Alloantibody assays and outcome of platelet transfusions

In this thesis we deal with two aspects of alloantibody assays: (i) test characteristics and (ii) performance of tests in different patient populations. The first part of this thesis focuses on the technical aspects of antibody detection guided by the following questions: 1. Is a technique using standardized antigens (ELIHLA) as sensitive as techniques using panel cells (LCT, LIFT, PIFT) and are the results of these 4 different techniques related? 2. Are the results of a technique that detects IgG bound to transfused platelets in vivo (IVBI-PIFT) related to those of an in vitro technique using panel cells ( crossmatchPIFT) or using standardized platelet antigens (ELIHLA)? 3. Is binding of IgG to transfused platelets in vivo related to poor platelet recovery? 4. Can the visual scoring method of the IVBI-PIFT reliably be objectivated by a mathematical method of histogram subtraction? The second part of the thesis deals with the predictive value of alloantibody tests on platelet recovery of random platelet transfusions in a non-selected patient population and of HLA-matched platelet transfusions in a heavely selected patient population. In some of the studies non-immunological factors jeopardizing the survival of platelets were taking into account too. These value of alloantibody assays were studied by the following questions: 1. What is the prevalence of immune and non-immune causes of platelet transfusion failures in a non-selected patient population? 2. Which alloantibody tests and what non-immune causes are best related to platelet transfusion failures in a non-selected patient population

Two patients with acute thrombocytopenia following gold administration and five-year follow-up

Thrombocytopenia is a well-known side effect following intramuscular gold therapy in patients with rheumatoid arthritis. Thrombocytopenia may occur at any time and it can be irreversible and sometimes fatal despite cytotoxic or immunosuppressive therapy. We describe two patients who presented with haemorrhagic diathesis on the day after the administration of aurothioglucose. The thrombocytopenia in these patients was caused by aurothioglucose-induced antibody-mediated platelet destruction. Both patients made an uneventful recovery and the platelet count returned to normal within severa

Prognostic impact of low muscle mass and low muscle density in patients with diffuse large B-cell lymphoma

Low muscle mass (LMM) and low muscle density (LMD) are increasingly recognized as prognostic factors for survival in different malignancies. This study determined the association of LMM and LMD with survival in DLBCL (diffuse large B-cell lymphoma) patients. CT-based measurement of muscle was performed in 164 DLBCL patients prior to chemo-immunotherapy. Z-scores adjusted for gender, age, and body mass index were derived from a healthy reference population. LMM or LMD were defined as a Z-score below −1 and were related to OS and PFS. The co-existence of both LMM and LMD was observed in 13% of the DLBCL patients and was significantly associated with shorter OS and PFS. Also, these patients more often did not complete the planned treatment. The combination of LMM and LMD is an independent prognosti

Postpartum microangiopathic disorders: A case report and review of the literature

Introduction Thrombotic microangiopathic disorders (TMA's) consist of five overlapping disorders: severe pre-eclampsia; HELLP (haemolysis, elevated liver enzyme, and low platelet count) syndrome; thrombotic thrombocytopenic purpura (TTP); haemolytic-uremic syndrome (HUS) a

Cardiac monitoring in HER2-positive patients on trastuzumab treatment

Trastuzumab prolongs progression-free and overall survival in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer. However, trastuzumab treatment is hampered by cardiotoxicity, defined as a left ventricular ejection fraction (LVEF) decline with a reported incidence ranging from 3 to 27% depending on variable factors. Early identification of patients at increased risk of trastuzumab-induced myocardial damage is of great importance to prevent deterioration to irreversible cardiotoxicity. Although current cardiac monitoring with multi gated acquisition (MUGA) scanning and/or conventional 2D-echocardiography (2DE) have a high availability, their reproducibility are modest, and more sensitive and reliable techniques are needed such as 3D-echocardiography (3DE) and speckle tracking echocardiography (STE). But which other diagnostic imaging modalities are available for patients before and during trastuzumab treatment? In addition, what is the optimal frequency and duration of cardiac monitoring? At last, which biomarker monitoring strategies are currently available for the identification of cardiotoxicity in patients treated with trastuzumab

Possible hampered effectiveness of second-line treatment with rituximab-containing chemotherapy without signs of rituximab resistance: a population-based study among patients with chronic lymphocytic leukemia

Rituximab-containing chemotherapy remains a viable frontline treatment option for patients with chronic lymphocytic leukemia (CLL) in the era of novel agents. However, its effectiveness in the second-line setting—in relation to previous rituximab exposure in first-line—has hardly been evaluated in a population-based setting. Therefore, in this comprehensive, population-based study, we assessed the impact of first-line treatment with rituximab-containing chemotherapy on the effectiveness of second-line treatment with rituximab-containing chemot

The effectiveness of ibrutinib in chronic lymphocytic leukaemia: a nationwide, population-based study in the Netherlands

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Prevalence of potential underlying aetiology of macrocytic anaemia in Dutch general practice

Background: Macrocytic anaemia (MCV \xe2\x89\xa5 100 fL) is a relatively common finding in general practice. However, literature on the prevalence of the different causes in this population is limited. The prevalence of macrocytic anaemia and its underlying aetiology were analysed in a general practice population. The potential effect of the different aetiology on survival was also evaluated. Methods: Between the 1st of February 2007 and the 1st of February 2015, patients aged 50 years or older and presenting to their general practitioner with a newly diagnosed anaemia, were included in the study. Anaemia was defined as haemoglobin level below 13.7 g/dL in men and below 12.1 g/dL in women. A broad range of laboratory tests was performed for each patient. The causes of anaemia were consequently determined by two independent observers based on the laboratory results. Results: Of the 3324 included patients, 249 (7.5 %) displayed a macrocytic anaemia and were subsequently analysed. An underlying explanation could be established in 204 patients (81.9 %) with 27 patients (13.2 %) displaying multiple causes. Classic aetiology (i.e. alcohol abuse, vitamin B12/folic acid deficiency, haemolysis and possible bone marrow disease) was found in 115 patients. Alternative causes (i.e. anaemia of chronic disease, iron deficiency, renal anaemia and other causes) were encountered in 101 patients. In addition, a notable finding was the median gamma GT of 277 U/L in patients diagnosed with alcohol abuse (N = 24, IQR 118.0-925.5) and 23 U/L in the remaining cohort (N = 138, IQR 14.0-61.0). The distribution of gamma GT values was statistically different (P < 0.001). Five year survival rates were determined for six categories of causes, ranging from 39.9 % (95 % CI 12.9-66.9) for renal anaemia to 76.2 % (95 % CI 49.4-103.0) for the category multiple causes. Conclusion: In addition to classic explanations for macrocytosis, alternative causes are frequently encountered in patients with macrocytic anaemia in general practice