Approccio combinato tra il monitoraggio terapeutico del farmaco (TDM) e farmacogenetica per l’applicazione della medicina personalizzata nella pratica clinica | ||
Combined approach of TDM and pharmacogenetics for application of personalized medicine in the clinical practice | ||
Therapeutic Drug Monitoring (TDM) can be defined as the assessing of the adequacy of the drug plasma concentrations to a target concentration or to a concentration window at a specific time in a dosing interval. Following appropriate clinical interpretation and according to the drug pharmacokinetic/pharmacodynamic (PK/PD) properties, this evaluation can guide dosing optimization. However, finding the optimal dosing in order to guarantee a therapeutic exposure remains complicated. Sources of PK variability, including age, genetic heritage, and disease conditions, influence the chances of achieving adequate therapeutic outcomes. Another important aspect related to drug efficacy and safety is the Pharmacogenetics (PGx). Genetic variants or single nucleotide polymorphisms (SNPs) in genes encoding for metabolizing enzymes and membrane carriers, may affect drug response and/or toxicity. A combination of TDM and PGx could represent a personalized approach in clinical practice especially for off-label drugs used in polytherapy and characterized by a narrow therapeutic index. TDM combined to PGx represents an useful tool that could help clinicians in tailoring pharmacological therapies. We present here three case reports related to pediatric patients who have shown adverse drug reactions in response to therapies with phenytoin (PHT), voriconazole (VO) and isoniazid (INH). | ||
Biochimica Clinica 2022; 46(4) e31 |
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Importanti informazioni dall’esame dello striscio periferico | ||
Important information from the peripheral smear examination | ||
Rarely, platelets can interact with other blood elements, forming platelet aggregates. This paper presents an isolated case of platelet satellitism around neutrophils, lymphocytes and monocytes with platelet phagocytosis by both neutrophils and monocytes. The subject was an 89-year-old woman with breast cancer on anti-estrogenic hormone cancer therapy. Whole blood sample collected in a tube with K2EDTA anticoagulant was analysed within 4 hours, using Sysmex XN-9000 analyzer. The complete blood count presented the following results: white blood cell 4.0x109/L, red blood cell 3.58x1012/L, haemoglobin 116 g/L, haematocrit 34.9%, mean corpuscular volume 97.5 fL, mean corpuscular haemoglobin 32.5 pg, mean corpuscular haemoglobin concentration 332 g/L, red blood cell distribution width 14.6% and platelet 136x109/L. The present case report describes the platelet satellitism around neutrophils, lymphocytes and monocytes and the interesting, and very rare phenomenon of platelet phagocytosis by not only neutrophils but also by monocytes. | ||
Biochimica Clinica 2022; 46(4) e25 |
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La metodica capillare per la misura della emoglobina glicata consente di rilevare varianti emoglobiniche | ||
Capilalry mthod for measuring glycated hemoglobin allows the detection of hemoglobin variants | ||
Diabetes mellitus is a worldwide disease and glycated hemoglobin (HbA1c) is the gold standard for the diagnosis and monitoring. Hemoglobin variants can interfere with HbA1c measurement in both preanalytical and analytical phases, and their incidental detection is continuously increasing, due to the recent migration waves. In the Roma 1 HUB Laboratory, HbA1c is measured by capillary electrophoresis (CE). A 51-year-old man from Bangladesh underwent HbA1c analysis and a variant was evident in the electrophoretic pattern. After informed consent for further analysis was given, a hemoglobin electrophoresis by CE was performed. A suspected HbE was found and then confirmed by molecular testing. The patient showed mild microcytosis and hypochromia, but no anemia. The presence of the variant HbE was without influence on HbA1c measurement by CE. This technique offers the advantage to detect hemoglobin variants as well as a reliable measurement of hemoglobin A2 (HbA2). These features allow a correct diagnosis of thalassemia and hemoglobinopathies without interfering with HbA1c measurement. | ||
Biochimica Clinica 2022; 46(3) e15-e17 |
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Informazioni inaspettate dall’esame emocromocitometrico: variante emoglobinica Hb Leiden rilevata tramite un analizzatore ematologico | ||
Unexpected information from a blood count test: a hemoglobin variant, Hb Leiden, detected with a hematology analyzer | ||
Hemoglobin variants are abnormal forms of hemoglobin that may cause hematological disorders. The variants can be (or not) associated with normal hematology parameters. We were able to identify a hemoglobin variant in a 56-year-old Italian Caucasian male using a hematology analyzer. | ||
Biochimica Clinica 2021; 45(3) e023-e026 |
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Remissione di iperparatiroidismo secondario dopo nefrectomia in un paziente emodializzato: ruolo di Etelcalcetide | ||
Secondary hyperparathyroidism remission after nephrectomy in a dialysis patient: role of Etelcalcetide | ||
Secondary hyperparathyroidism (HPT) is a common issue in dialysis patients; it contributes significantly to their morbidity and mortality. Here we describe the case of a hemodialysis patient with severe secondary HPT, treated with Etelcalcetide, the new intravenous calcimimetic agent, employed after a nephrectomy due to a renal neoplasm to reduce successfully the serum levels of parathyroid hormone (PTH) and bone specific alkaline phosphatase (BAP). No significant change in serum calcium was recorded during treatment, while the already high serum phosphorus concentrations further increased after surgery. By maintaining the calcium mimetic therapy, even if at lower doses, the concentrations of PTH and BAP remained constant over the time. | ||
Biochimica Clinica 2021; 45(3) s107-s110 |
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Interferenza analitica sul conteggio dei leucociti | ||
Analytical interference on leucocyte count | ||
Chronic lymphoproliferative disorders typically affect elderly patients with a median age at the diagnosis of 71 years. These disorders include a number of conditions characterized by an abnormal proliferation of lymphocytes towards a monoclonal lymphocytosis. The case of an 83-year-old man affected by chronic lymphocytic leukemia is presented; the peripheral blood cells count, performed on the analyzer Sysmex XN-20, showed significant differences between the white nucleated red (WNR) and white differentiation (WDF) channels that did not allow the differential counting of leukocytes. On the opposite, the reflex analysis channel white progenitor cell (WPC), returned the correct white blood cell count. Actually, when the peripheral blood sample was diluted (1:5) and resubmitted to analysis, leukocytes count resulting from WNR and WDF analysis channels corresponded to that obtained in the reflex WPC analysis channel on the undiluted sample. To verify if the instrumental anomaly found in the cell counting could be associated to an elevated plasma concentrations of immunoglobulins, a serum protein electrophoresis was performed, showing the presence of four monoclonal components. These data demonstrate that the WPC channel is an important tool for the clinical laboratory, since it is able to give a correct result even when interferents are present. | ||
Biochimica Clinica 2021; 45(2) e11-e14 |
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Un caso di falsa neutropenia | ||
A case of fictitious neutropenia | ||
A 2-month-old newborn was hospitalized for fever, persistent infections, failure to thrive. Complete differential blood count detected a severe neutropenia and monocytosis, associated to an anomalous scatterplot of the hematology analyzer. Blood film review showed that neutrophils had been misclassified as monocytes, due to hypogranulated cytoplasms and nuclear hyposegmentation. Re-analysis on a different hematology platform agreed with the manual differential count. These clinical-morphological features suggested a possible diagnosis of immune deficiency due to lack of neutrophil specific granules. Indeed, Sanger sequencing allowed the detection of a homozygous mutation in SMARCD2 gene, whose alterations very recently had been associated to a similar syndrome, encompassing both hematological and skeletal anomalies. This case shows that a proper interpretation of routine tests can successfully drive the choice of higher-level analysis and led to a prompt diagnosis of a very rare condition. The diagnosis paved the way to a precocious allogeneic hematopoietic stem-cell transplantation that successfully cured the condition of immune deficiency and the hematology abnormalities of the young patient. | ||
Biochimica Clinica 2021; 45(2) e15-e19 |
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Il valore aggiunto della diagnostica molecolare nelle forme monogeniche di diabete mellito | ||
Advantages of molecular diagnosis in monogenic diabetes | ||
Maturity Onset Diabetes of the Young (MODY), the most frequent form of monogenic diabetes, comprises a group of heterogeneous disorders, characterized by non-autoimmune diabetes due to mutations of at least 14 different genes. | ||
Biochimica Clinica 2021; 45(1) e1-e3 |
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Inspiegabili alterazioni di esami coagulativi | ||
Unexpected coagulation test abnormalities | ||
A 72 year-old female was screened before a minor orthopaedic surgery with routine coagulation tests, that resulted highly altered. Prothrombin time and activated partial thromboplastin time (PT and aPTT) could not be calculated because the system registered a biphasic curve, protein C and protein S (PC and PS) levels were not measurable and antiphospholipid antibodies were highly positive. Reviewing previous laboratory findings, a serum protein electrophoresis showing the presence of a monoclonal peak in the gamma region was retrieved. A serum immunofixation was then performed, and an IgM kappa monoclonal component was typed; a cryoglobulin test was positive for cryoglobulin type II. To investigate the possible relationship between these laboratory findings, a pool of normal plasma was spiked with the patient IgM monoclonal component at progressively higher concentrations registering a prolongation of PT and aPTT and a slight reduction of PC and PS. The presence of an IgM paraprotein, although not quantitatively relevant, was therefore functionally able to interfere with the coagulation time calculation system. Although coagulation abnormalities in monoclonal gammopathy of undetermined significance are uncommon, these should be attentively investigated, to guarantee a correct laboratory report. | ||
Biochimica Clinica 2021; 45(1) e7-e10 |
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Assenza di bande monoclonali liquorali e positività del rispettivo indice siero-liquor: una discrepanza da indagare attenatamente | ||
Absence of liquoral monoclonal bands and positivity of the respective serum-liquor index: an unespected findings to be carefully investigated | ||
A 13 year-old child whit headache, nausea and repeated episodes of vomiting was hospitalized at the Major Hospital of Charity of Novara. A lumbar puncture and biochemical investigations on cerebrospinal fluid (CSF) including oligoclonal bands (OCB) screen were performed. Kappa and Lambda free light chains (kFLC and λFLC) and IgG concentrations were measured in serum and CSF by nephelometry. OCB were evaluated by isoelectric focusing (IEF) followed by immunofixation (IMF). A negative IgG index, no OCB IgG (type I pattern), positive kFLC index with increased levels of kFLC (0.14 mg/dL) and λFLC (0.14 mg/dl in CSF) were found. The FLC data suggested an intrathecal synthesis. A CSF IMF was then performed using anti-IgM peroxidase together with the IgM index using Reiber’s hyperbolyc graphic. The presence of a monoclonal IgM band and 76% of intrathecal IgM synthesis was demonstrated. A subsequent molecular biology investigation was performed on CSF and revealed a clear positivity for enterovirus. | ||
Biochimica Clinica 2020; 44(4) e34-e36 |
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Monitoraggio molecolare di Isocitrato Deidrogenasi 2 in paziente con Leucemia Mieloide Acuta recidivata | ||
Molecular monitoring of Isocitrate Dehydrogenase 2 in a patient with relapsed Acute Myeloid Leukemia | ||
Isocitrate Dehydrogenase 2 (IDH2) mutations are reported in about 20% of Acute Myeloid Leukemia (AML) and they are promising Minimal/Measurable Residual Disease (MRD) molecular markers because of the possible therapy whit the inhibitor Enasidenib. A man with a diagnosis of AML, negative for the common molecular markers, resulted in complete remission (CR) only after three induction cycles. The patient underwent a transplant procedure but after 7 months a relapse was observed. We retrospectively studied the status of IDH2 mutation in this patient which was positive at diagnosis (29%), after two induction cycles and at the allogeneic transplantation (2%). In the next follow-up, both WT1 and IDH2 were normal. After 3 months, when the patient was in CR and WT1 was still normal, IDH2 resulted 0.12%. After further 2 months, the patient clinically relapsed; at that time, WT1 was very high and IDH2 was 7.8%. In this case, IDH2 monitoring by Droplet Digital PCR (ddPCR) predicted relapse two months before WT1 levels and clinical evidence. | ||
Biochimica Clinica 2020; 44(4) e37-e39 |
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I marcatori di clonalità per la diagnosi e la valutazione della risposta alla terapia nell’amiloidosi da catene leggere: il ruolo del laboratorio | ||
Clonal biomarkers for diagnosis and response to treatment assessment in light chain amyloidosis: the role of the laboratory | ||
Serum monoclonal components, Bence-Jones proteinuria (PBJ) and free light chains (FLC) are clonal biomarkers for diagnosis and response assessment in light chain (AL) amyloidosis. Two clinical reports are presented here toi llustrate the utility of these biomarkers. The first case is a patient with AL κappa renal amyloidosis. Serum and urine immunofixation were negative and the FLC ratio was abnormal. Immunoelectron microscopy on tissue biopsy was negative. Amyloid typing was achieved by mass spectrometry on fat pad aspirate. The second case is a patient with AL cardiac amyloidosis with PBJ lambdaand low concentration of amyloidogenic FLC (32 mg/L). Urine capillary electrophoresis was used to assess response to treatment. The progressive reduction of PBJ after treatment was accompanied by reduction of NT-proBNP and improvement of clinical conditions. Clonal biomarkers are irreplaceable tools in management of AL amyloidosis. There is a need for more sensitive techniques for identification of monoclonal FLC on serum and urine. | ||
Biochimica Clinica 2020; 44(2) E11-E15 |
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Un caso di gammopatia monoclonale di significato renale | ||
A case of monoclonal gammopathy of renal significance | ||
Monoclonal gammopathy of renal significance (MGRS) is a condition defined by the presence of a small-B cell clone causing a renal disease trough deposition in renal tissues of the monoclonal component (MC) secreted by the B cells. Since MGRS is associated with several types of renal diseases, characterization of renal damage caused by protein deposition is important to define the correct diagnosis as well as the identification of the MC. Adult Fanconi Syndrome (FS) is characterized by the presence of a MC and damage in the proximal tubule with impaired small molecules transport. We report the case of a 32 years old man with moderate kidney failure, normoglycemic glycosuria and hypouricemia. Further investigations revealed hypophosphoremia and phosphaturia; an IgGκ MC was detected by immunofixation. The kidney biopsy confirmed FS suspect. This case underlines that the results of the biochemical analysis carried on for the diagnosis of FS, need to be confirmed by histopathologic analysis. | ||
Biochimica Clinica 2020; 44(2) E08-E10 |
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Sofferenza tubulare in un paziente con recente trapianto di rene | ||
Tubular disfunction in a patient with a recent kidney transplant | ||
The case reports about a patient who underwenta kidney transplantation for chronic disease of unknown cause. The clinical course showed a delayed graft functionand acute tubular necrosis. Urine microscopy confirmed a tubular disfunction: presence of renal epithelial cells,cylindruria and crystals. The microscopy images showed brownish-colored crystals that, under polarized light,suggested a 2.8-dihydroxyadenine (DHA) urolithiasis, rare and underdiagnosed pathology, due to the deficiency ofadenine-phosphoribosyltransferase (APRT). The specific analysis, i.e. the determination of the enzyme activity onerythrocyte lysate, did not confirm our initial hypothesis, excluding de facto a DHA urolithiasis. Analysis of purine andpyrimidine profile confirmed the presence of a purine dysmetabolism. The patient was treated with allopurinol, whichimproved the clinical picture. This case underlines the need for more extensive studies of crystal and/or metabolicnephropathies before renal transplantation. The microscopy study was however useful to trigger investigations thathave then influenced the therapy and the clinical progress of the patient. | ||
Biochimica Clinica 2019; 43(3) e25-e27 |
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Paziente pediatrico con oliguria e adenopatia cervicale: il ruolo degli analizzatori a cattura di immagine per l’esame standard delle urine | ||
Urinalysis in a pediatric patient with oliguria and cervical lymphadenopathy: role of automated imageanalysis systems. | ||
Automated urinalysis instruments image-based for cell analysis can identify non-squamousepithelial cells (NSE). Among these elements, expert pathologists can distinguish the so called Decoy Cells (DC),Polyomavirus BK (BKV)-infected elements primarily seen in immunocompromised patients. Epstein-Barr virus (EBV)infection can induce a transient immunosuppression in immunocompetent patients, and this could lead to areactivation of a latent BKV infection in urothelial cells: this is a rare event in pediatric patients. This study reports thecase of a 4 year-old child with lateral lymphadenopathy, fever and oliguria. Automated urinary sediment analysisevidenced the presence of many NSEs identifed as DC, generating a subsequent virological investigation with a finaldiagnosis of concomitant BKV and EBV infection. The combination of an automated technology, an efficientmiddleware and the expertise of the laboratory professionals , allowed the proper identification of these peculiarreactive elements, which could easily be mistaken for malignant atypical cells. | ||
Biochimica Clinica 2019; 43(2) e20-e23 |
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Un effettivo vantaggio dello screening neonatale allargato | ||
A real benefit of an extended neonatal screening | ||
Methylenetetrahydrofolate Reductase (MTHFR) deficiency, is avery rare congenital defect of folate metabolism, inherited in an autosomal recessive pattern included in newbornscreening (NBS) programs in Italy. It is caused by mutations in the MTHFRgene and is characterized by elevatedplasma homocysteine and borderline-low or normal methionine levels, causing severe neurological signs, recurrentapnoea, microcephaly and convulsions, generally during the neonatal period. An early treatment may prevent theclinical manifestations with a positive impact on patient’s health. | ||
Biochimica Clinica 2019; 43(2) e12-e16 |
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Valutazione della risposta alla terapia in un paziente con amiloidosi AL e basse concentrazioni della catena leggera libera monoclonale | ||
Evaluation of response to treatment in a patient with light chain amyloidosis and low free light chain burden | ||
Evaluation of response to treatment in a patient with light chain amyloidosis and low free light chain burden. In patients with light chain (AL) amyloidosis, reduction of amyloidogenic circulating free light chain (FLC) concentration translates in improvement of organ dysfunction and is associated with an increase in overall survival. Validated criteria for hematologic response to therapy are based on FLC quantification. However, patients with a difference between involved and uninvolved FLC (dFLC) <50 mg/L are not evaluable for hematologic response. Here we report the case of a 69 year old man with AL (λ) amyloidosis with renal involvement, presenting a low-FLC burden (dFLC 41 mg/L) at diagnosis. After two lines of treatment, a profound reduction of amyloidogenic FLC (dFLC 0 mg/L) was associated with an improvement of organ dysfunction. This case emphasizes the role of FLC assessment in the monitoring also of patients with a low-dFLC burden.
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Biochimica Clinica 2019; 43(1) e4-e6 |
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Individuazione e identificazione di una nuova variante emoglobinica durante la quantificazione dell’emoglobina glicata | ||
Incidental detection of a new hemoglobin beta variant performing HbA1c measurement | ||
Incidental detection of a new hemoglobin beta variant performing HbA1c measurement. Hemoglobin α and β chain variants can be incidentally detected during the glycated hemoglobin (HbA1c) determination. A 58-year-old female was investigated for HbA1c with Tera 3 Capillarys system (CE, Sebia). Quantification of HbA1c was invalidated by the presence of a double peak in the HbA0 zone. Standard high performance liquid chromatography (HPLC), performed with VARIANT IITM Analyzer (Biorad), did not separate the variant from Hb A0. β-globin gene sequencing showed a heterozygous variation of nucleotide sequence HBB: c.376C>A; beta 125 (H3) Pro>Thr. The new variant, called Hb-Novara, was found also in the daughter of the proband, associated with an alpha-talassemic trait. The hemoglobin stability tests of both subjects were normal. A combination of different technologies (such as HPLC and CE) can be useful in the detection of new hemoglobin variants. Although Hb-Novara seems to be asymptomatic, it could produce relevant hematological phenotypes when associated with α or β chain defects
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Biochimica Clinica 2018; 42(4) e56-e58 |
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Ruolo del laboratorio nella valutazione di un donatore di organi con sospetta emofilia A | ||
Role of the laboratory in the evaluation of an organ donor with reported haemophilia A | ||
The case concerns a 82-year-old patient, organ donor, affected by diabetes mellitus, hypertension and reported type A haemophilia, showing a traumatic severe cerebral haemorrhage. The Medical Committee started the donor evaluation process: the liver was compatible for a recipient in life-threatening conditions. Although the first level coagulation tests were within the normal range, the Regional Center for Organ and Tissue Allocation of the Tuscany Region - Italy requested further investigations in order to clarify the reported diagnosis of haemophilia and to exclude the presence of a specific FVIII inhibitor. FVII activity was evaluated to assess the protein synthesis of the liver, and FVIII for suspected haemophilia; both of them were normal. Considering the importance of the diagnosis, the parallelisms of both FVII and FVIII were performed; the tests were negative for the presence of inhibitors. Second-level tests therefore rejected the diagnosis of haemophilia and excluded the presence of a specific inhibitor of FVIII. The absence of coagulative alterations allowed the liver explant, which was successfully transplanted on a 59-year-old male recipient. | ||
Biochimica Clinica 2018; 42(3) e37-e39 |
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La misura delle catene leggere libere indentifica la ricaduta di malattia e orienta per una rivalutazione della tipizzazione dell’amiloide in una paziente con amiloidosi AL | ||
Free light measurement identifies relapse and prompts to reconsider amyloid typing in a patient with AL amyloidosis | ||
The detection and quantification of amyloidogenic light-chains (LC) is necessary for diagnosis and evaluation of response in AL amyloidosis. A 69 years old woman was initially diagnosed, in another center, with AL-λ amyloidosis with renal and soft tissue involvement in December 2001. After 4 cycles of therapy with melphalan and dexamethasone serum and urine immunofixation were negative and, after cycle 6, complete remission was confirmed. Free light chain (FLC) ratio was normal until June 2006, when proteinuria increased, and an elevated k-FLC concentration with abnormal k/λ-ratio was documented. We repeated the abdominal fat aspirate for amyloid typing by immune-electron microscopy that revealed k-LC deposits. The diagnosis was AL-k. A relapse was documented and the patient was started on bortezomib and dexamethasone therapy. After 8 cycles, complete remission was obtained. In this case, FLC allowed the identification of the amyloidogenic-LC, enabling the detection of relapse. | ||
Biochimica Clinica 2018; 42(2) e15-e17 |
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Un liquor particolarmente informativo | ||
Cerebrospinal Fluid (CSF) analysis and CSF Free Light Chains (FLC) indices in a patient with Varicella Zooster Encephalitis | ||
A 3-year-old child was admitted to our Emergency Department with neurological multifocal symptoms. Magnetic resonance imaging showed pulvinar and lenticular nucleus involvement. The parents reported an infection from Varicella Zooster Virus (VZV) a few days earlier. After taking lumbar puncture, the patient was hospitalized with a preliminary diagnosis of viral encephalitis. Cerebrospinal fluid (CSF) examination was negative for albumin quotient, quantitative IgG synthesis, isoelectric focusing and Polimerase Chain Reaction (PCR) for Herpes viruses. High CSF intrathecal total IgM fraction (48% r.v. ≤0) was detected as well with highly positive IgM antibody indices specific for VZV. CSF free light chain (FLC) kappa and lambda indices were highly positive: respectively 34.12 (r.v. <6.39) and 17.78 (r.v. <5.51). The diagnosis of VZV encephalitis, was possible only after specific CSF serology and CSF FLC measurement. IgG isoelectric focusing is considered the best screening test to detect immune activation in CNS, however, in this patient we observed mainly an IgM response. Our case indicates that CSF FLC determination is perhaps a better test to screen for an immune activation of the central nervous system, as it becomes positive also in case of IgM intrathecal synthesis. | ||
Biochimica Clinica 2018; 42(2) e26-e28 |
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Un caso di mieloma multiplo IgG kappa in cui la misura delle catene leggere libere ha evidenziato precocemente una ripresa di malattia di tipo “light chain escape” | ||
A case of IgG kappa multiple myeloma where the measurement of the free light chains was an early marker of a “light chain escape” relapse | ||
Light chain escape (LCE) is a type of relapse where a serum free light chains (FLC) increase is observed, in the absence of a parallel increase of the original monoclonal component; this particular kind of relapse seems to be influenced by new therapeutic regimens. We present a case of a 55-years old man with a IgG kappa multiple myeloma (MM), who underwent double autologous bone marrow transplantation as first line therapy; after relapse, the patient was treated with lenalidomide/dexamethasone (LD). After more than three years of LD treatment, in September 2014, an increase of FLCs was observed, while serum and urine immunofixations remained negative until January and February 2015 respectively, when a LCE was diagnosed. Despite the new treatment, the patient died in June 2016. The FLCs measurement, although not reaching the IMWG criteria, detected relapse earlier than immunofixation. This case indicates that FLCs should be routinely performed during follow up of MM patients to ensure that LCE is not missed. | ||
Biochimica Clinica 2017; 41(3) e22-e24 |
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Presenza concomitante di anticorpi tipo Lupus e malattia di von Willebrand: una condizione reale? | ||
Combined von Willebrand factor and lupus anticoagulant abnormalities: a true finding? | ||
We present a case of a 74-year-old woman with myelofibrosis, hypothyroidism and negative bleeding history, showing a prolonged APTT performed within a pre-intervention screening. The laboratory tests showed a positivity for the presence of lupus anticoagulant antibodies (LA). Further investigations revealed normal intrinsic factor and von Willebrand factor (VWF) antigen concentrations, and normal to only slightly reduced VWF Ristocetin Cofactor (VWF:RCo) by chemiluminescent assay and by platelet agglutination. The VWF:RCo by a latex- immunoturbidimetric method was strongly reduced and the platelet function test was found to be abnormal. The negative bleeding history, the myeloproliferative chronic disease, the LA positivity and the other laboratory findings were consistent with the presence of acquired VWF disease. However, the disproportionate values of VWF:RCo measurements obtained by the latex method and all the other assays, made us to conclude for the presence of an interference (possibly due to autoantibodies) on latex VWF:RCo immunoassay and the patient went successfully to surgery without anti-haemorrhagic prophylaxis. | ||
Biochimica Clinica 2017; 41(1) e4-e8 |
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Utilità del saggio Hevylite nella gestione clinica di una paziente affetta da amiloidosi AL con gammopatia biclonale | ||
Usefulness of the Hevylite assay in the management of a patient with AL amyloidosis and biclonal gammopathy | ||
Patients with AL amyloidosis often have small monoclonal components (MCs) difficult to quantify by densitometry. IgA are the most problematic, due to anodic migration and possible masking under proteins migrating in β zone. We evaluated the usefulness of the Hevylite assay (Binding Site, Birmingham UK), at diagnosis and during follow-up, in a patient with AL amyloidosis and biclonal gammopathy. At diagnosis serum immunofixation identified an IgGλ and an IgAλ band (the last one not reliably quantifiable in capillary electrophoresis). The κ serum free light chain (FLC) concentration was 4.94 mg/L and λ 26 mg/L (κ/λ ratio 0.19). The Hevylite test showed both IgGλ and IgAλ above the reference limits, with abnormal κ/λ ratios. After treatment, a 27% decrease in IgGλ and a 56% decrease in IgAλ concentration were documented by Hevylite, which was the only mean to quantify the monoclonal components in this patient. | ||
Biochimica Clinica 2016; 40(2) e12-e15 |
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Sindrome POEMS: “Hevylite” e “Freelite” a confronto | ||
POEMS syndrome: Heavy Light Chains vs Free Light Chains measurements | ||
POEMS syndrome is a rare paraneoplastic, multisystemic, plasma cell discrasia characterized by Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes. Most patients have high serum free light chains (sFLC) concentrations but a normal sFLC ratio. Hevylite (HLC) is a new method that allows separated quantification of the serum k and l bounded levels of the six isotype specific immunoglobulins. In this study HLC and sFLC were measured in serum samples during the follow up of two patients with POEMS syndrome. The HLC ratio of the involved monoclonal immunoglobulin could provide additional information to assess residual disease, allowing detection of relapse earlier than clinical symptoms in patients with POEMS syndrome. | ||
Biochimica Clinica 2016; 40(1) e1-e3 |
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Il significato clinico degli eritroblasti: un insolito esordio di anemia refrattaria con eccesso di blasti di tipo 2 | ||
The clinical relevance of nucleated red blood cells: an unusual onset of refractory anaemia with excess blasts | ||
Nucleated red blood cells (NRBCs) in adult peripheral blood (PB) are often a signal of severe haemopoietic stress. Refractory anaemia with excess blasts (RAEB) is a myelodysplastic syndrome characterized by ineffective hemopoiesis and diserytropoiesis; two categories of RAEB (1-2) are recognized, defined by the amount of blasts in the bone marrow (BM) and in PB. We describe an unusual onset of RAEB-2 in a patient with asthenia, weigh loss and fatigue. The automated blood cells analysis and optical microscopic PB smear revision showed severe anemia, mild trombocytopenia, blasts, NRBCs and dysplasia. After definitive diagnosis (RAEB-2) and one year of appropriate treatment, the patient shows normalized haematological values with just some optical microscopic hints of dysplasia. NRBCs play a pivotal role to trigger the diagnostic process and are useful in the follow-up. We highlight the role of automated haematology analysers with improved features in NRBCs analysis. | ||
Biochimica Clinica 2015; 39(4) e4-e6 |
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Pemfigoide bolloso in una paziente di 106 anni | ||
Bullous pemphigoid in a 106-years old female | ||
Bullous pemhigoid (BP) is an autoimmune subepidermal blistering disease, usually occurring in the elderly. In Europe the incidence of BP has doubled in the last 10 years. The disease has a chronic relapsing course and a relatively benign prognosis. An increasing number of publications report altered expression of a number of cytokines. However, at the present it is not possible to establish a specific role for them in the disease. We report a case of a centenarian woman with a BP occurrence in otherwise optimal health conditions. Besides the usual biochemical investigations, plasma concentrations of a number of cytokines were evaluated during the disease course (relapse and remission). The majority of the measured cytokines were elevated in the active phase of the disease and returned to values similar to those presented by a group of apparently healthy subjects of similar age during the remission. This case could be useful to better understand the role of cytokines in autoimmune skin diseases of the aging. | ||
Biochimica Clinica 2015; 39(2) 152-156 |
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Osteoporosi maschile e anafilassi da imenotteri | ||
Male osteoporosis and hymenoptera venom anaphylaxis | ||
Mastocytosis is one of the rare causes of unexplained osteoporosis, above all in males. On the other hand, a strict association between severe systemic reactions after hymenoptera sting and mastocytosis was recently demonstrated. Here we report a case of unexplained severe osteoporosis with multiple vertebral fractures in a 48 years old male, which also suffered an anaphylactic reaction after hymenoptera sting. Among laboratory tests performed to clarify the cause of osteoporosis, serum tryptase concentrations were determined. The value of tryptase was 43.6 μg/L, four times higher than the upper reference limit. Skin did not show abnormalities; bone marrow vertebral biopsy was not valuable, but bone marrow aspirate from iliac crest demonstrated the presence of atypical mast cells expressing CD25; D816V mutation of KIT gene was also identified. These findings, in association with an increase of serum tryptase concentrations, fulfil all minor criteria requested for the diagnosis of systemic mastocytosis. Osteoporosis treatment with zolendronate and vitamin D supplementation was started, but later, for the persistence of bone pain, therapy with -interferon was added. This case confirms that an unexplained osteoporosis, especially if associated with hymenoptera sting systemic reaction, requires exclusion of a systemic mastocytosis. | ||
Biochimica Clinica 2014; 38(4) 347-349 |
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Interleuchine e necrolisi tossica epidermica | ||
Interleukins and toxic epidermal necrolysis (TEN) | ||
TEN is a rare disease characterized by the separation of skin and mucous membranes from the derma. The reported clinical case refers to an adult female hospitalized at the Burns Unit after allopurinol prescription. During hospitalization the patient underwent the therapeutic protocol established at the Burns Unit including intravenus immunoglobulin administration and plasmapheresis. At the end of therapy a clinical improvement of both local and global conditions was observed. During the course of disease, we measured plasma concentrations of a number of cytokines. Measurements were performed using commercially available multiplex bead-based sandwich immunoassays (Biorad). We found a marked decrease in concentrations of interleukin (IL)-6, interferon -induced protein (IP)-10 e IL-13 at various stages of apheresis therapy, particularly pronounced for IP-10. We also found a normalization of IL-6 and IP-10 concentrations during the follow-up. In addition, very high concentrations of the same cytokines in the plasma effluent after apheresis were observed. Although obtained in a single case, our results suggest a correlation between plasma concentrations of cytokines and the clinical course of TEN. It can be postulated that this approach could serve as a guide for future research in the development of targeted therapy based on the etiopathogenesis of TEN. | ||
Biochimica Clinica 2014; 38(1) 65-69 |
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A case of acquired hemophilia A | ||
We describe the case of a 82 years old female, who has been referred to the emergency department for a gross trauma of the right knee after an accidental fall. Physical examination revealed a palpable mass in the right pelvis, which was then identified as a large intramuscular hematoma of the right iliacus muscle by computerized tomography scan. The most suggestive laboratory findings were anemia and a prolonged activated partial thromboplastin time (APTT) (ratio 1.33), with physiological platelet count and prothrombin time. After ten days of hospitalization, when a spontaneous hematoma developed in the right arm, APTT had steadily increased, up to a value of 3.33. A mixing study and assessment of coagulation factors were rapidly performed. The former test was not effective to normalized the APTT, whereas concentrations of all factors were within the reference interval, except for factor VIII (0.6%). Factor VIII inhibitor titration using Bethesda assay confirmed the diagnosis of acquired hemophilia A, yielding a value of 77 Bethesda units. Acquired hemophilia A, which is caused by autoantibodies against coagulation factor VIII, is a rare condition that can be frequently overlooked or misdiagnosed. The role of laboratory diagnostics is thereby as important as the clinics, wherein serious hemorrhages accompanied by variable APTT prolongations onset in a previously asymptomatic patient. Along with discussion about laboratory and clinical aspects of acquired hemophilia A, we present a diagnostic algorithm for efficiently troubleshooting prolonged APTT values in clinical laboratories. | ||
Biochimica Clinica 2013; 37(2) 128-130 |
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