Lower Limb Weakness due to Spinal Venous Congestion in Chronic Inferior Vena Cava Occlusion: A Case Report.

CASE REPORT: A 31 year-old male presented with a long history of reduced sensation and motor function in his lower limbs upon waking every morning, lasting 30-50 minutes during which he was unable to ambulate. He was involved in a severe road traffic accident as a child, and was born prematurely requiring prolonged neonatal hospitalisation. Both duplex ultrasonography and magnetic resonance venography identified an occlusion of the IVC, with patent common femoral and iliac veins draining into large spinal collaterals. No other cause was identified for his symptoms. After appropriate multidisciplinary team discussion and patient counselling, the patient proceeded to have endovenous recanalization of his IVC and common iliac veins with dedicated venous stents. Post-operatively, the patient reported an immediate resolution of neurological symptoms, with an improvement in quality of life questionnaire scores and with stent patency at 9-month follow up. CONCLUSION: IVC occlusion with symptomatic spinal venous congestion is a rare condition which may be successfully treated with endovascular iliocaval recanalization, although long-term outcomes of this treatment are still unknown.

Clinical outcomes and the impact of prior oral anticoagulant use in patients with coronavirus disease 2019 admitted to hospitals in the UK - a multicentre observational study.

Coagulation dysfunction and thrombosis are major complications in patients with coronavirus disease 2019 (COVID-19). Patients on oral anticoagulants (OAC) prior to diagnosis of COVID-19 may therefore have better outcomes. In this multicentre observational study of 5 883 patients (≥18 years) admitted to 26 UK hospitals between 1 April 2020 and 31 July 2020, overall mortality was 29·2%. Incidences of thrombosis, major bleeding (MB) and multiorgan failure (MOF) were 5·4%, 1·7% and 3·3% respectively. The presence of thrombosis, MB, or MOF was associated with a 1·8, 4·5 or 5·9-fold increased risk of dying, respectively. Of the 5 883 patients studied, 83·6% (n = 4 920) were not on OAC and 16·4% (n = 963) were taking OAC at the time of admission. There was no difference in mortality between patients on OAC vs no OAC prior to admission when compared in an adjusted multivariate analysis [hazard ratio (HR) 1·05, 95% confidence interval (CI) 0·93-1·19; P = 0·15] or in an adjusted propensity score analysis (HR 0·92 95% CI 0·58-1·450; P = 0·18). In multivariate and adjusted propensity score analyses, the only significant association of no anticoagulation prior to diagnosis of COVID-19 was admission to the Intensive-Care Unit (ICU) (HR 1·98, 95% CI 1·37-2·85). Thrombosis, MB, and MOF were associated with higher mortality. Our results indicate that patients may have benefit from prior OAC use, especially reduced admission to ICU, without any increase in bleeding.

Pulmonary thrombosis in Covid-19: before, during and after hospital admission.

Disordered coagulation, endothelial dysfunction, dehydration and immobility contribute to a substantially elevated risk of deep venous thrombosis, pulmonary embolism (PE) and systemic thrombosis in coronavirus disease 2019 (Covid-19). We evaluated the prevalence of pulmonary thrombosis and reported RV (right ventricular) dilatation/dysfunction associated with Covid-19 in a tertiary referral Covid-19 centre. Of 370 patients, positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 39 patients (mean age 62.3 ± 15 years, 56% male) underwent computed tomography pulmonary angiography (CTPA), due to increasing oxygen requirements or refractory hypoxia, not improving on oxygen, very elevated D-dimer or tachycardia disproportionate to clinical condition. Thrombosis in the pulmonary vasculature was found in 18 (46.2%) patients. However, pulmonary thrombosis did not predict survival (46.2% survivors vs 41.7% non-survivors, p = 0.796), but RV dilatation was less frequent among survivors (11.5% survivors vs 58.3% non-survivors, p = 0.002). Over the following month, we observed four Covid-19 patients, who were admitted with high and intermediate-high risk PE, and we treated them with UACTD (ultrasound-assisted catheter-directed thrombolysis), and four further patients, who were admitted with PE up to 4 weeks after recovery from Covid-19. Finally, we observed a case of RV dysfunction and pre-capillary pulmonary hypertension, associated with Covid-19 extensive lung disease. We demonstrated that pulmonary thrombosis is common in association with Covid-19. Also, the thrombotic risk in the pulmonary vasculature is present before and during hospital admission, and continues at least up to four weeks after discharge, and we present UACTD for high and intermediate-high risk PE management in Covid-19 patients.

A 10-fold and greater increase in D-dimer at admission in COVID-19 patients is highly predictive of pulmonary embolism in a retrospective cohort study.

BACKGROUND: COVID-19 patients present with both elevated D-dimer and a higher incidence of pulmonary embolism (PE). This single-centre retrospective observational study investigated the prevalence of early PE in COVID-19 patients and its relation to D-dimer at presentation. METHODS: The study included 1038 COVID-19-positive patients, with 1222 emergency department (ED) attendances over 11 weeks (16 March to 31 May 2020). Computed tomography pulmonary angiogram (CTPA) for PE was performed in 123 patients within 48 h of ED presentation, of whom 118 had D-dimer results. The remaining 875 attendances had D-dimer performed. RESULTS: CTPA performed in 11.8% of patients within 48 h of ED presentation confirmed PE in 37.4% (46/123). Thrombosis was observed at all levels of pulmonary vasculature with and without right ventricular strain. In the CTPA cohort, patients with PE had significantly higher D-dimer, prothrombin time, C-reactive protein, troponin, total bilirubin, neutrophils, white cell count and lower albumin compared with non-PE patients. However, there was no difference in the median duration of inpatient stay or mortality. A receiver operator curve analysis demonstrated that D-dimer could discriminate between PE and non-PE COVID-19 patients (area under the curve of 0.79, p < 0.0001). Furthermore, 43% (n = 62/145) of patients with D-dimer >5000 ng/ml had CTPA with PE confirmed in 61% (n = 38/62), that is, 26% of >5000 ng/ml cohort. The sensitivity and specificity were related to D-dimer level; cutoffs of 2000, 3000, 4000, and 5000 ng/ml, respectively, had a sensitivity of 93%, 90%, 90% and 86%, and a specificity of 38%, 54%, 59% and 68%, and if implemented, an additional 229, 141, 106 and 83 CTPAs would be required. CONCLUSION: Our data suggested an increased PE prevalence in COVID-19 patients attending ED with an elevated D-dimer, and patients with levels >5000 ng/ml might benefit from CTPA to exclude concomitant PE.

Management of acute and chronic iliofemoral venous outflow obstruction: a multidisciplinary team consensus.

The aim of this manuscript was to establish a consensus for the management of acute and chronic venous obstruction among specialists in the UK. Specialist physicians representing vascular surgery, interventional radiology and hematology were invited to 3 meetings to discuss management of acute and chronic iliofemoral obstruction. The meetings outlined controversial areas, included a topic-by-topic review; and on completion reached a consensus when greater than 80% agreement was reached on each topic. Physicians from 19 UK hospitals agreed on treatment protocols and highlighted areas that need development. Potential standard treatment algorithms were created. It was decided to establish a national registry of venous patients led by representatives from the treating multidisciplinary teams. Technical improvements have facilitated invasive treatment of patients with acute and chronic venous obstruction; however, the evidence guiding treatment is weak. Treatment should be conducted in centers with multi-disciplinary input; robust, coordinated data collection; and regular outcome analysis to ensure safe and effective treatment and a basis for future evolvement.

Prothrombin Complex Concentrates for Coagulopathy in Liver Disease: Single-Center, Clinical Experience in 105 Patients.

Patients with liver disease frequently develop coagulopathy, and fresh frozen plasma is traditionally used for correction of coagulopathy to manage and prevent bleeding. Prothrombin complex concentrates (PCCs) offer an attractive alternative because they are more readily available and avoid large-volume transfusion. This retrospective, single-center study reviewed clinical use of PCC in patients with acute/chronic liver disease. A total of 105 patients with 194 episodes of PCC administration were reviewed. Data pertaining to indication, dosing, effectiveness, and safety were collected. The effect of PCC on coagulation was analyzed in patients for whom coagulation results were available 7 hours before and after PCC. Data on thromboembolic events and mortality within 4 weeks of PCC administration were captured. Most patients (77%) had chronic liver disease; the remainder had acute liver failure. Indications for PCC were preprocedure prophylaxis and treatment for active/recent bleeding in 48% and 52% of 194 treatment episodes, respectively. The median dose of PCC administered was 22 IU/kg (interquartile range, 16-29 IU/kg). Before PCC administration, 45% of patients had an international normalized ratio (INR) greater than 2.0, and 36% had fibrinogen levels of at least 1.5 g/L. PCC produced statistically significant reductions in prothrombin time and INR (coadministration with fibrinogen or cryoprecipitate: 3.1 versus 1.9; P < 0.001; no coadministration: 2.3 versus 1.8; P < 0.001). Three patients with multiple risk factors developed thrombotic events (hepatic artery thrombosis, incidental bilateral pulmonary embolism, nonocclusive portal vein thrombosis); there were no cardiovascular or cerebrovascular adverse events. Overall, 46 patients died of causes unrelated to PCC treatment. Conclusion: In patients with liver disease, PCC therapy was effective in improving coagulation test results without an excess of thrombotic events. Further assessment of PCC as hemostatic therapy in this setting is required.

Anticoagulation after Iliofemoral Vein Stenting - Old Versus New.

In recent years, there has been an increasing interest in endovascular iliofemoral vein stenting to prevent/ alleviate symptoms related to proximal venous outflow obstruction. Maintaining long-term stent patency is one of the main challenges, and risk factors for the development of re-thrombosis are not well understood. Published data on the safety and efficacy of the procedure predominantly come from cohort studies mainly focusing on mechanical aspects relating to stent placement and flow. Aetiology of thrombus formation and thrombotic tendencies of patients due to underlying medical conditions are not captured well or linked to clinical outcomes, and the impact of choice and length of antithrombotic therapy have not been specifically investigated. Here, we review different procedure-related factors and patient characteristics that might increase the risk of re-thrombosis and the utility of antithrombotic treatment options currently available.

Review of recombinant anti-haemophilic porcine sequence factor VIII in adults with acquired haemophilia A.

Acquired haemophilia A (AHA) is a rare, serious bleeding disorder most often encountered in elderly patients. The mainstay of haemostatic management is with bypassing agents (BPAs) including recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrates (aPCCs). Their major limitation is incomplete efficacy, potential risk for thrombosis and the lack of routine laboratory assays for monitoring treatment response. Plasma-derived porcine FVIII (pd-pFVIII, Hyate C®), first used in the 1950s for the management of congenital haemophilia, has sufficient sequence homology to be haemostatic in humans, but the lack of complete homology facilitates efficacy even in the presence of human allo- and autoantibodies against human FVIII (hFVIII). In a small phase II/III study, recombinant porcine FVIII (rpFVIII, Obizur®, OBI-1, susoctocog alfa) was shown to be safe and effective for the management of bleeding episodes in patients with AHA with anti-porcine FVIII (anti-pFVIII) antibody levels of 20 BU/ml or less. Treatment outcome was judged on clinical response and FVIII levels after an initial fixed dose of 200 IU/kg. The rise in FVIII levels showed considerable inter-individual variability and was significantly influenced by the presence of anti-pFVIII antibodies. Based on the baseline levels of anti-pFVIII antibodies and response to treatment, three potential patient groups were identifiable. In the first group, the absence of cross-reacting antibodies was associated with supra-therapeutic FVIII levels, fewer infusions and lower rpFVIII utilization per treatment episode. The second group had patients with low levels of cross-reacting anti-pFVIII antibodies (0.8-5 BU/ml) with near-normal response to rpFVIII. The last group had higher titres of anti-pFVIII antibody (10-30 BU/ml) associated with lower FVIII levels, more infusions and higher consumption of rpFVIII. We propose a new treatment algorithm for the haemostatic management of AHA that includes the potential first-line clinical use of rpFVIII that takes into account availability of anti-pFVIII antibody results, titre of anti-pFVIII antibodies and severity of bleeding episode.

Antiplatelet Treatment in Peripheral Arterial Disease: The Role of Novel Antiplatelet Agents.

BACKGROUND: Acetylsalicylic acid and clopidogrel are two antiplatelet agents currently used in the therapy of peripheral arterial disease. Cilostazol also inhibits platelet aggegration. These agents present limitations that novel antiplatelet agents may overcome. OBJECTIVE: The aim of this manuscript is to review current data on the use of novel antiplatelet agents in peripheral arterial disease. METHOD: An extensive search in the English medical literature has yielded a number of publications on a number of novel antiplatelet agents; atopaxar, vorapaxar, cangrelor, ticagrelor, elinogrel, and prasugrel. RESULTS: Data on atopaxar, vorapaxar, cangrelor, ticagrelor, elinogrel and prasugrel come mainly from cardiology publications. Limitations, side effects and effectiveness of each of these agents are studied, but their use in peripheral arterial disease is limited, especially for those agents that have not still been approved for this indication. As expected, main side effect of most of these agents is haemorrhage, but other important side effects limit the use of some of these agents in specific subgroups of patients. CONCLUSION: Novel antiplatelet agents demonstrate a range of promising characteristics, but further study and clinical trials are necessary for them to be considered safe and effective.