Factor XIII (FXIII) is a tetrameric zymogen (FXIII-A₂B₂) that is converted into an active transglutaminase (FXIIIa) by thrombin and Ca²⁺ in the terminal phase of the clotting cascade. By cross-linking fibrin chains and α₂ plasmin inhibitor to fibrin, FXIIIa mechanically stabilizes fibrin and protects it from fibrinolysis. Severe deficiency of the potentially active A subunit (FXIII-A) is a rare but severe hemorrhagic diathesis. Delayed umbilical stump bleeding is characteristic, and subcutaneous, intramuscular, and intracranial bleeding occurs with a relatively high frequency in nonsupplemented patients. In addition, impaired wound healing and spontaneous abortion in women are also features of FXIII deficiency. The extremely rare B subunit deficiency results in milder bleeding symptoms. FXIII concentrate is now available for on-demand treatment and primary prophylaxis. A quantitative FXIII activity assay is recommended as a screening test for the diagnosis of FXIII deficiency. For classification purposes, FXIII-A₂B₂ antigen in the plasma is first determined, and if decreased, further measurement of the individual subunits is recommended in the plasma and FXIII-A in platelet lysate. Analytical aspects of FXIII activity and antigen assays are discussed in this article. There are no hot-spot mutations in the F13A1 and F13B genes, and the majority of causative mutations are missense/nonsense point mutations.

Beta-thalassemia intermedia (β-TI) is a genetic variant of beta-thalassemias with a clinical disorder whose severity falls between thalassemia minor and thalassemia major. Different genetic defects are involved in this disorder and, based on severity of disease, clinical complications like skeletal deformities and growth retardation, splenomegaly, extramedullary hematopoiesis, heart failure, and endocrine disorders may be present in untreated patients. Precise diagnosis and management are essential in these patients for prevention of later clinical complications. Diagnosis of TI is based on clinical and laboratory data. There are some treatment strategies like modulation of gamma-globulin chain production with hydroxyurea or other drugs, transfusion, splenectomy, and stem cell transplantation. Iron chelation therapy is also needed in many of these patients even if they are not transfused. The aim of this manuscript is to review the clinical manifestations, complications, genetic defects, and unmet treatments needs in TI.

Hydroxyure (HU) is a chemotherapeutic agent that is capable of inducing HbF synthesis resulting in alleviates the symptoms in thalassemia patients. The aim of this study was to evaluate the tolerance and adverse effects of HU in thalassemia intermedia (TI) patients who had been treated with HU for a period of �� years. ��� TI patients who were treated with HU were investigated as a case study and ��� TI who were not received any HU therapy as a control group. Mean dose of HU used was ����� mg/kg/d (range: -�� mg/kg/d) and adverse effects of HU were recorded in �� (����� ) patients. Dermatologic side effects were most commonly seen, followed by neurological and gastrointestinal adverse effects. There were not any reports of hematologic toxicity or any signs of bone marrow suppression during HU treatment. Statistical analysis showed a positive correlation between advancing age and the presence of adverse effects during HU treatment (P<���� ). But there were not any significant relation between gender, HU dose and duration of HU treatment and the presence of adverse effects (P>���� ). It was also observed that splenectomized patients more frequently experienced adverse effects of HU (P<���� ). According to our study it seems that low-dose HU therapy in patients with thalassemia intermedia at least in short and medium terms can be tolerated well without serious side effects.