Mariano Linares

Autoimmune Thrombocytopenia Associated with Hepatitis C Virus Infection

We have retrospectively analyzed a series of 19 patients with hepatitis C virus (HCV) infection and chronic thrombocytopenia not attributable to hypersplenism or to other causes. Antiplatelet antibodies were present in 81% of cases. Response to prednisone was observed in 6 of 7 patients and 1 of 3 patients responded to intravenous immunoglobulins. No case of reactivation of liver disease was observed during or after therapy. We consider that the possibility of an underlying mechanism should be evaluated in thrombocytopenic patients with HCV infection who do not present hypersplenism. These patients could benefit from steroid treatment.

Evidence of an Increased Susceptibility to Lipid Peroxidation in Red Blood Cells of Chronic Renal Failure Patients

Amparo Miguel Sosa, Hospital General de Valencia, Servicio de Hematología, Avenida Tres Cruces s.n., E-46008 Valencia (Spain) Dear Sir, The study of the red blood cells (RBC) oxidative metabolism in chronic renal failure (CRF), has recently become of interest, and until now, the results have not been very concordant. It has been shown [1], that there is an alteration in RBC pentose-phosphate shunt of patients with CRF undergoing hemodialysis. This would mean an alteration in the detoxification of the hydroxyl and peroxide radicals, with the ensuing peroxidation of the polyunsaturated fatty acids (PUFA) in the RBC membranes [2]. Consequently, an increase in the rigidity and deformability of these membranes is produced and, as a result, an increase in the susceptibility to hemolysis appears. The malonyl-dialdehyde acid (MDA), a short-chain aldehyde, is an intermediate product of the oxidation of PUFA, and has been reported as a good indirect method to measure the oxidative degradation of PUFA [3,4]. In order to investigate the susceptibility to the oxidative damage in the RBC, we determined the RBC levels of MDA in a group of patients affected by CRF. The study was performed on 58 subjects with CRF, divided into two groups. Group I consisted of 30 patients, 16 males and 14 females, aged 39–82 years (mean 62). The creatinine clearance was lower than 15 ml/min, (preterminal renal failure). All of them followed a low-protein and low-salt diet, adapted to tension levels. Group II consisted of 28 patients, 24 males and 4 females, aged 22–74 years (mean 51). All these patients were subjected to a regular hemodialysis program with a mean treatment duration of 37.3 months (range 27–150). The patients were dialyzed three times weekly, each session lasting 4 h. The dialyses were all done with a 0.9to 1.3-m2 hollow-fiber dialyzer and a standard dialysate with an acetate concentration of 38 mEq/1, and a dialysate flow rate of 500 ml/min. Water was purified by an inversed-osmosis treatment. All patients were on a free diet, and none of them were taking any drugs that could interfere with the parameters considered, nor had they received any blood transfusion during the 3 months preceding the study. Patients presenting hepatic

Low Molecular Weight Heparin (CY-216) versus Unfractionated Heparin in Chronic Hemodialysis

In 14 patients undergoing chronic hemodialysis, we investigated the safety and efficacy of the low molecular fragment (CY-216) in comparison to unfractionated heparin (UFH) in the prevention of clotting in the extracorporeal circuit (ECC). In this study, 168 hemodialysis sessions were undertaken with UFH in 2 bolus doses (5,437 +/- 1,477 SD IU) and 231 with CY-216 in a single bolus dose [initial dose 150 anti-Xa U Institut Choay (IC)/kg]. There were no clots in the bubble trap in any UFH sessions, and 14.8% had coagulated fibers in the dialyzer. Clotting in the bubble trap was observed in 2 CY-216 sessions (0.8%) and coagulated fibers in 22.6% of the sessions. At the end of the study, the mean dose of CY-216 was 250 anti-Xa UIC/kg but a dose of 350 anti-Xa UIC/kg was needed in the 2 patients treated by recombinant human erythropoietin. Anti-Xa levels at the end of the runs were higher (0.47 +/- 0.1 U/ml) in the CY-216 group than in the UFH group (0.28 +/- 0.1 U/ml). There was a correlation between anti-Xa levels and efficacy in the CY-216 group. An anti-Xa activity above 0.4 U/ml was needed in order to minimize thrombus formation. Antithrombin III-protease complexes (ATM) and D dimer fibrin derivatives (D dimer) were used as thrombotic markers but they were of little value for the detection of fibrin formation in the ECC. Our findings suggest that CY-216 administered as a single bolus dose seems to be of similar effectiveness to UFH.

Chronic idiopathic thrombocytopenic purpura in the elderly.

From a group of 118 patients with chronic idiopathic thrombocytopenic purpura (ITP), 43 were older than 60 years at diagnosis. In this report, we describe the clinical evolution and therapeutic response in young and old patients. The overal rate of hemorrhagic manifestations was similar in the two age groups, but a greater risk for severe bleeding was observed in elderly patients. There were no significant differences between old and young patients in response to steroids. In none of our patients was mortality associated with bleeding or side effects of the treatment. In conclusion, we have observed a more benign clinical course in elderly patients with chronic ITP as compared to previous reports.

Slow infusion of vincristine in the treatment of refractory thrombocytopenic purpura

Eight patients with idiopathic thrombocytopenic purpura (ITP), who were refractory to glucocorticoid therapy, were given slow infusions of vincristine (VCR) over a 4- to 6-hour period at weekly intervals for 4 weeks. Three patients showed a return to normal platelet counts maintained for 3 months or longer. A transient recovery was observed in 1 patient and a partial response was observed in 3 patients. All patients tolerated therapy well, without side effects. In conclusion, therapy with slow infusion of VCR can be effective in refractory ITP.

Hepatocellular carcinoma and squamous cell carcinoma in a patient with Fanconi's anemia.

SummaryAcute leukemia, hepatocellular carcinoma, and squamous cell carcinoma have been reported in patients with Fanconis anemia. We report on a 31-year-old woman who developed squamous cell carcinoma of the esophagus and hepatocellular carcinoma. Jaundice and hepatic tumor developed in 1981, after she had received oxymetholone for 10 years. Liver biopsy revealed peliosis hepatis. Androgenic therapy was stopped and the jaundice resolved. However, the hepatic tumor was observed to be unchanged. The patient died of disseminated squamous cell carcinoma, but no metastatic lesions from hepatocellular carcinoma were detected in the autopsy. The association of Fanconis anemia and squamous cell carcinoma is reviewed, and the malignant potential of androgen-related hepatic tumors is discussed.

Red cell distribution width analysis in differentiation between iron deficiency and thalassemia minor.

Dr. Amparo Miguel, Servicio de Hematologia, Hospital General, Avenida Tres Cruces S.N., E-46008 Valencia (Spain) The use of flow cytometry for routine blood counts allows one to know the distribution of red cell volume, measured as coefficient of variation and reported as red cell distribution width (RDW). This parameter has been very useful in the initial classification of anemias [1, 2], and mainly as a discriminant between iron deficieny and αor ß-thalassemia minor [3–7]. Using a Coulter Counter, model S Plus II, we have studied the RDW in 477 microcytic anemias (116 with iron deficiency, 186 ß-thalassemia minor and 175 δ‚ß-thalassemia minor). Irondeficient patients were selected if their serum iron was below, and their total iron-binding capacity above the normal limits for the laboratory. According with Weatherall and Clegg [8], heterozygotes for ß-thalassemia were selected on the basis of high levels of hemoglobin A2, and heterozygotes for δ‚ß-thalassemia, by normal or decreased levels of hemoglobin A2 and high levels of hemoglobin F. RDW from iron deficiency (18.39 ± 4.18) and δ‚ß-thalassemia (19.67 ± 2.93) were significantly higher (p < 0.001) than ß-thalassemia values (16.67 ± 2.94), but no significant difference could be demonstrated between iron deficiency and δ‚ß-thalas-semia (unpaired t test). 84% patients with ß-thalas-semia minor had a RDW below 18%, and 72% with δ‚ß-thalassemia minor above 18%. If we consider a RDW of 18% as a discriminant factor between both thalassemias, the positive predictive value for ß-thal-assemia is 82% and 76% for δ‚ß-thalassemia. Several possible explanations can be proposed to account for this increased RDW in δ‚ßthalassemia minor. Anemia, iron deficiency and high reticulocyte count are the main factors that increase the RDW value in microcytic anemias [4, 9]. In this study, none of them are able to explain the difference between RDW from both groups of thalassemia, because no significant differences have been found between them. Our results show that the RDW does not discriminate between iron deficiency and δ‚ß-thalassemia, but it can be helpful in the screening between ßand δ‚ß-thalas-semia traits. References Bessman, J.D.: Heterogeneity of red cell volume: quantitations, clinical correlation, and possible mechanisms. Johns Hopkins Med.J. 146: 226–230(1980). Kaye, F.J.; Alter, B.P.: Red cell size distribution analysis: a non-invasive evaluation of microcytosis. Blood 60: suppl. 1, p. 362 (1982).

Auto-immune haemolytic anaemia in ulcerative colitis: report of three cases.

Dr. Fernando Hernández, Hospital General Universitario, Servicio de Hematologia, Avenida Tres Cruces s/n, E-46014 Valencia (Spain) Auto-immune haemolytic anaemia (AIHA) is a rare but severe complication of ulcerative colitis (UC) occurring in fewer than 1% of cases [1-4]. We present 3 cases of AIHA associated with UC. Case 1 A 31-year-old man with a 10-year history of UC was admitted to the hospital in December 1992 for total proctocolectomy because of persistent colitis. A subtotal colectomy was performed 9 years before. On admission, his haemoglobin (Hb) level was 10.7 g/dl; leucocyte and platelet counts were normal. Reticulocyte count was 304 × 109/1, bilirubin 1.6 mg/dl, haptoglobin 0.23 g/l (normal value 1-2) and LDH 525 U/l (normal value 150-450). The direct antiglobulin test (DAT) was positive (anti-IgG), indirect antiglobulin test and eluate were also positive. After 7 days prednisone treatment (1 mg/kg/day) his Hb rose to 13.8 g/dl. The patient underwent total proctocolectomy in January 1993. Steroids were reduced gradually and stopped in February 1993. Despite not having received treatment for 4 months, he felt perfectly well and his Hb level was 15 g/dl. He still had a weakly positive DAT. Case 2 A 39-year-old woman was diagnosed as having UC in 1986. In October 1989, she was admitted to the hospital with acute haemolytic anaemia. Her Hb level was 6.7 g/dl, reticulocyte count was 196 × 109/1, bilirubin 3.2 mg/l, haptoglobin 0 g/l and DAT was positive (anti-IgG). Indirect antiglobulin test and eluate were positive. The patient was started on 2 mg/kg/day of prednisone, and her Hb rose to 12.7 g/dl over 3 months. Steroids were discontinued but DAT remained positive although weaker than previously.

Immunological phenotype of plasma cells in monoclonal gammopathy of undetermined significance

Dear Sir: The differentiation of monoclonal gammopathy of undetermined significance (MGUS) from multiple myeloma (MM) is fraught with difficulty when the monoclonal protein is recognized. A number of parameters have been evaluated in patients with MGUS as compared to MM. However, no studies have been carried out to evaluate the usefulness of monoclonal antibodies in distinguishing between MGUS and MM. The immunological phenotype of MM has been studied in the last few years. Most of the plasma cells from patients with MM react with monoclonal antibodies (McAb) CD38 (OKT10) and CD9 (FMC 8), but usually lack Sm Ig and the I a. CD 19 (B 4), CD 20 (B 1), CD 21 (B 2), and CD 10 (CALLA) antigens [1, 2, 4, 5]. However, expression of plasma cells in monoclonal gammopathy of undetermined significance (MGUS) has so far not been reported. We analyzed the plasma cells of bone-marrow smears from 13 patients with MM and from 9 patients with MGUS. We used the alkaline-phosphatase/anti-alkaline phosphatase (APAAP) technique [3], with a panel of monoclonal antibodies against CD 38 (OKT 10), CD 10 (J 5), CD 21 (B 2), and I a. Our results are shown in Table 1. Most of the plasma cells in both groups were CALLA, B 2, and I a negative, as described in the literature on myeloma cells. Like plasma cells in MM, most of the plasma cells from patients with MGUS reacted with the McAb OKT 10, showing no difference between the groups when Students t-test was used. Based on the results from our study, plasma cells in MGUS express the same surface markers as myeloma cells. Consequently, the use of specific McAb (at least not the McAb used in this study) is