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Marchiafava Micheli syndrome [keywords]
- Presence of paroxysmal nocturnal hemoglobinuria (PNH) clones does not exclude inherited bone marrow failure syndromes (IBMFS). [JOURNAL ARTICLE]
- Eur J Haematol 2014 Apr 21.
I was reading the manuscript by DeZern et al. with interest. The authors stated that "the presence of GPI anchor-deficient cells in at least two lineages, especially in patients with no family history of bone marrow failure or other stigma of IBMFS, virtually excludes the diagnosis of IBMFS thereby eliminating the need for additional costly tests and delay in initiating definitive therapy". The authors made this conclusion based on their study comprising of only 20 patients with IBMFS . I believe this conclusion is premature because of the following reasons. This article is protected by copyright. All rights reserved.
- Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria phenotype in patients with splanchnic vein thrombosis. [JOURNAL ARTICLE]
- Thromb Res 2014 Apr 1.
Splanchnic vein thrombosis (SVT) is a serious complication in patients with paroxysmal nocturnal hemoglobinuria (PNH). Mutant PNH clones can be associated with an increased risk of SVT even in the absence of overt disease, but their prevalence in non-selected SVT patients remains unknown.Patients with objective diagnosis of SVT and without known PNH were tested for the presence of PNH clone using high-sensitivity flow cytometric analysis.A total of 202 SVT patients were eligible, 58.4% were males, mean age was 54.6years (range 17-94), site of thrombosis was portal in 103 patients, mesenteric in 67, splenic in 37, and supra-hepatic in 10. SVT was associated with JAK2 V6167F in 28 of 126 (22.2%) screened patients, liver cirrhosis in 15.3% patients, recent surgery in 10.9%, and myeloproliferative neoplasm in 10.6%, whereas in 34.6% of patients neither permanent nor transient risk factors were detected. None of the patients had a clearly demonstrable PNH clone, but in two patients (0.99%, 95% CI 0.17-3.91) we observed very small PNH clones (size 0.014% and 0.16%) confirmed in two independent samples. One patient had portal vein thrombosis and no associated risk factors, the second had superior mesenteric vein thrombosis and inflammatory bowel disease.Very small PNH clones can be detected in patients with SVT and no clinical manifestations of disease. Future studies are needed to explore the potential role of this finding in the pathogenesis of SVT.
- Concerns about unapproved meningococcal vaccination for eculizumab therapy in Japan. [Journal Article]
- Orphanet J Rare Dis 2014; 9(1):48.
An orphan medicinal product, eculizumab is approved in Japan and globally for treating paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Eculizumab therapy can cause late complement pathway deficiencies that predispose patients to meningococcal infections. Although meningococcal vaccinations are typically considered mandatory for eculizumab therapy, no approved vaccine is available in Japan as of March, 2014. Advertising unapproved, privately imported pharmaceuticals is prohibited under Japanese pharmaceutical law; detailed information concerning the unapproved meningococcal vaccines is therefore not widely available. The situation jeopardizes the safety of patients receiving eculizumab therapy, and Japanese clinicians are advised caution when prescribing this therapy.
- Standardizing leucocyte PNH clone detection: An international study. [JOURNAL ARTICLE]
- Cytometry B Clin Cytom 2014 Apr 9.
Consensus and Practical Guidelines for robust high-sensitivity detection of glycophosphatidylinostitol-deficient structures on red blood cells and white blood cells in paroxysmal nocturnal hemoglobinuria (PNH) were recently published.UK NEQAS LI issued three stabilized samples manufactured to contain no PNH cells (normal), approximately 0.1% and 8% PNH leucocyte populations, together with instrument-specific Standard Operating Procedures (SOPs) and pretitered antibody cocktails to 19 international laboratories experienced in PNH testing. Samples were tested using both standardized protocol/reagents and in-house protocols. Additionally, samples were issued to all participants in the full PNH External Quality Assessment (EQA) programs.Expert laboratory results showed no difference in PNH clone detection rates when using standardized and their "in-house" methods, though lower variation around the median was found for the standardized approach compared to in-house methods. Neutrophil analysis of the sample containing an 8% PNH population, for example, showed an interquartile range of 0.48% with the standardized approach compared with 1.29% for in-house methods. Results from the full EQA group showed the greatest variation with an interquartile range of 1.7% and this was demonstrated to be significantly different (P < 0.001) to the standardized cohort.The results not only demonstrate that stabilized whole PNH blood samples are suitable for use with currently recommended high-sensitivity reagent cocktails/protocols but also highlight the importance of using carefully selected conjugates alongside the standardized protocols. While much more variation was seen among the full UK NEQAS LI EQA group, the standardized approach lead to reduced variation around the median even for the experienced laboratories. © 2014 Clinical Cytometry Society.
- Rapidly evolving skin manifestations due to progressive thrombosis in a patient with paroxysmal nocturnal hemoglobinuria (PNH) resolved with prompt initiation of eculizumab. [LETTER]
- Br J Dermatol 2014 Apr 4.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal disorder of the haematopoietic stem cell. PNH arises from mutations in the PIG-A gene encoding glycosylphosphatidylinositol (GPI) anchored proteins consequently resulting in deficiency of GPI-anchored proteins the cell membranes.(1) This deficiency causes PNH red cells to be susceptible for complement induced intravascular hemolysis.(2) However, PNH is also characterized by a high rate of thrombosis.(3-4) This article is protected by copyright. All rights reserved.
- Selective splenic artery embolization for the treatment of thrombocytopenia and hypersplenism in paroxysmal nocturnal hemoglobinuria. [Journal Article]
- J Hematol Oncol 2014.:27.
PNH is associated with abdominal vein thrombosis, which can cause splenomegaly and hypersplenism. The combination of thrombosis, splenomegaly, and thrombocytopenia (TST) is challenging because anticoagulants are indicated but thrombocytopenia may increase the bleeding risk. Splenectomy could alleviate thrombocytopenia and reduce portal pressure, but it can cause post-operative thromboses and opportunistic infections. We therefore sought to determine whether selective splenic artery embolization (SSAE) is a safe and effective alternative to splenectomy for TST in patients with PNH.Four patients with PNH and TST received successive rounds of SSAE. By targeting distal vessels for occlusion, we aimed to infarct approximately 1/3 of the spleen with each procedure.Three of 4 patients had an improvement in their platelet count, and 3 of 3 had major improvement in abdominal pain/discomfort. The one patient whose platelet count did not respond had developed marrow failure, and she did well with an allo-SCT. Post-procedure pain and fever were common and manageable; only one patient developed a loculated pleural effusion requiring drainage. One patient, who had had only a partial response to eculizumab, responded to SSAE not only with an improved platelet count, but also with an increase in hemoglobin level and decreased transfusion requirement.These data indicate that SSAE can decrease spleen size and reverse hypersplenism, without exposing the patient to the complications of splenectomy. In addition, SSAE probably reduces the uptake of opsonised red cells in patients who have had a limited response to eculizumab, resulting in an improved quality of life for selected patients.
- An inter-laboratory comparison of PNH clone detection by high-sensitivity flow cytometry in a Russian cohort. [JOURNAL ARTICLE]
- Hematology 2014 Mar 26.
Objectives Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal stem cell disorder characterized by partial or absolute deficiency of glycophosphatidyl-inositol (GPI) anchor-linked surface proteins on blood cells. A lack of precise diagnostic standards for flow cytometry has hampered useful comparisons of data between laboratories. We report data from the first study evaluating the reproducibility of high-sensitivity flow cytometry for PNH in Russia. Methods PNH clone sizes were determined at diagnosis in PNH patients at a central laboratory and compared with follow-up measurements in six laboratories across the country. Analyses in each laboratory were performed according to recommendations from the International Clinical Cytometry Society (ICCS) and the more recent 'practical guidelines'. Follow-up measurements were compared with each other and with the values determined at diagnosis. Results PNH clone size measurements were determined in seven diagnosed PNH patients (five females, two males: mean age 37 years); five had a history of aplastic anemia and three (one with and two without aplastic anemia) had severe hemolytic PNH and elevated plasma lactate dehydrogenase. PNH clone sizes at diagnosis were low in patients with less severe clinical symptoms (0.41-9.7% of granulocytes) and high in patients with severe symptoms (58-99%). There were only minimal differences in the follow-up clone size measurement for each patient between the six laboratories, particularly in those with high values at diagnosis. Conclusions The ICCS-recommended high-sensitivity flow cytometry protocol was effective for detecting major and minor PNH clones in Russian PNH patients, and showed high reproducibility between laboratories.
- Evaluation and comparison of different approaches for the detection of PNH clones by flow cytometry following the ICCS guidelines. [Journal Article]
- Clin Lab 2014; 60(2):217-24.
Comparison between consensual approaches for the detection of paroxysmal nocturnal hemoglobinuria (PNH) clones by flow cytometry (FCM) following the international clinical cytometry society (ICCS) guidelines has not been widely reported.We determined the performance characteristics of 4, 5, and 6-color protocols for white blood cell (WBC) and one and two-color protocols for red blood cell (RBC) evaluation for different PNH target clones and compared results from PNH patient analysis.Coefficient of variation (CV) for precision/reproducibility analysis ranged from 0.01%/0.12% to 2.56%/ 3.59% for granulocytes, from 0.07%/0.08% to 3.87%/11.61% for monocytes and from 0.4%/1.02% to 6.53%/ 5.1% for RBCs within different approaches and target PNH clones. Comparison of individual protocols revealed excellent correlation (r = 0.99), Wilcoxon rank tests found no statistically significant differences (p > 0.05), Bland-Altman analysis proved agreement for all PNH clones (mean bias ranging from 0.02 to 2.2).Our results confirm good intralaboratory characteristics for precision and reproducibility analysis, excellent correlation and agreement between approaches underlining the primary role of optimally selected glycophosphatidylinositol (GPI)-specific reagents and secondary role of number, type of gating reagents and gating strategy.
- Standardizing Leucocyte PNH clone detection: An international study. [JOURNAL ARTICLE]
- Cytometry B Clin Cytom 2014 Mar 22.
Background: Consensus and Practical Guidelines for robust high-sensitivity detection of glycophosphatidylinostitol (GPI)-deficient structures on Red Blood Cells (RBCs) and White Blood Cells (WBCs) in Paroxysmal Nocturnal Hemoglobinuria (PNH) were recently published. Methods: UK NEQAS LI issued 3 stabilized samples manufactured to contain no PNH cells (normal), approximately 0.1% and 8% PNH leucocyte populations, together with instrument-specific SOPs and pre-titered antibody cocktails to 19 international laboratories experienced in PNH testing. Samples were tested using both standardized protocol/reagents and in-house protocols. Additionally, samples were issued to all participants in the full PNH EQA programmes. Results: Expert laboratory results showed no difference in PNH clone detection rates when using standardized and their 'in-house' methods though lower variation around the median was found for the standardized approach compared to in-house methods. Neutrophil analysis of the sample containing an 8% PNH population, for example, showed an interquartile range of 0.48% with the standardized approach compared with 1.29% for in-house methods. Results from the full EQA group showed the greatest variation with an inter-quartile range of 1.70 and this was demonstrated to be significantly different (P<0.001) to the standardized cohort. Conclusions: The results not only demonstrate that stabilized whole PNH blood samples are suitable for use with currently recommended high-sensitivity reagent cocktails/protocols but also highlight the importance of using carefully selected conjugates alongside the standardized protocols. While much more variation was seen amongst the full UK NEQAS LI EQA group, the standardized approach lead to reduced variation around the median even for the experienced laboratories. © 2014 Clinical Cytometry Society.
- Paroxysmal nocturnal hemoglobinuria diagnosed after influenza vaccine: coincidence or consequence? [Case Reports, Journal Article]
- Isr Med Assoc J 2014 Feb; 16(2):122-4.