informer

Hemoglobinopathies are unique amongst all genetic diseases because the identification of healthy carriers is possible by commonly available blood tests – blood count, osmotic fragility, hemoglobin profile (first line tests) and molecular analysis is not required. If any abnormal hemoglobin fraction appears, functional tests are applied to determine with a pretty good degree of reliability the type of pathological hemoglobin and its clinical significance, avoiding the usage of expensive molecular methods. Confirmation of gene mutations presence with molecular techniques is only necessary in small number of cases – in so-called “couples at risk” for the purpose of prevention of thalassemia major, for prenatal or pre-implantation diagnosis – when both parents are thalassemia carriers (or suspected carriers), or carriers of clinically significant hemoglobin variant.

By comparison and evaluation of the results of relevant blood tests, the patient’s history, and considering additional factors, the proper diagnosis of hemoglobinopathies with non-molecular methods is crucial for the prevention of a childbirth with a severe diagnosis. Read the full article here.

Factor XII deficiency is rare bleeding disorder and theoretically may carry either bleeding risk as a result of reduced coagulation factors or thrombosis risk as a consequence of reduced fibrinolytic activity. The incidence of factor XII deficiency is relatively low at 1 in 1,000,000 people.

The aim of reported case is to emphasise the importance of multidisciplinary approach in the management of pregnancy and delivery in the women with severe factor XII deficiency.

A woman with severe factor XII deficiency is successfully treated during her two pregnancies and deliveries. All coagulation tests are performed with standard Siemens reagents on the coagulometer Dade Behring BCS XP. A test for platelet aggregation for follow up of Aspirin treatment is performed on Siemens Innovance PFA-200 with standard Siemens collagen/epinephrin test cartridge.

During her two pregnancies, the woman with severe factor XII deficiency was regularly followed up in the Center for haemophilia in the Institute for Transfusion Medicine. According to coagulation tests in the first pregnancy she was treated with low molecular weight heparin in the postpartum period,  but in the second pregnancy it was necessary to be treated in the first and third trimester, as well as in the postpartum period. Bleeding prevention due to delivery was performed with tranexamic acid. Two pregnancies were successfully finished with vaginal delivery without any bleeding or thrombotic complications.

Regular follow up during pregnancy is necessary for women with bleeding disorders in Comprehensive Haemophilia Treatment Centre. Multidisciplinary approach is crucial for successful bleeding disorders care. Read the full article here.

Immune thrombocytopenia is a rare autoimmune disease. This is a diagnosis by the process of elimination. In children the disease is characterized by a sudden decrease in platelet count, with only 50% to 60% of patients having detectable anti-platelet antibodies in peripheral blood. The pathogenesis is heterogeneous, and the diagnosis is complex.

The challenge lies in immunohematological diagnosis – there is no standard test or biomarker. The immune response may be in the bone marrow, directed against megakaryocytes or newly formed platelets. Antiplatelet antibodies are undetectable at low titers and correlate with a certain type of treatment. Autoantibodies in immune thrombocytopenia are a challenge for immunohematologists and clinicians unlike autoantibodies in autoimmune hemolytic anemia. Read the full article here.

Beta-thalassemia is one of the most common autosomal-recessive disorders. The advances in the chelator treatment and the non-invasive methods for the assessment and follow up of the iron overload have led to an improved quality and longer duration of the life of patients with thalassemia. The liver is the primer target organ affected both directly and indirectly. In this article are reviewed the most common liver complications such as liver fibrosis and cirrhosis, non-invasive methods for evaluation of the iron deposition, chronic viral hepatitis, hepatocellular carcinoma and cholelithiasis. Read the full article here.

Acromegaly is a rare disease, usually caused by a pituitary tumor. It typically exhibits slow evolution and can result in numerous complications. In the present case report, the patient presents with hyperthyroidism associated with ophthalmopathy and right nodular goiter. The laboratory tests reveal persistent high levels of phosphorus without an apparent cause. After ruling out common pathologies associated with this finding, a focus ia placed on the clinical aspects associated with acromegaly, a rare cause of hyperphosphatemia. Laboratory tests and MRI confirm the diagnosis. This case highlights the challenges in diagnosing and managing a rare endocrine pathology. Read the full article here.

Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disease inherited in an autosomal dominant manner. Disease-causing variants in endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1) genes are detected in around 90% of the patients; also 2% of patients harbor pathogenic variants at SMAD4 and GDF2. Importantly, the genetic cause of 8% of patients with clinical HHT remains unknown.

In this study exome sequencing of 19 HHT patients and relatives with unknown HHT genetic etiology is performed, to identify new HHT genetic drivers.

Variants in the INHA, HIF1A, JAK2, DNM2, POSTN, ANGPTL4, FOXO1 and SMAD6 genes as putative drivers in HHT are identified. The SMAD6 p.(Glu407Lys) variant in one of the families is identified; this is a loss-of-function variant leading to the activation of the BMP/TGFβ signaling in endothelial cells.

Variants in these genes should be considered for genetic testing in patients with HHT phenotype and negative for ACVRL1/ENG mutations. Read the full article here.