A case of severe ADAMTS13 deficiency presenting as thrombotic thrombocytopenic purpura in pregnancy.

INTRODUCTION: Thrombotic thrombocytopenic purpura is a rare life-threatening disorder characterized by thrombocytopenia and microangiopathic hemolytic anemia. It is caused by the absent or severe deficiency of the von Willebrand Factor-cleaving protease named ADAMTS13. Pregnancy is a well recognized factor precipitating the appearance of the disease both in women that had reduced levels of ADAMTS13 activity prior to gestation and in those with other inherited or acquired thrombophilic syndromes. CASE REPORT: We report a 25-year old woman with severe ADAMTS13 deficiency presented early in her 1st pregnancy and relapsed in two subsequent gestations. This presentation is uncommon for thrombotic thrombocytopenic purpura is associated with pregnancy (ADAMTS13 deficiency < 5%, without an inhibitor). In the first pregnancy she started with daily plasma exchange 1.5 x volume, corticosteroids and IV immunoglobulin and finally entered remission after 23 sessions and termination of pregnancy. In the second pregnancy she did not receive prophylactic treatment and relapsed in the 3rd trimester. Prophylactic treatment during the third pregnancy with plasma infusions proved also ineffective to prevent relapse. DISCUSSION: Many issues regarding treatment and prevention of thrombotic thrombocytopenic purpura relapses in subsequent pregnancies are unclear. Proposed guidelines recommend that the same treatment should be performed on pregnant and non pregnant patients without modification of plasma replacement dose according to ADAMTS13 levels. In addition, many authors suggest that pregnant patients with history of thrombotic thrombocytopenic purpura and severe deficiency of ADAMTS13 levels should received prophylactic treatment for prevention of relapses in the subsequent pregnancies. CONCLUSION: Severe ADAMTS 13 deficiency may present as thrombotic thrombocytopenic purpura of pregnancy. Pregnant women with thrombotic thrombocytopenic purpura and especially with severe deficiency of ADAMTS13 levels require specific consideration regarding treatment and prophylaxis in subsequent pregnancies.

Lung function measurements in traditional bakers.

BACKGROUND: Respiratory disease is common and amenable to early detection and management in the primary care setting. Spirometric and phlethysmographic evaluation of ventilatory function plays a critical role in the diagnosis, differentiation and management of respiratory illness such as asthma, chronic obstructive pulmonary disease and restrictive disorders. METHODS: Study subjects consisted of 58 workers in the production of bread and 45 salesclerks of bread from the same bakeries. The lung function of employees was checked using a spirometry and body phlethysmography, calculating the indexes Forced expiratory volume 1 sec (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, residual volume (RV), total lung capacity (TLC), and RV/TLC ratio. The percentage of the obstructive and the restrictive impairment both in the bread producers and sellers was also searched as well as the percentage of response in the bronchodilation. RESULTS: Bread producers recorded significantly lower mean lung functions compared with salesclerks, for FEV1, FVC and FEV1/FVC ratio, when observed values were expressed as percentages of predicted normal values. Furthermore the percentage of obstructive impairment among the bread producers was 12.6%, while a percentage of 20.68% of them presented a response in bronchodilation (while the percentage in salesclerks was 6.6% respectively). The percentage of restrictive impairment was similar in both groups (12.6% for bread producers and 11.1% for salesclerks). CONCLUSION: The study concluded that bread producers in traditional bakeries in Greece are at increased risk of developing airway obstruction compared with salesclerks of bread from the same bakeries. A different degree of smoking status and of wheat flour dust exposure may explain this difference. Technical preventive measures such as well ventilated work areas and appropriate respiratory protective devices should be adopted.

Comparison of DXA, QCT and trabecular structure in beta-thalassaemia.

Osteopathy, as a major feature of homozygous beta-thalassaemia, is a multifactorial disorder, not fully understood. We studied the lumbar vertebrae of 48 patients using Dual-Energy X-ray Absorptiometry (DXA) and Quantitative Computed Tomography (QCT), and we focused on structural properties, assessed by High Resolution Computed Tomography (HRCT). Bone Mineral Density (BMD) values were expressed as Z-scores and the results were correlated. The effect of age, sex, and type of thalassaemia and hormonal factors on BMD was assessed. We estimated, with HRCT, the cortex integrity and the number and thickness of trabeculae; the latter were classified to a three-grade scale. Our results showed the overall prevalence of osteoporosis to be 44% with DXA and 6% with QCT. Both techniques revealed an inverse correlation between age and BMD, whereas hormonal factors demonstrated associations with QCT and DXA measurements. The correlation coefficient between DXA's BMD and QCT's trabecular BMD was 0.545 (P < 0.001) whereas the corresponding value for Z-scores was r = 0.491 (P < 0.001). The classification of the patients into normal, osteopenic and osteoporotic categories, using QCT's Z, was in better agreement with the assignment based on trabecular number (K = 0.209, P = 0.053) than the classification using DXA's Z (K = 0.145, P = 0.120). Cortex evaluation by HRCT showed discontinuity in 15 patients. Both methods indicate a progression of osteoporosis with age. Hormonal deficiency is associated with thalassaemic osteoporosis whereas the visual estimation of cortex indicates that Thalassaemia Intermedia (TI) patients could be more affected than Thalassaemia Major (TM). Using the trabecular number as an indicator of osteoporosis, it seems that QCT may evaluate osteopathy better than DXA. Since the former has the ability to measure trabecular and cortical BMD separately, it could give early indication of which changes more rapidly and to what degree.

Evaluation of the clinical relevance of the expression and function of P-glycoprotein, multidrug resistance protein and lung resistance protein in patients with primary acute myelogenous leukemia.

The multidrug resistance (MDR) transporter-proteins P-glycoprotein (Pgp), multidrug resistance protein (MRP) and lung resistance protein (LRP) have been associated with treatment failure. The aim of this study was to investigate prospectively the clinical significance of expression and function of the MDR proteins, considering other prognostic factors, such as age, immunophenotype, and cytogenetics. Mononuclear cells of peripheral blood or bone marrow from 61 patients with de novo acute myelogenous leukemia (AML) were analyzed. The monoclonal antibodies JSB1, MRPm6 and LRP56 were used for expression studies. Accumulation and retention studies were performed using the substrates Daunorubicin, Calcein-AM, Rhodamine-123 and DiOC(2) in the presence or absence of the modifiers Verapamil, Genistein, Probenecid, BIBW22S and PSC833. Induction treatment consisted of a 3+7 combination of Ida/Ara-C for patients < or = 60 years of age and a 3+5 Ida/VP-16 combination per OS for patients >60. MDR function was expressed as the ratio of mean fluorescence intensity substrate in the presence of modifier over the substrate alone (resistance index, RI). Patients with advanced age, low CD15 expression and high RI for accumulation of DiOC(2) in the presence of BIBW22S had significantly lower complete remission (CR) rates. No factor was prognostic for event-free survival analysis, which was limited to remitters only. Overall survival was shorter in patients with advanced age, poor prognosis cytogenetics, high CD7 expression, and high RI for Daunorubicin efflux modulated by Verapamil. These results suggest that MDR transporter-proteins have a limited role in the treatment failure of patients treated with Idarubicin-based regimens.