Acute lower limb ischemia caused by vaccine-induced immune thrombotic thrombocytopenia: focus on perioperative considerations for 2 cases.

BACKGROUND: ChAdOx1 nCoV-19 (AstraZeneca) and Ad26COV2.S (Johnson & Johnson/Janssen) adenoviral vector vaccines have been associated with vaccine-induced immune thrombotic thrombocytopenia (VITT). Arterial thrombosis and acute limb ischemia have been described in a minority of patients with VITT. These patients usually need a revascularization, but they potentially are at a higher risk of complications. Optimal perioperative care of patients undergoing vascular surgery in acute VITT is unknown and important considerations in such context need to be described. CASES PRESENTATIONS: We report 2 cases of VITT presenting with acute limb ischemia who needed vascular surgery and we describe the multidisciplinary team decisions for specific treatment surrounding the interventions. Both patients' platelet counts initially increased after either intravenous immune globulin (IVIG) or therapeutic plasma exchange (TPE). None received platelet transfusion. They both received argatroban as an alternative to heparin for their surgery. Despite persistent positivity of anti-platelet factor 4 (PF4) antibodies and serotonin-release assay with added PF4 (PF4-SRA) in both patients, only one received a repeated dose of IVIG before the intervention. Per- and post-operative courses were both unremarkable. CONCLUSION: In spite of persistent anti-PF4 and PF4-SRA positivity in the setting of VITT, after platelet count improvement using either IVIG or TPE, vascular interventions using argatroban can show favorable courses. Use of repeated IVIG or TPE before such interventions still needs to be defined.

Apixaban anti-Xa level monitoring in treatment of acute upper extremity deep vein thrombosis for patient on chronic hemodialysis: a case report.

BACKGROUND: Patients on dialysis are at higher risk of major bleeding and recurrent thrombosis creating acute venous thromboembolism (VTE) treatment challenges. DOACs represent an interesting option but there are concerns of bioaccumulation and increased bleeding risk. Anti-Xa trough levels may be used to monitor for bioaccumulation but there is little data. CASE PRESENTATION: We describe a case, a 51 yo female, 36 kg on hemodialysis with a provoked acute upper extremity deep vein thrombosis in whom body habitus and calciphylaxis contraindicated the use of standard therapy. She received apixaban 2.5 mg twice daily for 6 weeks. The apixaban anti-Xa trough levels were measured weekly 12 h after the morning dose and ranged from 58 to 84 ng/mL, similar to expected levels with normal renal function. There were no adverse events in the 3 months follow-up. CONCLUSIONS: We saw no evidence of bioaccumulation indicating a potential role for low dose apixaban for acute VTE in dialysis patients.

Persisting autoimmune heparin-induced thrombocytopenia after elective abdominal aortic aneurysm repair: a case report.

Persisting heparin-induced thrombocytopenia (HIT) is characterized by ongoing thrombocytopenia more than 7 days after stopping heparin. It is part of cases referred to as autoimmune HIT (aHIT). In contrast to typical HIT cases, aHIT involves heparin-independent platelet activation mechanism highlighted by a strongly positive functional assay done without heparin. We report the first case of persisting HIT after an elective abdominal aortic aneurysm repair presenting with arterial and venous thrombosis, and describe the potential role of intravenous immunoglobulin in such patients.

Long VITT: A case report.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) has been described following adenovirus vector-based COVID-19 vaccines. This condition is associated with important morbidity and mortality following thrombosis related complications. Diagnosis is confirmed based on results of platelet factor 4 ELISA detecting anti-PF4 antibodies and of platelet-activation assay. Initial treatment strategy has been established but long-term management and follow up remain unclear. Most platelet-activation tests become negative after 12 weeks. We describe a case of VITT which can now be characterized as long VITT. The patient initially had a lower limb ischemia, pulmonary embolism and cerebral vein thrombosis. He was treated with prednisone, intravenous immunoglobulin, argatroban and had a lower limb revascularization surgery. Rivaroxaban was then initiated for the acute treatment and continued for the secondary prevention of recurrent events. The patient still demonstrates positive platelet-activation tests and thrombocytopenia after more than 18 months of follow-up. No recurrent thrombosis or bleeding event have occurred. He is not known for any relevant past medical history other than alcohol consumption and slight thrombocytopenia (130 × 109/L since 2015). It is unclear if the ongoing and more important thrombocytopenia could be explained by the persistent platelet-activating anti-PF4 antibodies or the patient's habits. Managing long VITT is challenging considering uncertainty regarding risks and benefits of long-term anticoagulation and potential needs of additional treatment. Additional data is needed to offer optimal long-term management for this patient population. We suggest that long VITT diagnosis definition might include the persistence within patient serum/plasma of anti-PF4 platelet-activating antibodies with clinical manifestations (e.g., thrombocytopenia) for more than 3 months.

Prolonged Fasting as a Cause of Deep Vein Thrombosis: A Case Report.

Background Intermittent fasting is becoming more popular as health benefits are described in recent literature. Various forms of fasting exist, one of them involving a zero-calorie diet and drinking only water. However, the safety of water-only fasting is still not well established. We report a case of a man who developed a lower limb deep vein thrombosis at the end of a 2-week water-only fasting and characterized by an initial period of 5 days of no food and no water intake. We reviewed literature regarding potential links between fasting and venous thromboembolism (VTE). Clinical Approach We believe that fasting can induce important dehydration, leading to hypercoagulability and then contribute to the development of a venous thrombosis. The patient was treated with apixaban for 3 months as is recommended in patients with a provoked event caused by a transient risk factor. No thrombotic recurrence was observed during the 6-month follow-up. Conclusion The public needs to be aware of the potential life-threatening complications associated with important dehydration in the setting of medically unsupervised fasting, and these might include VTE. Whether a VTE with dehydration as the only identified risk factor should be approached as a low recurrence risk situation or not still needs to be clarified.

A unique presentation of NLRP3-associated autoinflammatory disease: case report.

BACKGROUND: NLRP3-associated autoinflammatory diseases (NLRP3-AID) are rare genetic autoinflammatory diseases characterized by chronic inflammation and an urticaria-like rash. We report an unusual presentation of severe NLRP3-AID resulting in a significant diagnostic delay of more than three decades. CASE PRESENTATION: The patient presented with early-onset serositis as well as prominent peripheral eosinophilia with organ infiltration, in the absence of the classic urticaria-like rash. DNA analysis by next generation sequencing revealed a sporadic class 4 mutation c.1991T > C (p.Met662Thr) in the NLRP3 gene, confirming a diagnosis of NLRP3-AID at 36 years old. Although treatment with anti-interleukin 1 agent led to clinical remission, irreversible sequelae, namely intellectual disability and deafness, remained. CONCLUSION: This case highlights unique manifestations of NLRP3-AID, namely the absence of urticaria-like rash, eosinophilic organ infiltration, and pseudoseptic serositis. In order to avoid diagnostic delay and its dire consequences, NLRP3-AID should be suspected in patients displaying autoinflammatory features combined with serum and tissue eosinophilia and/or marked serositis, regardless of skin involvement.

Challenging anticoagulation cases: A case of incidental subsegmental pulmonary embolism in a patient with cancer.

Cancer therapy and progress in quality of imaging technologies for cancer surveillance and staging are in cause for the increase incidence of smaller incidental pulmonary embolism (PE). The clinical significance of incidental subsegmental pulmonary embolism (SSPE) is hard to define, balancing between possible false positive result, hypercoagulability signal, and truly venous thromboembolism (VTE) event. Evidence for optimal management of such findings are largely extrapolated from symptomatic SSPE in non-cancer patients and from symptomatic, more proximal PE in cancer patients. Current practice guidelines vary but some suggest withholding anticoagulation in selected patients. However, most SSPEs, incidental or not, should be treated as any other cancer-associated PE due to likely similar prognosis. Choice and duration of anticoagulation are extended from existing knowledge on more proximal PE.

How to manage patients with symptomatic subsegmental pulmonary embolism?

Advances in modalities for the diagnosis of pulmonary embolism (PE) have led to a rise in the incidence of this disease. Some studies report a decrease in the case­fatality rate of PE with no changes in the mortality rate, suggesting potential overdiagnosis. A growing number of diagnoses of less severe, smaller PE (ie, perfusion defects affecting pulmonary arteries of smaller caliber) of unknown clinical significance may potentially explain this phenomenon. Potentially higher rates of false-positive results are also an important matter of clinical concern. Only low-quality evidence suggested that subsegmental PE may be safely managed without initiating anticoagulation. Based on an individualized risk-benefit ratio, current clinical practice guidelines suggest that a selected group of patients with subsegmental PE, deemed to be at low risk of recurrence and without concomitant deep vein thrombosis detected by serial bilateral leg ultrasound, might benefit from clinical surveillance instead of anticoagulation. This approach is currently assessed in an ongoing prospective cohort study.

Scientific impact increases when researchers publish in open access and international collaboration: A bibliometric analysis on poverty-related disease papers.

BACKGROUND: The European & Developing Countries Clinical Trials Partnership (EDCTP), like many other research funders, requires its grantees to make papers available via open access (OA). This article investigates the effect of publishing in OA journals and international collaboration within and between European and sub-Saharan African countries on citation impact and likelihood of falling into the top 1% and top 10% most cited papers in poverty-related disease (PRD) research. METHODS: Disease-specific research publications were identified in the Web of Science™ and MEDLINE using Medical Subject Heading (MeSH) terms. Data on the open accessibility of scientific literature were derived from 1science oaFindr. Publication data, including relative citation counts, were extracted for 2003-2015. Regression models were applied to quantify the relationship between relative citations and presence in the 1% and top 10% most cited papers versus OA and international collaboration. RESULTS: The results show that since 2003 papers on PRDs have become increasingly available in OA. Among all PRD areas, malaria research is most frequently published in OA and in international collaboration. The adjusted regression analyses show that holding other factors constant, publishing research in OA and in international collaboration has a significant and meaningful citation advantage over non-OA or non-international collaborative research. Publishing papers as part of a European-wide or European- sub-Saharan African collaboration increases research impact. In contrast, such collaboration advantage is not observed for research output involving sub-Saharan Africa only which seems to decrease research impact. CONCLUSIONS: Our results indicate that there is a real, measurable citation advantage for publishing PRD research in OA and international collaboration. However, the international collaboration advantage seems to be region-specific with increased research impact for European-wide and European-sub-Saharan African collaborations but a decrease in research impact of collaborations confined to sub-Saharan African research institutions. Further research is required to further verify this finding and to understand the underlying factors related to this observed decrease in research impact. To target future research capacity building activities in sub-Saharan Africa it is important to assess whether the observed decreased impact reflects the scientific competencies and geographic distribution of individual researchers or institutional-, national- or funder-specific research requirements.