Artefactual elevation of the automated white cell count in the context of a bone marrow aspirate analysis

2000 ◽  
Vol 22 (1) ◽  
pp. 57-57 ◽  
Author(s):  
J. F Lesesve ◽  
V Latger ◽  
J. Buisine ◽  
T. Lecompte
Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 165-165
Author(s):  
Anindita Roy ◽  
Mike Bradburn ◽  
Anthony V. Moorman ◽  
Julie Burrett ◽  
Chris Mitchell ◽  
...  

Abstract We report the outcome of children with Philadelphia positive acute lymphoblastic leukemia (Ph+ ALL) treated on the national trial for childhood ALL, MRC ALL 97/99, between Jan 1997 and Jun 2002. A diagnosis of Ph+ ALL was made by karyotyping and/or fluorescent in situ hybridisation. Outcome was evaluated according to NCI risk criteria and treatment response. Statistical methods included Kaplan Meier analysis, logrank and stratified logrank tests. Of the 1937 patients treated on the MRC ALL 97/99 protocol, 1836 were successfully screened for Ph chromosome and 42 (2.3%) were positive. This subgroup of patients was heterogeneous at the cytogenetic level with 27 (77%) out of 35 assessable cases having one or more abnormality in addition to the Ph translocation. Four recurrent secondary abnormalities were observed: an extra Ph chromosome, loss of 9p (del 9p), high hyperdiploidy and monosomy 7. The median age at diagnosis and presenting white cell count were 6.8 years and 32.5 × 109/L respectively. 19 (45%) had <25% bone marrow blasts within the first two weeks of treatment and were defined as a Good-response group (GRG), the others were classified as a Poor-response group (PRG). 6/10 (60%) of the patients with an extra Ph chromosome were in the GRG, whereas 8/10 (80%) of those with del 9p belonged to the PRG. 36/42 (86%) achieved complete remission (CR1) at the end of induction of whom 28 underwent bone marrow transplantation (BMT). The median follow up was 41 months (range 21–84 months). The 3-year estimate for event free survival (EFS) (with 95% confidence intervals) was 57% (41–70%). The EFS for the GRG and PRG were 74% (48–88%) and 44% (22–64%) respectively. Significant predictors for survival were presenting white cell count (p=0.02) and early response to treatment (p=0.03), but not age at diagnosis or gender. BMT in CR1 appeared to reduce the risk of a subsequent bone marrow relapse. These results are a significant improvement on previous results, particularly for the PRG. The EFS for the PRG in this report is 44% compared to a 4 yr. EFS of 10% in previously published data from the BFM/AIEOP group. We believe that the early introduction of intensive chemotherapy as in the MRC trial improves early response rates and overall outcome in Ph+ ALL, especially for the PRG. BMT in CR1 is recommended in children with Ph+ ALL, nonetheless newer alternative treatment strategies, such as the use of imatinib mesylate need to be evaluated for children with Ph+ ALL.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5271-5271
Author(s):  
Finella MC Brito-Babapulle ◽  
Barbara Czepulkowski

Abstract A 30 year old female presented@30 weeks pregnancy with a few circulating myeloid blasts in her blood but a normal full blood count. She had previously used an epipen for acute allergic reactions and had bone pain at presentation. There was splenomegaly on examination. Bone marrow aspirate was extremely difficult to obtain but trephine roll showed eosinophils, basophils, occasional mast cells and occasional blasts A population of 23% hypergranulated basophilic cells were seen on aspirate whose aetiology is not clear and are assigned to the basophil/mast cell series. For want of a better term these cells are called Finella’s cells. Histological examination of trephine biopsy showed extreme hypercellularity, Grade III/IV reticulin fibrosis large numbers of eosinophils and basophils with mast cells confirmed by CD 117 staining. The large hypergranulated basophilic cells (Finella’s cells) were not visible on trephine staining. An isodicentric X on cytogenetic analysis and a bcr-abl probe showed a split abl with 2 signals. An ETV6-ABL1 gene rearrangement was present. The c-kit D816V mutation was not identified nor was FIP1L1-PDGFRA present. Subsequently the morphologic features described above allowed the suspicion in a further case. Various appearances of the bone marrow and blood allow the suspicion of a particular disease which then leads to the performance of the diagnostic test to confirm the suspected genetic abnormality. This is epitomised in the diagnosis of chronic myeloid leukaemia based on a high white cell count, myelocyte peak and excess of myeloid cells with an increase in cells such as eosinophils and basophils. The diagnosis is then made by demonstrating the presence of the Philadelphia chromosome or bcr-abl gene rearrangement. In contrast in cases with an ETV6-abl, the patient has a white cell count that is not markedly increased with a leucoerythroblastic blood film and a bone marrow examination that shows a superficial resemblance to a chronic myeloproliferative disease with marked myelofibrosis and large numbers of eosinophils and basophils some of which are morphologically abnormal. Megakaryocytes when seen show discrete nuclear fragments and hypolobation and eosinophils and basophils are increased leading to the case being mistakenly diagnosed as an eosinophilic disorder rather than a specific disease entity i.e ETV6-abl. It cannot be classified with the mastocytic leukaemia’s as the number of masts cells is not greater than 5% and they are not clustered but loosely distributed. The aetiology of Finella’s cells are unclear. Mast cells in blood smears are easily identifiable by their large granules which disfigure the nuclear outline and a central area of pallor or by their “slipper” shape and granule content. In this case the cells are larger than mast cells circular, have no central area of pallor,the excessive granularity masking the nuclear outline and leading one to question whether a PML-RARA fusion is present which it is not. The presence of eosinophils, basophils and these cells should make the viewer suspect an ETV6-abl disorder which is normally a cryptic fusion which will not be identified without use of the appropriate FISH/ RT-PCR test. The disease appears to undergo blast transformation as seen with CML and early transplantation is recommended as happened successfully with our case. Although several other cases have been reported in the literature by various authors and called bcr-abl negative CML, myeloproliferative neoplasms, myeloproliferative disorders with eosinophilia etc peripheral blood eosinophilia is not present and FIP1L1-PDGFRA is not present. The morphologic features that lead one to suspect the presence of theETV6-abl have not been previously delineated. THE ETV6-ABL fusion protein has tyrosine kinase activity and responds to imatinib or second generation TKI’s and therefore demonstrating its presence when faced by the classic morphologic appearance is of clinical importance. Disclosures: No relevant conflicts of interest to declare.


VASA ◽  
1999 ◽  
Vol 28 (4) ◽  
pp. 301-303 ◽  
Author(s):  
Redlich ◽  
Parschalk ◽  
Ehringer ◽  
Minar

Ticlopidine is increasingly used in the secondary prophylaxis in patients with arterial occlusive diseases. Neutropenia is a well known side effect of this drug. We report a case of a 73 year old woman who was admitted because of severe prolonged ticlopidine induced leucopenia. The past medical history included an immunocytoma of the IgM-kappa type diagnosed seven years ago with less than 10% infiltration of the bone marrow and a chronic hepatitis C. On admission the white cell count was 1000/muL. Ticlopidine was stopped. The white cell count did not increase within one week, thus filgastrim was applied on two consecutive days. The leucocyte count promptly increased to 6000/muL but consecutively dropped within the next fortnight again to levels below 500/muL forcing daily filgastrim application for another 9 days. Four months after the initation of the therapy with filgastrim the patient had a white cell count of 4300/muL. We therefore conclude that in patients with a history of potentially bone marrow suppressing diseases the use of ticlopidine has to be carefully weighed against possible myelosuppressive effects.


Blood ◽  
1957 ◽  
Vol 12 (1) ◽  
pp. 11-23 ◽  
Author(s):  
HOWARD A. MEINEKE ◽  
ROGER C. CRAFTS

Abstract Adult female rats of the Wistar strain were hypophysectomized and divided into 3 groups, the first of which received no treatment for 100 days, the other 2 groups receiving no treatment for 50 days followed by daily subcutaneous injections of 0.6 mg. of cortisone alone or in combination with 0.005 mg. of thyroxin for another 50 days. Another group of rats served as normal unoperated controls. Hypophysectomy induced a decrease in the number of nucleated cells in the bone marrow, the erythroid elements being the cells responsible for this decrease; the myeloid elements remained normal in number. These marrow changes were reflected in a decrease in reticulocyte percentage and subsequent anemia, while the total white cell count remained normal. A combined thyroxin-cortisone therapy induced a decrease in myeloid elements in the bone marrow, which resulted in a decrease in the peripheral white cell count. It increased the number of erythroid elements in the bone marrow to a level above that of the hypophysectomized animals with no treatment but not to normal levels. This is undoubtedly due to a very rapid production and release of these cells, for the reticulocyte count was 72 per cent above normal and the anemia in these animals completely eliminated. Blood volume studies showed that these changes in the peripheral blood were not due to a hemoconcentration. Cortisone therapy alone induced changes in the myeloid elements in the bone marrow similar to that following the dual therapy, and produced a similar decrease in peripheral white cell count. This therapy did not, however, eliminate the post-hypophysectomy anemia as did the combined therapy. Although erythropoiesis in the marrows appeared stimulated and the reticulocyte percentage was elevated, the total cellular volume in these animals was not elevated. A combined thyroxin and cortisone therapy will not only prevent post-hypophysectomy anemia, as was found previously, but will eliminate the anemia once it has become established.


Blood ◽  
1948 ◽  
Vol 3 (3) ◽  
pp. 276-285 ◽  
Author(s):  
ROGER C. CRAFTS

Abstract Large doses of estrogens have a profound effect on the bone marrow of adult dogs. The initial reaction is a great increase in the number of neutrophilic elements in the bone marrow. These neutrophils are released into the blood stream causing a marked rise in the total white cell count. This is followed by congestion of the bone marrow and a destruction of the white cell elements in these marrows. Congested areas and locations formerly occupied by white cell elements are replaced by edema, leaving erythroid elements intact. This accounts for the marked drop in the total white cell count in the blood stream. This is followed by destruction of remaining erythroid elements in the bone marrow and replacement by "edema" until a stage is reached where practically no cells can be found in the marrow.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2841-2841
Author(s):  
Therese Vu ◽  
Claudia Bruedigam ◽  
Rebecca Austin ◽  
Catherine Paine-Kuhn ◽  
Hayley S. Ramshaw ◽  
...  

Abstract Myeloproliferative neoplasms (MPN) such as polycythemia vera, essential thrombocythemia and primary myelofibrosis are clonal diseases driven by acquired somatic mutations in hematopoietic stem cells (HSCs), the most common of which is JAK2V617F. JAK2V617F leads to cytokine hypersensitivity and activation of JAK-STAT signaling in the presence of an erythropoietin (EPO), thrombopoietin (TPO) or interleukin-3 (IL3) cytokine receptor scaffold (Nature 2005; 434:1144-8, Leukemia 2008; 22:1828-40). Physiological Jak2V617F expression in long-term hematopoietic stem cells (LT-HSCs; lineagelowcKit+Sca1+CD150+CD48-) is necessary and sufficient to generate MPN, and these LT-HSCs contain the sole reservoir of Jak2V617F MPN-initiating stem cells (Cancer Cell 2010; 17:584-96; Blood 2012; 120:166-72). Although Jak2V617F-mediated EPO hypersensitivity drives erythroid expansion and in vitro EPO-independent colony formation, the EPO receptor is not expressed on Jak2V617F HSC populations (Blood 2012; 120:166-72). This suggests that hypersensitivity to IL3 and/or TPO signaling is responsible for driving LT-HSC proliferation and survival in vivo. To determine the respective contributions of IL3 and TPO signaling to Jak2V617F-induced MPN, pStat5 was measured in HSC and progenitor populations from E2ACre+Jak2V617F+/- knockin mice (hereafter Jak2VF) after stimulation with rmIL3 or rmTPO. Committed myeloid progenitors showed robust pStat5 stimulation with rmIL3, but only low level stimulation with rmTPO (TPO 460.25 ± 25.02 MFI vs. IL3 598.25 ± 69.05 MFI, p<0.05, Vehicle 362.25 ± 76.66 MFI). In contrast, LT-HSCs showed strong induction of pStat5 signaling with rmTPO stimulation but less so with rmIL3 stimulation (TPO 571 ± 47.36 MFI vs. IL3 487.5 ± 53.69 MFI, p=0.05, Vehicle 249.5 ± 47.63 MFI). Concordant with these results, TPO signaling appears essential for the generation of Jak2V617F-induced MPN (ASH 2012 Abstract 427). To determine the contribution of IL3 receptor signaling in Jak2V617F-induced MPN, we crossed Jak2VF knockin mice with mice lacking the common beta subunit of the IL3 receptor that is responsible for signal transduction of IL3, IL5 and GM-CSF (Jak2VFIL3Rb-/-). Jak2VFIL3Rb-/- mice developed MPN with similar latency and mortality to Jak2VF controls. There were no differences in peripheral blood white cell count (16.51 ± 1.5×109/L vs. 14.89 ± 2.4×109/L, p=0.39, n=3), haematocrit (67.97 ± 7.85×109/L vs. 61.97 ± 5.73×109/L, p=0.35, n=3) or extramedullary erythropoiesis (spleen weight, 665 ± 107mg vs. 541 ± 106mg, p=0.22, n=3) between Jak2VFIL3Rb-/- and Jak2VF mice respectively. In competitive bone marrow transplantation assays, all recipients of Jak2VFIL3Rb-/- or Jak2VF bone marrow developed MPN with similar diagnostic parameters such as elevated white cell count (14.29 ± 3.41×109/L vs. 18.38 ± 5.78×109/L, p=0.11, n=8), hematocrit (63.4 ± 16.5% vs. 50.5 ± 13%, p=0.16, n=8) and splenomegaly (529 ± 86mg vs. 465 ± 119mg, p=0.23, n=8) in Jak2VFIL3Rb-/- and Jak2VF mice respectively. Jak2VFIL3Rb-/- bone marrow cells initially showed reduced short-term (4 weeks) engraftment and white cell count in recipients compared to the Jak2V617F group (p<0.0005). However after 16 weeks post-transplant there was no difference in chimerism between recipients of Jak2VFIL3Rb-/- or JakVF cells. IL3 was unable to stimulate pStat5 in Jak2VFIL3Rb-/- LT-HSCs or progenitors, but was preserved in Jak2VF LT-HSCs and progenitors. These data show that IL3Rb signaling is dispensable for Jak2V617F-induced MPN and LT-HSC function, however may regulate short-term myeloid progenitor cell expansion. TPO signaling appears preferentially important for Jak2VF LT-HSC pStat5 induction, whereas IL3 is more important for pStat5 induction in progenitor cells. These findings will help to inform strategies aimed at targeting long term Jak2V617F-initiating HSC populations. Disclosures: No relevant conflicts of interest to declare.


1973 ◽  
Vol 30 (01) ◽  
pp. 036-046 ◽  
Author(s):  
D.C Banks ◽  
J.R.A Mitchell

SummaryWhen heparinised blood is rotated in a glass flask at 37°C. the white cell count falls and it has been shown that this is due to the adherence and aggregation of polymorphonuclear white cells on the wall of the flask. The masses formed bear a close structural resemblance to thrombi and the mechanisms involved in white cell loss during rotation may therefore increase our knowledge of the thrombotic process.


1979 ◽  
Author(s):  
M Drummond ◽  
G Lowe ◽  
J Belch ◽  
C Forbes ◽  
J Barbenel

We investigated the reproducibility and validity of a simple method of measuring red cell deformability (filtration of whole blood through 5 µ sieves) and its relationship to haematocrit, blood viscosity, fibrinogen, white cell count, sex and smoking. The mean coefficient of variation in normals was 3. 7%. Tanned red cells showed marked loss of deformability. Blood filtration rate correlated with haematocrit (r = 0. 99 on dilution of samples, r = 0. 7 in 120 normals and patients). After correction for haematocrit, deformability correlated with high shear viscosity, but not low shear viscosity, fibrinogen or white cell count. In 60 normals there was no significant difference between males and females, or smokers and non-smokers, but in 11 smokers there was an acute fall in deformability after smoking 3 cigarettes (p<0. 05). Reduced deformability was found in acute myocardial infarction (n = 15, p<0. 01) and chronic peripheral arterial disease (n = 15, p<0. 01). The technique is reproducible, detects rigid cells and appears useful in the study of vascular disease.


Author(s):  
IT Parsons ◽  
AT Parsons ◽  
E Balme ◽  
G Hazell ◽  
R Gifford ◽  
...  

Introduction Specific patterns of blood test results are associated with COVID-19 infection. The aim of this study was to identify which blood tests could be used to assist in diagnosing COVID-19. Method A retrospective review was performed on consecutive patients referred to hospital with a clinical suspicion of COVID-19 over a period of four weeks. The patient’s clinical presentation and severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction (SARS-CoV-2 RT-PCR) were recorded. The patients were divided by diagnosis into COVID (COVID-19 infection) or CONTROL (an alternate diagnosis). A retrospective review of consecutive patients over a further two-week period was used for the purposes of validation. Results Overall, 399 patients (53% COVID, 47% CONTROL) were analysed. White cell count, neutrophils and lymphocytes were significantly lower, while lactate dehydrogenase and ferritin were significantly higher, in the COVID group in comparison to CONTROL. Combining the white cell count, lymphocytes and ferritin results into a COVID Combined Blood Test (CCBT) had an area under the curve of 0.79. Using a threshold CCBT of –0.8 resulted in a sensitivity of 0.85 and a specificity of 0.63. Analysing this against a further retrospective review of 181 suspected COVID-19 patients, using the same CCBT threshold, resulted in a sensitivity of 0.73 and a specificity of 0.75. The sensitivity was comparable to the SARS-CoV-2 RT PCR. Discussion Mathematically combining the blood tests has the potential to assist clinical acumen allowing for rapid streaming and more accurate patient flow pending definitive diagnosis. This may be of particular use in low-resource settings.


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