS: Ischemic complications were documented in 10 patients (7 receiving anticoagulant therapy, 70%): 6/10 small bowel ischemia (1 concomitant obstruction, 1 perforation) and 4/10 ischemic colitis. Main mesenteric vessels were patent except for 1 superior mesenteric vein thrombosis. Two ischemia cases also presented splenic infarctions. Bleeding complications were found in 20 patients (all receiving anticoagulant treatments), half with active bleeding: hematomas in soft tissues (15) and retroperitoneum (2) and gastro-intestinal bleeding (3). Platelet and lymphocyte were within the normal range. D-Dimer was significantly higher in ischemic cases (p < 0.001). Most of the patients had severe lung disease (45% peak, 29% absorption), two patients PE. CONCLUSIONS: Ischemic and haemorrhagic abdominal complications may occur in COVID-19 patients, particularly associated to extended lung disease. CT plays a key role in the diagnosis of these potentially life- threatening conditions.

Evaluation of nefrotoxicity by tacrolimus and micophenolate mofetil associated with kidney ischemia and reperfusion: experimental study in rats.

OBJECTIVE: to evaluate the renal toxicity caused by tacrolimus and mycophenolate mofetil (MMF) in a single kidney ischemia and reperfusion model. METHOD: experimental study using Wistar rats, submitted to right nephrectomy and left renal ischemia for 20 minutes, separated into groups in the postoperative period (PO): 1) Control (nonoperated); 2) Sham (operated, without PO drug); 3) TAC0.1, TAC1 and TAC10, tacrolimus administered PO at doses of 0.1mg/kg, 1mg/kg and 10mg/kg via gavage, respectively; 4) MMF, administered mycophenolate mofetil 20mg/kg; 5) MMF/TAC1 and MMF/TAC0.5, with an association of mycophenolate mofetil 20mg/kg and tacrolimus 1mg/kg and 0.5mg/kg, respectively. They were killed on the 14th PO and the kidney was removed for tissue oxidative stress analysis, by the dosage of reduced glutathione (GSH), lipoperoxidation (LPO) and protein carbonylation (PCO), and histological analysis by glomerular stereology (Glomerular volume density, Numerical density glomerular and mean glomerular volume). Renal function was evaluated by the measurement of serum creatinine and urea. RESULTS: both drugs caused alterations in renal function, and the toxicity of tacrolimus was dose-dependent. Subacute toxicity did not show significant glomerular histological changes, and there was renal and compensatory glomerular hypertrophy in all groups except TAC10. CONCLUSION: Both drugs cause changes in renal function. Glomerular morphometry and stereology showed negative interference of immunosuppressants during compensatory glomerular hypertrophy.

Hyperbaric oxygen therapy for treatment of a late presenting ischaemic complication from hyaluronic acid cosmetic filler injection.

Vascular compromise and resulting ischaemic injury are known rare complications of cosmetic filler injections. Most hyaluronic acid vascular compromises present early and can be treated effectively by hyaluronidase. Here we present a case of ischaemic wound and mucosal necrosis after cosmetic facial hyaluronic acid injection that appeared within hours of injection but was not diagnosed and treated for 5 days. At day 5, the patient was treated with hyaluronidase injection immediately followed by 14 sessions of daily hyperbaric oxygen therapy (HBOT). Despite the delayed treatment, the patient had essentially complete recovery and the hyperbaric therapy was overall well-tolerated. Our case report suggests that hyaluronidase injection with concurrent daily HBOT sessions may be effective to allow recovery from late-presenting filler ischaemic complication. Furthermore, given the safety profile of HBOT, we suggest a more deliberate approach to this modality as a therapeutic adjunct by cosmetic practitioners when similar complications arise.

Fatal adverse events of rivaroxaban combined with aspirin: an analysis using data from VigiBase.

PURPOSE: The aim of this study was to analyze the clinical characteristics of fatal adverse events (AEs) of rivaroxaban combined with aspirin and to underline the importance of the rational use of drugs. METHODS: The WHO global database of reported potential side effects of medicinal products (VigiBase) was searched for fatal AEs in the combined use of rivaroxaban and aspirin, and the clinical characteristics of those cases with sufficient information (vigiGrade completeness score ≥ 0.80) were analyzed. RESULTS: By January 19, 2020, 2309 fatal adverse event reports of rivaroxaban combined with aspirin from 21 countries were entered in VigiBase. One hundred and twenty cases contained further information, of which 42 were female (35%) and 78 were male (65%). The median age was 75 (range 34 to 93) years, and 109 cases (91%) were elderly patients (≥ 65 years). The AEs listed in the fatal case reports included bleeding in 114 cases (mainly intracranial hemorrhage and gastrointestinal hemorrhage, 59 and 46 respectively, accounting for 88%) and ischemic events in six cases (ischemic stroke in three, acute myocardial infarction in two, myocardial infarction combined with acute liver failure in one). Among the patients with bleeding events, 108 (95%) had existing risk factors for bleeding or for interacting with aspirin or rivaroxaban. These may be divided into the following: diseases (hypertension, renal impairment, history of stroke, peptic ulcer, or previous bleeding), drugs (high dose aspirin, antiplatelet drugs, anticoagulants, P-gp inhibitors/CYP3A4 inhibitors, non-steroidal anti-inflammatory drugs, steroids, and selective serotonin reuptake inhibitors), or other factors (e.g., elderly, low body weight, or excessive intake of ginger, fish oil, or alcohol). There were 45 cases with two or more of these risk factors in addition to rivaroxaban and aspirin. Patients with ischemic events are often in very high-risk groups of atherosclerotic cardiovascular disease (ASCVD) or self-discontinuation of treated drugs. Medication errors occurred in 24 patients (20%): excessive treatment in 17 cases, contraindication in three, frequency error in two, excessive treatment combined with contraindication in one, and self-discontinuation in one. CONCLUSIONS: Fatal AEs related to rivaroxaban combined with aspirin, including bleeding and ischemic events, have been reported mostly in the elderly, and sometimes involved medication errors. The fatal AEs mainly manifested as serious bleeding, and most of them occurred in patients with concurrent multiple risk factors. Monitoring coagulation during rivaroxaban treatment is recommended in very high-risk ASCVD populations, and attention should be paid to prevention of medication errors.

Clinical characteristics and treatment of terlipressin-induced ischemic skin necrosis: A synthesis of 35 literature reported cases.

WHAT IS KNOWN AND OBJECTIVE: The clinical features of terlipressin-induced ischemic skin necrosis are unknown. The purpose of this study is to explore the clinical features of terlipressin-induced skin necrosis. METHODS: We searched Chinese and English databases to collect case reports of terlipressin-induced skin necrosis for retrospective analysis. RESULTS AND DISCUSSION: A total of 42 patients (31 males and 11 females) from 35 studies were included, with a median age of 54 years (range 0.17-84). The onset of skin ischemia ranged from a few hours to 21 days. The most common clinical manifestations were bulla (15 cases, 35.7%), cyanosis (12 cases, 28.6%), necrosis (11 cases, 26.2%), and purpura (10 cases, 23.8%). The following were often affected: the legs (26 cases), 61.9%), abdomen (13, 31.0%), scrotum (10 cases, 23.8%), feet (10 cases, 23.8%), upper extremities (8 cases, 19.0%), and hands (7 cases, 16.7%). Skin biopsy showed fibrin thrombus (7 cases, 38.9%), nonspecific inflammation (6 cases, 33.3%), and necrosis (10 cases, 55.6%). After discontinuation of terlipressin, skin symptoms improved in most patients. WHAT IS NEW AND CONCLUSION: Ischemic skin necrosis is a rare and serious adverse effect of terlipressin. Patients receiving terlipressin therapy should be monitored closely for terlipressin-related ischemic complications. Terlipressin should be discontinued immediately if ischemic complications occur.