COVID-19 vaccination in patients with immune thrombocytopenia

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by low platelet count and increased bleeding risk. COVID-19 vaccination has been described as risk factor for de novo ITP, but the effects of COVID-19 vaccination in patients with ITP are unknown. Our aims were to investigate the effects of COVID-19 vaccination in ITP patients on platelet count, bleeding complications and ITP exacerbation (any of: ≥50% decline in platelet count; or nadir platelet count 20% decrease from baseline; or use of rescue therapy). Platelet counts of ITP patients and healthy controls were collected immediately before, 1 and 4 weeks after first and second vaccination. Linear mixed-effects modelling was applied to analyze platelet counts over time. We included 218 ITP patients (50.9% female, mean age 55 years and median platelet count of 106x109/L) and 200 healthy controls (60.0% female, mean age 58 years and median platelet count of 256x109/L). Platelet counts decreased by 6.3% after vaccination. We observed no difference in decrease between the groups. Thirty ITP patients (13.8%, 95%CI 9.5%-19.1%) had an exacerbation and 5 (2.2%, 95%CI 0.7%-5.3%) suffered from a bleeding event. Risk factors for ITP exacerbation were platelet count <50x109/L (OR 5.3, 95%CI 2.1-13.7), ITP treatment at time of vaccination (OR 3.4, 95%CI 1.5-8.0) and age (OR 0.96 per year, 95%CI 0.94-0.99). Our study highlights safety of COVID-19 vaccination in ITP patients and importance of close monitoring platelet counts in a subgroup of ITP patients. ITP patients with exacerbation responded well on therapy

A new population pharmacokinetic model for recombinant factor IX‐Fc fusion concentrate including young children with haemophilia B

Aims: Recombinant factor IX Fc fusion protein (rFIX‐Fc) is an extended half‐life factor concentrate administered to haemophilia B patients. So far, a population pharmacokinetic (PK) model has only been published for patients aged ≥12 years. The aim was to externally evaluate the predictive performance of the published rFIX‐Fc population PK model for patients of all ages and develop a model that describes rFIX‐Fc PK using real‐world data. Methods: We collected prospective and retrospective data from patients with haemophilia B treated with rFIX‐Fc and included in the OPTI‐CLOT TARGET study (NTR7523) or United Kindom (UK)‐EHL Outcomes Registry (NCT02938156). Predictive performance was assessed by comparing predicted with observed FIX activity levels. A new population PK model was constructed using nonlinear mixed‐effects modelling. Results: Real‐world data were obtained from 37 patients (median age: 16 years, range 2–71) of whom 14 were aged <12 years. Observed FIX activity levels were significantly higher than levels predicted using the published model, with a median prediction error of −48.8%. The new model showed a lower median prediction error (3.4%) and better described rFIX‐Fc PK, especially for children aged <12 years. In the new model, an increase in age was correlated with a decrease in clearance (P < .01). Conclusions: The published population PK model significantly underpredicted FIX activity levels. The new model better describes rFIX‐Fc PK, especially for children aged <12 years. This study underlines the necessity to strive for representative population PK models, thereby avoiding extrapolation outside the studied population

Congenital deficiency of the fibrinolysis - :Inhibitor alpha2 antiplasmin as the cause of a hemorrhage diathesis

In this article the clinical importance of α2-antiplasmin is demonstrated by presenting the history of a male aged 19 years suffering from α2-antiplasmin deficiency. In the literature 11 families with congenital α2-antiplasmin deficient members are reported, of which 5 families are Dutch. Information is given about the severe haemorrhagic tendency in these patients, and the difference from haemophilia is described in detail. Congenital α2-antiplasmin deficiency can be diagnosed with a simple enzymatic assay. Bleeding problems associated with α2-antiplasmin deficiency can be treated with fibrinolytic inhibitors such as epsilon aminocaproic acid and tranexamic acid (Cycklokapron).</p

Rhabdomyolysis associated with influenza A virus infection

Rhabdomyolysis is characterized by local or generalized skeletal muscle neclosis. It is caused by many clinical conditions and drug or alcohol abuse. Clinical symptoms are muscle pain and muscle weakness. Laboratory investigations show a rise in serum creatine phosphokinase and electrolyte disturbances. The most serious complication is acute renal failure. We present a patient with rhabdomyolysis and renal failure associated with a recent Influenza A virus infection.</p

Acute effect of pegvisomant on cardiovascular risk markers in healthy men: Implications for the pathogenesis of atherosclerosis in GH deficiency

Cardiovascular risk is increased in GH deficiency (GHD). GHD adults are frequently abdominally obese and display features of the metabolic syndrome. Otherwise healthy abdominally obese subjects have low GH levels and show features of the metabolic syndrome as well. We investigated in healthy nonobese males the effect of the GH receptor antagonist pegvisomant in different metabolic conditions. This is a model for acute GHD without the alterations in body composition associated with GHD. We compared the effect of pegvisomant with that of placebo before and after 3 d of fasting. In addition, we investigated the effect of pegvisomant under normal, i.e. fed, conditions. Three days of fasting as well as pegvisomant alone decreased serum free IGF-I levels (1.0 ± 0.15 vs. 0.31 ± 0.05 ng/ml and 0.86 ± 0.23 vs. 0.46 ± 0.23 ng/ml, respectively). Fasting in combination with pegvisomant also decreased serum free IGF-I levels (1.0 ± 0.15 vs. 0.31 ± 0.07 ng/ml), Treatment with pegvisomant had no additional influence on the decline of free IGF-I induced by fasting. Pegvisomant alone had no influence on insulin sensitivity. The increase in insulin sensitivity induced by fasting was comparable to the increase in insulin sensitivity induced by fasting combined with pegvisomant. Among serum lipid concentrations, only serum triglycerides increased significantly as a result of pegvisomant alone (1.0 ± 0.2 vs. 1.6 ± 0.4 mmol/liter). The changes in lipid concentrations induced by fasting alone or pegvisomant were not different from those induced by pegvisomant alone, von Wille-brand factor antigen levels declined significantly under the influence of pegvisomant alone (1.1 ± 0.07 vs. 0.8 ± 0.06 U/ml). In conclusion, in different metabolic conditions the GH receptor antagonist pegvisomant induces no significant acute changes in the major risk markers for cardiovascular disease. These data suggest that the secondary metabolic changes, e.g. abdominal obesity or inflammatory factors, that develop as a result of long-standing GHD are of primary importance in the pathogenesis of atherosclerosis in patients with GHD