Approach to the Patient with Benign Hematologic Disorders

2013 ◽  
Author(s):  
J Mark Sloan ◽  
David C Seldin
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Complete Blood Count ◽  
White Blood Cells ◽  
Peripheral Blood Smear ◽  
Coagulation System ◽  
Laboratory Findings ◽  
Hematopoietic Stem ◽  
Normal Ranges

Hematology principally concerns the function and disorders of the formed elements of the blood—red blood cells (RBCs), white blood cells (WBCs), and platelets—as well as those factors governing hemostasis. Hematologists have been a powerful force in basic biomedical and translational research. Their work, propelled partly by the ease of collection of blood and bone marrow for study, has enabled an understanding of many blood disorders at a fundamental molecular level. Techniques developed for the study of hematology are often adopted by other disciplines. This chapter discusses the anatomy of the hematopoietic system, hematopoiesis and the bone marrow, physical examination of the hematology patient, evaluation of the complete blood count (CBC) and peripheral blood smear, and coagulation. Tables delineate CBC parameters with normal ranges; peripheral smear findings, descriptions, and RBC indices and significance; laboratory findings in erythrocytosis; diseases commonly associated with eosinophilia and useful workup; common medications strongly associated with thrombocytopenia; and the 4Ts score for determining pretest probability of heparin-induced thrombocytopenia. Figures depict the three fractions of centrifuged blood, the lymph node, hematopoietic stem cells, bone marrow aspirate and biopsy procedure, architecture of the bone marrow microenvironment, petechiae, WBC types found in the smear of peripheral blood, the direct antiglobulin test, myeloid cells, and the coagulation system. This review contains 10 highly rendered figures, 6 tables, and 40 references.

Generation and Characterization of Transgenic Mice Expressing MplW515L.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3901-3901
Author(s):  
Wanming Zhao ◽  
Shu Xing ◽  
Rufei Gao ◽  
Aref Al-Kali ◽  
Wanting Tina Ho ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
B Cells ◽  
Transgenic Mice ◽  
Hematopoietic Stem Cells ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Blood Cells ◽  
White Blood Cells ◽  
Hematopoietic Stem

Abstract Abstract 3901 Poster Board III-837 Myeloproliferative neoplasias (MPNs) are a group of conditions characterized by chronic increases in some or all of the blood cells (platelets, white blood cells, and red blood cells). JAK2V617F, a gain-of-function mutation of tyrosine kinase JAK2, is found in over 90% of patients with polycythemia vera (PV) and about 50% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF). Attempt to identify other signaling components involving the JAK2 signaling pathways has led to discovery of acquired mutations of Mpl, the receptor of thrombopoietin, in 5-10% patients with PMF and ET. To prove the pathogenesis of Mpl mutants, we have generated transgenic mice expressing the most frequently occurred Mpl mutant designated MplW515L by using the vav gene promoter which drives expression of transgenes in the hematopoietic system. We obtained three lines of MplW515L transgenic mice which all displayed similar hematological abnormalities. As expected, the mice developed ET- and PMF-like phenotypes with much elevated platelet counts, severe splenomegaly/hepatomegaly, and bone marrow/spleen myelofibrosis. Interestingly, these mice also had markedly increased white blood cells in the peripheral blood, majority of which are IgD-positive mature B-cells. Histochemical staining and flow cytometric analyses revealed infiltrations of megkaryocytes and B cells into the spleen, the presence of megkaryocytes and erythroid blast cells in the liver, and infiltrations of the bone marrow with B-cells. Reticulin staining revealed that MplW515L transgenic mice developed profound myelofibrosis in the bone marrow and spleen. In vitro hematopoietic colony assays demonstrated increased numbers of hematopoietic progenitor cells including BFU-E, CFU-GM, CFU-Mk, and CFU-Pre-B in the bone marrow, mobilization of these stem/progenitor cells to peripheral blood and spleen, and their autonomous growth in the absence of growth factors and cytokines. Finally, transplantation of bone marrow cells from MplW515L mice into irradiated normal mice installed the aforementioned phenotypes into the recipient mice, indicating that expression of MplW515L altered the activity of hematopoietic stem cells. Together, our data demonstrated that transgenic expression of MplW515L not only causes PMF- and ET-like phenotypes but also lymphoproliferative disorders. Considering that Mpl is expressed in hematopoietic stem cells and that oncogenic gene mutations are often associated with alteration of gene expression, we believe that MplW515L may be involved in a wider spectrum of human hematological diseases than MPNs. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Acquired Pelger-Huët anomaly in a patient treated with valganciclovir

2019 ◽  
Vol 12 (10) ◽  
pp. e230958 ◽  
Author(s):  
Elva Nieto-Borrajo ◽  
Alfredo Bermejo-Rodriguez
Keyword(s):  
Peripheral Blood ◽  
Blood Cells ◽  
Blood Count ◽  
Blood Smear ◽  
Complete Blood Count ◽  
White Blood Cells ◽  
Peripheral Blood Smear ◽  
Condensed Chromatin ◽  
Morphological Abnormalities

A follow-up blood count was performed on a 74-year-old woman diagnosed with colitis due to cytomegalovirus and under treatment with valganciclovir. The automated complete blood count revealed an abnormal white blood cells (WBC) scattergram together with WBC alert flags. The peripheral blood smear showed neutrophils with markedly hyposegmented nuclei or bilobed nuclei and very condensed chromatin or clumping chromatin all consistent with Pelger-Huët anomaly (PHA). We checked previous blood counts, ruling out an inherited PHA. We assessed the haematological, infectious and iatrogenic aetiologies for an acquired PHA. Once the valganciclovir treatment was completed and the drug was withdrawn, without changing the rest of the treatment, the morphological abnormalities of neutrophils were completely resolved. We conclude therefore that the acquired PHA presented by our patient is probably related to valganciclovir treatment.

scholarly journals Adult Mice With Targeted Mutation of the Interleukin-11 Receptor (IL11Ra) Display Normal Hematopoiesis

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2148-2159 ◽  
Author(s):  
Harshal H. Nandurkar ◽  
Lorraine Robb ◽  
David Tarlinton ◽  
Louise Barnett ◽  
Frank Köntgen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Bone Marrow Cells ◽  
White Blood Cells ◽  
Null Mutation ◽  
Wild Type ◽  
Normal Numbers ◽  
Interleukin 11 ◽  
Marrow Cells

Abstract Interleukin-11 (IL-11) is a pleiotropic growth factor with a prominent effect on megakaryopoiesis and thrombopoiesis. The receptor for IL-11 is a heterodimer of the signal transduction unit gp130 and a specific receptor component, the α-chain (IL-11Rα). Two genes potentially encode the IL-11Rα: the IL11Ra and IL11Ra2 genes. The IL11Ra gene is widely expressed in hematopoietic and other organs, whereas the IL11Ra2 gene is restricted to only some strains of mice and its expression is confined to testis, lymph node, and thymus. To investigate the essential actions mediated by the IL-11Rα, we have generated mice with a null mutation of IL11Ra (IL11Ra−/−) by gene targeting. Analysis of IL11Ra expression by Northern blot and reverse transcriptase-polymerase chain reaction, as well as the absence of response of IL11Ra−/− bone marrow cells to IL-11 in hematopoietic assays, further confirmed the null mutation. Compensatory expression of the IL11Ra2 in bone marrow cells was not detected. IL11Ra−/− mice were healthy with normal numbers of peripheral blood white blood cells, hematocrit, and platelets. Bone marrow and spleen contained normal numbers of cells of all hematopoietic lineages, including megakaryocytes. Clonal cultures did not identify any perturbation of granulocyte-macrophage (GM), erythroid, or megakaryocyte progenitors. The number of day-12 colony-forming unit-spleen progenitors were similar in wild-type and IL11Ra−/− mice. The kinetics of recovery of peripheral blood white blood cells, platelets, and bone marrow GM progenitors after treatment with 5-flurouracil were the same in IL11Ra−/− and wild-type mice. Acute hemolytic stress was induced by phenylhydrazine and resulted in a 50% decrease in hematocrit. The recovery of hematocrit was comparable in IL11Ra−/− and wild-type mice. These observations indicate that IL-11 receptor signalling is dispensable for adult hematopoiesis.

Development of a robust algorithm for detection of nuclei of white blood cells in peripheral blood smear images

2019 ◽  
Vol 78 (13) ◽  
pp. 17879-17898 ◽  
Author(s):  
Roopa B. Hegde ◽  
Keerthana Prasad ◽  
Harishchandra Hebbar ◽  
Brij Mohan Kumar Singh
Keyword(s):  
Peripheral Blood ◽  
Blood Cells ◽  
Blood Smear ◽  
White Blood Cells ◽  
Peripheral Blood Smear ◽  
Robust Algorithm

The blood cells and blood count

2016 ◽  
Author(s):  
Tyler J. Albert ◽  
Erik R. Swenson
Keyword(s):  
Stem Cell ◽  
Blood Cells ◽  
White Blood Cells ◽  
Peripheral Blood Smear ◽  
Cell Types ◽  
Multiple Organ ◽  
Carbon Dioxide Transport ◽  
Vascular Integrity ◽  
Hematopoietic Stem ◽  
Critical Components

Blood is a dynamic fluid consisting of cellular and plasma components undergoing constant regeneration and recycling. Like most physiological systems, the concentrations of these components are tightly regulated within narrow limits under normal conditions. In the critically-ill population, however, haematological abnormalities frequently occur and are largely due to non-haematological single- or multiple-organ pathology. Haematopoiesis originates from the pluripotent stem cell, which undergoes replication, proliferation, and differentiation, giving rise to cells of the erythroid, myeloid, and lymphoid series, as well as megakaryocytes, the precursors to platelets. The haemostatic system is responsible for maintaining blood fluidity and, at the same time, prevents blood loss by initiating rapid, localized, and appropriate blood clotting at sites of vascular damage. This system is complex, comprising both cellular and plasma elements, i.e. platelets, coagulation and fibrinolytic cascades, the natural intrinsic and extrinsic pathways of anticoagulation, and the vascular endothelium. A rapid, reliable, and inexpensive method of examining haematological disorders is the peripheral blood smear, which allows practitioners to assess the functional status of the bone marrow during cytopenic states. Red blood cells, which are primarily concerned with oxygen and carbon dioxide transport, have a normal lifespan of only 120 days and require constant erythropoiesis. White blood cells represent a summation of several circulating cell types, each deriving from the hematopoietic stem cell, together forming the critical components of both the innate and adaptive immune systems. Platelets are integral to haemostasis, and also aid our inflammatory and immune responses, help maintain vascular integrity, and contribute to wound healing.

scholarly journals Megaloblastosis Produced by a Cytosine Antagonist

Blood ◽  
1963 ◽  
Vol 21 (3) ◽  
pp. 352-362 ◽  
Author(s):  
R. W. TALLEY ◽  
V. K. VAITKEVICIUS
Keyword(s):  
Bone Marrow ◽  
Dna Synthesis ◽  
Mechanism Of Action ◽  
Cytosine Arabinoside ◽  
Peripheral Blood ◽  
Blood Cells ◽  
White Blood Cells ◽  
Structural Similarity ◽  
Mitotic Abnormalities ◽  
Temporary Decrease

Abstract 1. Cytosine arabinoside induced objective, but temporary, decrease of tumor masses in three patients with lymphosarcoma and slight decrease in some lesions in two out of ten treated patients with disseminated carcinomatosis. 2. In doses of 3 to 50 mg./Kg. given at varying intervals, cytosine arabinoside induced definite megaloblastic changes in the marrow of all patients studied. Mitotic abnormalities similar to those found in other megaloblastic anemias also occurred. 3. Associated with bone marrow changes, depressions of hemoglobin, white blood cells and platelets in the peripheral blood were observed. 4. The exact mechanism of action of cytosine arabinoside has not been elucidated. It is speculated that because of the close structural similarity between cytidylic acid, cytosine arabinoside could interfere with DNA synthesis.

Novel Observation That Mice Lacking the Fifth Complement Cascade Protein Component (C5) Are Very Poor Stem Cell Mobilizers Explained by Defective Egress of Granulocytes: A Novel Role for Bone Marrow Granulocytes to Act as “ice Breaker” Cells in Facilitating Egress of Hematopoietic Stem/Progenitor Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 67-67
Author(s):  
Wan Wu ◽  
Hakmoo Lee ◽  
Marcin Wysoczynski ◽  
Magdalena Kucia ◽  
Janina Ratajczak ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
White Blood Cells ◽  
Membrane Attack Complex ◽  
Optimal Dose ◽  
Histochemical Staining ◽  
Complement Cascade ◽  
Hematopoietic Stem ◽  
Small Vessels

Abstract We reported that complement cascade (CC) becomes activated in bone marrow (BM) during mobilization of hematopoietic stem/progenitor cells (HSPCs) by immunoglobulin (Ig)-dependent pathway and/or by alternative Ig-independent pathway and, as result of this, several potent bioactive CC anaphylatoxins (C3a, desArgC3a, C5a and desArgC5a) are released (Blood2003;101,3784; Blood2004;103,2071; Blood2005;105,40). Bioactive CC anaphylatoxins (C5a and desArgC5a) are also potent chemoattractants of granulocytes that bind to G-protein-coupled, seven trans-membrane span C5a receptors (C5aR and C5L2) on these cells. To learn more on the role of C5 cleavage fragments in HSPC mobilization, we studied mobilization in C5−/− and C5aR−/− mice as well as their normal wildtype littermates. Mobilization was induced by granulocyte colony-stimulating factor (G-CSF; high 250 μg/kg/6 days and low dose 50 μg/kg/6 days) or zymosan (20 mg/1kg/1 hour), which activate classical and alternative pathways of CC, respectively. We evaluated mobilization efficiency by counting the number of SKL cells, colony-forming unit granulocyte-macrophages (CFU-GMs), and white blood cells circulating in peripheral blood. In parallel, we employed transmission electron microscopy (TEM) to study the morphology and integrity of BM vessels in the BM-blood barrier. Activation of CC was measured by ELISA for C3 cleavage fragments and by histochemical staining for membrane attack-complex (MAC) depositions in BM tissue. We found by ELISA and histochemistry that CC activation correlates with the level of HSPC mobilization in wildtype mice and that mobilization of HSPCs was always preceded by the release of granulocytes from BM. Thus, granulocytes are the first wave of cells that increase in number during mobilization in peripheral blood. Mobilization studies in C5−/− revealed that these animals are very poor mobilizers. TEM studies demonstrated that hematopoietic cells together with granulocytes accumulated around small vessels in the BM of C5−/− animals, but they did not migrate or cross the BM-endothelial barrier. Since C5 cleavage fragments C5a and desArgC5a are potent chemoatrractants for granulocytes but not HSPCs, we hypothesize that a lack of both these anaphylatoxins in C5−/− animals prevents egress of granulocytes from BM, which always precedes egress of HSPCs. Furthermore, in C5aR−/−, mice mobilization was normal after administration of a high optimal dose of G-CSF. However, mobilization was significantly lower after a suboptimal dose of G-CSF or administration of zymosan. This indicates that another alternative receptor for C5a and desArgC5a (C5L2) may compensate for C5aR deficiency and that it plays a role in the egress of granulocytes from the BM as well. Thus, this study demonstrates that cells from the granulocytic lineage are actively involved in mobilization in a C5a,-desArgC5a-C5aR manner not only by secreting proteases that create a proteoytic environment in BM, but also as a kind of “ice-breaker” type cells necessary for disintegration of the endothelial-BM barrier to enable HSPCs to egress from the BM microenvironment. In cases of granulocytopenia or if granulocytes are not mobilized as seen in C5−/− mutants, mobilization of HSPCs is very poor. Thus, modulation of CC activation in the BM and stimulation of granulocyte egress from the BM into circulation may help to develop more efficient strategies for HSPC mobilization.

Hematopoietic Stem Cell Differentiation Pathway in Humans Deduced From the Lineage Diversity of PNH-Type Cells in Patients with Bone Marrow Failure.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1489-1489
Author(s):  
Takamasa Katagiri ◽  
Zhirong Qi ◽  
Yu Kiyu ◽  
Naomi Sugimori ◽  
J. Luis Espinoza ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Bone Marrow Failure ◽  
Stem Cell Differentiation ◽  
Refractory Anemia ◽  
Hematopoietic Stem

Abstract Abstract 1489 Poster Board I-512 The hematopoietic stem cell (HSC) differentiation pathway in humans remains largely unknown due to the lack of an appropriate in vivo assay allowing the growth of HSCs as well as of clonal markers that enable the tracing of their progenies. Small populations of blood cells deficient in glycosylphosphatidylinositol-anchored proteins (GPI-APs) such as CD55 and CD59 are detectable in approximately 50% of patients with aplastic anemia (AA) and 15% of patients with refractory anemia (RA) of myelodysplastic syndrome defined by the FAB classification. Such blood cells with the paroxysmal nocturnal hemoglobinuria (PNH) phenotype (PNH-type cells) are derived from single PIGA mutant HSCs and their fate depends on the proliferation and self-maintenance properties of the individual HSCs that undergo PIG-A mutation by chance (Blood 2008;112:2160, Br J Haematol 2009 in press) Analyses of the PNH-type cells from a large number of patients on the diversity of lineage combination may help clarify the HSC differentiation pathway in humans because PIG-A mutant HSCs in patients with bone marrow failure appear to reflect the kinetics of healthy HSCs. Therefore, different lineages of peripheral blood cells were examined including glycophorin A+ erythrocytes (E), CD11b+ granulocytes (G), CD33+ monocytes (M), CD3+ T cells (T), CD19+ B cells (B), and NKp46+ NK cells (Nk) from 527 patients with AA or RA for the presence of CD55−CD59− cells in E and G, and CD55−CD59−CD48− cells in M,T, B, Nk with high sensitivity flow cytometry. Two hundred and twenty-eight patients (43%) displayed 0.003% to 99.1% PNH-type cells in at least one lineage of cells. The lineage combination patterns of PNH-type cells in these patients included EGM in 71 patients (31%), EGMTBNk in 43 (19%), EG in 37 (16%), T alone 14 (6%), EGMBNk in 11 (5%), G alone in 10 (4%), GM in 10 (4%), EGMNk in 7 (3%), EGMT in 7 (3%), EGMB in 6 (3%), EM in 5 (2%), EGMTB in 3 (1%), EGNk in 1 (0.4%), EGMTNk in 1 (0.4%), GMTB in 1 (0.4%), and GT in 1 (0.4%) (Table). All patterns included G or M, except for 14 patients displaying PNH-type T cells alone. No patients showed TB or TBNk patterns suggestive of the presence of common lymphoid progenitor cells. Peripheral blood specimens from 123 patients of the 228 patients possessing PNH-type cells were examined again after 3 to 10 months and all patients showed the same combination patterns as those revealed by the first examination. PIG-A gene analyses using sorted PNH-type cells from 3 patients revealed the same mutation in G and Nk for 1 patient and in G and T for 2 patients. These findings indicate that human HSCs may take a similar differentiation pathway to that of murine HSCs, the ‘myeloid-based model’ that was recently proposed by Kawamoto et al. (Nature 2008; 10:452), though the cases with PNH-type T cells alone remain to be elucidated. Table. Lineages of cells containing PNH-type cells in patients with AA or RA. The number in the parenthesis denotes the proportion of patients showing each combination pattern in the total patients possessing PNH-type cells. (+ ; presence of PNH-type cells) Disclosures No relevant conflicts of interest to declare.

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