Summary. Background: The European Network of Rare Bleeding Disorders (EN‐RBD) was established to bridge the gap between knowledge and practise in the care of patients with RBDs. Objectives: To explore the relationship between coagulation factor activity level and bleeding severity in patients with RBDs. Patients/Methods: Cross‐sectional study using data from 489 patients registered in the EN‐RBD. Coagulation factor activity levels were retrieved. Clinical bleeding episodes were classified into four categories according to severity. Results: The mean age of patients at data collection was 31 years (range, 7 months to 95 years), with an equal sex distribution. On linear regression analysis, there was a strong association between coagulation factor activity level and clinical bleeding severity for fibrinogen, factor (F) X, FXIII, and combined FV and FVIII deficiencies. A weaker association was present for FV and FVII deficiencies. There was no association between coagulation factor activity level and clinical bleeding severity for FXI. The coagulation factor activity levels that were necessary for patients to remain asymptomatic were: fibrinogen, > 100 mg dL⁻¹; FV, 12 U dL⁻¹; combined FV + VIII, 43 U dL⁻¹; FVII, 25 U dL⁻¹; FX, 56 U dL⁻¹; FXI, 26 U dL⁻¹; FXIII, 31 U dL⁻¹. Moreover, coagulation factor activity levels that corresponded with Grade III bleeding were: undetectable levels for fibrinogen, FV and FXIII, < 15 U dL⁻¹ for combined FV + VIII; < 8 U dL⁻¹ for FVI; < 10 U dL⁻¹ for FX; and < 25 U dL⁻¹ for FXI. Conclusions: There is a heterogeneous association between coagulation factor activity level and clinical bleeding severity in different RBDs. A strong association is only observed in fibrinogen, FX and FXIII deficiencies.

Iron deficiency is the most common nutritional deficiency worldwide and an important public health problem especially in developing countries. Since the most important indicator of iron deficieny is anemia, the terms "iron deficiency" and "iron deficiency anemia" are often used interchangeably. However, iron deficiency may develop in the absence of anemia and the tissues may be affected from this condition. The most common causes of iron deficiency in children include insufficient intake together with rapid growth, low birth weight and gastrointestinal losses related to excessive intake of cow's milk. If insufficient intake can be excluded and there is insufficient response to oral iron treatment in patients with iron deficiency especially in older children, blood loss should be considered as the underlying cause. The main principles in management of iron deficiency anemia include investigation and elimination of the cause leading to iron deficiency, replacement of deficiency, improvement of nutrition and education of the patient and family. In this article, the practical approaches in the diagnosis and treatment of iron deficiency and the experience of our center have been reviewed.

Excessive bleeding at surgery is a feared complication in patients with inherited platelet disorders. However, very few studies have evaluated the frequency of surgical bleeding in these hemorrhagic disorders. We performed a worldwide, multicentric, retrospective study to assess the bleeding complications of surgery, the preventive and therapeutic approaches adopted, and their efficacy in patients with inherited platelet disorders: the Surgery in Platelet disorders And Therapeutic Approach (SPATA) study. We rated the outcome of 829 surgical procedures carried out in 423 patients with well-defined forms of inherited platelet disorders: 238 inherited platelet function disorders and 185 inherited platelet number disorders. Frequency of surgical bleeding was high in patients with inherited platelet disorders (19.7%), with a significantly higher bleeding incidence in inherited platelet function disorders (24.8%) than in inherited platelet number disorders (13.4%). The frequency of bleeding varied according to the type of inherited platelet disorder, with biallelic Bernard Soulier syndrome having the highest occurrence (44.4%). Frequency of bleeding was predicted by a pre-operative World Health Organization bleeding score of 2 or higher. Some types of surgery were associated with a higher bleeding incidence, like cardiovascular and urological surgery. The use of pre-operative pro-hemostatic treatments was associated with a lower bleeding frequency in patients with inherited platelet function disorders but not in inherited platelet number disorders. Desmopressin, alone or with antifibrinolytic agents, was the preventive treatment associated with the lowest bleedings. Platelet transfusions were used more frequently in patients at higher bleeding risk. Surgical bleeding risk in inherited platelet disorders is substantial, especially in inherited platelet function disorders, and bleeding history, type of disorder, type of surgery and female sex are associated with higher bleeding frequency. Prophylactic pre-operative pro-hemostatic treatments appear to be required and are associated with a lower bleeding incidence.

Background: Infantile colic is a common problem of early infancy. There is limited data on the relation between postpartum maternal psychological problems and colic. Aim:: To investigate whether infantile colic is associated with postpartum mood disorders or insecure adult attachment style of the mother. Methods: Seventy eight mothers and newborns were enrolled in this prospective, longitudinal study. Maternal depressive symptoms were screened with Edinburgh Postpartum Depression Score (EPDS) and maternal anxiety was assessed with State-Trait Anxiety Inventory (STAI). The Adult Attachment Scale was used to determine the attachment style of the mother. Infantile colic was defined according to Wessel criteria. Results: Infantile colic was present in 17 infants (21.7%); 12.9% of the mothers had an EPDS ⩾13. The mean EPDS of the mothers whose infants had infantile colic (10.2±6.0) was significantly higher than that of the mothers of infants without colic (6.3±4.0). Among infants with infantile colic, 62.5% had mothers who had insecure attachment style, whereas only 31.1% of mothers had insecure attachment when the infant did not have infantile colic. Conclusion: Postpartum maternal depressive symptoms and insecure attachment style are associated with infantile colic. Screening and early intervention of postpartum depression might promote the health of both the mother and infant.

IKZF1/IKAROS is a key transcription factor of lymphocyte development expressed throughout hematopoiesis. Heterozygous germline IKZF1 haploinsufficient ( IKZF1 ^HI ) and dominant-negative ( IKZF1 ^DN ) variants in humans cause B cell immune deficiency and combined immunodeficiency. Here, we identified previously unidentified heterozygous IKZF1 variants (R183C/H) located in the DNA binding domain in eight individuals with inflammatory, autoimmune, allergic symptoms, and abnormal plasma cell (PC) proliferation. Leukocytes of patients exhibited specific defects including impaired IL-2 production by T cells, T helper (T _H ) skewing toward T _H 2, low numbers of regulatory T cells (T _reg ), eosinophilia, and abnormal PC proliferation. In contrast to IKZF1 ^HI and IKZF1 ^DN , IKZF1 ^R183H/C proteins showed increased DNA binding associated with increased gene expression of T _H 2 and PC differentiation, thus demonstrating that IKZF1 ^R183H/C behave as gain-of-function (GOF) alleles. In vitro treatment with lenalidomide, known to degrade IKZF1, corrected T _H 2 and PC abnormalities caused by IKZF1 ^R183H/C . These data extend the spectrum of pathological mechanisms associated with IKZF1 deficiencies and highlight the role of IKZF1 in late lymphoid differentiation stages.