Denise Menezes Brunetta

Hematological abnormalities in HIV-infected patients.

BACKGROUND Anemia, neutropenia, and thrombocytopenia are commonly observed in HIV-infected patients. This study was undertaken to evaluate the prevalence of cytopenias and their association with CD4 count. Furthermore, the association of hemoglobin concentration with mortality was also investigated. METHODS We reviewed the data of 701 HIV-infected patients followed at our institution. Blood cell counts, hemoglobin concentration, CD4 count, and viral load were recorded. We also recorded the mortality rate after 1 year in the groups with CD4 <200/μl and ≥ 200/μl according to hemoglobin concentration. RESULTS Of the total patients, 37.5% had anemia; 61.1% (110/180) were in the low CD4 group and 29.4% (153/521) were in the high CD4 group (p<0.01). Mean neutrophil counts were 2.610 × 10(9)/l and 3.204 × 10(9)/l in the low CD4 and high CD4 groups, respectively (p<0.01); mean platelet counts were 218.639 × 10(9)/l and 234.807 × 10(9)/l for the low CD4 and the high CD4 groups, respectively (p=0.03). Patients whose hemoglobin concentration was below the median value had a higher death rate in both the low CD4 (14 vs. 4 deaths, p=0.013) and high CD4 (8 vs. 1 death, p=0.0158) groups. CONCLUSIONS We found an association between CD4 count and hemoglobin level, neutrophil count, and platelet count, and that anemia was independently associated with a higher mortality.

Rhabdomyolysis and acute renal failure after strenuous exercise and alcohol abuse: case report and literature review

CONTEXT Rhabdomyolysis is a severe and life-threatening condition in which skeletal muscle is damaged. Acute renal failure due to rhabdomyolysis has been widely described and its main pathophysiological mechanisms are renal vasoconstriction, intraluminal cast formation and direct myoglobin toxicity. OBJECTIVE To report on a case of acute renal failure (ARF) induced by rhabdomyolysis due to strenuous exercise and alcohol abuse and to describe the pathophysiology of this type of ARF. CASE REPORT A 39-year-old man arrived at the hospital emergency service with swollen legs and lower extremity compartment syndrome. He was oliguric and had serum creatinine and urea levels of 8.1 mg/dl and 195 mg/dl, respectively. The diagnosis of rhabdomyolysis was made through clinical and laboratory findings (creatine kinase activity of 26320 IU/l). The initial treatment consisted of fluid replacement and forced diuresis. The specific treatment for compartment syndrome, such as fasciotomy, was avoided in order to prevent infection. Partial recovery of renal function was recorded, after ten hemodialysis sessions. Complete recovery was observed after two months of follow-up.

Clinical and hematological effects of hydroxyurea therapy in sickle cell patients: a single-center experience in Brazil

CONTEXT AND OBJECTIVES Sickle cell disease (SCD) is the most common genetic disorder among people of African descent, affecting approximately 3,500 newborns each year in Brazil. Hydroxyurea (HU) is the only effective drug to treating patients with SCD, thereby reducing morbidity and mortality. The objective was to analyze the effects of HU on SCD patients at our institution. DESIGN AND SETTING Retrospective study conducted at a sickle cell centre in Ribeirão Preto, São Paulo, Brazil. METHODS We analyzed clinical and laboratory data on 37 patients. The hematological parameters and clinical events that occurred during the year before and the first year of treatment with HU were analyzed. The mean dose of HU was 24.5 ± 5.5 mg/kg/day. RESULTS There were rises in three parameters: hemoglobin (8.3 g/dl to 9.0 g/dl, P = 0.0003), fetal hemoglobin (HbF) (2.6% to 19.8%, P < 0.0001) and mean cell volume MCV (89 to 105 fl, P = 0.001); and reductions in the numbers of leukocytes (10,050/µl to 5,700/µl, P < 0.0001), neutrophils (6,200/µl to 3,400/µl, P = 0.001), platelets (459,000/µl to 373,000/µl, P = 0.0002), painful crises (1.86 to 0.81, P = 0.0014), acute chest syndromes (0.35 to 0.08, P = 0.0045), infections (1.03 to 0.5, P = 0.047), hospitalizations (1.63 to 0.53, P = 0.0013) and transfusions (1.23 to 0.1, P = 0.0051). CONCLUSION The patients presented clinical and hematological improvements, with an increase in HbF and a reduction in the infection rate, which had not been addressed in most previous studies.

Intrahepatic Cholestasis in Sickle Cell Disease: A Case Report

Intrahepatic cholestasis (SCIC) is an uncommon but potentially fatal complication of sickle cell disease (SCD), with a high death rate, observed mainly in patients with homozygous sickle cell anemia. Herein, we describe a case of severe SCIC treated successfully with aggressive manual exchange transfusion (ET). The patient was admitted with enlarged liver and signs of hepatic failure, such as hyperbilirubinemia and coagulopathy. There was no evidence of viral hepatitis or biliary obstruction. We performed several sessions of ET in order to reduce the percentage of HbS to levels inferior to 30%, which was successfully accomplished. The patient had a complete recovery of hepatic function. This case has shown that ET is an effective treatment of SCIC and should be introduced early on the onset of this severe complication.

Hydroxyurea increases plasma concentrations of microparticles and reduces coagulation activation and fibrinolysis in patients with sickle cell anemia.

Microparticles (MPs) are present in healthy subjects and their concentration increases in patients at high risk of thrombosis. We evaluated 10 patients with sickle cell anemia (SCA) treated with hydroxyurea (HU) and 13 SCA patients without this treatment. MP concentrations were determined by flow cytometry. Coagulation was evaluated using the thrombin-antithrombin complex (TAT) and D-dimers. Total MP concentrations were increased in the HU-treated group (265 × 106/ml vs. 67.45 × 106/ml; p = 0.0026), as well as MPs derived from RBC (67.83 × 106/ml vs. 26.31 × 106/ml; p = 0.05), monocytes (51.31 × 106/ml vs. 9.03 × 106/ml; p = 0.0084), monocytes with tissue factor (TF) expression (2.27 × 106/ml vs. 0.27 × 106/ml; p = 0.0058), endothelium (49.42 × 106/ml vs. 7.23 × 106/ml; p = 0.007) and endothelium with TF (1.42 × 106/ml vs. 0.26 × 106/ml; p = 0.0043). Furthermore, the concentrations of TAT (7.56 vs. 10.98 µg/l; p = 0.014) and D-dimers (0.65 vs. 1.29 µg/ml; p = 0.007) were reduced with HU. The MP elevation may suggest a direct cytotoxic effect of HU. Another explanation is a cell surface increase secondary to a megaloblastic process, resulting in increased vesicle release. In our opinion, the known benefits of HU on SCA patients, along with the reduction in coagulation activation, surpass its potential detrimental effect on MPs. Future studies should elucidate the role of MPs and demonstrate their significance in different contexts.

Preoperative variables associated with transfusion requirements in orthotopic liver transplantation

BACKGROUND Patients with end-stage chronic liver disease (CLD) and submitted to orthotopic liver transplantation (OLT) usually require blood transfusion during the procedure or in the post-operative period due to hemorrhage. Risk factors for transfusion need are not fully known. This study aimed to identify the factors associated with blood components requirements. METHODS In this retrospective study a total of 166 consecutive patients submitted to OLT with the piggyback technique, between 2001 and 2011, were evaluated for number of blood components transfused during surgical procedure and the four subsequent days (total of 5 days). We evaluated the association between the number of units transfused and clinical variables, such as: Child-Turcotte-Pugh (CTP) and MELD scores, hemoglobin concentration (Hb), INR, serum creatinine, bilirubin and albumin concentrations, and total, hypothermic and normothermic time of graft ischemia. RESULTS 152 (91.6%) Patients were transfused (median of 24 units of blood components). Risk factors for higher blood transfusion requirements were CTP, INR, Hb and total time of graft ischemia. The group with CTP-A score received less blood components than CTP-B/C (11.5 vs 27; P=0.002). The group with Hb<10 required a higher number of blood units (34.5 vs 23; P=0.003). The group with INR<1.5 received less blood units (20.5 vs 31; P=0.012). The group transplanted with a graft exposed to less than the median of 555 min of ischemia received less transfusion (21 vs 27; P=0.03). MELD score and the other factors were not associated with blood requirements. CONCLUSION These results demonstrate that CTP, but not MELD score, hemoglobin concentration, INR, and total time of graft ischemia are preoperative variables associated with blood requirements during OLT and in the subsequent days.

Sickle cell disease and pregnancy: analysis of 34 patients followed at the Regional Blood Center of Ribeirão Preto, Brazil.

Objective The objective of this study was to verify the evolution of pregnancies in sickle cell patients followed at one institution over a period of 12 years (January 2000 to June 2012). Methods The study evaluated 34 pregnant women with sickle cell disease with a mean age of 23.9 ± 5.3 years. The incidence of obstetric complications, non-obstetric complications linked to sickle cell disease and complications in the newborn were analyzed. Results A total of 26% of the cases reported previous miscarriages, 20% had preterm labor, 10% had pre-eclampsia, and 5% had gestational diabetes. Forty-one percent of the deliveries were cesarean sections and 29% of patients required blood transfusions. In respect to sickle cell disease, 62% of patients had vaso-occlusive crises, 29% had acute chest syndrome, 23% had urinary tract infection, 15% had impaired cardiac function and 6% developed pulmonary hypertension. Only one patient died in the postnatal period due to acute chest syndrome. The mean gestational age was 37.8 ± 2.63 weeks, and mean newborn weight was 2.809 ± 643.8 g. There were seven fetal losses, including three stillbirths and four miscarriages. The impact of transfusion therapy on the incidence of maternal–fetal complications during pregnancy was evaluated. Conclusions Pregnancy in sickle cell patients is still associated with complications. Although no statistical difference was observed between transfused and non-transfused women, there were no deaths (fetal or maternal) in transfused patients whereas one maternal death and three stillbirths occurred in non-transfused women. A larger study of sickle cell pregnant women will be necessary to elucidate the actual role of transfusion during pregnancy in sickle cell disease.

Mobilization and harvesting of PBPC in newly diagnosed type 1 diabetes mellitus.

Autologous hematopoietic stem cell (HSC) transplantation is an established treatment for hematological malignancies, and recently has been employed to treat severe chronic autoimmune diseases (CAID), including newly diagnosed type 1 diabetes mellitus (T1DM). The objective of this modality of treatment in autoimmune diseases is the elimination of autoreactive clones of T cells to allow the regeneration of a ‘new’ immune system from the HSC infused. At diagnosis most of b-cell mass has been destroyed. However, blocking autoimmune aggression could spare the remaining b-cells and confer a clinical remission. Mobilization and harvesting of HSC from PBSC is an essential part of autologous transplantation, but the optimal strategy for it remains unclear. Usually, HSC mobilization includes administration of G-CSF, alone or in combination with chemotherapy, to harvest a minimum of 2.0 10 CD34þ cells/kg for rapid engraftment after a myeloablative conditioning regimen. Nevertheless, it is estimated that 2–40% of patients fail to achieve the minimal cellular dose for transplant. This retrospective study has the purpose to unveil the characteristics of HSC mobilization in patients with T1DM. We reviewed the records of 25 patients with T1DM enrolled at our institution. All the patients were within 6 weeks from diagnosis, when they were submitted to mobilization and harvesting of HSC. Our hypothesis is that these patients are ‘good mobilizers’ as they were not previously exposed to drugs toxic to HSC or BM stroma. CD34þ cells were mobilized with CY (2 g/m) associated with G-CSF (median 9.4 mg/kg/day; range 4.9–12.5mg/kg/ day), initiated the day after the CY administration and continued daily until cell collection, and harvested through peripheral access from all the patients. Harvesting was initiated when the CD34þ cell count reached a minimum of 10/mL in peripheral blood. Aphereses were performed using the continuous-flow blood cell separator COBE Spectra (Caridian BCT, Lakewood, CO, USA). The results were shown as median and range. To compare eventual differences Mann–Whitney test (significance set at Po0.05) was used. This study was approved by the local and National Research Ethics Committee. Median age of the patients was 17 years (13–31). Eighteen (72%) of them were male (Table 1). Median CD34þ cell concentration in peripheral blood was 80.9 (36.5–167.6)/mL on the day of apheresis, however, in males and females the CD34þ cell concentrations were 88.3 (36.5–167.6)/mL and 66.8 (38.2–83.1)/mL, respectively (P1⁄4 0.1088). All patients attained the target cell dose after a single apheresis session. The median CD34þ cell number collected was 9.1 (5.0–22.5) 10/kg. Male patients had a marginally superior CD34þ cell collection: 10.9 (5.0– 22.5) 10/kg vs 7.9 10/kg (5.2–9.60) for female patients (P1⁄4 0.0566), despite the similar total blood volumes processed (3 in female vs 2.5 in male patients; P1⁄4 0.1573). The processed total blood volume was 2.6mL (2.2–3.4) in 215 (152–280) minutes. CD34þ cell harvest was performed on day 8 (7–9) (Table 1). A total of seven patients (28%) presented adverse reactions that could be attributed to the mobilization regimen, such as headache, myalgia and malaise. One patient had febrile neutropenia. Eight patients (32%) had adverse reactions related to the apheresis procedure, especially due to citrate toxicity (Table 2). In two patients insulin could be discontinued during the conditioning regimen. No patients died before engraftment. Neutrophil engraftment occurred on day 11 (9–13) in both female and male patients. HSC mobilization characteristics in patients with CAID are relatively well established. The same cannot be asserted for patients with T1DM. Herein, we found that all 25 patients with T1DM had an efficient CD34þ cell mobilization with CY and G-CSF, demonstrated by the high concentration and the early peak of CD34þ cells in the peripheral blood. These phenomena are commonly observed in ‘good mobilizers’, and suggest that HSC and the BM microenvironment in T1DM patients are not damaged. According to Stiff, patients can be stratified into three categories regarding mobilization efficiency: (A) easily mobilizable (45 10/kg), (B) difficult to mobilize (1–5 10/kg) and (C) non-mobilizable (o1 10/kg) after repeated apheresis attempts. The patients in this study can be considered easily mobilizable as all of them had a CD34þ cell collection superior to 5 10/kg with a single apheresis. Mobilization characteristics are influenced by the strategies employed, patients’ diagnoses and type of previous treatment. Approximately 10% of patients with CAID failed to mobilize HSC. Patients with systemic lupus erythematosus achieved the lowest CD34þ number in peripheral blood and the lowest cell yield, whereas patients with multiple sclerosis or scleroderma achieved the highest. Furthermore, Statkute et al, had to perform a mean of 1.8 apheresis sessions per patient with CAID (2.5 for those with lupus). Overall, patients with T1DM needed approximately half the apheresis sessions relative to patients with other autoimmune diseases, possibly because T1DM patients were ‘healthier’ than patients with CAID. The good mobilization observed resulted in an adequate neutrophil engraftment (on day 11). Bone Marrow Transplantation (2012) 47, 993–994 & 2012 Macmillan Publishers Limited All rights reserved 0268-3369/12

Hematological differences between patients with different subtypes of sickle cell disease on hydroxyurea treatment

Objective Sickle cell anemia and the interaction S/Beta thalassemia differ in hematological values due to microcytosis and hypochromia caused by the thalassemic mutation. The clinical benefit of long-term hydroxyurea treatment is undeniable in sickle cell disease with monitoring of the biological action of the drug being by the complete blood count. The objective of this work is to compare changes in some of the erythrocytic indexes between S/Beta thalassemia and sickle cell anemia patients on long-term hydroxyurea treatment. Methods The values of erythrocyte indexes (mean corpuscular volume and mean corpuscular hemoglobin) were compared in a retrospective study of two groups of patients (Sickle cell anemia and S/Beta thalassemia) on hydroxyurea treatment over a mean of six years. Results The quantitative values of the two parameters differed between the groups. Increases in mean corpuscular volume and reductions in mean corpuscular hemoglobin delay longer in S/Beta thalassemia patients (p-value = 0.018). Conclusion Hematological changes are some of the beneficial effects of hydroxyurea in sickle cell disease as cellular hydration increases and the hemoglobin S concentration is reduced. The complete blood count is the best test to monitor changes, but the interpretation of the results in S/Beta thalassemia should be different.

Hematological particularities and co-infections in injected drug users with AIDS

HIV patients infected through injected drug use have poorer prognosis than other groups. We evaluated the hematological alterations and rates of co-infections in injected drug use patients with AIDS. Injected drug use patients were younger, predominantly of male gender, and presented lower CD4, total lymphocyte, and platelet counts, but not neutrophil count, than control group. Injected drug use patients had a higher rate of hepatitis C and mycobacteria infection. Furthermore, all injected drug use patients with hemoglobin <10.0 g dL(-1) and lymphocyte <1000μL(-1) had CD4 count lower than 100μL(-1). In conclusion, HIV-infected injected drug use patients constitute a special group of patients, and hemoglobin concentration and lymphocyte count can be used as surrogate markers for disease severity.