Rh(D) immune globulin administration in pregnancy: Retrospective audit of patient safety events followed by targeted educational intervention with Bayesian analysis.

OBJECTIVES: To examine local patient safety events related to the administration of anti-Rh(D) immune globin (RhIG) during pregnancy, and to follow-up with targeted educational intervention to improve knowledge of this process. BACKGROUND: Administration RhIG is established treatment for the prevention of haemolytic disease of the foetus and newborn (HDFN). However, patient safety events in relation to its correct use continue to occur. METHODS: A retrospective audit of patient safety events related to RhIG administration during pregnancy was performed. Targeted educational intervention in the form of PowerPoint® presentation were given to nursing staff, laboratory staff and physicians and evaluated with pre- and post-tests using multiple-choice questions given immediately before and after the presentation. RESULTS: An annual incidence of 0.24% of patient safety events related to the administration of RhIG during pregnancy was found. These events were mostly in the preanalytical phase, for example mislabelled samples or samples for D-rosette/Kleihauer-Betke testing drawn from the baby, not the mother. Using Bayesian analysis, the probability of positive effect for the targeted educational intervention was 100% with a median improved score of 29%. This was compared with a control group using standard curriculum education intervention based on the current curriculum for nursing, laboratory and medical students which showed a median improved score of only 4.4%. CONCLUSIONS: Administration of RhIG during pregnancy is a multistep process involving health care professionals of several disciplines providing opportunities to enhance the curriculum for nursing, laboratory and medical students and to ensure on-going education.

Practical application of mathematical calculations and statistical methods for the routine haematology laboratory.

BACKGROUND: Statistical analyses are embedded as critical functions in the routine haematology laboratory. AIM: This educational article is aimed at providing an overview of these topics and practical application examples. MATERIALS, METHODS, AND RESULTS: Topics covered include mathematical conversion between units, maintaining a quality control (QC) system, statistical methods for reagent validation, and determining uncertainty of measurement (UoM). DISCUSSION: Additional considerations may be required when a regional laboratory program is in place, such as the harmonization of INR results and determination of therapeutic reference intervals for unfractionated heparin therapy. CONCLUSION: The coauthors of this manuscript are fortunate to be part of regional network of hospital laboratories, the Eastern Ontario Regional Laboratory Association (EORLA).

Disseminated cryptococcal infection in a patient with treatment-naïve chronic lymphocytic leukemia (CLL).

We report a case of disseminated cryptococcosis in a treatment-naïve chronic lymphocytic leukemia (CLL) patient. A 60-year-old man presented with a two-week history of intermittent fevers, frontal headaches, night sweats, weight loss and multiple pink papules on hands and face. Cryptococcemia was found by blood culture unexpectedly. Further investigation confirmed cryptococcal meningitis and skin disease. He responded to two week amphotericin B and flucytosine followed by four-week amphotericin B and fluconazole, three-month high dose fluconazole (800 mg/day), and maintenance fluconazole (400 mg/day) thereafter. CSF pleocytosis persisted until day 203 while cryptococcal antigen in the CSF persisted at day 334 of treatment.

Anterior segment infiltration of acute lymphoblastic leukemia: case report and systematic review.

Acute lymphoblastic leukemia (ALL) relapse implies a poor prognosis and demands emergency treatment. Leukemic infiltration of the anterior segment can masquerade as intraocular inflammation; a high index of suspicion for this complication is essential. We describe a case of ocular relapse in a 2-year-old male on maintenance therapy for ALL. A systematic review of all known cases of similar leukemic infiltration of the anterior segment of the eye in ALL was performed. A total of 106 patients in 43 reports described leukemic infiltration of the eye as an initial presentation of ALL or relapse. Ocular relapse may be the first visible manifestation of systemic disease, with concurrent disease in the CNS, bone marrow, or testes. Prognosis for ALL patients with ocular relapse is poor, with death after initial presentation reported as early as 16 days. Patients with a history of ALL presenting with any sign of ocular inflammation should be assessed for relapse and leukemic infiltration. As soon as a diagnosis of relapse has been confirmed, appropriate leukemia therapy should be initiated.

Guidance for quality control practices and precision goals for CBCs based on IQMH patterns-of-practice survey.

INTRODUCTION: Effective medical laboratory quality management systems ensure confidence in analyzing and reporting accurate and reliable patient results. To guarantee quality assurance, each laboratory needs appropriate internal quality control (IQC) procedures to monitor their test systems. The Institute for Quality Management in Healthcare (IQMH) Centre for Proficiency Testing conducted a survey on quality control (QC) practices in routine hematology. METHODS: An online survey was sent to 184 Ontario laboratories performing complete blood counts (CBC) and leukocyte differentials. RESULTS: All participants used three levels of commercial QC for test system monitoring. Eighty percent of laboratories supplement with in-house patient QC. The frequency of QC analysis was variable based on: Manufacturer recommendations (80%) Parameter stability (25%) Clinical impact of incorrect results (21%) Number of samples potentially requiring retesting if there is a QC failure (11%). All laboratories used established QC rules and limits to monitor results. They utilized various methods in establishing limits including: Standard deviation of QC results (60%) Manufacturer precision goals (55%) Published precision goals (24%) IQMH allowable performance limits (APLs) (37%). CONCLUSION: Considerable variation in QC practices of Ontario laboratories was identified, and consensus practice recommendations and precision goals were developed to guide and standardize QC practice.

Characteristics of Lymphoproliferative Disorders with More Than One Aberrant Cell Population as Detected by 10-Color Flow Cytometry.

BACKGROUND: We have evaluated the frequency of lymphoproliferative disorders with more than one aberrant population of monotypic B-cells detected during routine hematopathological diagnostics. MATERIALS AND METHODS: 2600 samples peripheral (blood, bone marrow, fine-needle aspirate, lymph node, and pleural fluid cell suspensions) were analyzed using a 10-color B-cell panel and a 10-color T-cell panel. A 10-color plasma cell/lymphoplasmacytic panel was performed when appropriate. RESULTS: 790/2600 samples (30%) showed at least one aberrant B-cell population and 27(1%) showed an aberrant T-cell population. 41/790 samples (5.1%) showed two aberrant B-cell populations. Thirteen patients had two B-cell populations with different surface immunoglobulin restriction (one kappa+ and one lambda+), most with B-cell chronic lymphocytic leukemia-related phenotype. Five cases showed two B-cell populations with the same light chain restriction but distinctly different immunophenotypes. In 23 cases, two populations had the same light chain restriction and differed by expression of one or 2 markers, thus, a possibility of intraclonal differentiation could not be excluded. Cases with possible intraclonal differentiation had a significantly higher proportion of aberrant B-cells than those with two coexisting aberrant B-cell populations (49.9% vs. 27.7%, p = 0.008). In only one sample one population of clonal B-cell and one clonal T-cell population with large granular lymphocyte related phenotype were found. CONCLUSION: Using our panels 5.1% of cases with lymphoproliferative disorder-associated aberrant findings show two aberrant (clonal) lymphoid and/or plasma cell populations. © 2016 International Clinical Cytometry Society.

Prenatally Diagnosed Infant AML.

We report the first case of a fetus with acute myeloid leukemia, without Down syndrome, diagnosed in utero. A cordocentesis sample prepared to investigate hepatomegaly led to further evaluations revealing acute myeloid leukemia, monocytic type, in the fetus. Cytogenetic analysis showed mixed lineage leukemia duplication, no gene disruption or trisomy. Planned treatment included intrauterine exchange transfusion to extend gestation, low-dose chemotherapy at birth, and full chemotherapy once stable. Before any intervention, the child was delivered emergently for maternal condition and died 2 hours later. Although it is now possible to diagnose hematologic malignancy in a fetus, there is little information to direct management.

Possible mechanisms for intravenous immunoglobulin-associated hemolysis: clues obtained from review of clinical case reports.

BACKGROUND: Intravenous immunoglobulin (IVIG) is an efficacious treatment modality for a number of conditions and is usually well tolerated with few reports of serious adverse events; however, the administration of IVIG may occasionally result in clinically significant hemolysis. STUDY DESIGN AND METHODS: The literature was reviewed for case reports and case series of IVIG-associated hemolysis. The cases were scrutinized for clues as to the possible mechanism(s) of the hemolysis. RESULTS: Review of the 129 individual cases reported in the literature identifies clinical features shared by the majority of patients. These features included non-O blood group patients and treatment with high-dose IVIG as an immune-modulating agent for an underlying inflammatory or immune-mediated disorder. Other patient factors such as secretor phenotype, soluble ABH substance, and Fcgamma receptor polymorphisms may also play a role. CONCLUSIONS: It is known that high-dose IVIG given to non-O blood group patients with underlying inflammatory and/or immune-mediated disorders is associated with increased risk of hemolysis. This review reveals additional patient characteristics in cases of IVIG-associated hemolysis, including underrepresentation of D- and group B cases, higher incidence in pediatric Kawasaki disease and unique at-risk patient groups including allogeneic stem cell transplant recipients with group A donor in a group O recipient, and patients in whom soluble AB substance is removed by plasma exchange at the same time as receiving IVIG.

Disseminated histoplasmosis associated with acquired hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening clinical syndrome caused by uncontrolled activation of lymphocytes and histiocytes resulting in high levels of cytokines. Acquired HLH occurs in autoimmune, inflammatory, infectious, and immunosuppressive disorders. Prompt identification and treatment of an underlying triggering cause improves clinical outcome.

Acute extravascular hemolytic transfusion reaction due to anti-Kpa antibody missed by electronic crossmatch.

BACKGROUND: Kpa antigen is a low incidence red blood cell antigen within the Kell system. Anti-Kpa alloantibody may be associated with acute and delayed hemolytic transfusion reactions. CASE STUDY: We report a case of a clinically significant acute extravascular hemolytic transfusion reaction mediated by previously unrecognized (and undetected) anti-Kpa alloantibody. This reaction occurred in a patient who met all criteria for electronic crossmatch, resulting in the transfusion of an incompatible red cell unit. RESULTS: Post-transfusion investigation showed the transfused red cell unit was crossmatch compatible at the immediate spin phase but was 3 + incompatible at the antiglobulin phase. No evidence of intravascular hemolysis was observed upon visual comparison of the pre- and post-transfusion peripheral blood plasma. Further testing showed the presence of anti-Kpa antibody. The clinical course of the patient included acute febrile and systemic reaction. CONCLUSION: Acute extravascular hemolytic transfusion reaction may occur due to undetected anti-Kpa alloantibody. Various strategies for crossmatching are discussed in the context of antibodies to low incidence antigens.

B-lymphoblastic leukemia/lymphoma: overexpression of nuclear DNA repair protein PARP-1 correlates with antiapoptotic protein Bcl-2 and complex chromosomal abnormalities.

Poly(ADP-ribose) polymerase-1 (PARP-1) and Bcl-2 are emerging as therapeutic targets in various cancers. The former is a DNA repair protein associated with genomic stability and apoptosis, whereas the latter is an antiapoptotic protein having a DNA repair function through inhibition of PARP-1. Because genomic stability is critical for prognosis in B-lymphoblastic leukemia/lymphoma (B-ALL), we studied the expression of PARP-1 and Bcl-2 proteins in patients with B-ALL of different ages and compared the results with cytogenetic data. The PARP-1 protein was overexpressed in about two-thirds (61%) of patients with B-ALL. It had a nuclear location, whereas Bcl-2 protein was cytosolic. Expression of the 2 proteins showed a highly positive correlation (ρ = 0.367; P < .001). Overexpression of PARP-1 correlated with a complex karyotype (P = .030), and this correlation remained significant for coexpression of PARP-1 and Bcl-2 proteins (χ(2) = 7.498; P = .024) as well as after exclusion of pediatric patients (n = 9, P = .042). Overexpression of PARP-1 was not significantly more common in diploid versus aneuploid karyotypes (50% versus 59%, P = .610). The PARP-1 protein showed no correlation with specific chromosomal abnormalities associated with prognosis in B-ALL, as defined by the World Health Organization. In conclusion, high expression of the PARP-1 protein among patients with B-ALL is related to a complex karyotype and Bcl-2 positivity. Although these findings require validation in a larger population, the observations will be valuable in planning therapeutic trials (such as of PARP inhibitors and BH3 mimetics).

Langerhans cell sarcoma with an aberrant cytoplasmic CD3 expression.

Langerhans cell sarcoma is a rare and aggressive high grade hematopoietic neoplasm with a dismal prognosis. It has a unique morphological and immunotypic profile with a CD1a/ langerin/S100 + phenotype. T cell lineage markers except for CD4 in Langerhans cell sarcoma have not been documented previously. We report a case of 86 year-old male of Caucasian descent who presented with an enlarging right neck mass over 2 months with an underlying unknown cause of anemia. Computed tomography scan of the neck, chest and abdomen revealed generalized lymphadenopathy and mild splenomegaly suspicious for lymphoma. Diagnostic core biopsy performed on right neck mass revealed a possible T cell lymphoma with expression of T cell lineage specific marker CD3 but conclusive diagnosis could not be made due to insufficient core biopsy sample. Further excisional biopsy performed on a left inguinal node showed a hematopoietic neoplasm with features of Langerhans cell sarcoma with a focal cytoplasmic CD3 expression in 30-40% of the tumor cells. PCR for T cell receptor (TCR) gene rearrangement failed to demonstrate a clonal gene rearrangement in the tumor cells arguing against a T cell lineage transdifferentiation, suggesting an aberrant CD3 expression. To the best of our knowledge, this case represents the first report of Langerhans cell sarcoma with an aberrant cytoplasmic CD3 expression. VIRTUAL SLIDES: http://www.diagnosticpathology.diagnomx.eu/vs/2065486371761991.

Insights into origins of Human T-cell Lymphotropic Virus Type 1 based on new strains from aboriginal people of Canada.

The causes of the worldwide distribution of Human T-cell Lymphotropic Virus Type 1 (HTLV-1) remain incompletely understood, with competing hypotheses regarding the number and timing of events leading to intercontinental spread on historical and prehistoric timescales. Ongoing discovery of this virus in aboriginal populations of Asia and the Americas has been the main source of evidence for the latter. We conducted molecular phylogenetic and dating analyses for 13 newly reported HTLV-1 strains from Canada. We analyzed two full-length proviral genomes from aboriginal residents of Nunavut (an autonomous territory in Northern Canada including most of the Canadian Arctic), 11 long-terminal-repeat (LTR) sequences from aboriginal residents of British Columbia's Pacific coast, and 2 LTR sequences from non-aboriginal Canadians. Phylogenetic analysis demonstrated a well-supported affinity between the two Nunavut strains and two East Asian strains, suggesting the presence of an Asian-American sublineage within the widespread "transcontinental" subgroup A clade of HTLV-1 Cosmopolitan subtype a. This putative sublineage was estimated to be 5400-11,900 years in age, consistent with a long-term presence of HTLV-1 in aboriginal populations of the Canadian Arctic. Phylogenetic affinities of the other 11 Canadian HTLV-1 aboriginal strains were diverse, strengthening earlier evidence for multiple incursions of this virus into coastal aboriginal populations of British Columbia. Our results are consistent with the hypothesis of ancient presence of HTLV-1 in aboriginal populations of North America.