Identification of compound heterozygous mutations in the ITGA2B gene in a Chinese patient with Glanzmann thrombasthenia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Glanzmann thrombasthenia (GT) is an autosomal recessive bleeding disorder characterized by the tendency to hemorrhage and the inability of platelets to aggregate in response to agonists. GT is caused by a defect of the platelet glycoprotein IIb/IIIa complex. The objective of this study was to describe the clinical features and the genetic cause of GT in a 6-year-old girl from south China.</p><p><b>METHODS</b>A three-generation family was studied. The proband patient aged 6 years and her parents undertook examinations of platelet counts, blood film, bleeding time, platelet aggregation, and flow cytometry. All coding exons of the ITGA2B and ITGB3 genes were amplified by polymerase chain reaction (PCR), and direct sequencing was performed for mutational screening on the patient and normal controls consisted of 52 healthy blood donors. Reverse transcription PCR was conducted to test for exon skipping.</p><p><b>RESULTS</b>The proposita patient showed dispersing platelets, prolonged bleeding time, and severely reduced platelet aggregation in response to the physiological agonists adenosine diphosphate (ADP), epinephrine, collagen, and ristocetin. Flow cytometric measurements showed that the contents of alphaIIb and beta3 were significantly decreased. Sequencing results demonstrated two different types of heterozygous mutations existed in the alphaIIb gene (c.2930delG and IVS15-1delG). The compound mutations were also confirmed in the patient's mother and father separately.</p><p><b>CONCLUSIONS</b>The alphaIIbbeta3 deficiency of the proband was caused by two compound ITGA2B mutations, which were first reported in Chinese GT patients. The IVS15-1delG was first confirmed to cause an exon skipping.</p>

Dynamic change of plasma prethrombotic state molecular marker levels in perioperative period of patients and its clinical significance / 中国实验血液学杂志

This study was aimed to investigate the dynamic changes of plasma prethrombotic state molecular marker levels during perioperation of patients and to provide laboratorial evidence for clinical diagnosis of these patients so as to take intervenient measure to high risk patients. 40 patients with gynecological and urological malignant tumors (without metastasis) and 20 patients with benign tumors and 20 healthy individuals were selected for analysis. The levels of plasm prethrombotic state molecular markers including TF, TFPI, TpP, PAI-1, P-S, TAT and D-D were measured by using ELISA method and transmission immunity nephelometry. The results showed that the levels of TF, TpP, D-D, P-S and TAT in plasma of patients with malignant tumors at 6 hours after operation were higher than that before operation, but the levels of TFPI and PAI-1 in these patients after operation were lower than before operation, and there was significant difference as compared with the levels of these markers before operation. At day 3 after operation, the levels of TF, TpP and D-D continuously increased; the level of PAI-1 begins to elevate, there were significant difference in comparison with that before operation; the levels of P-S and TAT decreased, but still were higher than that before operation. At day 7 after operation, the levels of TpP, TAT, P-S, TFPI and PAI-1 returned to levels before operation, but the levels of TF and D-D were still higher than that before operation, and showed significant difference from that before operation. In patients with benign tumors and non-operation patients, the levels of prethrombotic state molecular markers mentioned above at different points of time after operation did not present difference, except levels of TF and D-D that at 6 hours after operation were higher than that before operation. It is concluded that at 6 hours after operation of patients with gynecological and urological malignant tumours, the plasma levels of prethrombotic state molecular markers are in higher state of coagulation and fibrinolysis, at 3 days after operation these levels are mainly in coagulation state. At 7 days after operation, the level of these markers returned to levels before operation. At 6 hours after operation the levels of these markers in patients with benign tumors are in mild coagulation state.