Genetic variants associated with platelet count are predictive of human disease and physiological markers.

Platelets play an important role in hemostasis and other aspects of vascular biology. We conducted a meta-analysis of platelet count GWAS using data on 536,974 Europeans and identified 577 independent associations. To search for mechanisms through which these variants affect platelets, we applied cis-expression quantitative trait locus, DEPICT and IPA analyses and assessed genetic sharing between platelet count and various traits using polygenic risk scoring. We found genetic sharing between platelet count and counts of other blood cells (except red blood cells), in addition to several other quantitative traits, including markers of cardiovascular, liver and kidney functions, height, and weight. Platelet count polygenic risk score was predictive of myeloproliferative neoplasms, rheumatoid arthritis, ankylosing spondylitis, hypertension, and benign prostate hyperplasia. Taken together, these results advance understanding of diverse aspects of platelet biology and how they affect biological processes in health and disease.

To Wash or Not to Wash? Comparison of Patient Outcome after Infusion of Cryopreserved Autologous Hematopoietic Stem Cells before and after the Replacement of Manual Washing by Bedside Thawing.

BACKGROUND: Prior to infusion, cryopreserved autologous peripheral blood stem cell (auto-PBSC) grafts can either be thawed at the bedside or thawed and washed at the laboratory. At our center, manual washing of grafts prior to infusion was discontinued in April 2012 and bedside thawing was implemented. METHODS: This study compares the outcomes of two patient groups who received auto-PBSC either after post-thaw washing (n = 84) or bedside thawing (n = 83). RESULTS: No life-threatening infusion-related side effects were reported in either group. There was no significant difference in the mean CD34+ cells/kg dose of infused auto-PBSC in the two groups (p = 0.41), nor in the number of days to neutrophils > 0.5 × 10(9)/L (p = 0.14), days to platelets > 20 × 10(9)/L (p = 0.64), or days to platelets > 50 × 10(9)/L (p = 0.62) after transplant. There was also no difference in the number of days on total parenteral nutrition (p = 0.69), days on G-CSF therapy (p = 0.48), or days with fever (p = 0.73). Finally, there was no significant difference in the number of red cell units transfused (p = 0.32), or platelet units transfused (p = 0.94) after the transplant. One-hundred-day mortality was identical in the two groups (2.4%). CONCLUSION: Both thawing procedures are safe and result in acceptable engraftment and patient outcomes.

The evolution of cellular deficiency in GATA2 mutation.

Constitutive heterozygous GATA2 mutation is associated with deafness, lymphedema, mononuclear cytopenias, infection, myelodysplasia (MDS), and acute myeloid leukemia. In this study, we describe a cross-sectional analysis of 24 patients and 6 relatives with 14 different frameshift or substitution mutations of GATA2. A pattern of dendritic cell, monocyte, B, and natural killer (NK) lymphoid deficiency (DCML deficiency) with elevated Fms-like tyrosine kinase 3 ligand (Flt3L) was observed in all 20 patients phenotyped, including patients with Emberger syndrome, monocytopenia with Mycobacterium avium complex (MonoMAC), and MDS. Four unaffected relatives had a normal phenotype indicating that cellular deficiency may evolve over time or is incompletely penetrant, while 2 developed subclinical cytopenias or elevated Flt3L. Patients with GATA2 mutation maintained higher hemoglobin, neutrophils, and platelets and were younger than controls with acquired MDS and wild-type GATA2. Frameshift mutations were associated with earlier age of clinical presentation than substitution mutations. Elevated Flt3L, loss of bone marrow progenitors, and clonal myelopoiesis were early signs of disease evolution. Clinical progression was associated with increasingly elevated Flt3L, depletion of transitional B cells, CD56(bright) NK cells, naïve T cells, and accumulation of terminally differentiated NK and CD8(+) memory T cells. These studies provide a framework for clinical and laboratory monitoring of patients with GATA2 mutation and may inform therapeutic decision-making.

[The Iron-man: a case-report]. / Járnmadurinn--sjúkratilfelli.

The most common cause of microcytic anemia is iron deficiency. We report a 29 year old man with history of dyspnea, fatigue and severe microcytic anemia despite iron therapy for 3 years. Blood transfusions elevated the hemoglobin levels temporarily, but iv iron did not. Bone marrow showed sideroblastic anemia. The anemia resolved with pyridoxine treatment but severe iron overload necessitated multiple phlebotomies. Today the patient is asymptomatic on pyridoxine with a normal hemoglobin level.

Epidemiology of hairy cell leukemia in Iceland.

INTRODUCTION: Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder. Previous epidemiological studies have mainly focused on cases derived from single institutions or from localized cancer registries. This is the first study in which all cases diagnosed nationwide over a long period of time in a well defined population are analysed. We report the epidemiology of all HCL patients in Iceland, their clinical characteristics, treatment and follow-up. PATIENTS AND METHODS: : All patients diagnosed with HCL in Iceland over a 20 year period, were included in this study. Data was collected retrospectively. RESULTS: Sixteen patients, 13 males and three females were diagnosed with HCL in Iceland from 1981-2000, giving a mean incidence of 4.7/million/year (95% CI: 2.7-7.6) in the population 20 years and older. Eleven patients were treated with a purine analogue, 10 of whom achieved CR. One other patient obtained CR following splenectomy and IFN, giving a total CR rate of 69%. Three other patients (19%) obtained PR, giving a total response rate of 88%. One patient had a variant of HCL and did not respond to any therapy and one patient died of sepsis before any chemotherapy could be given. Six patients with HCL have died, one from complications of HCL. Three patients developed a second malignancy (19%). CONCLUSIONS: The mean incidence of HCL in Iceland is 4.7/million/year. This is slighty higher than the reported incidence in England and Wales, although not significantly higher. The incidence is based on a nationwide information from a well defined stable and racially homogenous island population. Other results are in accordance with previously published studies.