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
Conteggio e contenuto di emoglobina reticolocitario in un caso di grave anemia
Reticulocyte count and hemoglobin content in a case of severe anemia
A 4 years old child from Sry Lanka was admitted in our hospital after several blood transfusions for severe anemia in her country. Very low hemoglobin (65 g/L) and ferritin (<1 ng/mL) concentrations were detected, consistent with iron deficiency anemia. The reticulocyte count and the hemoglobin content (Ret-He) were low (49,20x109/L and 13.7 pg respectively). An important number of causes of iron deficiency anemia were excluded. The patient was treated with iron infusion for two weeks, with good recovery of hemoglobin levels iron stores, Ret-He and reticulocyte number. The patient was then treated with oral iron supplementation, but a considerable decrease of Ret-He and reticulocyte count was observed, so the infusive therapy was reintroduced. Diagnosis and treatment were optimized by the synergy between the clinical laboratory and pediatricians, utilizing these hematological parameters. The blood transfusions could thus be stopped and the bone marrow biopsy could be avoided. This case demonstrates the importance of the reticulocyte count and the Ret-He in the management of iron deficiency anemia.
|Biochimica Clinica 2017; 41(2) e09-e12
Utilità della spettroscopia all’infrarosso per l’analisi dei calcoli urinari
Usefulness of infrared spectroscopy for stone analysis: a case study
A 22-year-old male with recurrent bilateral stone disease and positive family history for stones was referred in March 2015 to the Metabolic Stone Clinic of the Policlinico Gemelli Hospital; a metabolic assessment revealed a number of abnormalities including hypercalciuria, hypocitraturia and abnormally high fasting urine pH. The previously expelled urinary calculus was sent to the clinical laboratory for the biochemical analysis by the infrared method. Fourier transform infrared spectroscopy (FT-IR) analysis identifying brushite and carbapatite, together with the finding of high urine pH, raised the suspicion of distal renal tubular acidosis which was subsequently confirmed by the urinary acidification test. The semiquantitative method of stone composition analysis would have yielded a mixture of calcium, ammonium, phosphate and magnesium, thus likely directing the diagnostic work-up, together with the abnormally high urine pH, towards infectious stones (e.g., by urease-producing bacteria). The information obtained by FT-IR analysis allowed clinicians to correctly hypothesize a urinary acidification deficit, which was subsequently treated with potassium citrate supplements.
|Biochimica Clinica 2017; 41(2) e13-e14
Gestire il rischio clinico in medicina di laboratorio: un’inaspettata piastrinopenia
Clinical risk management in laboratory medicine: an unexpected thrombocytopenia
It is acknowledged that the risk management strategy is cardinal to maintain safety in health care organisations. Clinical risk assessment and management is a continuous and dynamic process aimed to evaluate risks and to develop appropriate plans to reduce them. Internationally, there is an increasing recognition of the need to collect and analyse data on patient safety incidents to facilitate cultural growth and to develop appropriate solutions. The practice of reporting is commonly used, and several countries have established national reporting systems to facilitate large scale monitoring and analysis of data. This activity provides information on the extent, types and causes of errors, adverse events and near misses, supporting healthcare workers in the activity of reporting errors. This case shows how a non-optimal communication between laboratory and clinicians has caused an adverse advent and which corrective actions have been undertaken.
|Biochimica Clinica 2017; 41(1) e1-e3
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
Sensibilità al glutine: il test di attivazione dei basofili (BAT) può aiutare nella diagnosi differenziale?
Gluten hypersensitivity: basophil activation test (BAT) may help in the differential diagnosis
Gluten hypersensitivity: basophil activation test (BAT) may help in the differential diagnosis? The main forms of gluten-related disorders are wheat allergy (WA), celiac disease (CD) and possibly immune-mediated disease (gluten sensitivity). S-IgE play an essential role in WA. For CD tests available are anti-tissue transglutaminase (tTG) IgA, anti-endomysium (EMA) and deamidated gliadin peptides (DGP) antibodies IgG particular. For other immunemediated diseases there is currently no test available. The usefulness of basophil activation test (BAT) in anaphylactic adverse reactions, late-onset allergy has been demonstrated. We report the case of a woman of 46 years old with disorders of wheat tied overt clinical signs, intestinal and extra-intestinal symptoms, whose tests above were all negative. Only the BAT showed a stimulation of basophils exposed (52.9%) to extract wheat. We diagnosed gluten sensitivity (GS) on the basis of an algorithm for the differential diagnosis of gluten-related disorders, including CD, GS and WA. We believe that the BAT confirms a hypersensitivity reaction to wheat not-IgE-mediated, not CD.
|Biochimica Clinica 2016; 40(4) e31-e34
Discordance between phenotype and genotype study in Factor V Leiden carriers: a real life experience
Factor V Leiden (FVL) mutation causes activated protein C (APC) resistance by decreasing the susceptibility of FVa to APC-mediated inactivation. In our Laboratory, the usual approach to the identification of FV deficit includes a combination of genetic and functional tests. The aim of this paper was to highlight the importance to investigate both the genotype and the phenotype in the diagnosis of FVL-APC resistance related thrombophilia. Among a group of 292 subjects examined for thrombophilia, we observed three patients with discordant results of genetic test for the detection of G1691A FV gene mutation and functional APCr assay: the first subject has a mild APC resistance with a wild type genotype; the second one, and her sister, shows a severe APC resistance with a heterozygous genotype. To determine the FV deficit, it is important to associate the molecular analysis of G1691A mutation with the APC resistance test.
|Biochimica Clinica 2016; 40(3) e22-e26
Piastrine grigie sullo striscio di sangue periferico: patologia o artefatto?
Gray platelets on peripheral blood smear: syndrome or artifact?
This case reports on a 6-year-old child, suffering from phenylketonuria treated with levetiracetam. The complete blood count showed degranulated platelets, confirmed by optical microscopy of the peripheral blood smear. Medical history revealed no bleeding or thrombocytopenia, so a correlation between the phenomenon and the pharmacological treatment was postulated. However, among the adverse effect of this drug, only cases of drug-induced thrombocytopenia are known. From a literature research, we were able to retrieve a description of a "pseudo gray platelet syndrome induced by EDTA". The blood sampling was thus repeated using sodium-citrate as anticoagulant besides EDTA; smears were performed using these samples and directly from a finger stick. The smear from the EDTA sample confirmed the presence of degranulated platelets; while the one from the sodium-citrate sample showed no platelet abnormalities. Platelet morphology was also normal in the smear from the finger stick. Pseudo Gray Syndrome Platelet (PGSP) by EDTA is an “in vitro” phenomenon not associated with bleeding disorders. The observation of different peripheral blood smears (EDTA, sodium-citrate and finger stick) allowed us to correctly identified a harmless condition, distinguishing it from the true gray platelet syndrome, a much more severe disorder.
|Biochimica Clinica 2016; 40(3) e15-e17
Quando l’apparenza inganna: un caso di leucemia acuta con imponente vacuolizzazione dei blasti
Appearance can be deceptive: a case of acute leukemia with marked vacuolation of blasts
A 69-year-old female, suffering from myelodysplastic syndrome, is admitted to the hospital because of worsening of anemia and thrombocytopenia. The blood count confirms anemia (hemoglobin 97 g/L) and thrombocytopenia (platelets 43x109/L) At the optical microscopy 87% blast cells are observed; these are characterized by numerous cytoplasmic vacuoles, mimicking an acute lymphoid leukemia. A similar finding is obtained in myeloaspirate smears. By means of 6-color immunophenotyping, blast cells appear to be positive for CD13, CD33, CD34, CD117, CD38, CD45RA, CD71, myeloperoxidase, and partially positive for CD235a. The positivity for myeloperoxidase is confirmed by standard cytochemistry. Acute myeloid leukemia with myelodysplasia-related changes is diagnosed. This case shows that marked vacuolation of blasts, although more frequent in cases of B-cell acute leukemia, may be present in sporadic cases of acute myeloid leukemia.
|Biochimica Clinica 2016; 40(3) e18-e21
Il ruolo di CA 15-3 nel monitoraggio della terapia nel carcinoma mammario metastatico
Role of CA15-3 to guide therapy in metastatic breast cancer
The National Academy of Clinical Biochemistry states that cancer antigen 15-3 (CA15-3) in combination with imaging and clinical examinations can be used for therapeutic monitoring in patients with advanced breast cancer. In a 62 year old patient with a 2 year history of invasive ductal breast carcinoma and bone metastasis, treated with an aromatase inhibitor, the imaging showed bone marrow infiltration and liver metastasis. The oncologist planned a close monitoring of the disease and the patient has been followed for two years by CA15-3 every month and imaging when necessary. It has been observed that the clinician modified the therapy on the basis of the CA15-3 values during two phases of apparent stability of the disease. This case report shows that the CA15-3 has contributed to a large extent to stop ineffective treatments and has effectively helped the clinician in selecting the most appropriate treatment options. However, it is to be noted that the monthly request of the marker is not appropriate.
|Biochimica Clinica 2016; 40(2) e08-e11
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
Determinazione delle immunoglobuline e delle catene leggere libere nel siero e nel liquido cefalorachidiano di un paziente con patologia autoinfiammatoria
Serum and cerebrospinal fluid immunoglobulins and free light chains measurements in a patient with autoinflammatory disease
Serum and cerebrospinal fluid immunoglobulins and free light chains measurements in a patient with autoinflammatory disease. We report a case of a patient with chronic meningitis, headache, deafness, leukoencephalopathy, and osteomyelitis who showed a selective interleukin-6 (IL-6) overproduction. An inflammatory pattern was observed in serum; the cerebrospinal fluid (CSF) examination revealed positive oligoclonal IgG bands and IgG, IgA, IgM intrathecal synthesis. CSF free light chains (FLC) indices were very high. Steroids gave modest benefits. IL-6 was persistently increased in CSF and serum; after treatment with Tocilizumab, an anti IL6-receptor monoclonal antibody, the serum inflammatory pattern normalized and FLC decreased. Central neurological symptoms improved to a lesser degree than systemic ones, probably due to Tocilizumab blood-brain barrier restriction. The biochemical CSF parameters showed partial improvement: the albumin ratio decreased, immunoglobulin intrathecal synthesis and oligoclonal bands were no more detectable, but FLC absolute values and indices remained elevated, confirming persisting CSF inflammation. This is the first report on Tocilizumab and steroid treatment effects on FLC concentrations. FLC measurement both in serum and CSF could be useful markers both for diagnosis and evaluation of the response to therapy in the inflammatory and immunological processes of SNC.
|Biochimica Clinica 2016; 40(1) e4-e7
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
Ferritina e siderofagi liquorali nella diagnosi di siderosi cerebrale superficiale
Cerebrospinal fluid ferritin and siderophages in the diagnosis of superficial cerebral siderosis
We observed a case of superficial siderosis (SS) of the central nervous system caused by an hemorrhagic trauma forty years before. We questioned whether SS was the stabilized effect of a remote bleeding or an evolutionary process indirectly related to the trauma. Moreover, we aimed to evaluate whether an iron chelator can affect the level of iron deposition. Magnetic Resonance (MRI) demonstrated iron accumulation mainly on the surface of the cerebellum and brain stem. Cerebrospinal fluid (CSF) microscopic analysis revealed few siderophages; CSF ferritin level was 76 ng/mL (reference value <12). After treatment with an iron chelator (deferiprone) for three months, MRI was unchanged, but the CSF ferritin was about 20% less. The presence of few siderophages supported the hypothesis of a persistent subarachnoid microbleeding. CSF ferritin, as an iron deposition index, allowed a diagnosis of SS and a
|Biochimica Clinica 2015; 39(6) e19-e21
Un caso di gammopatia monoclonale di significato renale in un paziente con glomerulopatia immunotattoide
A case of monoclonal gammopathy of renal significance in a patient affected by immunotactoid glomerulopathy
Monoclonal gammopathy of renal significance is defined by the causal relationship between a small B-cell clone and the renal disease. Immunotactoid glomerulopathy is a rare glomerular disease characterized by
|Biochimica Clinica 2015; 39(6) e22-e24
Caso atipico di orticaria
A case of atypical urticaria
Adult onset Still’s disease (AOSD) is a rare clinical entity with unknown etiology and pathogenesis, characterized by high spiking fevers, arthritis, typical evanescent, nonpruritic, macular and salmon
|Biochimica Clinica 2015; 39(5) e10-e12
Disfibrinogenemia indotta da una catena leggera libera kappa delle immunoglobuline
Ig-free light chains induced dysfibrinogenemia
Despite several pathological conditions are associated with free light chains (FLC) deposition in human tissues, only few cases of human diseases caused by the specific binding activity of monoclonal FLC are described. A 65-year old male patient, with highly abnormal functional coagulation tests and undetectable functional fibrinogen was admitted to the Hematological Clinic of the University Hospital of Pisa. The same tests were within the reference intervals one year before. After excluding a number of causes for abnormal coagulation tests, we focused on potential causes of acquired dysfibrinogenemia. Due to the presence of abnormal values of FLC, we performed an immunofixation: while serum did not show any detectable monoclonal band, the immunofixation of a plasma sample revealed the presence of monoclonal FLC of kappa type co-migrating with fibrinogen. The serum kappa FLC concentrations were much lower than plasma levels, suggesting that the majority of these FLC were bound to fibrinogen, remaining associated to fibrin after clotting. Bone marrow biopsy showed 4% monoclonal plasma cells producing kappa light chains. The patient was diagnosed as affected by a FLC MGUS. After two courses of dexamethasone, the plasma concentration of kappa FLC decreased substantially and most of the coagulation tests normalized. The nature of the interaction between fibrinogen and kappa FLC is currently under investigation to elucidate the mechanism able to inhibit fibrinogen polymerization.
|Biochimica Clinica 2015; 39(5) e16-e18
Mielopatia di incerto significato
A myelopathy of uncertain origin
In November 2013, following a febrile episode lasting for one week, a 51-year-old male reported fatigue and increasing clumsiness and rigidity of lower limbs. Two months after the symptoms onset, neurological examination showed ataxic-spastic gait, diffuse accentuation of deep tendon reflexes with extensor plantar response and abolition of the abdominal reflexes. The clinical suspicion of an autoimmune para-infectious myelo-neuropathy, prompted us to a comprehensive clinical chemistry, hematology and autoimmunity work-up: the only pathological result was an IgG monoclonal gammopathy. Nerve conduction studies showed a very mild sensory neuropathy, while visual evoked potentials were abnormal. Contrast magnetic resonance imaging showed a contrastfree parenchymal C2 spinal cord lesion. Cerebrospinal fluid examination, obtained to rule out multiple sclerosis (MS), demonstrated a moderate barrier disruption without oligoclonal bands reaction. These features rule out MS suggesting Devic's disease (neuromyelitis optica). Additional serological testing to detect aquaporin-4 antibodies (NMO-IgG) was positive, underscoring the paramount importance of laboratory testing in this differential diagnosis.
|Biochimica Clinica 2015; 39(5) e13-e15
Duplicazione sul cromosoma 22q11.21 in una paziente con difetto cardiaco congenito
Chromosome 22q11.21 duplication in a patient with congenital heart defect
The newly described 22q11.2 microduplication syndrome is an association of a broad clinical spectrum and up to now more than 50 unrelated cases have been reported. The clinical presentation of patients is extremely variable and shares features with 22q11.2 deletion syndromes (DG/VCFS), including heart defects, urogenital abnormalities, velopharyngeal insufficiency with or without cleft palate; it ranges from multiple defects to mild learning difficulties with some individuals being essentially normal. A high resolution array comparative genomic hybridization (a-CGH) 4x180K was performed on a patient with a congenital heart defect, a pulmonary valve stenosis, in order to identify potential mutations and to characterize the clinical phenotype at molecular level. Using a-CGH analysis, we identified a duplication in 22q11.21 region of approximately 2.5 Mbp containing several genes including TBX1. The obtained results demonstrate the relevance of a-CGH as a screening method to detect genomic rearrangements responsible for congenital heart defects.
|Biochimica Clinica 2015; 39(4) e1-e3
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
Prolungamento del tempo di tromboplastina parziale attivata in una paziente asintomatica: la carenza di precallicreina
Prolonged activated partial thromboplastin time in an asymptomatic patient: the prekallikrein deficiency
Prekallikrein (PK) is a contact factor of the intrinsic pathway of the coagulation cascade. Patients with PK deficiency usually do not show a bleeding tendency despite a prolonged activated partial thromboplastin time (aPTT) test. Here we report a case of a 72-years-old Caucasian woman manifesting a prolonged aPTT test. The aPTT correction after 1:1 mixing with normal pool plasma (NPP) indicated a coagulation factor deficiency; however factors XII, XI, IX and VIII activities were normal. A 100:1 mixing with NPP was performed, resulting in an aPTT test correction; the aPTT test was then performed increasing the pre-incubation time of the patient’s plasma. This resulted in a significant reduction of the aPTT. The PK deficiency was ultimately confirmed by direct measurement of PK plasma activity. This experience shows that PK deficiency should be considered for asymptomatic patients with prolonged aPTT and that, whenever a PK deficient plasma is not available, the diagnosis can be correctly oriented on the basis of simple aPTT tests.
|Biochimica Clinica 2015; 39(4) e7-e9
Amiloidosi AL: il cuore del problema
AL amyloidosis: the heart of the problem
Immunoglobulin light chain amyloidosis (AL) is characterized by the production of immunoglobulin light chains with conformational abnormalities that cause systemic toxicity with rapid deterioration of the function of vital organs. When the heart is involved, as it is the case in ~3/4 of patients, clinical signs and symptoms often appear when organ damage is already irreversible and the treatment cannot longer change the course of disease. Although in recent years new powerful therapeutic regimens have become available, which are able to significantly improve long-term survival, the mortality rate in the first year after diagnosis has indeed not improved, still being 25-30%. Cardiac involvement is responsible for almost all of these deaths. Early diagnosis based on biochemical markers of the disease rather than on clinical symptoms and signs can allow for early detection of patients with cardiac amyloidosis and to establish an effective therapy. To this end, our group has proposed the introduction of the measurement of natriuretic peptides that can identify the presence of amyloid cardiomyopathy with a sensitivity of 100% in the monitoring of subjects with monoclonal gammopathies of undetermined significance (MGUS) and altered ratio of circulating free light chains (FLC). Individuals with MGUS and altered FLC ratio are at intermediate/high risk of developing a malignant disease (AL amyloidosis in 10-15% of cases) and, according to the guidelines of the International Myeloma Working Group, they should be monitored regularly for their entire life. Here we describe a case where the application of these recent recommendations has allowed the timely recognition of amyloid cardiomyopathy.
|Biochimica Clinica 2015; 39(3) 220-222
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
Effect of dabigatran and rivaroxaban treatment on a prothrombinase-based assay for assessment of activated C protein resistance
We present a report about the interference due to factor IIa and factor Xa direct oral inhibitors on activated C protein resistance ratio (APCr), evaluated with a prothrombinase-based assay, in a patient heterozygous for factor V Leiden treated first with dabigatran and then with rivaroxaban. In this patient dabigatran increased the APCr ratio to a degree compatible with values observed in homozygous wild-type carriers, thus causing a potential misdiagnosis. We also found that rivaroxaban therapy was effective in lowering the APCr ratio.
|Biochimica Clinica 2015; 39(1) 073-075
Identificazione casuale di atrofia gastrica severa con macrocitosi complicata da sindrome coronarica acuta
Casual identification of severe gastric atrophy with macrocytosis complicated by acute coronary syndrome
Chronic atrophic gastritis (CAG) and gastric cancer are leading causes of morbidity and mortality worldwide. Serum pepsinogens have been used as biomarkers of gastric mucosa status, including gastric inflammation, so that they might be useful for detection of gastric atrophy or gastric neoplasm at an early stage. Serum pepsinogen 1 and pepsinogen 2 concentrations are known to increase in the presence of Helicobacter pylori-related non-atrophic chronic gastritis, and the eradication of this pathogen is associated with a significant decrease in their values. We describe here the case of an asymptomatic 60 years old man, with a casual serological diagnosis of severe gastric atrophy, macrocytosis and severe complications, culminating in an acute coronary syndrome. This case report raises some important considerations, such as the fact that CAG could not be correctly and early diagnosed and that it may be misleadingly regarded as a rare condition, whereas its prevalence is conversely largely underestimated. This may lead to severe complications that may include gastric malabsorption and vitamin B12 deficiency, along with gastrointestinal, neurologic, psychiatric, cardiovascular, cerebral and peripheral vascular disorders.
|Biochimica Clinica 2015; 39(1) 068-072
Due nuovi casi di emofilia acquisita A
Two new cases of acquired hemophilia A
Acquired hemophilia A is a rare autoimmune syndrome characterized by the presence of autoantibodies directed to clotting factor VIII. This disorder most commonly occurs in the elderly. Although it may be associated with several underlying pathologies, up to 50% of cases are idiopatic. Typical clinical manifestations are extensive cutaneous purpura and internal hemorrhage. The steps of the diagnostic process include: the presence of a prolonged activated partial thromboplastin time, non corrected by incubation with normal plasma, the absence of lupus anticoagulant, the selective deficiency of factor VIII and, finally, the dosage of the inhibitor anti-factor VIII, using the Bethesda assay or its Nijmegen modification. Here we describe two new cases of acquired hemophilia A. After the diagnosis confirmation, patients were treated with a bypassing agent, the recombinant activated factor VII.
|Biochimica Clinica 2014; 38(6) 651-655
Serum free light chain assays for monitoring response to treatment in a patient with pharmacoresistant light chain multiple myeloma
We describe the case of a 78 year old man admitted to the Nephrology ward with strangury. Laboratory tests showed proteinuria with preserved renal function. Serum and urine immunofixation showed a faint monoclonal l band, while serum free light chain (FLC) assays (Freelite, The Binding Site) resulted in an abnormal k/l ratio, confirming the presence of a lFLC monoclonal component. After bone marrow examination, the diagnosis was stage IIA l light chain multiple myeloma. The patient started bortezomib, melphalan and prednisone treatment. In the following days, l FLC concentrations still remained elevated indicating therapy failure. A week later, the patient became anuric and laboratory tests showed a pattern of acute renal failure and increased serum l FLC concentrations. The patient started a new treatment with bicarbonate, mannitol and dexamethasone, but therapy was not effective again and l FLC concentrations resulted persistently high and associated with anury. Clinicians decided to suspend pharmacological therapy and to dialyze the patient. FLC assay was performed every two hours to monitor FLC removal. After six sessions of hemodialysis, l FLC concentrations decreased, diuresis was restored and renal function improved. Myeloma treatment was re-initiated with steroids and, after kidney recovery, dialysis was suspended. In this case, FLC assays helped to confirm myeloma suspicion, to define the most effective therapy and to assess the response to treatment.
|Biochimica Clinica 2014; 38(5) 389-391
L’esame automatizzato delle urine come approccio “bottom-up” per la diagnosi di rabdomiolisi
Automated urinalysis as a bottom-up approach to rhabdomyolysis diagnosis
Rhabdomyolysis is a clinicopathological situation of heterogeneous origin, characterized by skeletal muscle damage followed by the release into the circulation of various myocyte components, including myoglobin. This small protein, which plays a pivotal role in the myocyte function, is easily filtered through the glomerulus in the urine, representing a potential factor of tubular toxicity. In this report, we describe three cases in which standard urine samples were analyzed with the integrated system iRICELL 3000 (Beckman Coulter): the observed discrepancy between a strong strip positivity for hemoglobin and an absent hematuria induced to perform an immunoassay measurement of myoglobin, leading to a well grounded suspect of rhabdomyolysis. The management of patients was thus optimized, suggesting to clinicians the elements for a rapid diagnosis.
|Biochimica Clinica 2014; 38(4) 344-346
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
“Smart drugs”, le nuove droghe sul web: due casi di intossicazione acuta
“Smart drugs”, the new drugs on the web: two cases of acute intoxication
New psychoactive substances that in some cases are not subjected to any legal restriction recently overwhelmed web market. They were historically defined “smart drugs”: substances either natural or synthetic with alleged psychoactive effects as well as effects on sexual performance. We present here two intoxication cases: the first concernes a male subject hospitalized for deep unconsciousness, who took in yohimbine and kawaine, two psychoactive alkaloids present in herbal preparations of Pausinystalia yohimbe and Piper methysticum, sold on the sexy shop websites; the second concernes a female with a previous history of drug poliabuse, hospitalized for dysphoric syndrome/hallucinations, who took in benzydamine, a local anesthetic and analgesic drug, contained in an antibacterial gynecological powder that in oral mis-overdosage acts as a deliriant and central nervous system stimulant.
|Biochimica Clinica 2014; 38(3) 268-271
Un caso di carenza di glucosio-6-fosfato deidrogenasi e anemia emolitica cronica non sferocitica
Glucose-6-phosphate dehydrogenase (G6PD) deficiency and chronic non-spherocytic hemolytic anemia: a case report
G6PD deficiency is an X-linked disorder, due to more than 190 mutations that determine ~400 different phenotypes. Herein, we report a case of a symptomatic male newborn affected by severe G6PD deficiency due to a novel “de novo” mutation in the exon 13 of the G6PD gene: c.1465C>T (named “G6PD Buenos Aires”)”. G6PD activity is affected by NADP+ amount through at least two mechanisms. On one hand, the activity of the enzyme is directly related to the NADP+/NADPH ratio; on the other hand, NADP+ is necessary for stabilizing the enzyme in the proper conformation. The c.1465C>T mutation, causing a proline to serine substitution at 489 amino-acid position in the “NADP+ structural site”, prevents the NADP+ to play the latter function, explaining the severe phenotype of the child.
|Biochimica Clinica 2014; 38(2) 151-153
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
Valori falsamente elevati di triodotironina libera in una paziente affetta da tiroidite cronica e gozzo multinodulare
Falsely increased free triiodothyronine values in a woman affected by thyroiditis and multinodular goiter
We describe a case of a 63-years old woman affected by Hashimoto’s thyroiditis and multinodular goiter. Her laboratory results showed elevated free triiodothyronine (FT3) concentrations (18.5 ng/L), with free thyroxine (FT4) and thyrotropin (TSH) within the physiologic range. On the basis of these results, she started methimazole therapy, with persistence of inappropriately elevated FT3 concentrations. The therapy was thus stopped and blood examination was repeated after one month in our laboratory: concentrations of thyroid tests were within the physiologic range, including FT3 (2.8 ng/L). The difference between this result and that previously obtained raised the suspicion of the presence of an interference in the first result. In fact, in our laboratory a competitive electrochemiluminescence immunoassay with labeled antibody is used, while the first laboratory employed a competitive chemiluminescence immunoassay with labeled analogue, which has a more important risk of interference. After treating sample by polyethylene glycol, FT3 resulted indeed normal also by the immunoassay used by the first laboratory.
|Biochimica Clinica 2014; 38(1) 70-72
Utilità della misura dell’attività plasmatica di eparina-anti fattore Xa durante trattamento antitrombotico in gravidanza
Usefulness of heparin-anti factor Xa assay during antithrombotic treatment in pregnancy
A case of successful pregnancy in a woman with previous episodes of unprovoked deep vein thrombosis treated with vitamin K antagonist (warfarin) therapy is described. As the patient became pregnant, warfarin therapy was immediately stopped and lowmolecular-weight heparin (LMWH) prophylaxis was started. In the second and third trimesters of pregnancy we observed an increase in body weight (from 64 to 80 kg) and in body mass index (from 21 to 26.4). During the pregnancy, we used the heparin-anti factor Xa assay (Anti-FXa) to monitor the LMWH treatment and to adjust the dosage in a increasing way. The Anti-FXa can be very useful in improving safety and efficacy of LMWH treatment in pregnancy.
|Biochimica Clinica 2013; 37(6) 504-507
Un caso di emoglobinuria parossistica notturna associata a mielodisplasia
A case of paroxysmal nocturnal hemoglobinuria in a patient with myelodysplasia
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematological disease of the hematopoietic stem cell. PNH arises as a consequence of non-malignant clonal expansion of hematopoietic stem cells and progeny mature blood cells of both myeloid and monocyte lineage, which are deficient in some surface proteins, including the two complement regulators CD55 and CD59. As a result, PNH erythrocytes are incapable to modulate on their surface physiologic complement activation, leading to complement-mediated intravascular hemolysis, which is the central clinical feature of PNH. We present a case of a 16 years old Ukrainian boy who presented with a diagnosis of myelodysplastic syndrome and who was found to be affected by PNH.
|Biochimica Clinica 2013; 37(4) 326-328
Un raro caso di mesotelioma multicistico del peritoneo associato ad aumento di CA 125 e CA 19.9 nel siero
A rare case of benign multicystic mesothelioma of the peritoneum associated to CA 125 and CA 19.9 elevations in serum
Markedly increased CA 125 and CA 19.9 concentrations in serum are considered specific enough to reliably identify malignant cancers (ovarian and gastrointestinal tumours, respectively), although a consistent body of literature has reported marker elevations in several benign conditions. Here we report the case of a woman in post-menopausal status, with a previous history of hysterectomy, presenting with a 12-cm pelvic mass at sonography and serum CA 125 and CA 19.9 concentrations >400 kU/L. One month after initial presentation, she underwent surgical evaluation for laparoscopy, repeating marker determinations. Concentrations of CA 125 and CA 19.9 were still elevated, but decreased if compared with the previous data (~200 kU/L). Magnetic resonance imaging characterized a multicystic mass in the mesentery, allowing to hypothesize a benign multicystic mesothelioma of the peritoneum (BMMP). The laparoscopy revealed multiple cysts, some of them resulting in colliquation, associated to ascites. Histological examination of biopsy specimens confirmed BMMP as composed of multiple, thin-walled, irregularly spaced cysts lined by flattened and cuboidal mesothelial cells. The cystic colliquation was though as the main cause for decrease in marker concentrations. To our knowledge, this is the first case of BMMP associated with significantly increased concentrations of CA 125 and CA 19.9 and their decrease before any surgical treatment.
|Biochimica Clinica 2013; 37(3) 241-245
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
Una gammopatia monoclonale di difficile tipizzazione
A monoclonal gammopathy of difficult characterization
IgD monoclonal gammopathy is a rare event, but its recognition and management are quite important because the condition is potentially life-threatening. This paper reports a peculiar case of IgD monoclonal gammopathy. The monoclonal protein was rapidly degraded by proteolysis and the usual laboratory tests showed different immunochemical patterns. The study of the proteolitic dynamic of the monoclonal immunoglobulin allowed us to obtain the complete characterization of the monoclonal component.
|Biochimica Clinica 2013; 37(1) 64-67
Frequenza e significato clinico di valori di antigene carboidratico (CA) 19.9 marcatamente elevati in una popolazione di pazienti ospedalizzati
Prevalence and clinical significance of enormously increased carbohydrate antigen (CA) 19.9 concentrations in hospitalised patients
Markedly elevated CA 19.9 concentrations in serum are regarded as specific enough to reliably identify pancreatic cancer, even if a consistent body of literature shows CA 19.9 concentrations >1000 kU/L in a variety of benign conditions. Scarce data are, however, available on the prevalence and clinical significance of CA 19.9 values >10,000 kU/L. Here we present a case series of 18 consecutive patients admitted to our hospital in a time period of 14 months showing an enormous elevation of CA19.9 concentrations (11,568 to >100,000 kU/L), with the aim to assess the association of such concentrations with the presence of pancreatic cancer and, more in general, with tumours of the gastrointestinal system. We also tried to define whether the exact measurement of CA 19.9 concentrations in this range, which needs serial sample dilutions, is cost-effective. CA 19.9 measurements, including sample dilutions according to a defined laboratory protocol, were performed on Roche Modular EVO system. The yearly prevalence of hospitalized patients tested for CA 19.9 and with marker concentrations >10,000 kU/L was 2.9%. All recruited patients were diagnosed as malignancies: 15 had primary or secondary pancreatic cancer, two had gastric cancer, and one a cholangiocarcinoma. CA 19.9 concentrations ranged between >10,000-30,000 kU/L in 9 cases, >30,000-60,000 kU/L in two, >60,000-100,000 kU/L in three, and >100,000 kU/L in four cases, respectively. A surgical resection of the tumour was performed in five patients, independently of CA 19.9 concentrations. The median patient’s survival was <6 months. In conclusion, CA 19.9 concentrations >10,000 kU/L unequivocally identify a gastrointestinal malignancy, more frequently (~83%) a primary or secondary pancreatic cancer. Exactly measuring CA 19.9 concentrations >10,000 kU/L after multiple sample dilution does not add relevant information for patients’ prognosis and treatment.
|Biochimica Clinica 2012; 36(6) 436-440
Un caso clinicamente rilevante di gammopatia monoclonale in età pediatrica
A clinically relevant monoclonal gammopathy in pediatric age
Monoclonal gammopathy is a uncommon finding in pediatric age. Only viral infections, bone marrow or solid organ transplantation, and immunosuppressive therapy may induce B-lymphocyte clonal proliferation leading to monoclonal components (MC) in serum. Here we present a case of clinically relevant monoclonal gammopathy in pediatric age. After receiving an unusual request for a serum protein electrophoresis (SPE) test in 12 years-old boy, information on the patient was collected. The boy was affected by Crohn’s disease and treated with prednisone, azathioprine, and antibodies against tumor necrosis factor-V (infliximab and, later, adalimumab). As both disease and treatment made the patient at risk for developing lymphoid/myeloid malignancies (LMM), the search for MC in serum was indeed recommended. On SPE three MC were detected and typed by agarose gel immunofixation (IFE) as IgAk, IgMk, and IgGg. Moreover, a k-type Bence Jones protein was detected by urine IFE. Bone marrow examination was then carried out to exclude LMM, resulting in a negative pattern. It is known that Crohn’s disease in adults, particularly when treated by means of immunosuppresive therapies, can be associated with monoclonal gammopathies and an increased risk of developing leukemia or lymphoma and, rarely, myeloma. However, at our best knowledge, no report of such association has been previously reported in pediatrics. This case illustrates a specific situation in which the request and execution of a SPE in the young is not only appropriate, but even recommended to prevent the risk of silent LMM development.
|Biochimica Clinica 2012; 36(5) 378-383
Un caso di gammopatia monoclonale IgD clinicamente asintomatica e stabile dopo 15 anni di monitoraggio
A case of IgD monoclonal gammopathy showing clinical and laboratory stability after a follow-up of 15 years
IgD monoclonal gammopathies represent a rare subset of the universe of monoclonal immunoglobulin abnormalities. They are often characterized by a clinically progressive myelomatous behaviour and by peculiar laboratory aspects. We present here a case of IgD monoclonal gammopathy, detected in a 44-years old woman, which was stable from a clinical and laboratory point of view for 15 years. This case represents a quite unusual figure of a very long lasting IgD monoclonal gammopathy of undetermined significance.
|Biochimica Clinica 2012; 36(5) 384-385
Un caso di ipercupremia
A case of hypercupremia
This report presents a case of an incidental detection of very high concentrations of serum copper in an apparently healthy adult male. Clinical and laboratory investigations for Wilson’s disease were negative. The electrophoresis of serum proteins showed a IgG monoclonal peak of 10 g/L. To clarify the nature of this unusual association (high concentration of copper and monoclonal immunoglobulin), an immunosubtraction experiment was performed: after incubation with an anti-IgG antiserum, the vast majority of serum copper was found in the IgG-anti IgG complex when the patient serum was tested; when other samples with monoclonal IgG and physiological copper concentrations were incubated, the copper remained in surnatants. The experiment allowed us to establish that the monoclonal immunoglobulin showed a high affinity for copper. Similar reports can be found in the literature; the main difference with the present case is that our patient did not show any ocular problems due to the copper deposition in the Descemet’s membrane, while in all the previously reported cases an ocular deposition of copper was observed. It is possible to speculate that in our case the affinity of the protein for copper was very high, while in other cases a lower affinity made possible the intraocular release of copper.
|Biochimica Clinica 2012; 36(4) 275-277
Due casi di malaria diagnosticati incidentalmente con un analizzatore ematologico
Two cases of malaria incidentally diagnosed with a hematology analyzer
Although the malaria infection is essentially a problem in tropical countries, it has becoming a health issue even in Western countries due to tourism and immigration. The specific diagnostic tests are ordered if a clinical suspicion is raised, but symptoms of malaria infection can be vague and easily attributed to minor febrile affections, particularly in non-endemic regions. The diagnosis of malaria cannot be dismissed to rapidly establish the appropriate treatment, avoiding harmful complications of the disease. Recently, hematological analyzers have been proposed as potentially useful tools to detect in the blood count of affected patients abnormalities that can guide a timely malaria diagnosis. We present here two cases of malaria infection in which the first diagnostic suspicion was posed on the basis of abnormal scattergrams of a hematological analyzer. The aim is to present this relatively new diagnostic opportunity, increasing the awareness of laboratorians on the possibility to raise a suspicion of malaria infection, even if specific diagnostic tests have not been ordered.
|Biochimica Clinica 2012; 36(3) 204-208
Quando l’urina diventa rossa: un’inattesa macroematuria
If urines become red: an unexpected case of gross hematuria.
The physiological colour of urine is usually yellow. Urine discoloration is a common situation in clinical practice and a variety of colours may be seen. When a patient complains of green or blue urine, there is no confusion with a pathological origin. However, when the urine is red, the first thought is usually hematuria leading to anxiety for patient himself and for physicians too. We present a case of a 54 years old man presenting with asymptomatic apparent gross hematuria ruled out by chemical urinalysis and visual microscopic evaluation of the sediment showing neither hemoglobin nor red blood cells in his urine specimen. Possible causes of red urine not related to presence of blood are critically presented and discussed.
|Biochimica Clinica 2012; 36(2) 139-143
Un caso di macrolattatodeidrogenasemia
A case of macrolactatedehydrogenasemia
We present here the detection of a lactate dehydrogenase (LDH) macroenzyme in the blood of an apparently healthy female. The finding of an increased LDH activity during routine biochemical investigations led to a number of further laboratory and imaging examinations. When the diagnostic problem was finally posed to the laboratory consultant, a serum treatment with polyethylene glycol and an isoenzyme electrophoretic separation allowed to demonstrate the presence of a circulating macroenzyme. Macroenzymes have been described from almost 50 years, but despite many efforts it was difficult to recognize a pathogenetic role. Their recognition is, however, important in order to avoid expensive and cumbersome procedures to explain elevated enzyme values.
|Biochimica Clinica 2012; 36(1) 66-68
Mieloma multiplo IgD lambda: “switch” isotipico immunoglobulinico dopo trapianto autologo
IgD lambda multiple myeloma: immunoglobulin isotype switch after autologous stem cell transplantation
IgD multiple myeloma (MM) is a rare disease affecting less than 2% of patients with MM, and it is frequently characterized by an aggressive course. It is usually associated with low monoclonal protein levels, so adequate diagnostic procedures have to be performed in order to identify the involved monoclonal component (MC). We present a case of a 38-year-old man with acute kidney disease caused by an IgD lambda MM. Diagnosis was achieved by serum protein electrophoresis and immunofixation with anti IgD and IgE antisera. After autologous stem cell transplantations (ASCT) the patient developed a MC different from the original isotype, followed by an oligoclonal bands (OB) pattern. Recently, the occurrence of MC and OB unrelated to the original clone has been proven to be an important favorable prognostic factor in patients with MM who undergo ASCT. The role of the protein laboratory at diagnosis and during follow up of MM patients is highlighted.
|Biochimica Clinica 1970; 17(1)