Diagnostic utility of comparing fibrinogen Clauss and prothrombin time derived method.
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Biomedical subjects
Publications and source records attributed to J Outeiriño.
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Clinically significant endogenous circulating heparin-like anticoagulant activity has been associated with hematological malignancies, liver damage, and other pathological conditions. The source of high plasma concentrations of endogenous heparin-like anticoagulants is poorly understood. We report three cases of circulating heparin-like anticoagulants in three patients with hematological malignancies: CLL, multiple myeloma, and T-prolymphocytic leukemia. The severity of bleeding in our patients ranged from severe epistaxis and deep-site hematoma to bleeding of biopsy site and occasional ecchymosis.
UNLABELLED: Factor V Leiden and G20210A mutation of the prothrombin gene have been described as risk factors in thrombophilic pathologies. Our objective has been to know the prevalence of these two mutations in a group of patients with thrombophilic pathology and to compare it with its prevalence in a control group of Spanish population. PATIENTS AND METHODS: 64 patients were divided in two groups. First, 39 patients with deep venous thrombosis (DVT): 24 with an unique episode of DVT; 11 with more than one episode; 3 with DVT and pulmonary thromboembolism, and one with DVT and more than one episode of cerebral thrombosis. Second, 25 patients with other pathologies, such as pulmonary thromboembolism (9 patients), acute cerebrovascular accident (10 patients) and 6 who came to our Department because there were some carrier in their families. The 20210A allele was analyzed in 37 of the 64 patients. Some of the 64 patients had haematological determinations of the activated protein C resistance (APC resistance). As well, 103 unrelated subjects with unknown thrombotic pathologies were analyzed. RESULTS: We have found a prevalence of factor V Leiden in the group of patients of 14.1% (9 carriers in 64 patients, all of them in the first group of 39 patients with DVT) versus 1% in the control group (1 carrier in 103 controls). On the other hand, the difference between the prevalence of the 20210A allele was not statistically significant between the group of patients and the control group (2.7% vs 2.9%). In 75% of the patients no haematological results of APC resistance were obtained, generally because they were with anticoagulant treatment, and in 11.1% of the carriers the result of the determination was considered as ambiguous or false negative. CONCLUSION: Factor V Leiden is well established as risk factor in the thrombophilic pathology, but more studies are needed to know the meaning of the G20210A mutation of the prothrombin gene.
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PURPOSE: 1. To recognise the clinico-biological profile of a group of patients diagnosed of polycythaemia vera (PV) in our centre in the last 30 years. 2. To identify the evolutive patterns of haematological transformation. 3. To evaluate the effect of therapy on the survival. PATIENTS AND METHODS: The clinical records of 74 patients (median age 62 years, male/female = 0.94, followed-up for 6-357 months, median 64 months) were reviewed. Clinico-biological data at diagnosis, therapy, complications and evolution of the haematological picture were evaluated in each case. The actuarial survival in the series was compared to that of the normal population. RESULTS: The clinico-analytical data and diagnostic features were identical to other series reported. Mild increases of bone marrow reticulin was present in two thirds of the cases, overt myelofibrosis being found in only 10% of the patients. Abnormal karyotype was seen in 9% of the patients (11q-, -Y). Phlebotomy was the only treatment in eight cases, without increased incidence of thrombotic phenomena. The remainders received myelosuppressive therapy (32P, busulphan, pipobroman, hydroxyurea, etc.), thrombotic complications appearing in 8 cases and haemorrhagic complications in 4 others. One of these latter patients developed oesophageal carcinoma. The haematological picture evolved into toxic aplastic anaemia in 2 cases; myelofibrosis with myeloid metaplasia (MF/MM) in 8; myelodysplastic sindromes (MDS) in 5, three of them RAEB; and acute myelogenous leukaemia in 3 cases, two of them as the final stage of previous MF/MM and MDS/ RAEB. The actuarial survival was 71% at ten years and 46% at fifteen years, and the median survival as a whole was 13.5 years. CONCLUSIONS: 1: The treatment, mostly myelosuppressive, given to these patients attained a survival similar to that of the general population. 2: Of the cases with known evolution, 15.6% developed MF/MM, its incidence being higher in patients treated only with phlebotomy (37%). 3: The incidence of malignant evolution, i.e., to RAEB/AML, amongst those patients followed-up was 10.6%.
Twenty-three hemodialysis patients exposed to an accidental aluminum overload, showed increased erythropoietin requirements and decreased erythrocyte mean corpuscular volume (MCV). At the peak of the intoxication, MCV and plasma aluminum levels changed from unrelated (r = 0.02) to strongly related (r = 0.425) variables. The molar proportion of plasma aluminum to plasma iron increased dramatically (from 1:13.8 to 1:2.4). This significant increment in the aluminum/iron ratio made higher the relative offer of aluminum with respect to iron to the erythroid precursor cells. Accordingly, in a subset of 13 randomly selected aluminum-intoxicated patients we found increased intraerythrocytic aluminum, which paralleled the increase in plasma aluminum. Furthermore, in the aluminum-intoxicated group, intraerythrocytic ferritin, a marker of iron content, and the ratio between erythrocyte and plasma ferritin were lower (P < 0.01 and < 0.001, respectively), than in the control group. These findings support the hypothesis that in some cases of aluminum-related microcytosis, a ferropenic mycrocitosis, as expression of erythroid ferropenia, may exist in spite of the presence of normal body iron stores.
To determine the role of nitric oxide (NO)-dependent mechanisms on erythrocyte properties, we exposed red cells to L-arginine competitive analogues, 8Br-cyclic guanosine monophosphate (8Br-cGMP) and neutrophil-eliminating filters. These treatments significantly decreased hypotonic hemolysis, increased potassium efflux and caused a spiculate change in erythrocyte morphology. These effects were related to a decrease of NO caused by the three types of treatments.
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Auto-immune haemolytic anaemia (AIHA) has been found in a case of alpha-interferon treatment. Serum antibody and eluate were positive in the absence of the drug. Although the patient recovered after the treatment was stopped, DAGT remained positive for at least 8 months. The mechanism proposed to explain why this drug induced AIHA is similar to that proposed for alpha-methyl-dopa. Drugs could alter the red cell membrane and impair the immune system. Such changes have been observed with alpha-interferon and were related with increased autoimmunity.
PURPOSE: To evaluate in retrospect the response to therapy and long-term evolution of a series of primitive intestinal lymphomas. PATIENTS AND METHODS: The series was comprised of 42 patients diagnosed in our hospital during 1960-1962. The mean age was 34.5 years (range, 3-73), the M/F ratio was 21/21, and the histopathology distributes as follows: high grade (HG), 24 cases, low grade (LG), 12 cases, and mixed (LG/HG), 6 cases. B/T immunophenotype: 40/2. Staging: IE1,29 cases, IIE2-IV, 11 cases. The treatment applied in the series was classified in various types: ample surgical resection (aSR), 21 cases; partial surgical resection (pSR), 9 cases; abdominal radiation therapy (RT), 7 cases; monochemotherapy (MCT), 7 cases, and polychemotherapy (PCT), 28 cases. The correlation of clinicobiological variables with immediate response to treatment was evaluated by means of the chi square test, and the acturial post-therapeutic survival curves in accordance to the life tables, differences being calculated by the log rank test. RESULTS: Small intestine was the commonest site of involvement, 31 cases; ileocecal region, 7 cases; colon, 2 cases, and colon plus small intestine, 2 cases. Regardless of therapy type, complete remission (CR) was attained in 20 patients (47.5%), partial remission in 5; 11 cases were unresponsive (26.5%) and early death occurred in 6 instances (14.2%). The acturial post-therapeutic survival offered an 8-year expectancy of 47%. The correlation between immediate complete response and 16 clinico-biologic variables showed favourable significance for tumoral proliferation index (i.e., Pc10-positive cells < 15%) and for therapeutic regimens including PCT+aSR. On the other hand, the necessity of emergency surgery for diagnosis was a poor-risk factor. The correlation between a post-therapeutic survival and 19 other variables showed the following as favorable data: female sex, tumour proliferative index (i.e., Pc10-positive cells < 15%), the use of PCT+aSR, and attaining CR. Poor-risk factors were the need of emergency surgery, multicentric lymphomatous involvement and serum LDH rates 350 UI/L. Although immediate response (CR) and long-term results (survival) were better in the patients with favourable histology (LG+LG/HG) and in those with loco-regional disease (stages IE-IE1), the differences had no statistical significance, possibly due to the low number of cases. CONCLUSIONS: 1) Even though these findings should be carefully evaluated, dut to lack of homogeneity of the series and the fact of being a retrospective study, the rate of CR in this series (47.5%) is similar to that of current studies. 2) Female sex, type of therapy, multifocal involvement, the need of emergency surgery and high LDH levels have significant value in univariate analyses.
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PURPOSE: To retrospectively analyse all the patients diagnosed and treated in the same hospital for acute lymphoblastic leukaemia (ALL) in whom therapy was suppressed after sustained complete remission (CR) for a variable period. PATIENTS AND METHODS: Eighty cases of ALL treated at the Jiménez Díaz Foundation between 1968 and 1991 were revised. Treatment had been suppressed after 60 months of maintained CR (1968-1974) or after 28 months (1986-1991), with a median follow-up after suppression of 6 years. All the patients had been treated with several protocols (FJD-68, FJD/BFM, APO, BFM-83, BFM-86 and BFM-90). Maintained CR, relapses and course after therapy cessation were analysed. Actuarial curves of RC duration and survival were drawn according to the Cutler and Ederer life tables. RESULTS: The age at diagnosis ranged from 1.5 to 68 years. Childhood (< 15 years) ALL presented in 49 cases; 25 were young adults (15-30 years), and 6 others were over 30 years of age. Two of the 80 patients (2.5%) died in CR (astrocytoma and demyelinating leukoencephalopathy). Fifty-eight patients (72.5%) are living in maintained CR; 20 others relapsed (25%), 14 of them (70%) attaining a second CR. Allogenic BMT was carried out in 4 such cases. Four patients are out of any treatment after the second CR. The actuarial curves of CR duration after suppression of therapy gave a stable plateau at 73% for children, at 75% for young adults and at 22% for patients over 30 years. The survival after suppression of therapy showed a plateau at 75% for children and at 86% for young adults. CONCLUSIONS: 1) Relapse was seen in 25% of the patients after cessation of therapy. 2) Relapse occurred in the first two years after therapy cessation in 75% of the instances. 3) At this writing, 78.7% of the patients keep up the CR. 4) Adults over 30 years of age comprise the poorest prognosis. 5) The course of young adults in this series after cessation of therapy is as good as that of children.
Forty-four cases of essential thrombocytosis (ET) were diagnosed in the last 20 years, 19 males and 24 females (M/F: 0.76), aged between 3 and 86 years (median, 62 years), and 9 of them being under 40 years of age. The M/F ratio for patients under 60 years was 0.5, whereas it was 1.09 for patients over 60. The clinical forms at onset were: asymptomatic, 36.5%; as a bleeding disorder (BD), 20.4%; as thrombotic disease (TD) 22.7%; BD/TD, 13.6%, and others, 6.8%. The most important biological features included platelet count over 1.000 x 10(9)/L (59.1%), abnormal platelet aggregation, chiefly with ADR (56.5), mild reticulin myelofibrosis (55%), abnormal karyotype (2.6%), moderately high LDH levels (56.8%) and pseudo-hyperkalaemia (40%). The initial therapeutic approach was: observation (12 cases), antiaggregating agents (6 cases), and chemotherapy (BSF, HU, etc.) in the remainders. One patient evolved quickly into acute myelogenous leukaemia and two others suffered a late transformation into polycythaemia vera (PV) and myeloid metaplasia, respectively. The median survival was over 11 years, this being longer in patients under 60 years of age, in those with platelet count at diagnosis between 600 and 1000 x 10(9)/L and in those without initial symptoms of thrombosis. The advent of electronic blood-cell counters has made ET no longer a rare chronic myeloproliferative disease, its incidence coming now closer to that of PV; thus, in the last four quinquennial periods the incidence of ET/PV has evolved as following: 1/19, 4/16, 13/18 and 26/29.
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An 80 year-old woman presented subleukaemic acute monoblastic leukaemia (AML-M5a). Her bone marrow showed invasion by highly dysplastic histio-monocytic cells of great size and wide cytoplasm, with intense phagocytic activity (erythrophagocytosis was frequently seen), and with abnormal karyotype (50XX, +8, +8, +16, +21). The different malignant and reactive features of the mononuclear phagocytic system are commented, along with the haemophagocytic activity of the histio-monocytic cells in different states. The cytogenetic anomalies more frequently found in AML-M5 are also dealt with as compared to this patient's. The case reported here seems to correspond to subleukaemic acute "monophagocytic" leukaemia, with a biologic phenotype close to that of malignant histiocytosis.
A defect of haemoglobin synthesis is the classically recognized mechanism affecting the erythron functionalism in chronic iron deficiency. The poor erythroblastic bone-marrow response, plus a number of dyserythropoietic nuclear features, have led to think of an impairment of the cell cycle of erythroblasts in iron-lack anaemia. The aim of the present work was to study such hypothesis, not proven so far. Ten subjects with normal haemopoiesis and 39 patients with iron-lack anaemia of different aetiologies (namely, 19 with digestive tract bleeding, 16 with gynaecological bleeding, and 4 with haemorrhages on other locations) were included in a previously reported protocol. The scheme of such protocol consisted of: 1) bone-marrow erythroblast quantification; 2) analysis of their maturation gradient; 3) erythroblast mitotic index; 4) measure of the mitotic time in bone-marrow culture; 5) tritiated-thymidine incorporation to short-term bone-marrow culture and quantification of the erythroblastic labelling index. To these were added the degree of nuclear dyserythropoiesis according to Hill and Lewis, and the reticulocyte production index. The following mean values were found in the control group: erythroblasts, 25.5 (+/- 3.63) %; E1-E4, 47.66 (+/- 3.09) %; IDN, 0.67 (+/- 0.27); MI, 2.82 (+/- 0.66) %; MT, 1.05 (+/- 0.15 hr); LI, 34.88 (+/- 5.82) %. The mean values found in iron-lack anaemias were as follows: erythroblasts 39.42 (+/- 9.1) %; E1-E4, 42.25 (+/- 4.11) %; IDN, 7.77 (+/- 4.69); MT, 1.81 (+/- 0.95) hr; LI, 13.08 (+/- 6.51) %. The statistical analysis (Student's t) showed highly significant differences (p less than 0.001) in the increased IDN and decreased MI and LI in iron deficiency patients.(ABSTRACT TRUNCATED AT 250 WORDS)