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

Haemovigilance:current practices and future developments

Haemovigilance is the systematic surveillance of adverse events in the transfusion chain, and encompasses activities that contribute to the safety and quality in the process of blood donation and transfusion. From the start in the early 1990s, haemovigilance has put emphasis on different adverse reactions and incidents in recipients and subsequently in donors, pointing to vulnerabilities in the transfusion chain and areas for prevention. More recently, the monitoring of efficacy and efficiency of transfusion practice has been introduced in the concept of haemovigilance. The purpose of this review is to present an overview of the current status and future developments of haemovigilance. Haemovigilance is part of the quality systems of the blood collection establishments, transfusion laboratories and the transfusion institutions. The monitoring, investigation and analysis of adverse events generates relevant data for the quality cycle of these systems, driving continuous improvement in transfusion practice. Recommendations based on haemovigilance findings have led to changes in clinical guidelines and policies. Despite the progress haemovigilance has made, further developments are needed. Current challenges lie in the field of the establishment of haemovigilance systems in low resource settings, the international harmonisation of definitions and the prevention of underreporting. In addition, the causal relationship between the transfusion and the reaction is often unclear. Biomarkers may aid in the imputability assessment and their role in the diagnosis of transfusion reactions needs to be further investigated. Future developments are expected in automated reporting, the use of big data and increased shareability of international data, contributing to a better understanding of the causal mechanisms and risk factors, and to prevention of adverse events. Haemovigilance is an evolving discipline and will continue to contribute to improving the safety of blood donation and transfusion

Anti-glycoprotein antibodies and sequestration pattern of indium-labeled platelets in immune thrombocytopenia

Antiglycoprotein (anti-GP) antibodies play an important role in the pathophysiology of immune thrombocytopenia (ITP). The sequestration pattern of platelets in the spleen and liver can be studied with (111)In-labeled autologous platelet scans. No studies have investigated the role of anti-GP antibodies in sequestration patterns in ITP patients. In this study, we examined the association between antibodies and (1) platelet sequestration site and (2) clearance rate of platelets. All ITP patients receiving an (111)In-labeled autologous platelet study between 2014 and 2018 were included. Antibodies were measured using the direct MAIPA method to determine the presence and titer of anti-GPIIb/IIIa, anti-GPIb/IX, and anti-GPV antibodies. Multivariate regression models were used to study the association between anti-GP antibodies, sequestration site, and clearance rate. Seventy-four patients were included, with a mean age of 36 years. Forty-seven percent of the patients showed a predominantly splenic sequestration pattern, 29% mixed, and 25% a hepatic pattern. In 53% of the patients, anti-GP antibodies were detected. Regression models showed a significant association between splenic sequestration and GPV autoantibodies. Furthermore, in patients where antibodies were present, the clearance rate was higher in patients with a splenic sequestration. Anti-GPV antibodies are associated with a splenic sequestration pattern in ITP patients. These associations provide insight into the possible pathophysiological mechanisms of ITP, which may lead to better detection and treatment of this partly idiopathic and prevalent disease

Should HLA and HPA-matched platelet transfusions for patients with Glanzmann Thrombasthenia or Bernard-Soulier syndrome be standardized care? A Dutch survey and recommendations

Background: Glanzmann thrombasthenia (GT) and Bernard-Soulier syndrome (BSS) patients require frequent platelet transfusions and hence have an increased risk for alloimmunization against donor Human Leukocyte Antigens (HLA) when no HLA-matching is performed. Knowing that Human Platelet Antigens (HPA) are located on the platelet glycoproteins that can be absent in these patients, preventive HPA-matching may also be considered. Uniform recommendations on this topic lack in transfusion guidelines making standard practice unclear, therefore, we aimed to provide a framework for matched platelet transfusions. Study Design and Methods: We conducted a targeted literature search and a national survey of Dutch (pediatric) hematologists from July to September 2021. Results: We found 20 articles describing platelet transfusion policies in 483 GT-patients and 29 BSS-patients, both adults and children. Twenty surveys were returned for full analysis. All responders treated patients with platelet disorders, including GT (n = 36 reported) and BSS (n = 29 reported). Of respondents, 75% estimated the risk of antibody formation as “likely” for HLA and 65% for HPA. Formation of HLA antibodies was reported in 5 GT and in 5 BSS-patients, including one child. Fifteen respondents gave preventive HLA-matched platelets in elective setting (75%). Three respondents additionally matched for HPA in GT-patients (15%). Main argument for matched platelet transfusions was preventing alloimmunization to safeguard the effectivity of ‘random’ donor-platelets in acute settings. Conclusion: Elective HLA-matching for GT and BSS-patients is already conducted by most Dutch (pediatric) hematologists. HPA-matching is mainly applied when HPA-antibodies are formed. Based on the current literature and the survey, recommendations are proposed.</p

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

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 examined 53 patients with chronic and nonsplenectomized ITP for whom we conducted indium-labeled autologous platelet scintigraphy and measured platelet antibodies and TPO levels. Upon stratification toward 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, but not 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 increased platelet hepatic sequestration and elevated TPO levels in patients with severe thrombocytopenic ITP; however, further research is warranted to elucidate the pathophysiologic mechanisms.</p