The myelodysplastic syndrome: in vitro growth characteristics of hemopoietic progenitor cells.

Blood cell formation results from the continuous proliferation, differentiation and maturation of pluripotent hemopoietic stem cells located in the human bone marrow. In vitro culture assays, developed in the last twenty years, have enabled the identification of the various pluripotent and committed progenitor cells present in human bone marrow by their capacity to form colonies of mature blood cells in vitro. Colony formation dependens on the presence of hemopoietic growth factors in the culture medium, which have become known as the colony stimulating factors (CSFs). At present a number of CSFs can be produced on a large scale through recombinant DNA technology and their biological activities have subsequently been defined. In chapter 1.1 and 1.2 the general principles of hemopoiesis are introduced, i.e., the different models of stem cell renewal and commitment, the various in vitro clonogenic assays for normal as well as for leukemic colony forming cells and the effects of the CSF on progenitor cells and mature blood cells. The myelodysplastic syndrome (MDS) comprises a group of acquired disorders, which are characterized by an ineffective hemopoiesis resulting in cytopenia of one or more cell lineages. Cytogenetic and G-6-PD studies have demonstrated that MDS is a clonal disease of the hemopoietic stem celL The results of some studies suggest that normal hemopoiesis is replaced by the abnormal clone already in an early stage of the disease. Up to fourty percent of the MDS patients eventually develop an acute myeloblastic leukemia. The preleukemic nature of the MDS makes this syndrome of particular interest in the study of leukemogenesis. In chapter 1.3 the clinical, morphological and in vitro growth characteristics of the MDS are introduced

Prevalence of iron deficiency and red blood cell transfusions in surgical patients

Background and Objectives While iron deficiency (ID) is the most common cause of anaemia, little is known about the prevalence and type of ID in preoperative surgical patients. The aims of the present study were to investigate the prevalence and types of ID in a large cohort of surgical patients, and how these are related to perioperative blood use after correction for confounders such as haemoglobin level. Materials and Methods Data were retrospectively extracted from electronic case records of all patients who underwent elective surgery between September 2016 and November 2017 (n = 2711). Iron parameters, haemoglobin and details of perioperative red cell transfusions were collected. Results Of 2711 patients, 618 (22.8%) were iron deficient (= transferrin saturation [TSAT] = 30 mu g/L). Corrected for Hb level, iron-deficient patients received significantly more red cell units than patients without ID (p = 0.026). AID was not associated with a significantly higher incidence of transfusions (7.5% of patients transfused; p = 0.12 after correction for Hb) than patients without ID, whereas patients with functional/mixed deficiency did receive significantly more transfusions (6.1%; p = 0.021) as compared to patients without ID (1.7%). Conclusion Preoperative ID, in particular the functional/mixed type, was associated with a higher risk of receiving perioperative red cell transfusions as compared to patients without ID. Adequately treating ID might, therefore, reduce the need for perioperative red cell transfusions.Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Helicobacter pylori infection is not correlated with subclinical thrombocytopenia: A cross-sectional study

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Hemoglobin modulation affects physiology and patient reported outcomes in anemic and non-anemic subjects: an umbrella review

Background:An abnormal hemoglobin concentration has a substantial effect on a person's quality of life and physiology. Lack of tools that effectively evaluate hemoglobin-related outcomes leads to uncertainty regarding optimal hemoglobin levels, transfusion thresholds and treatment targets. We therefore aim to summarize reviews that assess the effects of hemoglobin modulation on the human physiology at various baseline hemoglobin levels, and identify gaps in existing evidence. Methods:We conducted an umbrella review of systematic reviews. PubMed, MEDLINE (OVID), Embase, Web of Science, Cochrane Library and Emcare were searched from inception to the 15th of April 2022 for studies that reported on physiological and patient reported outcomes following a hemoglobin change. Results:Thirty-three reviews were included of which 7 were scored as of high quality and 24 of critically low quality using the AMSTAR-2 tool. The reported data generally show that an increase in hemoglobin leads to improvement of patient reported and physical outcomes in anaemic and non-anaemic subjects. At lower hemoglobin levels, the effect of a hemoglobin modulation on quality of life measures appears more pronounced. Conclusion:This overview has revealed many knowledge gaps due to a lack of high-quality evidence. For chronic kidney disease patients, a clinically relevant benefit of increasing the hemoglobin levels up until 12 g/dL was found. However, a personalized approach remains necessary due to the many patient-specific factors that affect outcomes. We strongly encourage future trials to incorporate physiological outcomes as objective parameters together with subjective, but still very important, patient reported outcome measures.Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

The role of preoperative iron deficiency in colorectal cancer patients: prevalence and treatment

Background: In preoperative blood management of colorectal cancer patients, intravenous iron therapy is increasingly used to treat anaemia and prevent red blood cell transfusions. However, while iron deficiency is the most common cause of anaemia, little is known about the prevalence and namely type of iron deficiency in this population, whereas both types of iron deficiency (i.e. absolute and functional iron deficiency) are recommended to be treated differently by international cancer guidelines. Objective: The aim of present study is to investigate the prevalence and namely type of iron deficiency in colorectal cancer patients, and to assess its clinical relevance. Methods: Preoperative iron status, clinical parameters (i.e. age, ASA classification, tumour location, tumour stage) and postoperative complications were retrospectively collected for all newly diagnosed colorectal cancer patients in our institution over a 3-year period. Results: Iron deficiency was observed in 163 (48.1%) of 339 patients. Of these iron-deficient patients, 3.7% had an isolated absolute iron deficiency (AID) and 15.3% a functional iron deficiency (FID), while the rest had a combination of AID and FID. Anaemia was present in 66.1% of iron-deficient patients. Iron deficiency was significantly associated with an increased postoperative complication rate (univariable OR 1.94, p = 0.03, multivariable OR 1.84, p = 0.07), with right-sided tumours (p < 0.001), high ASA classification (p = 0.002), advanced tumour stage (p = 0.01) and advanced age (p = 0.04). In comparing clinical parameters between patients with AID and FID, advanced age was significantly associated with FID (p = 0.03), and the presence of anaemia with AID (p = 0.02). Conclusion: In preoperative colorectal cancer patients, there is a high prevalence of iron deficiency, including a high percentage of patients with—a component of—functional iron deficiency, associated with the increased postoperative complication rate. As both types of iron deficiency require a different treatment strategy, our results illustrate the therapeutic potential of especially intravenous iron supplementation in patients with severe iron deficiency and stress the urgency of routinely monitoring preoperative iron status and differentiation between types of iron deficiency. As iron therapy may also be potentially harmful in respect to stimulation of tumour growth, future clinical trials assessing the long-term effect of iron therapy are necessary

Guideline development for prevention of transfusion-associated graft-versus-host disease: reduction of indications for irradiated blood components after prestorage leukodepletion of blood components

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare, commonly fatal complication of transfusion preventable by irradiation of blood units. The revision of the Dutch transfusion guideline addressed the question whether irradiation is still necessary if blood components are prestorage leukodepleted. We searched for published cases of TA-GVHD following transfusion of prestorage leukodepleted blood and through contacting haemovigilance systems. Six presumed cases were found, dating from 1998 to 2013. Four out of six patients had received one or more non-irradiated units despite recognised indications for irradiated blood components. In the countries providing information, over 50 million prestorage leukodepleted, non-irradiated, non-pathogen-reduced cellular components were transfused in a 10-year period. Potential benefits of lifting indications for irradiation were considered. These include reduced irradiation costs (euro 1.5 million annually in the Netherlands) and less donor exposure for neonates. Findings were presented in an invitational expert meeting. Recommendations linked to human leukocyte antigen similarity between donor and recipient or intra-uterine transfusion were left unchanged. Indications linked to long-lasting deep T-cell suppression were defined with durations of 6 or 12 months after end of treatment (e.g. autologous or allogeneic stem cell transplantation). Need for continued alertness to TA-GVHD and haemovigilance reporting of erroneous non-irradiated transfusions was emphasised.Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

The interplay between GPIb/IX-antibodies, platelet hepatic sequestration, and TPO levels in patients with chronic ITP.

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with an incompletely understood pathophysiology, but includes platelet-clearance in the spleen and liver via T-cells and/or platelet-autoantibodies. Strikingly, thrombopoietin (TPO) levels remain low in ITP. Platelet-glycoprotein (GP)Ibα has been described to be required for hepatic TPO generation, however, the role of GPIb-antibodies in relation to platelet hepatic sequestration and TPO-levels, with consideration of platelet counts, remains to be elucidated. Therefore, we performed a study in which we included 53 chronic and non-splenectomized ITP patients for which we conducted indium labeled autologous platelet scintigraphy, measured platelet-antibody profiles and TPO-levels. Upon stratification towards the severity of thrombocytopenia, no negative association was observed between GPIb/IX-antibodies and TPO levels, suggesting that GPIb/IX-antibodies do not inhibit or block TPO levels. Surprisingly, we observed a positive association between GPIb/IX-antibody levels and TPO levels, and GPIb/IX-antibodies and platelet hepatic sequestration, in patients with severe thrombocytopenia, but not in patients with mild or moderate thrombocytopenia. In addition, platelet hepatic sequestration and TPO levels were positively associated. This collectively indicates that GPIb/IX-antibodies may be associated with an increased platelet hepatic sequestration and elevated TPO levels in severe thrombocytopenic ITP patients, however, further research is warranted to elucidate the pathophysiological mechanisms.Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease