Cases of unusual thrombosis and thrombocytopenia after administration of the ChAdOx1 nCoV‐19 vaccine (AstraZeneca) have been reported. The term vaccine‐induced prothrombotic immune thrombocytopenia (VIPIT) was coined to reflect this new phenomenon. In vitro experiments with VIPIT patient sera indicated that high‐dose intravenous immunoglobulins (IVIG) competitively inhibit the platelet‐activating properties of ChAdOx1 nCoV‐19 vaccine induced antibodies. Here, we report a case of a 62‐year‐old woman who had received this vaccine and developed VIPIT. She visited the emergency ward because of petechiae and hematomas. In the laboratory work‐up, thrombocytopenia, low fibrinogen, elevated D‐dimer, and positivity in the platelet factor 4/heparin‐enzyme‐immunoassay were present. Signs and symptoms of thrombosis were absent. Upon immediate therapy with non‐heparin anticoagulation, high‐dose IVIG, and prednisolone, laboratory parameters steadily improved and the patient was discharged from hospital without thrombotic complications. We conclude that early initiation of VIPIT treatment results in a swift response without thrombotic complications.
Background COVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19. Methods This systematic review was registered at PROSPERO under CRD42020177154. We systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31st 2020. Random-effects meta-analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies. Results Of 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10 mg/L, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49 U/L, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88 pg/mL, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 to 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73). Discussion This comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors that predict severe COVID-19 outcomes and will inform clinical scores to support early decision-making.
Aim: Prior studies suggest that the use of personal protective equipment might impair the quality of critical care. We investigated the influence of personal protective equipment on out-of-hospital cardiopulmonary resuscitation. Methods: Randomised controlled non-inferiority triple-crossover study. Forty-eight emergency medical service providers, randomized into teams of two, performed 12 min of basic life support (BLS) on a manikin after climbing 3 flights of stairs. Three scenarios were completed in a randomised order: Without personal protective equipment, with personal protective equipment including a filtering face piece (FFP) 2 mask with valve, and with personal protective equipment including an FFP2 mask without valve. The primary outcome was mean depth of chest compressions with a pre-defined non-inferiority margin of 3.5 mm. Secondary outcomes included other measurements of CPR quality, providers' subjective exhaustion levels, and providers' vital signs, including end-tidal CO 2. Results: Differences regarding the primary outcome were well below the pre-defined non-inferiority margins for both control vs. personal protective equipment without valve (absolute difference 1 mm, 95% CI [À1, 2]) and control vs. personal protective equipment with valve (absolute difference 1 mm, [À0.2, 2]). This was also true for secondary outcomes regarding quality of chest compressions and providers' vital signs including etCO 2. Subjective physical strain after BLS was higher in the personal protective equipment groups (Borg 4 (SD 3) without valve, 4 (SD 2) with valve) than in the control group (Borg 3 (SD 2)). Conclusion: PPE including masks with and without expiration valve is safe for use without concerns regarding the impairment of CPR quality.
Von Willebrand Factor (VWF) and Factor VIII (FVIII) circulate in a noncovalent complex in blood and promote primary haemostasis and clotting respectively. A new VWF A1-domain binding aptamer, BT200, demonstrated good subcutaneous bioavailability and a long half-life in non-human primates. This first-in-human, randomised, placebo-controlled, double-blind trial tested the hypothesis that BT200 is well tolerated and has favourable pharmacokinetic and pharmacodynamic effects in 112 volunteers. Participants received one of the following: Single ascending dose of BT200 (0.18-48mg) subcutaneously, an intravenous dose, BT200 with concomitant desmopressin or multiple doses. Pharmacokinetics were characterised, and the pharmacodynamic effects were measured by VWF levels, FVIII clotting activity, ristocetin induced aggregation, platelet function under high shear rates, and thrombin generation. Mean half-lives ranged from 7-12 days and subcutaneous bioavailability increased dosedependently exceeding 55% for doses of 6-48 mg. By blocking free A1 domains, BT200 dose-dependently decreased ristocetin-induced aggregation, and prolonged collagenadenosine diphosphate and shear-induced platelet plug formation times. However, BT200 also increased VWF antigen and FVIII levels 4-fold (p
Background The COVID-19 pandemic led to widespread use of personal protection equipment (PPE), including filtering face piece (FFP) masks, throughout the world. PPE. Previous studies indicate that PPE impairs neurocognitive performance in healthcare workers. Concerns for personnel safety have led to special recommendations regarding basic life support (BLS) in patients with a potential SARS-CoV-2 infection, including the use of PPE. Established instruments are available to assess attention and dexterity in BLS settings, respectively. We aimed to evaluate the influence of PPE with different types of FFP masks on these two neuropsychological components of EMS personnel during BLS. Methods This was a randomized controlled non-inferiority triple-crossover study. Teams of paramedics completed three 12-min long BLS scenarios on a manikin after having climbed three flights of stairs with equipment, each in three experimental conditions: (a) without pandemic PPE, (b) with PPE including a FFP2 mask with an expiration valve and (c) with PPE including an FFP2 mask without an expiration valve. The teams and intervention sequences were randomized. We measured the shift in concentration performance using the d2 test and dexterity using the nine-hole peg test (NHPT). We compared results between the three conditions. For the primary outcome, the non-inferiority margin was set at 20 points. Results Forty-eight paramedics participated. Concentration performance was significantly better after each scenario, with no differences noted between groups: d2 shift control versus with valve − 8.3 (95% CI − 19.4 to 2.7) points; control versus without valve − 8.5 (− 19.7 to 2.7) points; with valve versus without valve 0.1 (− 11.1 to 11.3) points. Similar results were found for the NHPT: + 0.3 (− 0.7 to 1.4), − 0.4 (− 1.4 to 0.7), 0.7 (− 0.4 to 1.8) s respectively. Conclusion Attention increases when performing BLS. Attention and dexterity are not inferior when wearing PPE, including FFP2 masks. PPE should be used on a low-threshold basis.
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