Reyhan Diz-Küçükkaya

Assessment of Cardiac Structure and Left Atrial Appendage Functions in Primary Antiphospholipid Syndrome A Transesophageal Echocardiographic Study

Background and Purpose— Although thromboembolic events are the major complication of primary antiphospholipid syndrome (PAPS), cardiac involvement is commonly present. Left atrial appendage (LAA) is recognized as an important source for thrombus formation and thromboembolism. The purpose of the study was to assess the structure and function of LAA with transesophageal echocardiography (TEE) in PAPS patients. Methods— Thirty-one PAPS patients (22 women, mean age 36±9 years) in sinus rhythm and 31 (17 women, mean age 37±7 years) controls with normal TEE examination were investigated. Results— Eighty-four percent of the PAPS patients had functional and structural valvular defect predominantly in the mitral valve. Valvular lesions were especially frequent in PAPS patients with a history of cerebrovascular events, patients with history of arterial thrombosis (91.6%), and patients with high titers of IgG anticardiolipin antibodies (100%). Intracardiac thrombus was present in 5 patients and in 1 of them it was located in LAA. The structure of LAA was similar between groups. Left atrial appendix ejection fraction (51.8±4 versus 48.6±5.5%; P<0.05) and LAA peak outflow velocity (87±10.9 versus 80.6±10.3 cm/s; P=0.02) was significantly higher in PAPS group compared with controls. In PAPS patients with mitral regurgitation (MR), LAA outflow peak velocity (84.3±10 versus 98.6±6.5 cm/s; P=0.002) and LAA inflow peak velocity (67.8±10.5 versus 80.8±8.6 cm/s; P=0.009) were significantly lower compared with PAPS patients without MR. Conclusions— It was concluded that disease process in PAPS frequently involved cardiac valves especially mitral valve but spared LAA function. LAA function was normal, but intracardiac thrombus was present in 5 patients and 1 of them was located in LAA. MR in PAPS patients seems to impair LAA function.

Inherited disorders of platelets: membrane glycoprotein disorders.

Platelet membrane glycoproteins play a key role in hemostasis and thrombosis. Although disorders of platelet membrane glycoproteins are rare, their effects on the lives of those affected are very important. Severe deficiencies manifest themselves early during childhood with mucocutaneous bleeding. Mild deficiencies may not be diagnosed until adulthood or until the hemostatic system is stressed by surgery or trauma. The diagnosis of these disorders requires detailed laboratory investigation. Management of bleeding in patients with inherited platelet disorders requires both preventive measures and the treatment of individual bleeding episodes according to severity. The study of platelet membrane disorders also has yielded important insights into the functions of affected proteins, information that has produced some of the most successful antithrombotic drugs currently in use.

Coexistence of homozygous factor V Leiden mutation and antiphospholipid antibodies in two patients presented with Budd-Chiari syndrome.

Two female patients are reported, who presented with Budd-Chiari syndrome (hepatic vein thrombosis), and were found to have both, antiphospholipid antibodies and homozygous factor V Leiden mutation. Both patients also had recurrent fetal losses, as well as splenic and portal vein thrombosis. The coexistence of homozygous factor V Leiden mutation and antiphospholipid antibodies in patients with Budd-Chiari syndrome is extremely rare. The interaction of antiphospholipid antibodies and factor V Leiden mutation in the pathogenesis of antiphospholipid syndrome and their contribution to Budd-Chiari syndrome are discussed.

MPL W515L/K Mutations in Chronic Myeloproliferative Neoplasms

OBJECTIVE The MPL gene encodes the thrombopoietin receptor. Recently MPL mutations (MPL W515L or MPL W515K) were described in patients with essential thrombocythemia (ET) and primary (idiopathic) myelofibrosis (PMF). The prevalence and the clinical importance of these mutations are not clear. In the present study, we aimed to investigate the frequency and clinical significance of MPL W515L/K mutations in our patients with ET and PMF. MATERIALS AND METHODS A total of 77 patients (66 were diagnosed with ET and 11 with PMF) and 42 healthy controls were included in the study. Using peripheral blood samples, the presence of MPL W515L/K mutations and JAK-2 V617F mutation were analyzed by real-time polymerase chain reaction. RESULTS In our study, MPL W515L/K or JAK-2 V617F mutations were not observed in healthy controls. JAK-2 V617F mutation was present in 35 patients, of whom 29 had ET (43.9%, 29/66) and 6 had PMF (54.5%, 6/11). In the patient group, MPL W515L/K mutations were found in only 2 PMF cases, and these cases were negative for JAK-2 V617F mutation. The prevalence of MPL W515L/K mutations in the patient group was 2.6%, and the prevalence of MPL W515L/K mutations among the cases negative for the JAK-2 V617F mutation was found to be 4.8%. The 2 cases with MPL W515L/K mutations had long follow-up times (124 months and 71 months, respectively), had no thrombotic or hemorrhagic complications, and had no additional cytogenetic anomalies. CONCLUSION MPL W515L/K mutations may be helpful for identifying clonal disease in MPN patients with no established Ph chromosome or JAK-2 V617F mutation. CONFLICT OF INTEREST None declared.

Cytotoxic T lymphocyte antigen-4 (CTLA-4) A49G polymorphism and autoimmune blood diseases

OBJECTIVE The cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is expressed on T lymphocytes, and inhibits the T-cell responses. In animal models, it has been shown that complete CTLA-4 deficiency was lethal due to massive infiltration of tissues by polyclonally proliferating lymphocytes. CTLA-4 A49G polymorphism, which has been suggested to reduce the inhibitory function of the CTLA-4 molecule, was found to be associated with various autoimmune diseases in recent studies. METHODS In this study, we evaluated the frequency of CTLA-4 A49G polymorphism in 46 patients with autoimmune hemolytic anemia (AIHA), 62 patients with immune thrombocytopenic purpura (ITP), and 150 healthy individuals. RESULTS Allele frequencies and genotype distributions were similar in both ITP and AIHA patients compared to healthy individuals. In subgroup analysis, however, we found that in chronic lymphocytic leukemia (CLL) patients with AIHA (n=4), all patients had CTLA-4 A49G polymorphism (3 had AG, 1 had GG). There was no significant statistical association between G allele and systemic lupus erythematosus (SLE) or AIHA. CONCLUSION These data suggest that CTLA-4 A49G polymorphism does not contribute to the pathogenesis of lymphoproliferative diseases itself, nor does it increase the risk of autoimmune complications in patients with lymphoproliferative disease.

Comparison of the cytogenetic and molecular analyses in the assessment of imatinib response in chronic myelocytic leukemia.

We aimed to compare the cytogenetic and molecular analyses in the assessment of imatinib mesylate response in patients suffering the chronic phase of chronic myelocytic leukemia who were refractory to alpha-interferon treatment. A total of 117 patients in the chronic phase of chronic myelocytic leukemia were included. The patients were treated with 400 mg/day imatinib mesylate. Bone marrow samples were obtained for the cytogenetic and molecular analyses. Patients without the Ph chromosome were defined as complete cytogenetic responders. Partial cytogenetic response was determined when the Ph chromosome was detected in 1-35% of the cells. Molecular response was determined by quantitative real-time reverse transcriptase polymerase chain reaction (QR-PCR) and defined as no detection of BCR-ABL mRNA. The frequencies of complete and partial cytogenetic response were 29% (n = 34) and 15% (n = 18), respectively. No cytogenetic response was achieved in 56% (n = 65) of the patients. Molecular response was achieved in 62% (n = 21) and 33% (n = 6) of the complete and partial cytogenetic responders, respectively. All of the 65 patients with no cytogenetic response were also molecular nonresponders. We conclude that there is reasonable agreement between the cytogenetic and molecular analyses. Both methods are complementary in the assessment of response to therapy.