Primary Hematologic Disease Research Articles

Adjusting MtDNA Quantification in Whole Blood for Peripheral Blood Platelet and Leukocyte Counts.

Alterations of mitochondrial DNA copy number (mtDNAcn) in the blood (mitochondrial to nuclear DNA ratio) appear associated with several systemic diseases, including primary mitochondrial disorders, carcinogenesis, and hematologic diseases. Measuring mtDNAcn in DNA extracted from whole blood (WB) instead of from peripheral blood mononuclear cells or buffy coat may yield different results due to mitochondrial DNA present in platelets. The aim of this work is to quantify the contribution of platelets to mtDNAcn in whole blood [mtDNAcn(WB)] and to propose a correction formula to estimate leukocytes' mtDNAcn [mtDNAcn(L)] from mtDNAcn(WB). Blood samples from 10 healthy adults were combined with platelet-enriched plasma and saline solution to produce artificial blood preparations. Aliquots of each sample were combined with five different platelet concentrations. In 46 of these blood preparations, mtDNAcn was measured by qPCR. MtDNAcn(WB) increased 1.07 (95%CI 0.86, 1.29; p<0.001) per 1000 platelets present in the preparation. We proved that leukocyte count should also be taken into account as mtDNAcn(WB) was inversely associated with leukocyte count; it increased 1.10 (95%CI 0.95, 1.25, p<0.001) per unit increase of the ratio between platelet and leukocyte counts. If hematological measurements are available, subtracting 1.10 the platelets/leukocyte ratio from mtDNAcn(WB) may serve as an estimation for mtDNAcn(L). Both platelet and leukocyte counts in the sample are important sources of variation if comparing mtDNAcn among groups of patients when mtDNAcn is measured in DNA extracted from whole blood. Not taking the platelet/leukocyte ratio into account in whole blood measurements, may lead to overestimation and misclassification if interpreted as leukocytes' mtDNAcn.

Azacitidine Use After Allogeneic Stem Cell Transplantation—Results From the Polish Adult Leukemia Group

BackgroundRelapse of primary hematologic disease constitutes an important reason for failure of allogeneic hematopoietic stem cell transplantation (alloHSCT). There are very few treatment modalities for this indications. Therefore, there is a need for novel effective therapies and even more for the prevention of relapse. There are scarce data that azacitidine can be used for these purposes. MethodsAt the Polish Adult Leukemia Group, we retrospectively analyzed the results of azacitidine treatment after alloHSCT. Relapsing patients, patients with minimal residual disease/mixed chimerism, and patients in complete remission with high risk of relapse were analyzed separately. There were 17 patients, 6 with myelodysplastic syndrome, 11 with acute myeloid leukemia, 8 male, and overall median age of 56 years (range, 15–78); 7 patients received donor lymphocyte infusion (DLI). ResultsPatients treated because of relapse received a median of 3 (range, 1–6) cycles of azacitidine, patients receiving preemptive treatment received a median of 4 cycles (range, 2–6), and those on maintenance received a median of 5 cycles (range, 3–5). Toxicity was considerable, especially in relapse—neutropenia (67%), anemia (67%), thrombocytopenia (100%), serious infections (78%)—and preemptive settings. Median overall survival of patients treated for relapse reached 6.8 months (95% confidence interval [CI], 0.7–∞), with better survival observed in patients with temporary disease control (7.7 vs 4.7 mo) and without previous exposure to azacitidine (7.7 vs 3.4 mo). One-year overall survival reached 75% (95% CI, 13%–96%) for preemptive and 50% (95% CI, 0%–91%) for maintenance treatment. DLI did not aggravate graft-versus-host disease. ConclusionsEffectiveness of azacitidine in relapsing patients is disappointing. Azacitidine seems to be promising in preemptive and maintenance settings. Toxicity is considerable. Further research is needed.

Progress in the clinical management of pure red cell aplasia and future prospects

Pure red cell aplasia (PRCA) is a type of bone marrow failure syndrome (stem cell failure) and is characterized by severe normocytic, normochromic anemia associated with reticulocytopenia and the absence of erythroblasts in otherwise normal bone marrow. The acquired form of chronic PRCA may present as a primary hematological disease in the absence of any other diseases or secondary to thymoma, lymphoproliferative disorders, infections and collagen vascular diseases or after exposure to various drugs or chemicals. Thus, identifying the cause of PRCA is crucial for the optimal management of this disorder. Idiopathic PRCA and secondary PRCA refractory to treatment of the underlying diseases are both generally treated as an immune-mediated disorder. Most chronic PRCA patients successfully treated with immunosuppressants require maintenance immunosuppressive therapy. Refractoriness to induction immunosuppressive therapy and relapse of anemia may be risk factors for death in idiopathic, thymoma-associated and large granular lymphocyte leukemia-associated PRCA. The major causes of death are infections and organ failure. Standard treatment options for refractory and relapsed PRCA patients and the immunopathophysiology of acquired chronic PRCA merit further research.

Factors related to allergic transfusion reactions and febrile non-haemolytic transfusion reactions in children.

Allergic transfusion reactions (ATRs) and febrile non-haemolytic transfusion reactions (FNHTRs) are the two major types of transfusion-related adverse reactions (TRARs). Although prestorage leucocyte reduction and diversion of the first aliquot of blood (LR/D) could reduce FNHTRs and bacterial contamination in adult transfusion, ATRs are still problematic. In addition, there is little information about TRARs in paediatric population. We conducted a single-centre retrospective analysis of all transfusions, except washing products, and TRARs for 153 months to evaluate related factors such as delivery of treatment and the characteristics of recipients. Most TRARs were FNHTRs and/or ATRs in children. In delivering blood products with LR/D, the frequencies of not only FNHTRs but also ATRs were significantly reduced with both platelet concentrates (PCs) and red cell concentrates (RCCs). TRARs of fresh-frozen plasma were infrequent in children. In addition, even after the introduction of LR/D, ATRs were significantly more frequent in patients with primary haematological and malignant diseases who received PCs and RCCs, older patients who received PCs and patients who received frequent RCCs. These results suggest that leucocytes or mediators from leucocytes are underlying cause of ATRs in addition to FNHTRs in children. Furthermore, particular characteristics of patients would be other risk factors for ATRs.

Could “red cell distribution width” predict COPD severity?

Background and objectivesErythrocyte morphology changes not only by primary hematological diseases but also by systemic inflammation, ineffective erythropoiesis and nutritional deficiencies. Red blood cell distribution width (RDW) is a parameter reflecting erythrocyte morphology. We aimed to investigate the relationship of RDW with chronic obstructive pulmonary disease (COPD) stages, BODE index and survival in COPD patients. MethodsMedical records of 385 COPD patients between July 2004 and November 2005 were studied retrospectively. Demographic features, BODE index factors and oxygen saturation were recorded. Survival analysis of all patients by 2014 was performed. Measured RDW values at the time of the inclusion were evaluated. ResultsMean age of the patients was 65.6±9.6 years. Distribution of the COPD stages of the patients were stage 1: 16%, stage 2: 52%, stage 3: 26%, stage 4: 6%. RDW was found significantly different between stages. The highest RDW was observed in the very severe stage (p<0.001). Median of BODE index was 1 (0–3). As the BODE index increased RDW also increased (p<0.001). When the patients were grouped according to the laboratory upper limit of RDW, survival rate was 31% in the RDW >14.3% group and 75% in the RDW <14.3% group. ConclusionThe variability in the size of circulating erythrocytes increases as the COPD severity progresses. Therefore, a simple and noninvasive test, such as RDW, might be used as a biomarker in the evaluation of the severity of COPD. At the same time, there seems to be a correlation between the survival of COPD patients and RDW.

Implications of Intrathecal Chemotherapy for Anaesthesiologists: A Brief Review.

Intrathecal chemotherapy is routinely prescribed in medical oncology practice, either for prophylaxis or for treatment of leptomeningeal disease due to a primary haematological disease or a metastatic disease due to any other malignancy. As these groups of patients are coagulopathic either because of the disease per se or due to systemic chemotherapy, lumbar puncture in them is considered challenging and is expected to be performed by an anaesthesiologist because of their expertise in this procedure. However, the challenge is not only in performing the lumbar puncture safely but also in dealing with other issues like explaining and handling complications that can happen either due to the drug injected intrathecally or due to a neurodeficit occurring either due to the underlying coagulopathy or due to the progression of leptomeningeal disease.

Cyclic Thrombocytopenia: A Case Report

Cyclic thrombocytopenia (CTP) is a very rare disorder characterized by periodic fluctuations in platelet counts, typically resulting in episodes of thrombocytopenia alternating with normal platelet counts. Most cases are idiopathic while some are associated with a primary hematologic disease. Frequently CTP patients are misdiagnosed as idiopathic thrombocytopenic purpura (ITP), but usually they do not respond to standard ITP treatment.A 49 year-old male presented a history of one year of symptomatic thrombocytopenia (<10x10(9)). He had been treated initially with corticosteroids without a consistent response. Later, he was subjected to splenectomy. After splenectomy platelet counts was checked weekly. On the first week the cont was 1.000x10(9)/L falling on the third week to 27x10(9)/L. As the patient had no bleeding we decided for no treatment, and platelet counts had been fluctuating from 800x10(9)/L to 20x10(9)/L about every four weeks, for three months of monitoring. No treatment was further required.When evaluating patients with suspected ITP, CTP should always be included in the differential diagnosis, especially if they are not responding to standard ITP treatment. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Study in the Clinical Characteristics of Stenotrophomonas Maltophilia Bacteremia in Hematological Patients

Introduction: Stenotrophomonas maltophilia is an important nosocomial pathogen, particularly in immunocompromised patients, especially in patients with hematologic diseases.Methods: We reviewed the clinical characteristics and prognosis of patients with S. maltophilia bacteremia over a five-year period from January 2010 to December 2014. Species identification was performed using the automated Vitek 2 compact system (bioMe rieux).Results: The incidence of S. maltophilia bacteremia was 25.1 per 10 000 admissions in our study. Thirty-four patients (median age: 34 years; 64.7% males) with S. maltophilia bacteremia were analyzed. The S. maltophilia bacteremia related 30-day mortality was 44.1%. Risk factors associated with mortality in patients with S. maltophilia infection in the univariate and multivariate analysis were represented in Tables I and II. In the univariate analysis, risk factors included T>39.0¡æ, septic shock, respiratory failure and non-remission after treatment for primary hematological diseases (P <0.05). In the multivariate analysis, respiratory failure and non-remission status after treatment forhematological diseases were independent prognostic factors for mortality. In vitro susceptibility was higher to ciprofloxacin(82.4%), ceftazidime(70.6%), sulbactam and cefoperazone(58.8%), which was shown in Table III.Conclusion: Combination regimens with ciprofloxacin and ceftazidime, or sulbactam and cefoperazone could be alternative treatment. Novel antibiotics are required for treatment of S. maltophilia infection, as well as infection control practices of environmental reserves, rapid detection of pathogens, risk stratification strategy and appropriate treatment for primary hematologic malignancies, which might conjointly contribute to better survival outcome of S. maltophilia bacteremia.Univariate analysis of prognostic factors associated with mortality from S. maltophilia bacteremiaTable 1FactorMortalityHR95%CIP-valueWithfactorWithoutfactorT>39.0¡æ75%16.7%2.4901.318-4.7040.005Septic shock90.0%25.0%2.5441.473-4.3930.001Respiratory failure100%20.8%4.6722.366-9.2250.000Treatment outcome for hematological diseasesRemission10.0%85.7%0.2470.116-0.5260.000HR, hazard ratio; CI, confidence interval; HSCT, Hematopoietic stem cell transplantationTable 2Multivariate analysis of prognostic factors associated with mortality from S. maltophilia bacteremiaFactorHR95%CIP-valueRespiratory failure2.6881.297-5.5690.008Remission after treatment for hematological diseases0.3670.153-0.8790.025HR, hazard ratio; CI, confidence intervalTable 3Susceptibility pattern of the 34 patients with Stenotrophomonas maltophilia bacteremiaAntimicrobial agentsS (%)I (%)Ceftazidime24(70.6%)1(2.9%)Cefoperazone19(44.1%)6(17.6%)Sulbactam and Cefoperazone20(58.8%)5(14.7%)Piperacillin7(20.6%)6(17.6%)Piperacillin-Tazobactam11(32.3%)7(20.6%)Amikacin6(17.6%)0(0%)Ciprofloxacin28(82.4%)1(2.9%)S, susceptible; I, intermediately susceptible. DisclosuresNo relevant conflicts of interest to declare.

Diagnosis and management of pure red cell aplasia

Pure red cell aplasia (PRCA) is a type of bone marrow failure syndrome (stem cell failure) and is characterized by severe normocytic, normochromic anemia associated with reticulocytopenia, and the absence of erythroblasts in otherwise normal bone marrow. PRCA may be congenital or acquired, and the acquired form of chronic PRCA may present as a primary hematological disease in the absence of any other diseases or secondary to thymoma, lymphoproliferative disorders, infections, and collagen vascular diseases or after exposure to various drugs or chemicals. The most common types of acquired chronic PRCA in Japan are idiopathic, thymoma-associated and lymphoid neoplasm-associated PRCA. Initial treatment of PRCA includes the cessation of potentially deleterious drugs and careful observation for one month while making efforts to identify the cause of PRCA. Idiopathic PRCA and secondary PRCA refractory to treatment of the underlying diseases are generally treated as immune-mediated disorders. Most chronic PRCA patients successfully treated with immunosuppressants require maintenance immunosuppressive therapy. Thus, identifying the cause of PRCA is crucial for the optimal management of this disorder.

Hematological Changes in Patients Undergoing Coronary Artery Bypass Surgery: a Prospective Study.

Objectives:Removal of pro inflammatory stimuli after CABG, wound closure and the regenerative ability of the bone marrow will ensure a gradual recovery of hematological parameters. The aim of this study was to assess the hematological changes after CABG.Materials and Methods:A prospective cohort study included 164 consecutive patients undergoing on pump CABG surgery between January 2012 and January 2013. Patients with primary hematologic disease, emergent or urgent CABG and off-pump CABG were not included. A time line protocol was employed.Results:All patients survived surgery. Average values of erythrocytes, hemoglobin and hematocrit declined, to reach lower values on day 3 after surgery (-33.6 %, -33.1 %, -32.6 % versus preoperative value, p<0.001) and then gradually increased to reach normal values after one month and the preoperative values after three months. The average values of leukocytes and neutrophils increased rapidly to achieve the highest value on day 2, while the average value of lymphocytes decreased quickly to achieve lower value on day 1 after surgery (+74.7 %, +127.1 %, -52.4 % respectively from the preoperative value, p<0.001). The average platelet count decreased to the lowest value on day 2 after surgery (-26.4 % from the preoperative value, p<0.001), after which gradually increased up to +100.8 % of preoperative value on day 14 (p<0.001) and then gradually decreased to reach normal values on day 21 and preoperative values after three months.Conclusions:Average values of the three peripheral blood cells parameters undergo important changes after CABG, but not life threatening, and regain normal and preoperative values after 1-3 months after surgery.

Increased Mortality in Patients with Autoimmune Hemolytic Anemia after Allogeneic Hematopoietic Stem Cell Transplantation

IntroductionAutoimmune hemolytic anemia (AIHA) is the most commonly reported autoimmune complication following hematopoietic stem cell transplantation (HSCT) with incidence of 2-6%. The risk factors and pathogenesis remain poorly understood. Treatment often requires multiple therapeutic agents with variable efficacy and outcome. However no study to date has shown whether AIHA directly results in increased mortality. In order to better understand the risk factors, mortality and management of post-HSCT AIHA, we carried out a retrospective analysis of 533 allogeneic HSCTs in adult patients performed at King’s College Hospital between 2005-2011.MethodThe median follow-up period after HSCT was 31 months (range 2.9 – 100 months). The primary endpoint was the onset of AIHA, defined by positive direct agglutinin test (DAT) arising after the HSCT, with biochemical markers of hemolysis (raised serum lactate dehydrogenase (LDH), reduced haptoglobin, or spherocytes on the blood film). Hemolysis was considered significant if the drop in hemoglobin was more than 20 g/l. Cases of DAT positivity due to ABO antibodies, as well as those with history of AIHA or positive DAT prior to HSCT were excluded. Potential risk factors for development of AIHA were calculated with univariate followed by multivariate analysis comparisons of incidence of AIHA for each clinical stratum. Kaplan-Meier method was used to compare mortality caused by AIHA against overall mortality (OM), and transplant-related mortality (TRM). AIHA was modelled as a time-dependent variable when estimating mortality. All patients alive at last follow-up who did not develop AIHA were censored.ResultsWe identified 19 cases of AIHA following HSCT (overall incidence 3.6%). The median time to onset from HSCT to AIHA was 202 days. AIHA was associated with HSCT from unrelated donors (p = 0.026; Hazard Ratio = 5.28, 95% CI = 1.22 – 22.9), and concordant sex between HSCT recipients and donors (p = 0.045; Hazard Ratio = 3.52; 95% CI = 1.03 – 12.1). No significant association was observed between AIHA and the following eight factors: recipient gender; primary hematological disease; source of hematopoietic stem cells; conditioning regimen (alemtuzumab/ATG versus non-alemtuzumab/ATG, and reduced intensity versus myeloablative); HLA mismatch between donor/recipient; ABO mismatch; recipient CMV status; and concurrent chronic GvHD. AIHA patients also exhibited high frequency of simultaneous alloimmunization to Rh antigens coinciding with the onset of AIHA, which was not due to difference in transfusion rates, and not observed in the population who tested negative for DAT.Majority of AIHA patients (14/19; 72%) required multiple agents for treatment, but only 9/19 (47%) cases achieved complete resolution of AIHA (1 with intravenous immunoglobulin; 2 with prednisolone alone; 6 with rituximab in combination with other agents). The median survival from onset of AIHA was 487 days (range 26 – 1977 days). We compared the mortality of the AIHA versus non-AIHA population that survived beyond the median time of onset for AIHA (202 days). Patients with post-transplant AIHA had a higher OM (p = 0.006, Hazard Ratio = 2.37, 95% CI = 1.28 – 4.39), 1-year OM of 22% versus 10% (p = 0.04) and 1-year TRM of 18% versus 4% (p = 0.001), respectively (Figure 1). 36% (4/11 cases) of deaths were attributable to AIHA.ConclusionThe overall incidence of AIHA following allogeneic HSCT in our study was 3.6%. The risk factors associated with AIHA were receiving HSCT from unrelated donors, and matched gender between the donor/recipient, which has not been previously reported. We observed an association between allo and autoimmunization in the AIHA patients, suggesting a common immune defect underlying both phenomena. The most effective treatment was a combination regimen of rituximab with prednisolone or other immunosuppressive agents. The overall mortality rate for our AIHA patients was high at 53% (10/19 cases), with AIHA as a cause of death in 36% of deceased patients. We have shown that AIHA following HSCTs indeed leads to increased mortality with over 2 fold higher OM in the patients with AIHA. [Display omitted] DisclosuresMcLornan:Novartis: Research Funding.

Prevention and treatment of invasive aspergillosis in Slovenia: data obtained in »OSPIA« observational clinical study

Background: Invasive aspergillosis (IA) is a common opportunistic infection in patients with critical neutropenia. Mostly, patients are located on hematological wards. In Slovenija, because of unsuitable hospital enviroment the problem of IA is huge. With clinical observational study OSPIA (»Observational Study of Patients with Invasive Aspergillosis«) we tried to evaluate prevention, diagnostics and treatment of IA. Methods: During three-year period we included 55 patients with IA. Besides the primary disease, we evaluated risk factors, prevention measures, diagnostic approaches and treatment of IA. Results: In most cases, patients had acute leukemia and major risk factor was critical neutropenia. Because of inadequate hospital conditions, almost every patient received prophylaxis with posoconasol. The most frequently used diagnostic procedure is test for galactomannan antigenemia, followed by radiological approach. Most casas were treated with amphothericin, followed with caspofungin. The treatment was not effective in cases of therapy-refractory primary hematological disease. Conclusions: In Slovenia, IA remains a huge problem in patients with critical neutropenia. The primary reason lays in inadequate hospital treatment conditions for hematological patients. The latter we try to mitigate with posoconasole prophylaxis.

Brucellosis-Induced Autoimmune Hemolytic Anemia Treated with Rituximab

To present a case of brucellosis-induced severe autoimmune hemolytic anemia (AIHA) that was refractory to traditional corticosteroid treatment and eventually treated with rituximab apart from antibiotic therapy and to discuss the potential role of rituximab in similar cases of AIHA triggered by an underlying reversible cause. A 79-year-old woman was diagnosed with severe AIHA (reticulocyte count 21.5%, hemoglobin 6 g/dL). Initial treatment with prednisone in a regional hospital was not efficacious. Brucellosis was diagnosed by serology; the disease was further complicated by hepatic and splenic granulomatous involvement and sacral bone localization. Due to the severity of AIHA as demonstrated by reticulocyte count and hemoglobin levels, the initial unresponsiveness to corticosteroid therapy, the potential of the underlying infectious cause to relapse along with AIHA, and the localization of the pathogen in a focal site (bone involvement) that could act as a constant AIHA trigger, the patient was treated aggressively with rituximab, apart from the typical antimicrobial therapy. Brucellosis can induce autoimmunity and mimic primary hematologic diseases. We reviewed reports on the unique forms of Brucella-induced hemolysis available in the literature. Massive hemolysis, though, is rare, and in the case of a pathogen such as brucellosis, one cannot ignore the potential for infection relapse accompanied by hemolysis relapse. Cases refractory to corticosteroids are typically treated with invasive amputative procedures such as splenectomy. However, in cases where an underlying therapeutically reversible cause of infection can be identified, the proven short-term efficacy and safety profile of rituximab can be of significance. Novel therapeutic approaches with molecular agents such as rituximab may assist in treatment of considerably severe infectious pathogen-induced autoimmune hemolytic anemia that is refractory to first-line therapy.

How Immunocompromised Are Short Bowel Patients Receiving Home Parenteral Nutrition? Apropos a Case of Disseminated Fusarium Oxysporum Sepsis

Catheter-related sepsis is the most frequent complication in patients receiving home parenteral nutrition (HPN) for short bowel syndrome (SBS). A low-grade systemic inflammatory state and an altered mucosal immune response, as well as diminished intestinal barrier function have been characterized in these patients. The possibility of systemic immunocompromise has only recently been suggested. A 45-year-old female with traumatic SBS was admitted for possible catheter-related sepsis. She was asplenic and had insulin-dependent diabetes mellitus as a result of a pancreatic resection. A large skin ulceration was present on her left calf, which appeared unusual for a disseminated bacterial infection. Chest x-ray and computed tomography scan revealed multiple subpleural pulmonary infiltrates consistent with bacterial or fungal dissemination. Blood cultures from the port system and from the peripheral blood grew Staphylococcus haemolyticus and Fusarium oxysporum. The port system was removed, and flucloxacillin and voriconazole were given for 33 and 35 days, respectively. Clinical signs of disseminated sepsis resolved slowly. Bone marrow biopsy ruled out primary hematologic disease. (1) Catheter-related sepsis in patients on HPN is usually caused by Gram-positive or Gram-negative bacteria or by Candida species. Identification of molds in blood cultures strongly suggests Fusarium species, which should be treated appropriately with voriconazole or amphotericin B. (2) HPN and SBS aggravated by asplenism and diabetes mellitus can cause severe immunocompromise. (3) Fusaria have a strong tendency to persist or reappear after bone marrow transplantation, which is therefore relatively contraindicated in these patients.

ZNS-Beteiligung bei Leukämien und Lymphomen – Meningeosis im Liquor cerebrospinalis und Möglichkeiten der immunzytochemischen Zellphänotypisierung

The detection of tumour cells in the cerebrospinal fluid (CSF) of leukaemia and lymphoma patients is a challenge for CSF cytological investigation. Nevertheless, it is generally possible to confirm the involvement of the central nervous system (CNS) by conventional microscopic detection of tumour cells. Immunocytochemical staining techniques are a valuable complement of conventional cytology. Immunocytochemical cell phenotyping is indicated for identification of atypical cells in patients with suspected primary CNS lymphoma or malignant haematological disease.

Pattern of Consultation Referrals for Cytopenia Evaluations to a Hematologist at An Academic Medical Center: The Expanding Role of a Consultant Hematologist

Purpose: It appears that many cytopenia consultation referrals to Hematology outpatient clinics turn out to have diseases related to primary care practice. The aim of this retrospective study is to see what proportion and what kind of cytopenia consultations in a Hematology clinic are due to disorders related to primary care practice.Methods: Retrospective chart review analysis of all outpatient referrals from July 2002 to June 2008 to a Hematologist at a tertiary university hospital was performed. Of those, only cytopenia consultations were analyzed. Cases were analyzed according to the presenting cytopenias and the final diagnoses.Results: There were a total of 942 outpatient consultation referrals during this period. 435 consultations were for cytopenia evaluations (46%). Of cytopenia evaluations, the demographics were as follows; male: female = 1: 1.5, age: <60: >60 = 1:1, Caucasian: non-non-Caucasian = 3:1. Distributions of cytopenia consultations were as follows: anemia (60%), thrombocytopenia (15%), leucopenia (10%), pancytopenia (6%), anemia and thrombocytopenia (4%), anemia and leucopenia (2.5%), leucopenia and thrombocytopenia (2.5%). Fortysix cases of cytopenia (11%) resolved on its own without any intervention. Final diagnoses of the rest were iron deficiency anemia 28% (65 cases of gastrointestinal bleeding, 47 cases of menorrhagia, 5 cases due to malabsorption, 5 cases of vegetarianism), myelodysplasia 8%, anemia of multifactorial origin (> more than 1 cause) 7%, anemia due to chronic renal failure only 6%, anemia of chronic disease 2%, drug-induced myelosuppression 6%, ITP 5%, ethnic leucopenia 4%, vitamin B12 deficiency 3%, thalassemia 3%, acute leukemia 2%, myeloma 2%, cirrhosis/hypersplenism 2%, sickle cell/hemoglobinopathy 1.5%, gestational thrombocytopenia 1.5%, viral hepatitis 1%, hereditary spherocytosis 1%, hemolytic anemia 1%, low grade lymphomas 1%, myelofibrosis 1%, non-immune chronic idiopathic neutropenia of adult 1%, immune leucopenia 0.5%, human immunodeficiency virus infection 0.5%, alcoholism 0.5%, paroxysmal nocturnal hemoglobinuria 0.25%. Primary hematologic diseases accounted for 34.25% while the remaining cases were diseases related to primary care practice.Conclusion: Cytopenia consultations accounted for 46% of all referrals. Anemia made up the majority of cytopenia consultations. Iron deficiency anemia due to gastrointestinal bleeding turned out to be the commonest final diagnosis while iron deficiency anemia due to menorrhagia was the second commonest diagnosis. Two-thirds of cytopenia consultations turned out to have diseases related to primary care medicine while primary hematologic diseases accounted for only one-third of the consultations. It appears hematologists are seeing more and more cases of cytopenias due to primary medical diseases (hematologic manifestations of medical diseases) rather than true primary hematologic disorders. Thus, the hematologist's role as a consultant to primary care practitioners continues to expand.

Clinical analysis of hematologic changes on 25 Brucellosis patients

Objective To study the characteristics of hemogram and myelogram with Brucellosis patients.Methods 25 Brucellosis patients' bone marrow and peripheral blood smears were observed,at the same time a deep clinical inverstigation on the patients was conducted. Results The counts of blood cells were decreased in part pa-tients, and a typical lymphocytes were found in peripheral blood of 64% patients. The marrow proliferative activities were normal(92% ) or higher(8% ),and all patients had poisonous granules. Red cell proliferative activities were normal(68% ) or lower(32% ). The counts of megakaryocytes were normal,but the maturity of megakaryocyte was hindered. All patients' histocytes were increased at different degrees. NAP were increased. Conclusion The changes of hemogram and myelogram have clinical significance for diagnosis of Brucellosis, but primary hematologic disease with Brucellosis should be distinguished. Key words: Brucellosis; Leukocyte count; Bone marrow examination; Diagnosis,differential

An Unusual Presentation of Secondary Involvement of B-Cell Chronic Lymphocytic Leukemia. A Case Report

Extramammary tumors rarely metastasize to the breast. The commonest tumors to metastasize in breast tissue are lymphoproliferative diseases, melanoma, lung cancer and gynecological malignancies. Primary breast lymphoma has been reported in the literature with a maximum percentage of about 0.5% of all breast malignancies, while secondary localizations of lymphomas in the breast are less well studied in the literature than primary ones. The authors report a rare case of a secondary localization of B-cell chronic lymphocytic leukemia to the breast in which the diagnosis was obtained by histopathology and immunohistochemistry and further confirmed by molecular data. This occurrence must be considered in the differential diagnosis of a breast lump so that the primary hematological disease can be adequately treated and the correct type of breast surgery performed.

An Unusal Case of Acute Brucellosis Presenting with Coombs-positive Autoimmune Hemolytic Anemia

Brucellosis can mimic several primary hematological diseases. Mild anemia and leukopenia have been frequently associated with acute brucellosis, but pancytopenia, thrombocytopenia, and hemolysis are less frequently seen. To our knowledge, brucellosis has not previously been described in association with Coombs-positive autoimmune hemolytic anemia. Here, we report a case of acute brucellosis presenting with coombs-positive autoimmune hemolytic anemia. The patient responded well to short-term pulse corticosteroid therapy followed by antibrucellosis treatment. We suggest that Brucella infection may be the probable cause of the immune hemolytic anemia in this patient. Therefore, the differential diagnosis of Coombs-positive autoimmune hemolytic anemia should include brucellosis, especially in areas where the disease is endemic.

Splenic peliosis and rupture in patients with dyskeratosis congenita on androgens and granulocyte colony‐stimulating factor

Splenic peliosis and rupture in patients with dyskeratosis congenita on androgens and granulocyte colony‐stimulating factor