Bone marrow histiocytic hyperplasia and hemophagocytosis with pancytopenia in typhoid fever

Typhoid fever was associated with pancytopenia in five patients. Bone marrow examinations revealed histiocytic hyperplasia with marked phagocytosis of platelets, leukocytes, and red blood cells in these individuals. This phagocytosis may contribute to the pancytopenia that occurs in some patients with typhoid fever. The striking degree of the histiocytic hemophagocytosis is reminiscent of the malignant disease, histiocytic medullary reticulosis. The importance of careful exclusion of infectious etiologies in illnesses involving marrow histiocytic proliferation is emphasized.     

Occurrence of pancytopenia in the course of acute brucellosis

Leuconeutropenia is a common manifestation of acute brucellosis, whereas other hematological abnormalities and pancytopenia are uncommon. We report a patient presenting with acute brucellosis and pancytopenia.

Résumé

Si la leuconeutropénie est fréquente au cours de la brucellose aiguë, les anomalies des autres lignées sanguines et la pancytopénie sont beaucoup plus rares. Nous rapportons une nouvelle observation de pancytopénie fébrile au cours d'une brucellose aiguë.     

The first documented case of brucellosis manifested with pancytopenia and capillary leak syndrome

Hematological complications have been frequently associated with acute brucellosis, but pancytopenia is less frequently seen. Also, capillary leak syndrome has been rarely reported in the literature. In this report, we present a case of brucellosis with pancytopenia leading to capillary leak syndrome. A 21-year-old man was admitted to hospital with complaints of a one-month history of weakness, sweats, and fever and he had hepatosplenomegaly and edema over the pretibial areas. Hemogram revealed pancytopenia and biochemical tests revealed moderate hypoalbuminemia, elevations of lactate dehydrogenase and aspartate aminotransferase. He was diagnosed as brucellosis and capillary leak syndrome. He was given doxycycline and rifampicin. The patient's symptoms were resolved after treatment.     

Transient pancytopenia

Summary From a population-based study on the incidence of potentially drug-associated blood dyscrasias 28 cases were identified with pancytopenia. Who recovered within 90 days after diagnosis. Early recovery occured more frequently in patients showing normal or increased cellularity of the bone marrow than in patients with bone marrow hypoplasia. Median recovery times of leukocytes were 14 and 10 days and of platelets 21 and 9 days in patients with and without bone marrow hypoplasia, respectively. Age and sex distribution were similar in both groups. Of 28 patients, 11 reported a period of fever before onset of pancytopenia. Sixteen patients in whom information on drug use was available had taken a median of 4 drugs before the onset of symptoms that were related to pancytopenia. From these results we present the hypothesis that transient pancytopenia with or without marrow hypoplasia can be the expression of the same type of bone marrow injury and that drugs or viral infections should be considered as etiological factors.     

A brucellosis case with ascites, hearing loss and pancytopenia.

To date there has been no association of ascites, hearing loss and pancytopenia in brucellosis in the literature. A 25-year-old female patient was hospitalized with fever, hearing loss, ascites and pancytopenia. Cultures from bone marrow and ascites yielded growth of Brucella melitensis and Brucella standard tube agglutination was found to be positive at a titer of 1/1280. The patient completely recovered by the sixth week following combined antibacterial treatment of ciprofloxacin, rifampin and doxychline.     

Development of a histiocytic medullary reticulosis-like syndrome during the course of acute lymphocytic leukemia.

A 54 year old woman presented with acute lymphocytic leukemia. Following an initial response to chemotherapy with vincristine and prednisone, progressive pancytopenia developed coincident with intense bone marrow infiltration by abnormal histiocytes. At autopsy two months later, no evidence of leukemia was found, but the bone marrow was replaced by abnormal histiocytes showing active erythrophagocytosis, consistent with histiocytic medullary reticulosis. Detailed morphologic, ultrastructural and histochemical studies performed throughout the course of the patient's illness served to confirm the transition from leukemia to histiocytosis. Four similar cases of acute lymphocytic leukemia terminating in histiocytic medullary reticulosis have been reported. This association may represent a distinct clinicopathologic syndrome.     

Conversion of polycythemia vera to refractory anemia with hyperplastic bone marrow

Summary Clinical and morphologic findings in the conversion of treated polycythemia vera to pancytopenia with hyperplastic bone marrow (refractory anemia or pancytopenia with hyperplastic bone marrow) are described in light of our own observation. The nomenclature associated with this condition (pancytopenia, chronic erythroleukemia, preleukemia) is not uniform, whereas the morphologic findings are virtually identical. Some patients subsequently develop acute leukemia. The prognosis in cases of refractory anemia with hyperplastic bone marrow following polycythemia vera is, independent of the subsequent acute leukemia, invariably terminal.     

Fatal virus-associated hemophagocytic syndrome associated with coexistent chronic active hepatitis B and acute hepatitis C virus infection.

A 28-year-old man was admitted to our department with intermittent fever, hepatosplenomegaly and pancytopenia. Liver parameters and serum ferritin were markedly elevated. Bone marrow biopsy showed hypocellularity, histiocytic hyperplasia, and hemophagocytosis consistent with a virus-associated hemophagocytic syndrome (VAHS). There was serological evidence of chronic active hepatitis B and acute hepatitis C virus infection. The patient died despite aggressive immunosuppressive and supportive treatment. Autopsy revealed signs of acute viral hepatitis with cholestasis. Histiocytes engaged in hemophagocytosis were observed in bone marrow and spleen. The condition was interpreted as VAHS associated with chronic active hepatitis B and acute hepatitis C virus infection. To our knowledge this is the first report of a hemophagocytic syndrome in that setting.     

Hemophagocytic syndrome in patients with acute myeloid leukemia undergoing intensive chemotherapy

Hemophagocytic lymphohistiocytosis is a condition of immune dysregulation characterized by severe organ damage induced by a hyperinflammatory response and uncontrolled T-cell and macrophage activation. Secondary hemophagocytic lymphohistiocytosis typically occurs in association with severe infections or malignancies. Patients with acute myeloid leukemia may be prone to develop hemophagocytic lymphohistiocytosis because of an impaired immune response and a high susceptibility to severe infections. In a series of 343 patients treated by intensive chemotherapy over a 5-year period in our center, we identified 32 patients (9.3%) with fever, very high ferritin levels, and marrow hemophagocytosis (i.e. patients with hemophagocytic lymphohistiocytosis). Compared to patients without hemophagocytic lymphohistiocytosis, these 32 patients had hepatomegaly, pulmonary or neurological symptoms, liver abnormalities, lower platelet count and higher levels of C-reactive protein as well as prolonged pancytopenia. A microbial etiology for the hemophagocytosis was documented in 24 patients: 14 bacterial infections, 9 Herpesviridae infections and 11 fungal infections. The treatment of hemophagocytic lymphohistiocytosis consisted of corticosteroids and/or intravenous immunoglobulins along with adapted antimicrobial therapy. Patients with hemophagocytic lymphohistiocytosis had a median overall survival of 14.9 months, which was significantly shorter than that of patients without hemophagocytic lymphohistiocytosis (22.1 months) (P=0.0016). Hemophagocytic lymphohistiocytosis was significantly associated with a higher rate of induction failure, mainly due to deaths in aplasia. Hemophagocytic lymphohistiocytosis can be diagnosed in up to 10% of patients with acute myeloid leukemia undergoing intensive chemotherapy and is associated with early mortality. Fever, very high ferritin levels and marrow hemophagocytosis represent the cornerstone of the diagnosis. Further biological studies are needed to better characterize and recognize this syndrome in patients with acute myeloid leukemia.     

Aplastic anemia and severe pancytopenia during treatment with peg-interferon,ribavirin and telaprevir for chronic hepatitis C

Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin.Pancytopenia due to myelotoxicity caused by these drugs may occur,but severe hematological abnormalities or aplastic anemia(AA) have not been described.We collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in 2011.Among 142 cirrhotic patients receiving treatment,7 cases of severe pancytopenia(5%) were identified and three were consistent with the diagnosis of AA.Mean age was 59 years,five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver transplantation.Severe pancytopenia was diagnosed a median of 10 wk after the initiation of therapy.Three patients had pre-treatment hematological abnormalities related to splenomegaly.In six patients,antiviral treatment was interrupted at the onset of hematological abnormalities.Two patients died due to septic complications and one patient due to acute alveolar hemorrhage.The remaining patients recovered.Severe pancytopenia and especially AA,are not rare during triple therapy with telaprevir in patients with advanced liver disease.Close monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications.     

Bone marrow necrosis in malignant diseases. A report on seven intravitally recognized cases

Bone marrow necrosis (BMN) is a necrosis of the hemopoietic tissue including the fibrovascular medullary stroma. Most frequently, it is caused by failure of bone marrow microcirculation. It is a complication in a wide spectrum of diseases, most frequently of malignancies, and is only rarely diagnosed ante mortem. In 6 of our 7 intravitally diagnosed cases, BMN was recognized already at the cytological examination of the bone marrow and was verified by the histological examination of the biopsy specimens as well as at necropsy. All our patients suffered from various malignant diseases. Three had generalized gastric carcinoma, the remaining hematological neoplasias: Acute lymphoblastic leukemia, acute monocytic leukemia, blastic transformation of chronic granulomegakaryocytic myelosis and primary medullary centrocytic lymphoma. The survival varied from 4 to 14 weeks after the BMN diagnosis. Clinical, hematological and autopsy findings as well as the etiopathogenetic views and prognostic implications of the diagnosis are discussed.     

Approach to pancytopenia: Diagnostic algorithm for clinical hematologists

Pancytopenia is a relatively common phenomenon encountered in clinical practice. The evaluation of a patient with pancytopenia requires a comprehensive approach and identifying the underlying cause can be challenging given the wide range of etiologies including drugs, autoimmune conditions, malignancies, infections, hemophagocytosis, and inheritable conditions. Recent advances in molecular hematology which include genomic profiling and next-generation sequencing have helped gain major insights into various hematological conditions and can guide diagnosing specific diseases in a shorter time at lower costs. However the approach to manage patients with pancytopenia in the current era of genomics is not well defined in the literature and is widely variable in practice. Herein, we conducted a systematic review to help devise an algorithm and management approach for pancytopenia, which serves as a general consultative approach.     

Nontuberculous atypical mycobacterial infection with progressive pancytopenia in a patient with myelodysplastic syndrome

We describe a patient with myelodysplastic syndrome (MDS) who developed disseminated infection due to nontuberculous mycobacteria (NTM). A 64-year-old man was admitted because of persistent fever that had been unresponsive to antibiotics. Bone marrow aspiration specimens showed myelodysplasia (RA), but the origin of the fever was unclear. Cytopenia worsened to a level that required transfusion of red blood cells and platelets. Repeated bone marrow examination revealed hypoplasia with hemophagocytosis. Several weeks later, photochromogenic NTM was isolated from bone marrow specimens, sputum and broncho-alveolar lavage (BAL) fluid which had been obtained on admission. Antituberculosis treatment with clarithromycin markedly improved the patient's general condition and hematological abnormalities. Three months after resolution of the NTM infection, the peripheral blood monocyte count increased, the fever recurred, and the patient suddenly died of myocardial infarction. Disseminated infection with NTM has gained attention as a frequent complication of AIDS, and NTM can also be one of the pathogens causing disseminated infection in patients with MDS. In the present case, infection with mycobacteria that normally would have been digested by macrophages and would not have caused disseminated infection in a healthy individual, was probably related to the clinical features including high fever, severe pancytopenia and hemophagocytosis.     

A case of Plasmodium vivax malaria complicated with pancytopenia due to hypoplasia of the bone marrow

The patient is a 39 year-old Japanese male who had traveled to Southeast Asia from March 14, 1987 and returned on April 2. On April 3 and 5, he had a high fever with chills and he was admitted to our hospital. Despite initial treatment with antibiotics, a high fever over 39 degrees C appeared with a 48 hour periodicity. On the 8th day after admission, malarial parasites were identified on the peripheral blood smear after repeated trials. Combined with a raised serum antibody titer, Plasmodium vivax malaria was diagnosed. He was successfully treated with the sulfadoxine 500 mg and pyrimethamine 25 mg (Fansidar) and body temperature was normalized after the 12th day. More interestingly, the patient showed pancytopenia without splenomegaly. The bone marrow aspiration revealed hypoplasia of erythroblasts, granulocytes and megakaryocytes. Because of this pancytopenia in the peripheral blood and hypoplasia of the bone marrow which improved after recovery from malarial infection, it was indicated that they were caused by the malarial infection. Generally, it is considered that anemia in malarial patients is caused by destruction of the blood cells by parasites and/or hypersplenism and compensatory hyperplasia of the bone marrow is seen. On the contrary, this case showed pancytopenia accompanied with hypoplasia of the bone marrow probably due to the malarial infection suggesting a new aspect of pathogenesis in the hematological abnormality of the malarial infection.     

A case of disseminated intravascular coagulation caused by <Emphasis Type="Italic">Brucella melitensis</Emphasis>

OBJECTIVE: Although the haematological abnormalities were common accompaniments of brucellosis, overt disseminated intravascular coagulopathy was reported only in a case at the literature. We report here a case of Brucella melitensis sepsis which showed an acute onset with clinical and hematological findings disseminated intravascular coagulopathy METHODS: The patient had a physical examination, coagulation screening tests, tests of thrombin generation and fibrinolysis, bone marrow aspirate, serum Brucella agglutination test and blood culture. A case of Brucella infection presenting at the onset as a disseminated intravascular coagulation with gingival bleeding and echimotic lesions on abdomen is reported. A hemogram showed severe thrombocytopenia, anemia, and leukopenia. Anisocytozis, poikilocytozis, shift to the left of the granulocytic series, fragmented red blood cells, toksic granulation, were present in the peripheral smear. Bone marrow aspirate revealed a hypercellular marrow without granulomata or malignant precursors. Prothrombin time: 20 s, activated partial thromboplastin time:53.9 s were found longer than normal. D-dimer: 1056 mug/l (50-228 mug/l) was found. Fibrinogen was too low to detected in serum. Patient had Brucella melitensis isolated from blood cultures. RESULTS: After appropriate antimicrobial therapy, the clinical and hematological status of the patient improved, and 4 days later with disappearance of all hematological abnormalities. Conclusison: Diagnosis of brucellosis may be delayed, particularly if uncommon features such as pancytopenia and disseminated intravascular coagulopathy are present. Hence, brucellosis must be considered in the differential diagnosis of all those conditions leading to pancytopenia and disseminated intravascular coagulopathy in areas endemic for brucellosis.     

Hemophagocytic syndrome as an initial presentation of miliary tuberculosis without pulmonary findings

A 9-y-old girl was admitted with fever, weakness and weight loss. She had pancytopenia in peripheral blood, hypocellularity and hemophagocytosis in bone marrow. Disseminated tuberculosis was diagnosed after a long delay, with involvement of the lungs, bone marrow, liver, spleen and central nervous system. Tuberculosis can be a cause of hemophagocytosis and should be taken into account in the differential diagnosis of fever of unknown origin associated with pancytopenia and hemophagocytosis.     

Unusual clinical presentations of brucellosis

The purpose of this paper is to draw attention to atypical presentations of brucellosis. A prospective study identified 240 consecutive patients with brucellosis admitted to our department between December 1999 and July 2002. From these cases we present 11 patients with unusual clinical presentations. Neurobrucellosis, peritonitis, pericarditis, pancytopenia, and uveitis were diagnosed in 2 patients each and 1 presented with epididymo-orchitis.     

Spontaneous tumor lysis syndrome with resolution of pancytopenia and disappearance of lymphadenopathy in a patient with peripheral T cell lymphoma unspecified

Tumor lysis syndrome is a well-described, serious complication of chemotherapy administered to treat malignancies. However, a very rare event resulting in the spontaneous necrosis of a tumor prior to therapy can also occur, which is termed spontaneous tumor lysis syndrome (STLS). We present a case of a 27-year-old male who presented to the hospital with epistaxis, dyspnea, and cervical lymphadenopathy. Laboratory findings included progressive pancytopenia, hyperuricemia, and acute renal failure. Bone marrow biopsy showed a T cell lymphoid neoplasm that had entirely infiltrated the marrow stroma. The patient was diagnosed with STLS in the setting of a T cell lymphoma with bone marrow infiltration. The patient was immediately treated with a blood transfusion and hemodialysis. After this urgent treatment, the patient’s pancytopenia resolved and the lymphadenopathy disappeared spontaneously. One month post-treatment, the patient’s cervical lymphadenopathy recurred and peripheral T cell lymphoma, not otherwise specified, was confirmed. STLS has previously been reported, however, most known cases of STLS did not show a decreased tumor burden resulting from massive tumor cell death. We present a rare case of STLS with resolution of pancytopenia and disappearance of lymphadenopathy in a patient with peripheral T cell lymphoma not otherwise specified.     

Case series of pediatric acute leukemia without a peripheral blood abnormality, detected by magnetic resonance imaging

Although abnormal peripheral blood counts are a key diagnostic finding for acute leukemia in children, between 2003 and 2010 we observed seven pediatric cases without peripheral blood abnormalities and showing abnormal signals in the bone marrow by magnetic resonance imaging (MRI). The common chief complaint in these patients was bone pain and fever. Bone marrow tests revealed six out of the seven cases to be acute leukemia, whereas one patient was diagnosed with juvenile idiopathic arthritis (JIA). There was no evident difference in MRI findings between leukemia patients and JIA patient. In three cases of leukemia, initial bone marrow aspiration failed to show the presence of leukemic cells, and diagnosis was only made by repeated bone marrow examination. Our findings indicate that in some cases MRI detects leukemia at an earlier phase than does bone marrow aspiration, suggesting that MRI is useful for the diagnosis of acute leukemia.     

Bone marrow changes mimicking myelodysplasia in patients with hemophagocytic lymphohistiocytosis

In hemophagocytic lymphohistiocytosis (HLH), cytokine-induced pancytopenia is a common finding and is associated with hypoplastic and hypocellular bone marrow and abundant hemophagocytosis. To date, neutrophil nuclear segmentation abnormalities have not been clarified in HLH patients. We report a study of bone marrow from 6 cases of HLH that showed abnormal granulocytes, dyserythropoietic changes, and micromegakaryocytes mimicking the findings in myelodysplasia at the onset of disease. Pelger-Hu?t anomalies were particularly noted in all cases. The increased levels of cytokines in these cases may have caused cellular damage leading to the morphological changes in the bone marrow of these HLH patients. The impact of these findings on pathophysiology and prognosis in HLH patients remains to be determined.