Patients with COVID-19 have a coagulopathy and high thrombotic risk. In a cohort of 69 intensive care unit (ICU) patients we investigated for evidence of heparin resistance in those that have received therapeutic anticoagulation. 15 of the patients have received therapeutic anticoagulation with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH), of which full information was available on 14 patients. Heparin resistance to UFH was documented in 8/10 (80%) patients and sub-optimal peak anti-Xa following therapeutic LMWH in 5/5 (100%) patients where this was measured (some patients received both anticoagulants sequentially). Spiking plasma from 12 COVID-19 ICU patient samples demonstrated decreased in-vitro recovery of anti-Xa compared to normal pooled plasma. In conclusion, we have found evidence of heparin resistance in critically unwell COVID-19 patients. Further studies investigating this are required to determine the optimal thromboprophylaxis in COVID-19 and management of thrombotic episodes. Keywords Thrombosis • Intensive care • COVID-19 • Heparin Highlights• Heparin resistance with unfractionated heparin or suboptimal anti-Xa peak with low molecular weight heparin appeared common in COVID-19 intensive care unit patients that received therapeutic anticoagulation. • In-vitro spiking of COVID-19 samples from patients in intensive care unit with low molecular weight heparin failed to recover the anti-Xa level as would have been predicted. • COVID-19 patients have high factor VIII and fibrinogen with low antithrombin which could contribute to the picture seen. • Further studies are needed to confirm our findings and also describe the mechanism of heparin resistance in these patients as well as optimal management of thrombosis in COVID-19.

Key points• During cardiac contraction, left ventricular (LV) mechanics play an important role in equalising transmural fibre stress and ensuring efficient ejection of blood.• The factors responsible for altered LV mechanics in humans with high aerobic exercise capacity are unknown but are believed to be related to changes in LV structure or heart rate.• We performed a comprehensive assessment of LV mechanics and cardiovascular function at rest and during dynamic exercise in individuals with moderate and high aerobic exercise capacity.• Our novel data indicate that there is no direct association between altered LV mechanics in humans with high aerobic fitness and classic indicators of cardiovascular adaptation.• The findings provide evidence of a previously unknown type of physiological LV adaptation that may have important implications for exercise training in various healthy and diseased populations.Abstract Individuals with high aerobic fitness have lower systolic left ventricular strain, rotation and twist ('left ventricular (LV) mechanics') at rest, suggesting a beneficial reduction in LV myofibre stress and more efficient systolic function. However, the mechanisms responsible for this functional adaptation are not known and the influence of aerobic fitness on LV mechanics during dynamic exercise has never been studied. We assessed LV mechanics, LV wall thickness and dimensions, central augmentation index (AIx), aortic pulse wave velocity (aPWV), blood pressure and heart rate in 28 males (age: 21 ± 2 years SD) with a consistent physical activity level (no change >6 months). Individuals were examined at rest and during exercise (40% peak exercise capacity) and separated post hoc into a moderate and high aerobic fitness group (V O 2 peak : 49 ± 5 and 63 ± 7 ml kg −1 min −1 , respectively, P < 0.0001). At rest and during exercise, there were no significant differences in gross LV structure, AIx, blood pressure or heart rate (P > 0.05). However, for the same AIx, the highV O 2 peak group had significantly lower LV apical rotation (P = 0.002) and LV twist (P = 0.003) while basal rotation and strain indices did not differ between groups (P > 0.05). We conclude that young males with high aerobic fitness have lower LV apical rotation at rest and during submaximal exercise that can occur without changes in gross LV structure, arterial haemodynamics or heart rate. The findings suggest a previously unknown type of physiological adaptation of the left ventricle that may have important implications for exercise training in older individuals and patient populations in which exercise training has previously failed to show clear benefits for LV function.

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A single 1 g/kg dose of intravenous immunoglobulin is a safe and effective treatment for immune thrombocytopenia; results of the first HaemSTAR 'Flash-Mob' retrospective study incorporating 961 patients Key Messages 1 A one off 1 g/kg infusion of intravenous immunoglobulin (IVIg) may be as effective as two consecutive 1 g/kg doses. 2 This is the largest ever study of the efficacy of IVIg for immune thrombocytopenia (ITP). 3 There is poor adherence to the 2016 NHS England guidelines on IVIg dosing.

A 35-year-old woman presented with a widespread petechial rash and pancytopenia. She underwent simultaneous pancreas and kidney transplantation for type 1 diabetes 8 years previously followed by a renal transplant 1 year prior to presentation, and was taking tacrolimus as long-term immunosuppression. The full blood count showed haemoglobin 97 g/L, platelet count 2×109/L and neutrophil count 0.22×109/L. Peripheral blood film examination confirmed genuine thrombocytopenia in the absence of any haemolytic or malignant features. Serological testing identified autoantibodies against all three blood lineages, consistent with a diagnosis of autoimmune pancytopenia. Treatment with steroids, intravenous immunoglobulins, romiplostim and mycophenolate mofetil achieved only fleeting remissions. Blood counts eventually normalised following the administration of rituximab and a change from tacrolimus to ciclosporin immunosuppression. Cytopenias are a well-recognised complication of post-transplantation care but we believe this to be the first reported case of autoimmune pancytopenia following solid organ transplantation. In this case report, we discuss the approach to investigation of haematological abnormalities post-transplant and the rationale for, and outcome of, the management of this rare case.