COVID-19 and acute limb ischemia: a systematic review.

INTRODUCTION: The main goal of this systematic review was to analyze the outcomes of acute limb ischemia (ALI) in patients suffering from the novel Coronavirus: COVID-19 (SARS-CoV-2). EVIDENCE ACQUISITION: A systematic review on Medline and Embase was conducted up to May 15, 2021. All papers were sorted by abstract and full text by two independent authors. Systematic reviews, commentaries, and studies that did not distinguish status of COVID-19 infection were excluded from review. Patient demographics were recorded along with modality of treatment (endovascular and/or surgical). We analyzed 30-day outcomes, including mortality. Primary outcome was to evaluate clinical characteristic of ALI in patients affected by SARS-CoV-2 in term of location of ischemia, treatment options and 30-day outcomes. EVINDENCE SYNTHESIS: We selected 36 articles with a total of 194 patients. Most patients were male (80%) with a median age of 60 years old. The treatment most used was thromboembolectomy (31% of all surgical interventions). A total of 32 patients (19%) were not submitted to revascularization due to critical status. The rate of technical success was low (68%), and mortality rate was high (35%). CONCLUSIONS: This review confirms that SARS-CoV-2 is associated with a high risk of ALI. Further studies are needed to investigate the association and elucidate potential mechanisms, which may include a hypercoagulable state and hyperactivation of the immune response. Furthermore, management of ALI is not standardized and depends on patient condition and extension of the thrombosed segment. ALI in COVID-19 patients is associated with high risk of failure of revascularization and perioperative mortality.

COVID-19 and aortic disease: a practical systematic review of the literature on management and outcomes.

INTRODUCTION: Since the outbreak of the 2019 coronavirus (COVID-19), vascular specialists have faced dramatic changes in clinical and surgical practice. Although COVID-19 pulmonary signs and symptoms were the most pertinent problems initially, in the long term, cardiovascular complications became the most fearsome, with poor outcomes in terms of morbidity and mortality. Algorithms and decision-making procedures have been modified, not only to treat new clinical findings in COVID-19 positive patients, but also to avoid complications related to pulmonary and systemic infections. Additionally, COVID-19-negative patients experienced challenging management, due to hospital crowding, the risk of nosocomial COVID-19 transmission, and pandemic emergencies. In this context, aortic interventions were subject to several difficulties. First, in COVID-19-positive patients, there was the onset of new pathological scenarios including thrombotic manifestations and the subsequent complications. Second, in both COVID-19-negative and positive patients, there was a need to deliver optimal treatment with acceptable perioperative risks, forcing a rethinking of decision-making especially in terms of indications for treatments. The aim of this systematic review is to present evidence published on COVID-19 and aortic-related issues, highlighting some challenging aspects regarding management, treatment and outcomes. EVIDENCE ACQUISITION: Data search was performed on PubMed, Scopus and Web of Science, using as time range "January 1st, 2000 - May 1st, 2021." Only articles in English language were included. Key words used for the query were "Aorta" AND "COVID-19" OR "SARS-CoV-2." Furthermore, the NCBI database of "SARS-CoV-2 Resources" was interrogated to find further relevant studies. EVIDENCE SYNTHESIS: The search retrieved 416 papers; among these, 46 studies were eligible and reviewed in depth. The published literature suggests the existence of a hypercoagulable state in patients with COVID-19 disease occurring via direct and indirect mechanisms. COVID-19 infection seems to promote a prothrombotic status that aggravates vascular disease. Regardless of clinical laboratory or status, active COVID-19 infection is considered a risk factor for poor vascular surgery outcomes. Specifically, it is associated with a fourfold increased risk of death and a threefold increased risk of major adverse events. Prognosis of patients hospitalized with COVID-19 disease is often determined by the extent of pulmonary disease, although vascular complications also greatly affect outcomes. Nevertheless, although COVID­19 is highly morbid, in high­risk operations good outcomes can still be achieved even in elderly patients with COVID­19. CONCLUSIONS: In the case of aortic disease during active COVID-19 infection, poor outcomes are associated with COVID-19 vascular and non-vascular complications, while for COVID-19-negative patients not much changed in terms of outcomes, despite the difficulties in management. Endovascular repair, when possible, minimized the impact of treatment, reducing the risk of COVID-related postoperative complications or acquired infection in negative patients.

Clinical Characteristics and Analysis of Lung Cancer- Associated Acute Ischemic Stroke.

INTRODUCTION: The incidence of lung cancer and acute ischemic stroke remains high in recent years, both of which occur mostly in people over 60 years old. In the present study, we aimed to further clarify the pathogenesis of lung cancer-associated acute ischemic stroke (LCA-AIS) by comparing and analyzing clinical characteristics of stroke patients with or without lung cancer. METHODS: A total of 51 patients with lung cancer were selected as the case group (LCSG), and 78 patients without cancer history were adopted as the control group (SG). The data collected in this study included sex, age, traditional cerebrovascular disease risk factors (TCDRFs), blood test index, imaging findings, etiological typing, and prognosis evaluation. SPSS21.0 software was used for statistical analysis. Normally distributed data were analyzed by t-test, and count data were analyzed by chi-square test or exact probability method. P < 0.05 was considered statistically significant. RESULTS: In the case group, the levels of plasma D-dimer, fibrinogen degradation products (FDPs) and NIHSS, as well as the mRS score and mortality of patients, were higher, while the levels of RBC, Hb and Hcy were lower compared with the control group. Imaging findings showed that multivessel involvement was more common in the case group, and the infarcts were more likely to be multiple and involved in both the anterior and posterior circulations. The TOAST classification of LCSG was dominated by stroke of undetermined etiology (SUE) and stroke of other determined etiology (SOE). Statistical analysis showed that the patients were more likely to suffer from acute ischemic stroke within 1 year after the diagnosis of lung cancer (41 cases, 80.39%). CONCLUSIONS: Hypercoagulability and acute multiple brain infarcts were more common in patients with LCA-AIS, and hypoproteinemia and hyponatremia were more likely to occur in these patients, leading to worse prognosis. Patients were most likely to have a stroke within 1 year after the diagnosis of lung cancer.

Evaluation of coagulation function by rotation thromboelastometry in critically ill patients with severe COVID-19 pneumonia.

Critically ill patients with COVID-19 pneumonia suffered both high thrombotic and bleeding risk. The effect of SARS-CoV-2 on coagulation and fibrinolysis is not well known. We conducted a retrospective study of critically ill patients admitted to an intensive care unit (ICU) a cause of severe COVID-19 pneumonia and we evaluated coagulation function using rotational thromboelastometry (ROTEM) on day of admission (T0) and 5 (T5) and 10 (T10) days after admission to ICU. Coagulation standard parameters were also evaluated. Forty patients were enrolled into the study. The ICU and the hospital mortality were 10% and 12.5%, respectively. On ICU admission, prothrombin time was slightly reduced and it increased significantly at T10 (T0 = 65.1 ± 9.8 vs T10 = 85.7 ± 1.5, p = 0.002), while activated partial thromboplastin time and fibrinogen values were higher at T0 than T10 (32.2 ± 2.9 vs 27.2 ± 2.1, p = 0.017 and 895.1 ± 110 vs 332.5 ± 50, p = 0.002, respectively); moreover, whole blood thromboelastometry profiles were consistent with hypercoagulability characterized by an acceleration of the propagation phase of blood clot formation [i.e., CFT below the lower limit in INTEM 16/40 patients (40%) and EXTEM 20/40 patients (50%)] and significant higher clot strength [MCF above the upper limit in INTEM 20/40 patients (50%), in EXTEM 28/40 patients (70%) and in FIBTEM 29/40 patients (72.5%)]; however, this hypercoagulable state persists in the first five days, but it decreases ten day after, without returning to normal values. No sign of secondary hyperfibrinolysis or sepsis induced coagulopathy (SIC) were found during the study period. In six patients (15%) a deep vein thrombosis and in 2 patients (5%) a thromboembolic event, were found; 12 patients (30%) had a catheter-related thrombosis. ROTEM analysis confirms that patients with severe COVID-19 pneumonia had a hypercoagulation state that persisted over time.

Thrombophilic risk factors in hemodialysis: Association with early vascular access occlusion and patient survival in long-term follow-up.

OBJECTIVE: Thrombophilic risk factors (TRFs) occur rather frequently in hemodialysis (HD) patients. However, little is known about their significance in HD patients, besides their potential impact on arteriovenous (AV) access failure, with varying results. We examined the effects of a wide variety of TRFs on both early AV fistula occlusion and survival among HD patients in long-term follow-up. METHODS: In this single-center, observational study, 70 consecutive HD patients from our dialysis center were examined with respect to shunt occlusion within the first 2 years after fistula creation and patient survival in a long-term follow-up (at least 16 years). We examined the presence of factor V, prothrombin, and MTHFR mutations using real-time fluorescence polymerase chain reaction. Furthermore, antithrombin (AT), protein C, protein S, and antiphospholipid antibodies (APL-Abs) were assessed. RESULTS: Among the 70 patients, 32 had MTHFR mutations, 10 had heterozygous factor V Leiden mutations, 4 had prothrombin mutations, 4 had protein S deficiency, 2 had protein C deficiency, 9 had AT deficiency, and 14 had APL-Abs. 40 patients had shunt occlusion. TRFs were associated with a significantly increased risk for shunt thrombosis (P<0.02). Kaplan-Meier analysis with a log-rank test revealed significantly shorter survival in HD patients with TRFs (P<0.02). Cox regression analysis showed that the presence of TRFs (P<0.05; hazard ratio, 1.94; 95% CI: 1.07-3.56), but not early shunt occlusion, was associated with short patient survival. CONCLUSIONS: TRFs in hemodialysis patients have a strong impact on patient survival and early AV fistula failure; however, patient survival is not significantly affected by early shunt occlusion.

Role of inherited thrombophilic profile on survival of patients with sepsis.

The existence of various coagulation and/or fibrinolytic system disorders (such as inherited thrombophilia) in patients with sepsis could possibly modify host response to infection as well as patient outcome. The aim of the study is to investigate inherited thrombophilic profile in patients with sepsis. Eighty-three patients with sepsis admitted at the Department of Internal Medicine of the University General Hospital of Patras, Greece were included. Thrombophilic profile (factor V G1691A (Leiden), factor V H1299R (R2), prothrombin G20210A, MTHFR C677T, MTHFR A1298C, factor XIII V34L, ß-fibrinogen-455 G-A and plasminogen activator inhibitor (PAI)-1 4G/5G) was evaluated using the cardiovascular diseases (CVD) StripAssay based on DNA isolation, PCR and reverse hybridisation. Data were collected from patients' chart reviews. Seventy patients (84.3%) of the 83 enrolled had at least one thrombophilic mutation. The most common mutations were heterozygous for ß-fibrinogen-455 G-A (43.4%), heterozygous for factor XIII V34L (32.5%), PAI-1 4G/4G (26.5%), homozygous MTHFR C677T (22.9%), heterozygous factor V H1299R (R2) (13.3%) and homozygous MTHFR A1298C (12.0%). A 30-day mortality was 14.5%. Multivariate analysis revealed that mortality was independently associated with Simplified Acute Physiology Score II score on admission, pneumonia and fibrinogen on admission. Nine patients (10.8%) developed septic shock. Coagulation disorders on admission, bacteraemia and PAI-1 genotype 5G/5G were independently associated with development of septic shock. The presence of thrombophilic mutations in patients with sepsis may affect their clinical response, and future studies are needed in order to elucidate the role of isolated thrombophilic mutations in patients with sepsis or septic shock.

Association of Preoperative Hypercoagulability with Poor Prognosis in Hepatocellular Carcinoma Patients with Microvascular Invasion After Liver Resection: A Multicenter Study.

BACKGROUND: Microvascular invasion (MVI) predicts poor prognosis in patients with hepatocellular carcinoma (HCC). HCC patients with hypercoagulability are prone to develop thrombosis; however, the relationship between preoperative coagulability state, as reflected by the international normalized ratio (INR) level, and MVI remains unclear. METHODS: From January 2009 to December 2012, HCC patients who underwent R0 liver resection (LR) from four cancer centers entered into this study. The overall survival (OS) and recurrence-free survival (RFS) rates were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: Of the 2509 HCC patients who were included into this study, 1104 were found to have MVI in the resected specimens. These patients were divided into the low (n = 151), normal (n = 796), and high (n = 157) INR subgroups based on the preoperative INR levels. The low INR subgroup had a significantly higher incidence of MVI than the normal or high INR subgroups (61.6% vs. 41.6% vs. 44.6%; p < 0.001). HCC patients with MVI were significantly more likely to have a low preoperative INR level (p < 0.001); the INR level (p < 0.001) was an independent risk factor of OS and RFS. HCC patients with MVI in the low INR subgroup had significantly worse RFS and OS than the normal or high INR subgroups (median RFS 13.5 vs. 20.2 vs. 21.6 months, p < 0.001; median OS 35.5 vs. 59.5 vs. 57.0 months, p < 0.001). CONCLUSIONS: Preoperative hypercoagulability was associated with poor long-term prognosis in HCC patients with MVI after R0 LR.

Thrombelastography Suggests Hypercoagulability in Patients with Renal Dysfunction and Intracerebral Hemorrhage.

BACKGROUND: The objective of this study was to quantify coagulopathy using thrombelastography (TEG) in patients with renal dysfunction and intracerebral hemorrhage (ICH). METHODS: We reviewed patients admitted with spontaneous ICH between November 2009 and May 2015. TEG was performed at the time of admission. Creatinine clearance (CCr) was calculated using the Cockroft-Gault equation. Patients were divided into 2 groups based on normal (CCr ≥ 90) or reduced renal function (CCr < 90). Multivariable regression models were conducted to compare the differences of TEG components. RESULTS: A total of 120 patients were included in the analysis. The normal CCr group was younger (56.1 versus 62.3 years, P < .01), was more often male (73.6% versus 53.7%, P = .03), and had higher mean admission hemoglobin (14.2 versus 13.2 mEq/L, P < .01) than the reduced renal function group. The 2 groups were similar with respect to antiplatelet or anticoagulant use, coagulation studies, and baseline ICH volume. Following multivariate analysis, the reduced renal function group was found to have shorter K (1.5 versus 2.2 min, P = 004), increased angle (66 versus 62.2 degrees, P = .04), increased MA (67.3 versus 62.3, P = .02), and increased G (11.3 versus 9.9 dynes/cm2, P = .04) compared with the normal group. Mortality, poor functional outcome (modified Rankin Scale score 4-6), hematoma enlargement, hospital length of stay, and surgical interventions were not different between the 2 groups. CONCLUSIONS: Patients with ICH and reduced CCr display faster clotting rate and increased clot strength, suggesting that patients with renal dysfunction present with a relatively hypercoagulable state based on TEG parameters thought to reflect platelet activity.

Thrombosis after liver transplantation for hepatocellular carcinoma.

The influence of thrombosis on the prognosis of patients with hepatocellular carcinoma (HCC) after liver transplantation (LT) and the role of the commonest inherited thrombophilia abnormalities factor V Leiden and prothrombin G20210A in the development of thrombosis are unknown. We investigated a cohort of patients who underwent LT for HCC with the aim to estimate the incidence rate (IR) of thrombosis, its influence on mortality and re-transplantation rates and, in the frame of a nested case-control study, the role of thrombophilia in donors and recipients for the development of thrombosis. Four-hundred and thirty patients underwent LT and were followed for a median of 7.2 years. Twenty-six recipients (6%) developed thrombosis (IR 1.06 [95%CI: 0.71-1.53] per 100 pts-yr). Mortality rate after LT was 3.95 (95%CI: 3.22-4.79) per 100 pts-yr and was not influenced by thrombosis. Re-transplantation was planned for 33 patients and was more common in patients with thrombosis than in those without (HR 2.50 [95%CI: 0.87-7.17]). The risk of thrombosis was 4 times higher in recipients with thrombophilia than in those without (OR 4.23 [95%CI: 0.99-18.04]) and 6 times higher when the analysis was restricted to venous thrombosis (OR 6.26 [95%CI: 1.19-32.85]). The presence of inherited thrombophilia in the donors did not increase the risk of thrombosis of the recipient. In conclusion, thrombosis is a complication of 6% of patients transplanted for HCC and increases the risk of re-transplantation but not of mortality. The risk of thrombosis, particularly venous, is increased in the presence of thrombophilia abnormalities in the recipients.

Surgical Interventions for Organ and Limb Ischemia Associated With Primary and Secondary Antiphospholipid Antibody Syndrome With Arterial Involvement.

OBJECTIVE: The association of antiphospholipid antibody syndrome (APS) and hypercoagulability is well known. Arterial compromise leading to ischemia of organs and/or limbs in patients with APS is uncommon, frequently unrecognized, and rarely described. We evaluated our institutional experience. METHODS: Retrospective review was conducted. From August 2007 to September 2016, 807 patients with diagnosis of APS were managed in our Institution. Patients with primary and secondary APS who required interventions were examined. Demographics, comorbidities, manifestations, procedures, complications, and other factors affecting outcomes were recorded. RESULTS: Fourteen patients (mean age 35 years old, standard deviation ±14) were evaluated and treated by our service. Six (43%) of them had primary APS and 8 (57%) had secondary APS; 11 (79%) were female. Two (14%) experienced distal aorta and iliac arteries involvement, 3 (21%) visceral vessels disease, 2 (14%) in upper and 7 (50%) in the lower extremity vasculatures. Thirteen (93%) patients underwent direct open revascularization and 1 with hand ischemia (Raynaud disease) underwent sympathectomy. During the mean follow-up period of 48 months, reinterventions included a revision of the proximal anastomosis of an aortobifemoral bypass graft, 1 (7%) abdominal exploration for bleeding, 1 (7%) graft thrombectomy, and 4 (29%) amputations (2 below the knee, 1 above the knee, and 1 transmetatarsal). One (7%) death occurred secondary to sepsis in a patient who had acute mesenteric ischemia. Significant differences in clinical manifestations and outcomes were not observed among patients with primary and secondary APS. All patients remained on systemic anticoagulation. CONCLUSION: APS is a prothrombotic disorder that may lead to arterial involvement with less frequency than the venous circulation but has significant morbidity and limb loss rate. Arterial reconstruction seems feasible in an attempt to salvage organs and limbs; however, research is necessary to establish the optimal anticoagulation regime and long-term management following surgical interventions.