Monoclonal gammopathy of undetermined significance causing large vessel vasculitis.

A man in his late 50s presented with unilateral pain and discolouration of his fourth and fifth toes suggestive of digital ischaemia. He had a medical history of two unprovoked venous thromboembolisms in the preceding 18 months and a history of monoclonal gammopathy of undetermined significance (MGUS). A CT scan showed evidence of large vessels vasculitis in the absence of circulating antineutrophil cytoplasmic antibodies. Biopsy of the toes showed evidence of light chain and immunoglobulin deposition on immunofluorescence suggesting vasculitis secondary to his haematological diagnosis of MGUS. The patient was treated with high dose glucocorticoids and immunosuppressive treatment with a significant improvement in his symptoms and features of digital ischaemia.

A COVID-19 patient with recurrent acute limb ischaemia despite two successive types of therapeutic dose anticoagulation and thrombolysis.

COVID-19 is caused by the SARS-CoV-2, and its presentation ranges from mild upper respiratory illness to critical disease including acute respiratory distress syndrome and multiorgan dysfunction. While it was initially believed to primarily target the respiratory system, numerous studies have demonstrated it to cause a hypercoagulable state that predisposes to arterial and venous thrombosis. We present a case where a patient with COVID-19 developed acute lower limb ischaemia due to arterial thrombosis in the setting of full-dose enoxaparin, followed by heparin infusion protocol. The patient developed recurrent ischaemia despite thrombolysis in addition to anticoagulation, and eventually required open thrombectomy before making a full recovery.

Incidence, Characteristics, Laboratory Findings and Outcomes in Acro-Ischemia in COVID-19 Patients.

AIM: In addition to its respiratory impact of SARS-CoV2, skin lesions of probable vascular origin have been described. This study intends to quantify the incidence of acro-ischemic lesions in COVID-19 infected adult subjects in our population, describing clinical patterns and associated findings. METHODS: All adult confirmed cases of COVID-19 infection who presented with acro-ischemic lesions and received care in our institution were prospectively enrolled up to May 15th, 2020. The variables included demographics, comorbidities, analytical parameters, clinical presentations and COVID-19 treatment. RESULTS: We enrolled 24 patients. The overall rate of acro-ischemic findings in COVID-19 patients was 1.2% [0.6% for outpatients and 2.9% for hospitalized (ICU and non-ICU patients)], but the observed incidence for acro-ischemia in ICU patients was remarkably higher (23.0%, p<0.001). We have described four different clinical patterns of acroischemia: atypical Raynaud´s phenomenon (ARP), (4); pseudo-pernio (PP), (5); severe microcirculatory ischemia with preserved pulse (SMI), (6); and dry gangrene with arteriosclerosis obliterans (AO), (9). Kendall´s τ correlation with lung disease severity was 0.877 (95% CI, 0.756 to 0.968); p<0.01). ARP individuals were predominantly female, while SMI appeared lately in elderly hospitalized subjects with better prognosis. AO occurred in patients with more comorbidity and younger than those with SMI. We observed other associated lesions of suggestive ischemic nature in other organs in all groups (15 patients of total sample). Plasma procalcitonin was significantly higher in patients who developed SMI (median and interquartile range: 9.99 (4.2, 12.3) mg/mL vs 0.26 (0.11, 0.89) mg/mL; p<0.001), and D-dimer level at hospital admission was significantly higher in AO patients (median and interquartile range: 1166 (1050, 2111) mg/L vs 502 (448, 777) mg/L; p<0.001). CONCLUSION: The observed risk for acroischemia in COVID-19 is high in ICU patients (23%). We have described four different clinical patterns of acroischemia (ARP, PP, SMI and AO) associated with lung disease severity. Authors have communicated various lesions of suggestive ischemic nature in other organs. Raynaud-like pattern is reported as a "novelty".

Successful Catheter-Directed Thrombolysis for Acute Lower Limb Ischemia Secondary to COVID-19 Infection.

A 49-year-old man was admitted to his local hospital with left leg pain and breathing difficulties. He had negative nasopharyngeal polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2. Chest X-ray and Computed tomography pulmonary angiogram displayed typical coronavirus disease 2019 (COVID-19) radiological features as ground-glass opacities and bronchovascular thickening. His respiratory symptoms resolved after four days of supportive treatment, whereas his left leg became more painful and discolored. He was referred to our center with acute left leg ischemia. computed tomography angiogram revealed eccentric mural thrombus at the aortic bifurcation, extending into left common iliac and an abrupt occlusion of left popliteal, tibioperoneal, and posterior tibial arteries. He was treated with catheter-directed thrombolysis for 48-hours that achieved successful revascularization of the ischemic limb with no intervention-related complications. At six-week follow-up, he showed full recovery. Our case demonstrates that catheter-directed thrombolysis is a successful and safe treatment option in a COVID-19 patient with acute arterial occlusion.

Rationale and design of the TAILOR-PCI digital study: Transitioning a randomized controlled trial to a digital registry.

BACKGROUND: Tailored Antiplatelet Initiation to Lessen Outcomes Due to Decreased Clopidogrel Response after Percutaneous Coronary Intervention (TAILOR-PCI) is the largest cardiovascular genotype-based randomized pragmatic trial (NCT#01742117) to evaluate the role of genotype-guided selection of oral P2Y12 inhibitor therapy in improving ischemic outcomes after PCI. The trial has been extended from the original 12- to 24-month follow-up, using study coordinator-initiated telephone visits. TAILOR-PCI Digital Study tests the feasibility of extending the trial follow-up in a subset of patients for up to 24 months using state-of-the-art digital solutions. The rationale, design, and approach of extended digital study of patients recruited into a large, international, multi-center clinical trial has not been previously described. METHODS: A total of 930 patients from U.S. and Canadian sites previously enrolled in the 5,302 patient TAILOR-PCI trial within 23 months of randomization are invited by mail to the Digital Study website (http://tailorpci.eurekaplatform.org) and by up to 2 recruiting telephone calls. Eureka, a direct-to-participant digital research platform, is used to consent and collect prospective data on patients for the digital study. Patients are asked to answer health-related surveys at fixed intervals using the Eureka mobile app and or desktop platform. The likelihood of patients enrolled in a randomized clinical trial transitioning to a registry using digital technology, the reasons for nonparticipation and engagement rates are evaluated. To capture hospitalizations, patients may optionally enable geofencing, a process that allows background location tracking and triggering of surveys if a hospital visit greater than 4 hours is detected. In addition, patients answer digital hospitalization surveys every month. Hospitalization data received from the Digital Study will be compared to data collected from study coordinator telephone visits during the same time frame. CONCLUSIONS: The TAILOR-PCI Digital Study evaluates the feasibility of transitioning a large multicenter randomized clinical trial to a digital registry. The study could provide evidence for the ability of digital technology to follow clinical trial patients and to ascertain trial-related events thus also building the foundation for conducting digital clinical trials. Such a digital approach may be especially pertinent in the era of COVID-19.

Aspirin with or without statin in the treatment of endotheliitis, thrombosis, and ischemia in coronavirus disease.

INTRODUCTION: In the genesis of coronavirus disease (COVID-19), there is a process of endotheliitis associated with thrombotic changes, no studies have reported the use of acetylsalicylic acid (ASA) as a possible therapeutic approach. Statins could potentiate the ASA therapy. METHODS: This is a series of 14 cases with a laboratory-confirmed diagnosis of COVID-19. All patients underwent the ASA therapy. Those who had risk factors for vascular disease also underwent the high-potency statin therapy. When symptoms were totally or practically resolved, patients were discharged and advised to continue medications for a complementary time, according to the clinical evolution of each patient. RESULTS: The mean age of monitored patients was 48.6 years. A total of 78.6% patients presented with at least one comorbidity, which could have contributed as a risk factor for a poor prognosis in the evolution of COVID-19. Four patients had secondary bacterial infections; three patients needed hospitalization. None of the cases progress to stage III, and all patients had remission of symptoms, with 100% survival. CONCLUSIONS: the process of endothelial dysfunction in COVID-19 involves disseminated thrombosis, initially microvascular and later expansion into larger vessels. ASA could act as a secondary prophylaxis and prevent thrombosis from developing and reaching stage III of the disease. As this was a case series, we cannot provide definitive conclusions; however, this study allows us to formulate hypotheses and support clinical trials to evaluate benefits of the ASA therapy in the treatment of COVID-19.

A Case of Covid-19 Patient with Acute Limb Ischemia and Heparin Resistance.

Heparin resistance is an uncommon phenomenon defined as the need for high-dose unfractionated heparin (UFH) of more than 35,000 IU/day to achieve the target activated partial-thromboplastin time ratio or the failure to achieve the desired activated clotting time after a full UFH dose. This rare phenomenon is being more commonly observed in Covid-19 patients in a hypercoagulable state. We describe a Covid-19 patient confirmed by reverse-transcriptase polymerase chain reaction assay, with acute limb ischemia, who developed heparin resistance. The patient was managed by the departments of vascular surgery, anesthesia and intensive care, and the Coagulation Service and Thrombosis Research from San Raffaele Scientific Institute, Milan, Italy.

[Clinical and coagulation characteristics in 7 patients with critical COVID-2019 pneumonia and acro-ischemia].

Objective: To investigate the clinical and coagulation characteristics in patients with critical Coronavirus disease 2019 (COVID-19) and acro-ischemia. Methods: The retrospective study included 7 critical COVID-19 patients with acro-ischemia in an intensive care unit (ICU) in Wuhan, from Feb 4 to Feb 15, 2020. The clinical and laboratory data before and during the ICU stay were analyzed. Results: The median age of 7 patients was 59 years and 4 of them were men. Three patients were associated with underlying comorbidities. Fever, cough, dyspnea and diarrhea were common clinical symptoms. All patients had acro-ischemia presentations including finger/toe cyanosis, skin bulla and dry gangrene. D-dimer, fibrinogen and fibrinogen degradation product (FDP) were significantly elevated in most patients. Prothrombin time was prolonged in 4 patients. D-dimer and FDP levels progressively elevated consistent with COVID-2019 exacerbation. Four patients were diagnosed with disseminated intravascular coagulation (DIC) . Low molecular weight heparin (LMWH) was administrated in 6 patients, which reduced D-dimer and FDP rather than improved clinical symptoms. Five patients died finally and the median time from acro-ischemia to death was 12 days. Conclusions: Coagulation parameters should be monitored closely in critical COVID-2019 patients. The timing and protocol of anticoagulation therapy are still under investigation based on more clinical data.

Digital Ischemia in COVID-19 Patients: Case Report.

As coronavirus 2019 (COVID-19) continues to cause an immense burden on the global health care systems, it is crucial to understand the breadth of this disease process. Recent reports identified hypercoagulability in a subset of critically ill patients and extremity ischemia in an even smaller cohort. Because abnormal coagulation parameters and extremity ischemia have been shown to correlate with poor disease prognosis, understanding how to treat these patients is crucial. To better describe the identification and management of this phenomenon, we present 2 cases of critically ill patients with COVID-19 who developed fingertip ischemia while in the intensive care unit.