Thrombophilia in women with pregnancy-associated complications: fetal loss and pregnancy-related venous thromboembolism.

BACKGROUND/AIMS: Existing data regarding the prevalence of thrombophilia in women with pregnancy complications are conflicting. METHODS: To investigate the relationship between pregnancy-associated complications and the presence of thrombophilia, we studied the records of 453 women with pregnancy-associated complications. In 55 women, intrauterine fetal death (fetus mortus in utero, FMU) after 20 weeks of gestation was recorded, in 231 two or more consecutive recurrent fetal losses (RFL) were recorded, while 167 had a venous thromboembolism (VTE) during one of their pregnancies. The control group consisted of 128 healthy women, with no previous history of thrombotic events or miscarriages. RESULTS: In the FMU group we found 54.5% of women had thrombophilia, in the RFL group 38%, and in the VTE group 52.7%. The most frequent thrombophilia in the VTE group was the FV Leiden (OR 17.9, 95% CI 4.2-75.9). The most frequent thrombophilia in the FMU group was the FII G20210A (OR 7.09, 95% CI 1.8-27.9). Statistical difference between RFL and the control group was observed only for FV Leiden (OR 6.8, 95% CI 1.6-29.7). CONCLUSION: Thrombophilia was found to be considerably more common in women with pregnancy-associated complications in comparison with the women with normal pregnancies, most frequently in patients with VTE or FMU.

PCR amplification on whole blood samples treated with different commonly used anticoagulants.

The aim of this study was to explore the influence of different anticoagulants on PCR amplification, as well as to optimize PCR amplification of blood samples for successful mutation detection. For the purpose of this study the amplification of part of methylenetetrahydrofolate reductase (MTHFR) gene exon 4, in which mutation C677T is located, was performed. With the exception of sodium heparin, the presence of other commonly used anticoagulants (sodium citrate, K3EDTA, lithium heparin) made it possible to obtain satisfactory amplification. The described method, apart from saving time and material, enables successful PCR-based analysis even when a very small amount of blood sample is available.

Multifocal plasmacytoma of hand and foot bones.

Simultaneous occurrence of localized plasmacytomas of both hands and feet has not been reported so far. Here we report a 40-year old female patient, who had at presentation pain and deformity. Of hands and feet, with numerous cystic lytic lesions of phalangeal, metacarpal and metatarsal bones, detected by X-rays. The biopsy of the affected bone showed moderately differentiated plasmacytoma of lambda light chain type (lambda-LC). Serum and urine biochemical analysis revealed the existence of lambda LC monoclonal component. The patient was treated by local radiotherapy and subsequent systemic chemotherapy, which consisted of 3 cycles of the M-2 protocol and 7 cycles of melphalan-prednisone. Five years after the diagnosis, the absence of plasmacytoma was confirmed by puncture biopsy of the left hand phalanx. Monoclonal protein in serum and urine was not detected.

[Anemia in hypothyroidism]. / Anemije u hipotireozi.

INTRODUCTION: Anemias are diagnosed in 20-60% patients with hypothyroidism. Real values of the degree of anemia are estimated by radioisotopic analysis due to the lower volume of plasma in hypothyroidism causing false high levels of hemoglobin in blood. Anemia is often the first sign of hypothyroidism. Diagnosis of hypothyroidism should be considered in every case of anemia with uncertain etiology because sometimes signs of overt hypothyroidism needn't necessarily be evident. Microcytic, macrocytic and normocytic are regularly described anemias. CLASSIFICATION: Microcytic anemia is usually ascribed to malabsorption of iron and loss of iron by menorrhagia. Macrocytic anemia is caused by malabsorption of vitamin B12, folic acid, pernicious anemia and inadequate nutrition. Pernicious anemia occurs 20 times more frequently in patients with hypothyroidism than generally. Macrocytosis is found in up to 55% patients with hypothyroidism and may result from the insufficiency of the thyroid hormones themselves without nutritive deficit. Normocytic anemia, so-called uncomplicated anemia, arises due to thyroid hormones deficit itself not followed by nutritive deficit. This type of anemia is considered to be an adaptation to a decreased basal metabolism. Thyroid hormones directly or indirectly, through erythropoietin, stimulate growth of erythroid colonies (BFU-E, CFU-E). Normocytic anemia is characterized by reticulopenia, hypoplasia of erythroid lineage, decreased level of erythropoietin, mainly regular erythrocyte survival. Acanthocytosis findings in cytologic blood smear suggest hypothyroidism in about 90% of cases.

[Non-Hodgkin's lymphoma of the thyroid gland--2 case reports]. / Nehockinski limfomi stitaste zlezde--prikaz dve bolesnice.

The authors present two female patients with Non-Hodgkin's lymphoma of the thyroid gland. The first had Non-Hodgkin's lymphoma, follicular, diffuse of centrocytic cells (FCC-intermediate grade risk), and the second had an immunoblastic Non-Hodgkin's lymphoma with large cells (high grade risk). After "staging" procedures, it was estimated that the first patient was in I EA and the second in II EB clinical stage. They were treated by surgical removal of involved tissue, combined chemotherapy and local radiotherapy. A complete remission was achieved in both patients without signs of recidivation for 8 months in one patient and 18 months in the second subject, after treatment. The elder patients more often manifest this type of lymphoma, especially if they already had chronic thyroiditis of Hashimoto's type. Using the combined, contemporary treatment, the overall five-years survival is about 56 +/- 7 percent.

[Histopathologic characteristics of bone marrow in patients with aplastic anemia]. / Histopatoloske osobine kostne srzi kod osoba obolelih od aplasticne anemije.

INTRODUCTION: Histopathologic findings in bone marrow biopsies in patients are with aplastic anaemia crucial for the diagnosis of the disease. Changes observed by the examination of bone marrow such as cellularity, histopathologic type, presence of irregular cells maturation in all three blood lineages, condition of medullar stroma can be of great prognostic significance [1, 2, 4, 5]. The aim of the study was to make histopathological analyses in patients with aplastic anaemia and to establish parameters significant for the prognosis of the disease. PATIENTS AND METHODS: Thirty-three patients with aplastic anaemia treated in the Institute of Haematology, Clinical Centre of Serbia, from 1988 to 1995 were included in the study. Bone marrow specimens were analysed for: cellularity, number of megakaryocytes, condition of medullar stroma, presence/absence of blood and oedema, lymphoid elements, presence of plasma and reticular cells, and determination of histopathologic type on the basis of bone marrow changes. For data description we used the arithmetic mean and standard deviation for parametric results. Results of analyses were explained by Kaplan-Mayer's method and two factors analysis of variance. RESULTS: In all analysed marrow biopsy specimens a 100% hypocellularity was observed: 1. Weak hypocellularity in two specimens (6%); 2. Mild hypocellularity in six cases (19%); 3. Severe hypocellularity in 24 (75%), In one case (3%) the finding was not known. In 25 specimens (75%) megakaryocytes were not found, in 5 (16%) they were rare; in two cases (6%) they were numerous. Medullar stroma changes were not found in 30 (94%) byopsies, but in two (6%) they were found. Blood and oedema liquid were found in 26 (81%) cases and not in 6 (19%). Lympho-plasmocytic bone marrow infiltration was found in 23 specimens (72%) and not in nine (28%). First histopathologic types two (one-a and one-b) were present in 25 (78%) cases, histopathologic type two in 5 (16%) and type three in 2 (6%) specimens. The two factors analysis of variance regarding proportions between dead and alive patients revealed a significant difference in proportions according to histopathologic types (FD = 7.52; DF = 2; p = 0.002). Significant statistical differences were found between alive and dead patients in all three histopathologic types, tip one (one-a and one-b) (FD = 8; DF = 1; p = 0.06); type two (FD = 4.286; DF = 1; p = 0.041) and type three (FD = 4.762; DF = 1; p = 0.031). Histopathologic type two had the best prognosis regarding survival probability; p = 0.800; in histopathologic type two survival prognosis was worse p = 0.300, and type three it was the worst, p = 0.000. With regard to survival time, there was no statistical difference in patients with weak and mild bone marrow hypocellularity (p = 0.487). We also compared patients with severe bone marrow hypocellularity with patients with weak and mild hypocellularity. The difference in survival was statistically significant (p = 0.026), Consequently, survival was shorter in patients with severe bone marrow hypocellularity. DISCUSSION: Bone marrow biopsy and histopathologic examination are necessary for definitive diagnosis of aplastic anaemia [1-3]. Cellularity estimation in bone marrow based on biopsy and histopathologic examination is more reliable than that made by bone marrow aspiration [7]. Aplastic anaemia is a disease that can be associated with abnormal clones development. Most frequently paroxysmal nocturnal haemoglobinuria, acute leukaemias and myelodysplastic syndrome occur. Therefore, repeated bone marrow biopsies are necessary to follow-up the course of the disease [10, 11]. The presence of megakaryocytes in bone marrow specimens has favourable prognostic significance. Their appearance is a reliable sign of disease improvement [6, 7]. However, lymphocytosis, plasmocytosis and damaged marrow stroma are markers of bad prognosis [7]. (ABSTRACT TRUNCATED)

[Simultaneous occurrence of localized plasmacytoma in hands and feet bones]. / Istovremena pojava lokalizovanog plasmocitoma kostiju saka i stopala.

Localized plasmacytomas in the bones account for less than 10% of all myelomas. Axial skeletal bones are most commonly affected, while isolated lesions in the hands and feet are very rare. Simultaneous occurrence of localized lesions on both hands and feet has not been reported so far. We repor on a female patient, 40 years old, whose symptoms developed simultaneosly: pain and deformity of the hands and feet were radiologically confirmed as numerous cystic transilluminations and destruction of the bones. Specific diagnostic procedures in the affected bones showed moderately differentiated plasmacytoma with lamda light-chains. Serum and urine analysis revealed a monoclonal component (lambda light-chains). The patient received local radiotherapy and combined chemotherapy. Subsequently, bone changes regressed, and monoclonal protein disappeared from both serum and urine. Four years after the onset of the disease the phalanx of the left hand was punctured confirming the absence of plasmacytoma.

[Aplastic anemia--clinical characteristics and survival analysis]. / Aplasticna anemija--klinicke odlike i analiza prezivnjavanja.

UNLABELLED: Aplastic anaemia is a relatively rare disease, characterized by the loss of haemopoietic "stem" cells in the bone marrow, exchanged with fat cells and pancytopenia. The treatment of this disease consists of supportive therapy with blood products and finally phase, where there are two possibilities: immunosuppression and bone marrow transplantation. Immunosuppression means the use of antilymphocyte or antithymocyte globulins, anabolic steroids, Cyclosporine A, corticosteroids, and recently haemopoietic growth factors [1]. The advantage of bone marrow transplantation compared to other kinds of treatment has been established in multicentric trials [2]. Goals of study: 1. To show and analyze clinical characteristics in patients with aplastic anaemia; 2. To study survival according to gender, age and kinds of treatment. METHODS: Thirty three patients with aplastic anaemia are included in the study. They were treated at the Institute of Haematology, Clinical Centre of Serbia, from 1988 to 1995. For description of data we used parameters for the arithmetic mean and standard deviation; for nonparametric tests-median. Student's T-test was used for comparison of differences among the mean values from nonparametric analytic models. From nonparametric models, Fisher's test was used. For data analysis of survival Kaplan-Mayer's model was used. RESULTS: Thirty three patients with aplastic anaemia were examined. There were 17 (52%) men and 16 (48%) women. The youngest patient was 15 and the oldest 73 years. The average age of patients was 40.18 years. In the group up to 30 years there were 16 (48%) patients. In the group from 31 to 45 years there were 4 (12%) patients. In the group from 46 to 60 years there were 4 (12%) patients, and in the group from 61 to 75 years 9 (28%); clinical signs (fatigue, exhaustion) and anaemic signs (pallor) were present in all patients (33). In 12 (36%) patients high body temperature was established and in 21 (64%) patients there was no temperature. Signs of haemorrhagic syndrome were established in 26 (79%) patients and 7 (21%) patients had no such signs. No significant statistical difference in survival (Lee-Desu = 0.071; DF = 1; p = 0.789) related to sex, was observed. According to the duration of the disease by year, and over this period, the difference was statically very significant (Lee-Desu = 20.735; DF = 1; p = 0.000). Therefore, in patients with a longer duration of the disease than one year the chance for a longer survival is better. We compared the group of patients treated with antilymphocytic globulin with the group treated with other methods (androgenic hormones and Prednisolone, Cyclosporine A and bone marrow transplantation). Between these two groups the difference was statistically significant (Lee-Desu = 2.742; DF = 1; p = 0.018). Therefore, survival of patients of the second group was longer thanks to a successful bone marrow transplantation. The group of patients treated by bone marrow transplantation was compared with the group of patients treated with other three methods; the difference was statistically significant (Lee-Desu = 7.346; DF = 1; p = 0.006). The best method of treatment is bone marrow transplantation in comparison to the other three methods. Survival was also analyzed in all four studied age groups. No statistically significant difference was found. CONCLUSIONS: Aplastic anaemia is a serious, relatively rare illness, appearing with almost equal frequency in men and women. Two peaks were noticed: in the younger age group up to 30 years (48%) and over 60 years (27%). According to survival, there was a group with short survival, up to 12 months, and a group with longer survival, over 12 months. Gender and age had no influence on duration of survival. Only the duration of the disease had a positive effect on survival. In comparison to other methods, the most efficacious treatment was allogenic bone marrow transplantation.