Loading...
4 results
Search Results
Now showing 1 - 4 of 4
- Guidelines on COVID-19 Vaccine Induced Thrombosis, Bleeding, and ThrombocytopeniaPublication . Morais, Sara; Cruz, EugéniaAfter widespread vaccination with COVID-19 vaccines, there have been worldwide reports on thrombosis, bleeding, and thrombocytopenia. Recently, a rare syndrome with a high mortality rate consisting of an unusual combination of thrombocytopenia and thrombosis, in particular cerebral venous sinus thrombosis, which clinically resembles heparin-induced thrombocytopenia, was reported following vaccination. Different statements and recommendations were developed regarding the definition, diagnosis, and treatment of these rare complications. We present here a protocol with recommendations, based on current evidence.
- HFE Related Hemochromatosis: Uncovering the Inextricable Link between Iron Homeostasis and the Immunological SystemPublication . Porto, Graça; Cruz, Eugénia; Teles, M.; de Sousa, MariaThe HFE gene (OMIM 235200), most commonly associated with the genetic iron overload disorder Hemochromatosis, was identified by Feder et al. in 1996, as a major histocompatibilty complex (MHC) class I like gene, first designated human leukocyte antigen-H (HLA-H). This discovery was thus accomplished 20 years after the realization of the first link between the then "idiopathic" hemochromatosis and the human leukocyte antigens (HLA). The availability of a good genetic marker in subjects homozygous for the C282Y variant in HFE (hereditary Fe), the reliability in serum markers such as transferrin saturation and serum ferritin, plus the establishment of noninvasive methods for the estimation of hepatic iron overload, all transformed hemochromatosis into a unique age related disease where prevention became the major goal. We were challenged by the finding of iron overload in a 9-year-old boy homozygous for the C282Y HFE variant, with two brothers aged 11 and 5 also homozygous for the mutation. We report a 20 year follow-up during which the three boys were seen yearly with serial determinations of iron parameters and lymphocyte counts. This paper is divided in three sections: Learning, applying, and questioning. The result is the illustration of hemochromatosis as an age related disease in the transition from childhood to adult life and the confirmation of the inextricable link between iron overload and the cells of the immune system.
- Aggressive Neuroblastoma in a Pediatric Patient with Severe Hemophilia APublication . Costa, Lídia; Couto, Maria Eduarda; Moutinho, Juliana; Ferreira, Ana Maia; Costa, Emilia; Roncon, Susana; Santos, Luisa Lopes; Cruz, Eugénia; Morais, SaraDespite the extensive information regarding hemophilia's hemorrhagic complications, the literature on cancer in hemophilia is scarce, especially in pediatric patients. Many uncertainties remain concerning diagnosis and workup. We report a rare case of two severe diseases (neuroblastoma and hemophilia A (HA)) concomitantly present in the same pediatric patient. We highlight that the diagnosis of severe HA did not have a negative impact on the patient's oncologic course. This case also illustrates the significance of the cooperation among different specialties and hospitals when caring for the same patient.
- αIIbβ3 variants in ten families with autosomal dominant macrothrombocytopenia: Expanding the mutational and clinical spectrumPublication . Morais, Sara; Oliveira, Jorge; Lau, Catarina; Pereira, Mónica; Gonçalves, Marta; Monteiro, Catarina; Gonçalves, Ana; Matos, Rui; Sampaio, Marco; Cruz, Eugénia; Freitas, Inês; Santos, Rosário; Lima, MargaridaBackground: Rare pathogenic variants in either the ITGA2B or ITGB3 genes have been linked to autosomal dominant macrothrombocytopenia associated with abnormal platelet production and function, deserving the designation of Glanzmann Thrombasthenia-Like Syndrome (GTLS) or ITGA2B/ITGB3-related thrombocytopenia. Objectives: To describe a series of patients with familial macrothrombocytopenia and decreased expression of αIIbβ3 integrin due to defects in the ITGA2B or ITGB3 genes. Methods: We reviewed the clinical and laboratory records of 10 Portuguese families with GTLS (33 patients and 11 unaffected relatives), including the functional and genetic defects. Results: Patients had absent to moderate bleeding, macrothrombocytopenia, low αIIbβ3 expression, impaired platelet aggregation/ATP release to physiological agonists and low expression of activation-induced binding sites on αIIbβ3 (PAC-1) and receptor-induced binding sites on its ligand (bound fibrinogen), upon stimulation with TRAP-6 and ADP. Evidence for constitutive αIIbβ3 activation, occurred in 2 out of 9 patients from 8 families studied, but also in 2 out of 12 healthy controls. We identified 7 missense variants: 3 in ITGA2B (5 families), and 4 in ITGB3 (5 families). Three variants (αIIb: p.Arg1026Trp and p.Arg1026Gln and β3: p.Asp749His) were previously reported. The remaining (αIIb: p.Gly1007Val and β3: p.Thr746Pro, p.His748Pro and p.Arg760Cys) are new, expanding the αIIbβ3 defects associated with GTLS. The integration of the clinical and laboratory data allowed the identification of two GTLS subgroups, with distinct disease severity. Conclusions: Previously reported ITGA2B and ITGB3 variants related to thrombocytopenia were clustered in a confined region of the membrane-proximal cytoplasmic domains, the inner membrane clasp. For the first time, variants are reported at the outer membrane clasp, at the transmembrane domain of αIIb, and at the membrane distal cytoplasmic domains of β3. This is the largest single-center series of inherited macrothrombocytopenia associated with αIIbβ3 variants published to date.