Iron prophylaxis in pregnancy—general or individual and in which dose?

Iron is mandatory for normal fetal development, including the brain. Iron deficiency may have deleterious effects for intelligence and behavioral development. It is important to prevent iron deficiency in the fetus by preventing iron deficiency in the pregnant woman. Iron deficiency anemia during pregnancy is a risk factor for preterm delivery and low birth weight. In the Western countries there is no consensus on iron prophylaxis to pregnant women. An adequate iron balance during pregnancy implies body iron reserves of ≥500 mg at conception. The physiologic iron requirements in the second half of gestation cannot be fulfilled solely through dietary iron. Iron supplements during gestation consistently increase serum ferritin and hemoglobin and reduce the prevalence of iron deficiency anemia. Iron has a negative influence on absorption of other divalent metals and increases oxidative stress in pregnancy, for which reason minimum effective iron dose should be advised. From a physiologic point of view, individual iron prophylaxis according to serum ferritin concentration should be preferred to general prophylaxis. Suggested guidelines are (1) ferritin >70 μg/l: no iron supplements; (2) ferritin 30–70 μg/l: 40 mg ferrous iron daily; and (3) ferritin <30 μg/l: 80–100 mg ferrous iron daily. In controlled studies, there are no documented side effects of iron supplements below 100 mg/day. Iron supplements should be taken at bedtime or between meals to ensure optimum absorption.     

Platelet aggregation according to body mass index in patients undergoing coronary stenting: should clopidogrel loading-dose be weight adjusted?

BACKGROUND: A 300 mg clopidogrel loading-dose (LD) is widely used as an adjunct antithrombotic treatment to reduce the risk of thrombotic events early after coronary stenting (CS). Antithrombotic drugs commonly used during percutaneous coronary interventions, such as heparin and platelet glycoprotein IIb/IIIa inhibitors, but not clopidogrel LD, are weight-adjusted, and few data are available on which is the most effective clopidogrel LD regimen. The aim of this study was to assess whether body mass index (BMI) influenced platelet response to clopidogrel LD in patients undergoing CS. METHODS: Adenosine diphosphate (ADP)-induced platelet aggregation (PA) was assessed by light transmittance aggregometry in 48 patients on aspirin treatment undergoing CS receiving a 300 mg clopidogrel LD at intervention time. PA was assessed at baseline and up to 24 hours after intervention. Patients were divided into 2 groups according to BMI: overweight (BMI greater than or equal to 25 kg/m2; 29 patients) and normal weight (BMI<25 kg/m2; 19 patients). PA was significantly higher in overweight than in normal weight patients at baseline (60.1+/-18.6%; versus 47.6+/-13.5%; p=0.01), at 24 hours (42.3+/-18.4% versus 38.5+/-18.3%; p=0.02) and during the overall study time (p=0.025). Percentage of inhibition of PA 24 hours following clopidogrel LD was suboptimal (<40%) in 59% and 26% of overweight and normal weight patients, respectively (p=0.04). An elevated BMI was the only independent predictor of suboptimal platelet response. CONCLUSION: These data suggest that overweight patients may need a higher loading-dose of clopidogrel and/or an adjunct antithrombotic treatment to adequately inhibit platelet aggregation early after CS.     

Thrombophilia and pregnancy: who should be tested? Which tests should be performed? The biologist point of view

Pregnancy is associated with an increased risk of venous thromboembolism, especially in women with a congenital predisposition. The detection of these thrombophilias, with an autosomal dominant transmission, is justified if an appropriate prophylaxis is administered during pregnancy and/or post-partum. The aim of the prophylaxis is to prevent thrombotic events and possibly adverse pregnancy complications, such as pregnancy loss at the second or third trimester, intra-uterine fetal growth retardation or pre-eclampsia. The magnitude of the pregnancy-associated risk in the different thrombophilias is taken into account for the selection of the patients to be tested for the detection of thrombophilia. Tests to be performed are proposed and their interpretation depends on whether the patient is pregnant, receiving oral contraception or oral anticoagulants.     

Is it useful to measure serum ferritin level in systemic lupus erythematosus patients?

BackgroundSerum ferritin is elevated due to various conditions as inflammation and malignancy and could be up regulated in systemic lupus erythematosus (SLE).Aim of workTo evaluate serum ferritin level in SLE patients and correlate it with different clinical and laboratory parameters as well as disease activity.Patients and methodsThe study was carried out on 46 SLE patients and 20 matched controls. SLE Disease Activity Index (SLEDAI) was assessed and patients subdivided into severe (SLEDAI ≥ 11) and mild to moderate (SLEDAI < 11) activity. Serum ferritin, iron and total iron binding capacity (TIBC) levels were assessed.ResultsThey were 40 females and 6 males with a mean age of 36.7 ± 10.3 years and disease duration of 4.9 ± 2.3 years. Serum ferritin was significantly higher in patients than controls (163.5 ± 27.8 vs. 47.1 ± 10.6 ng/ml, p = 0.009). In patients, serum iron (49.2 ± 4.5 mg/dl) and TIBC (284.2 ± 80.8 mg/dl) were comparable with those in controls. Serum ferritin was significantly higher in patients with severe (220.9 ± 50.7 ng/ml) than those with mild-moderate activity (122.9 ± 29.7 ng/ml; p < 0.001). Serum ferritin was significantly higher in patients with anemia (p < 0.001) and thrombocytopenia (p = 0.03) and lower in those with leucopenia (p < 0.001) compared to those without. Ferritin significantly correlated only with hemoglobin (r = 0.5, p = 0.02), platelet count (r = 0.65, p = 0.03) and inversely with leucocytic count (r = −0.08, p = 0.006).ConclusionSerum ferritin is elevated significantly in SLE patients especially those with severe activity. A remarkable difference in serum ferritin levels in patients with hematological manifestations was found making it a potentially useful inflammatory marker for disease activity in patients with blood dyscrasia.     

When should iron chelation therapy be considered in patients with myelodysplasia and other bone marrow failure syndromes with iron overload?

Despite the absence of a robust evidence base, there is growing consensus that effective treatment of iron overload leads to decreased morbidity and premature mortality in patients with good prognosis myelodysplastic syndromes (MDSs). Furthermore, new treatment modalities, including disease-modifying therapies (lenalidamide and azacytidine) and reduced intensity conditioning therapies for allogeneic blood stem cell transplants, are offering the prospect of longer survival for patients with traditionally less favourable prognosis MDS, who might also benefit from iron chelation. This article proposes assessment of patients with MDS and related bone marrow failure syndromes to determine suitability for iron chelation. Iron chelation therapy options and monitoring are discussed.     

Controversies in the treatment of hypercholesterolemia in the elderly: who should be treated and how?

High levels of low-density lipoprotein cholesterol may contribute to the development of coronary heart disease in the absence of other risk factors. This paper reviews major cholesterol prevention trials since 1994 concerning possible beneficial results of lowering cholesterol in persons over 65 years of age.     

How far should life-style be corrected in the elderly?

To ensure a healthy elderly population, correction of life-style is one of the most important approaches. Smoking cessation, regulation of alcohol intake, prevention of obesity, improvement of nutrition, promotion of physical activity are key factors for prevention of bed-ridden and extension of healthy life span. Although corrections of life-style are essential in childhood, adolescence, and the middle-aged and elderly periods, the methods and purpose are different in each life stage. The risks of emaciation and malnutrition are more important rather than that of obesity in the elderly aged 75 years or over. As for the influence of smoking in cardiovascular and respiratory diseases, smoking can be a trigger for arrhythmia, peripheral vascular constriction, and irritation of the respiratory tract in the elderly. Smoking cessation is necessary even among elderly people. It is also necessary to decrease the amount of alcohol intake, because the ability of metabolize alcohol is limited in the elderly. Physical activity in the elderly people is fundamental not only to maintain the ability of daily living, but also to improve metabolic function and to prevent depression. Vigorous intervention to increase physical activity such as exercise class is recommended, especially in the elderly.     

Iron in pregnancy: How do we secure an appropriate iron status in the mother and child?

Iron deficiency and iron deficiency anemia (IDA) during pregnancy are risk factors for preterm delivery, prematurity, and small for gestational age birth weight. Iron deficiency has a negative effect on intelligence and behavioral development in the infant. It is essential to prevent iron deficiency in the fetus by preventing iron deficiency in the pregnant woman. The requirements for absorbed iron increase during pregnancy from ～1.0 mg/day in the first trimester to 7.5 mg/day in the third trimester. More than 90% of Scandinavian women of reproductive age have a dietary iron intake below the recommended 15 mg/day. Among nonpregnant women of reproductive age, ～40% have plasma ferritin ≤30 μg/l, i.e. an unfavorable iron status with respect to pregnancy. An adequate iron status during pregnancy implies body iron reserves ≥500 mg at conception, but only 15-20% of women have iron reserves of such a magnitude. Iron supplements during pregnancy reduce the prevalence of IDA. In Europe, IDA can be prevented by a general low-dose iron prophylaxis of 30-40 mg ferrous iron taken between meals from early pregnancy to delivery. In affluent societies, individual iron prophylaxis tailored by the ferritin concentration should be preferred to general prophylaxis. Suggested guidelines are: ferritin >70 μg/l, no iron supplements; ferritin 31-70 μg/l, 30-40 mg ferrous iron per day, and ferritin ≤30 μg/l, 60-80 mg ferrous iron per day. In women with ferritin <15 μg/l, i.e. depleted iron reserves and possible IDA, therapeutic doses of 100 mg ferrous iron per day should be advised.     

Should the levothyroxine starting dose be tailored to disease severity in neonates with congenital hypothyroidism?

Early levothyroxine treatment is crucial to minimize neurocognitive impairment associated with congenital hypothyroidism. In this Practice Point commentary, I discuss the findings, implications, and limitations of the study of Mathai et al. in which neonates with congenital hypothyroidism were treated with variable initial doses of levothyroxine. A high initial levothyroxine dose was used for newborn babies with athyreosis, an intermediate dose for those with ectopic glands, and a low dose for those with dyshormonogenesis. Serum free T(4) levels normalized within 2 weeks, but serum TSH levels within up to 4 weeks. A dose adjustment (mostly a dose reduction) was required in about half of the neonates in the first 2 weeks of life. As Mathai et al. carried out no neuropsychological tests, we do not know if their approach has a more beneficial effect on neurocognitive outcomes than other treatment strategies. Nevertheless, as tailoring the levothyroxine dose to severity rapidly normalized serum free T(4) levels, one would predict a beneficial effect of this approach on neurocognitive outcome.     

Which antiphospholipid antibodies should be measured in the antiphospholipid syndrome?

The results of an analysis of studies published over a 10-year period that addressed the association between antiphospholipid antibodies (aPLs) and thromboembolic events in patients with the antiphospholipid syndrome (APS) are reported. It would appear that lupus anticoagulants are the strongest risk factor for thromboembolic events in aPL-positive patients. Consequently, it is suggested that all patients with clinical manifestations of APS should be tested for these antibodies. On the other hand, the results do not unequivocally show that measurement of anticardiolipin antibodies is of help in defining the thrombotic risk of patients. Furthermore, they only partially support the notion that anti-beta 2-glycoprotein I and antiprothrombin antibodies may be independent risk factors for thrombosis.     

Safety and efficacy of contraception—Why should the obese woman be any different?

The public health impact of obesity and unintended pregnancy is profound with far reaching consequences. Obese women are less likely to use contraception due to a variety of self-induced and systems-based barriers but their risk of becoming pregnant is similar to their normal weight counterparts. However, pregnancy-associated risks for obese women are higher than that of normal weight women and thus, pregnancy generally outweighs the risks of contraceptive use. Adequate counselling to prevent and/or plan for pregnancy is imperative for these women. Research that investigates the relationship between obesity and contraceptive use is urgently needed.