Background Thirty percent of Covid‐19 patients admitted to intensive care units present with thrombotic complications despite thromboprophylaxis. Bed rest, obesity, hypoxia, coagulopathy, and acute excessive inflammation are potential mechanisms reported by previous studies. Better understanding of the underlying mechanisms leading to thrombosis is crucial for developing more appropriate prophylaxis and treatment strategies. Objective We aimed to assess fibrinolytic activity and thrombin generation in 78 Covid‐19 patients. Patients and Methods Forty‐eight patients admitted to the intensive care unit and 30 patients admitted to the internal medicine department were included in the study. All patients received thromboprophylaxis. We measured fibrinolytic parameters (tissue plasminogen activator, PAI‐1, thrombin activatable fibrinolysis inhibitor, alpha2 anti‐plasmin, and tissue plasminogen activator‐modified ROTEM device), thrombin generation, and other coagulation tests (D‐dimer, fibrinogen, factor VIII, antithrombin). Results and Conclusions We observed two key findings: a high thrombin generation capacity that remained within normal values despite heparin therapy and a hypofibrinolysis mainly associated with increased PAI‐1 levels. A modified ROTEM is able to detect both hypercoagulability and hypofibrinolysis simultaneously in Covid‐19 patients with thrombosis.

Erdheim-Chester disease (ECD) is a rare, non-Langerhans form of histiocytosis of unknown etiology that affects multiple organs. We report 6 cases of ECD with neurological involvement and neuroradiological abnormalities on brain MRI. A literature review revealed 60 other cases of ECD with neurological involvement. We therefore analyzed 66 ECD patients with neurological involvement. Cerebellar and pyramidal syndromes were the most frequent clinical manifestations (41% and 45% of cases), but seizures, headaches, neuropsychiatric or cognitive troubles, sensory disturbances, cranial nerve paralysis or asymptomatic lesions were also reported. Neurological manifestations were always associated with other organ involvement, especially of bones (at least 86%) and diabetes insipidus (47%). Neurological involvement was responsible for severe functional handicaps in almost all patients and was responsible for the death of 6 of the 66 patients (9%). Neuroradiological findings could be separated into three patterns: the infiltrative pattern (44%), with widespread lesions, nodules or intracerebral masses, the meningeal pattern (37%), with either thickening of the dura mater or meningioma-like tumors, and the composite pattern (19%), with both infiltrative and meningeal lesions.

Although low [HCQ] is associated with higher SLE activity, adapting the HCQ dose did not reduce SLE flares over a 7-month follow-up.

Objective Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations. Methods We conducted a retrospective analysis of patient data, including data from the Plaquenil Lupus Systemic (PLUS) study, to determine the association of epidemiologic, clinical, and biologic factors with blood HCQ concentrations. Data for nonadherent patients (blood HCQ concentration <200 ng/ml) were excluded. Results To examine homogeneous pharmacologic data, we restricted the analyses of the PLUS data to the 509 SLE patients receiving 400 mg/day. We found no association of ethnicity or smoking with blood HCQ concentrations and no pharmacokinetic drug–drug interaction with antacids or with inhibitors or inducers of cytochrome P450 enzymes. On multivariate analysis, high body mass index (P = 0.008), no treatment with corticosteroids (P = 0.04), increased time between the last tablet intake and measurement of blood HCQ concentrations (P = 0.017), low platelet count (P < 0.001), low neutrophil count (P < 0.001), and high estimated creatinine clearance (P < 0.001) were associated with low blood HCQ concentrations. In 22 SLE patients with chronic renal insufficiency (median serum creatinine clearance 52 ml/minute [range 23–58 ml/minute]) who received 400 mg/day HCQ, the median blood HCQ concentration was significantly higher than that in the 509 patients from the PLUS study (1,338 ng/ml [range 504–2,229 ng/ml] versus 917 ng/ml [range 208–3316 ng/ml]) (P < 0.001). Conclusion We provide a comprehensive analysis of determinants of blood HCQ concentrations. Because this measurement is increasingly being used, these data might be useful for clinicians.

NCT00748644.