scholarly journals A review of the treatment landscape in paroxysmal nocturnal haemoglobinuria: where are we now and where are we going?

2020 ◽  
Vol 1 ◽  
pp. 263300402095934
Author(s):  
Morag Griffin ◽  
Richard Kelly ◽  
Alexandra Pike
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Life Expectancy ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Treatment Options ◽  
White Blood Cells ◽  
Paroxysmal Nocturnal Haemoglobinuria ◽  
Complement Cascade ◽  
Future Treatments

Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-orphan disease, which until 15 years ago had limited treatment options. Eculizumab, a monoclonal antibody that inhibits C5 in the terminal complement cascade, has revolutionised treatment for this disease, near normalising life expectancy and improving quality of life for patients. The treatment landscape of PNH is now evolving, with ravulizumab a second longer acting intravenous C5 inhibitor now licenced by the FDA and EMA. With different therapeutic targets in the complement cascade and difference modalities of treatment, including subcutaneous, oral and intravenous therapies being developed, increasing independence for patients and reducing healthcare requirements. This review discusses the current and future therapies for PNH. Lay summary Review of current and future treatments for patients with Paroxysmal Nocturnal Haemoglobinuria What is Paroxysmal Nocturnal Haemoglobinuria? Paroxysmal nocturnal haemoglobinuria (PNH) is a very rare disease. It arises from PNH stem cells in the bone marrow. In a normal bone marrow these are inactive; however, if there has been a problem in the bone marrow, the PNH stem cells can expand and make PNH red blood cells, white blood cells and platelets. The problem with these cells is that they lack the cell surface markers that usually protect them. Red blood cells are broken down in the circulation rather than the spleen, which gives rise to PNH symptoms such as abdominal pain, difficulty swallowing, erectile dysfunction and red or black urine (known as haemoglobinuria). The white blood cells and platelets are ‘stickier’ increasing the risk of blood clots. Previously life expectancy was reduced as there were limited treatment options available. What was the aim of this review? To provide an overview of current and future treatment options for PNH Which treatments are available? • Eculizumab is an treatment given through a vein (intravenous) every week for 5 weeks then every 2 weeks after this, and has been available for 13 years, improving life expectancy to near normal. • Ravulizumab is a newer intravenous treatment similar to eculizumab but is given every 8 weeks instead of every 2 weeks. In clinical studies it was comparable with eculizumab. • Future Treatments - There is new research looking at different methods of treatment delivery, including injections under the skin (subcutaneous) that patients can give themselves, treatments taken by mouth (oral) or a combination of an intravenous and oral treatment for those patients who are not optimally controlled on eculizumab or ravulizumab. What does this mean? PNH is now treatable. For years, the only drug available was eculizumab, but now different targets and drug trials are available. Ravulizumab is currently the only second licenced product available, in USA and Europe, there are other medications active in clinical trials. Why is this important? The benefit for patients, from treatment every 2 weeks to every 8 weeks is likely to be improved further with the development of these new treatments, providing patients with improved disease control and independence. As we move into an era of more patient-friendly treatment options, the PNH community both physicians and patients look forward to new developments as discussed in this article.

Red blood cells

2016 ◽  
Author(s):  
Shaun R. McCann
Keyword(s):  
Bone Marrow ◽  
Blood Loss ◽  
Red Blood Cells ◽  
Haemolytic Anaemia ◽  
Blood Cells ◽  
G6pd Deficiency ◽  
Paroxysmal Nocturnal Haemoglobinuria ◽  
Globin Chains ◽  
Glucose 6 Phosphate Dehydrogenase

Red blood cells, erythrocytes, are unique in that they do not contain a nucleus. This fact facilitates the study of their metabolism. Erythrocytes contain the protein pigment haemoglobin, which is in solution in the cells and consists of globin chains and iron. In this chapter, the development of the understanding of erythrocytes is linked to the blood conditions haemolytic anaemia and paroxysmal nocturnal haemoglobinuria. Premature destruction of erythrocytes, in the absence of blood loss, is termed haemolysis. If the bone marrow is unable to compensate adequately, then anaemia ensues and the condition is called haemolytic anaemia. The underlying defect is a deficiency in the activity of the enzyme glucose-6-phosphate dehydrogenase, termed G6PD deficiency.

scholarly journals Reliable assessment of bone marrow and bone marrow concentrates using automated hematology analyzer

2019 ◽  
Vol 14 (7) ◽  
pp. 639-646 ◽  
Author(s):  
Venkata P Mantripragada ◽  
Nicolas S Piuzzi ◽  
Jaiben George ◽  
Wesley Bova ◽  
Mitchell Ng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Red Blood Cells ◽  
Blood Cells ◽  
White Blood Cells ◽  
Limiting Factor ◽  
Cell Therapies ◽  
Reliable Assessment ◽  
Hematology Analyzer ◽  
Automated Hematology Analyzer

Aim: A limiting factor in advancement of bone marrow based cell therapies is the lack of characterization of cell products delivered to patients. Methods: Using an automated hematology analyzer that can be implemented in clinical setting, the composition of bone marrow aspirates (n = 17 patients) and bone marrow concentrates (n = 12 patients) were assessed. ICC estimates were calculated for measuring reliability. Results: Bone marrow aspirates assessment resulted in excellent reliability for determining white blood cells (ICC – 0.96; 95% CI: 0.92–0.99), red blood cells (ICC – 0.9; 95% CI: 0.77–0.96), platelets (ICC – 0.93; 95% CI: 0.85–0.97) composition. Bone marrow concentrate assessment resulted in excellent reliability for determining white blood cells (ICC – 0.97; 95% CI: 0.93–0.99), platelets (ICC – 0.95; 95% CI: 0.89–0.99) and moderate reliability for red blood cells (ICC – 0.66; 95% CI: 0.36–0.87) composition. Conclusion: Modern automated hematology analyzers could assist to better characterize the cell therapy products to provide reliable and consistent outcomes.

scholarly journals Role of White Blood Cells in Blood- and Bone Marrow-Based Autologous Therapies

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
William King ◽  
Krista Toler ◽  
Jennifer Woodell-May
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Growth Factors ◽  
Blood Cells ◽  
Platelet Rich Plasma ◽  
White Blood Cells ◽  
Complex Mixture ◽  
Negative Results

There has been significant debate over the role of white blood cells (WBCs) in autologous therapies, with several groups suggesting that WBCs are purely inflammatory. Misconceptions in the practice of biologic orthopedics result in the simplified principle that platelets deliver growth factors, WBCs cause inflammation, and the singular value of bone marrow is the stem cells. The aim of this review is to address these common misconceptions which will enable better development of future orthopedic medical devices. WBC behavior is adaptive in nature and, depending on their environment, WBCs can hinder or induce healing. Successful tissue repair occurs when platelets arrive at a wound site, degranulate, and release growth factors and cytokines which, in turn, recruit WBCs to the damaged tissue. Therefore, a key role of even pure platelet-rich plasma is to recruit WBCs to a wound. Bone marrow contains a complex mixture of vascular cells, white blood cells present at much greater concentrations than in blood, and a small number of progenitor cells and stem cells. The negative results observed for WBC-containing autologous therapies in vitro have not translated to human clinical studies. With an enhanced understanding of the complex WBC biology, the next generation of biologics will be more specific, likely resulting in improved effectiveness.

The Therapeutic Effect of Umbilical Mesenchymal Stem Cells Injected Directly Into Medullary Cavity of Ilium to Treat Refractory Aplastic Anemia and Bone Marrow Fibrosis,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3226-3226
Author(s):  
Zhuanzhen Zheng ◽  
Zhenhua Qiao ◽  
Wenliang Chen ◽  
Rong Gong ◽  
Yalin Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Red Blood Cells ◽  
Aplastic Anemia ◽  
Blood Cells ◽  
Medullary Cavity ◽  
Bone Marrow Fibrosis ◽  
Routine Therapy ◽  
Marrow Fibrosis

Abstract Abstract 3226 Objective To evaluate mesenchymal stem cells(MSCs) combination with routine therapy to treat refractory aplastic anemia and bone marrow fibrosis, observe the course of the hematopoitic reconstitution and evaluate the security and curative effect. Methods 12 primary myelofibrosis and 19 chronic aplastic anemia patients who had all accepted routine therapy more than 6 months,because of pathogenetic condition, they needed infusing constituent blood such as at least condensed red blood cells 6 units and platelet 4 units per months, and despite this, whole blood cells counts were very lower. Those patients all had intermittent dizzy, fatigue, bad appetite and purpura. Because of age, complication, and psychological reasons, they refused Allogenic stem cell transplantation. So besides routine therapy, they received umbilical MSCs 1×107, every two weeks one time, those cells were injected directly into medullary cavity of ilium. Results 28 recipients showed hematopoietic reconstitution when PLT was up to 20×109/L and granulocytes was up to 2.0×109/L on day 28 post MSCs infusion. Bone marrow biopsy showed hyperplasia from hypoplasia to evident hyperplasia. On day 28, Th cells ascended from 23.0 to 36.2, Ts cells descended from 24.2 to 14.6, Th.. MTs from 0.95 to 2.47:1, IgG from 6.6 to 13.3, NK cells from 2.40 to 13.5, indicating earlier immune recorrect. At the last follow-up of 12 months, 17 patients showed normal hemoglobin and platelet counts, immune globulin was in the normal level, indicating the hematopoietisis and immune persistent reconstitution. 5 patients still needed infusing constituent blood cells, although, the interval of platelet and red blood cells infusion obviously prolonged, and the times to see doctor decreased and life quality elevated greatly. Conclusion This is a novel clinical research of successful treatment of refractory CAA and MF, it tell us infusion HLA-mismatched allogenic MSCs directly into medullary cavity of ilium is efficiency and security. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Laboratory and clinical management of leukocytospermia and hematospermia: a review

2020 ◽  
Vol 14 ◽  
pp. 263349412092251
Author(s):  
Kajal Khodamoradi ◽  
Manish Kuchakulla ◽  
Manish Narasimman ◽  
Zahra Khosravizadeh ◽  
Aleena Ali ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Clinical Management ◽  
Cell Concentration ◽  
Sperm Quality ◽  
Treatment Options ◽  
White Blood Cells ◽  
Diagnostic Methods ◽  
Cryopreservation Techniques

Leukocytospermia and hematospermia are defined as the presence of abnormally high white blood cell and red blood cell concentration in the semen, respectively. Numerous etiologies and various implications on fertility have been identified. In a small proportion of men, the presence of white blood cells or red blood cells can adversely affect sperm quality by the production of reactive oxygen species. Several methods have been used to assess the presence of white blood cells and red blood cells in samples, such as identification of round cells, immunohistochemical staining using monoclonal antibodies, the Endtz test, the peroxidase test, and flow cytometry or microscopy. In addition, techniques have been identified to separate sperm samples from white blood cells and red blood cells for cryopreservation to improve outcomes in assisted reproductive technology. In this review, laboratory and clinical management of leukocytospermia and hematospermia are discussed. Currently available diagnostic methods and treatment options are outlined, and available optimal cryopreservation techniques for samples with white blood cells or red blood cells are summarized.

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 Red blood cells derived from peripheral blood and bone marrow CD34+ human haematopoietic stem cells are permissive to Plasmodium parasites infection

2013 ◽  
Vol 108 (6) ◽  
pp. 801-803 ◽  
Author(s):  
Carmen Fernandez-Becerra ◽  
Joel Lelievre ◽  
Mireia Ferrer ◽  
Nuria Anton ◽  
Richard Thomson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Red Blood Cells ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Haematopoietic Stem Cells

scholarly journals Bone Marrow Contains High Levels of Microparticles

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5145-5145
Author(s):  
Andreas Rank ◽  
Rienk Nieuwland ◽  
Anton Koehler ◽  
Hans Jochem Kolb ◽  
Bettina Toth
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Red Blood Cells ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Conflicts Of Interest ◽  
White Blood Cells ◽  
Cell Source ◽  
Bone Marrow Blood

Abstract Background: Microparticles (MP) are shed in humans from a broad variety of cells and play an important role in activation of coagulation, cell to cell interaction and transport of membrane components. Alternations in plasma levels have been found in a variety of diseases, mostly associated with thrombosis and inflammation. However, little is known about tissue levels of MP. The aim of this pilot study was to investigate the bone marrow compartment as a possible source of circulating MP. Material and Methods: MP were analysed in bone marrow blood and peripheral blood in 12 healthy stem cell donors. MPs were isolated and measured by flow-cytometric double-staining (FACScalibur, BD) with Anexin V and cell-specific antibodies for hematopoietic cells, platelets, white blood cells, red blood cells and endothelial cells. Statistical analysis was performed with SPSS for Windows 20.0. Results: Total MP levels differed between bone marrow and peripheral blood: 14.8 x109/l [8.5–19.3] vs. 9.2 x109/l [3.8–14.8] (median value [25-75 percentile]), p=0.060. Pattern of MP´s origin varied likewise: in bone marrow blood (bmb), main cell source of MP were CD235a positive red blood cells/erythropoetic cells (6.4x109/l [3.7–13.7], 43.2% of total bmb MP), CD61 positive platelets/megacaryocytes (4.1x109/l [1.7–10.1], 27.7% of total bmb MP), CD45 positive leucocytes/myeloic and lymphatic progenitor cells (3.8x109/l [2.7-4.9], 25.7% of total bmb MP) and CD62e positive endothelial cells (0.3x109/l [0.1-1.0], 2.0% of total bmb MP). In contrast, MP in peripheral blood (pb) mainly derived from CD61 positive platelets/megacaryocytes (8.5x109/l [2.4–14.4], 92.0% of total pb MP), CD45 positive leucocytes/myeloic and lymphatic progenitor cells (0.5x109/l [0.2–1.1], 4.5% of total pb MP), CD235a positive red blood cells/erythropoetic cells (0.2x109/l [0.1–0.6], 1.8% of total pb MP), and CD62e positive endothelial cells (0.1x109/l [0.0–0.1], 0.9% of total pb MP). Mean levels of tissue factor bearing MP were low in bone marrow blood as well as in peripheral blood (0.19 x109/l [0.16 – 0.29] and 0.08 x109/l [0.05 – 0.12], respectively, p=0.004). Conclusion: Within our study we were able to detect MP in bone marrow blood. When comparing MP from bone marrow and peripheral blood, major differences with regard to cell source and concentration was present. Our data suggest that the blood – bone marrow barrier is not only existentant for cells, but also for circulating MP. Disclosures No relevant conflicts of interest to declare.

scholarly journals A case of acute leukaemia in a 38-years old female

2012 ◽  
Vol 18 (2) ◽  
pp. 83-85 ◽  
Author(s):  
Barbu Adina
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Blood Cell ◽  
Microscopic Examination ◽  
Blood Cells ◽  
Acute Leukaemia ◽  
Blood Smear ◽  
White Blood Cells ◽  
Peripheral Blood Smear ◽  
Large Numbers

Abstract Leukaemia is cancer that starts in blood-forming tissues, such as bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the bloodstream. The stem cells usually develop into a type of white blood cell called myeloblasts which do not mature into healthy white blood cells. The leukaemia cells are unable to do their usual work and can build up in the blood and bone marrow so there is less space for healthy white blood cells, red blood cells and platelets. Anemia is a major sign but diagnosis is provided only microscopic examination of peripheral blood smear.

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