Differential Diagnosis Of Thrombocytopenia Research Articles

Low ADAMTS13 Activity in Patients with Liver Disease- Thrombotic Thrombocytopenic Purpura or Not?

Introduction: Patients with liver injury have hemostatic defects including reduced ADAMTS13 (A disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13). Severe deficiency of ADAMTS13 (ADMS13) activity (< 10%) is pathognomonic for thrombotic thrombocytopenic purpura (TTP), a rare thrombotic microangiopathy (TMA). Differentiating TTP from severe liver injury is complex for multiple reasons including 1) low baseline ADMS13 2) concomitant coagulopathies complicating differentiation from disseminated intravascular coagulation (DIC) 3) ADMS13 activity (ADMS13:AC) assay interference (hyperbilirubinemia (>30mg/dL) can cause artifactual reduction of ADMS13:AC). Here we sought to characterize the clinical presentation, management, and outcomes of patients with liver injury presenting with thrombocytopenia (TCP), microangiopathic hemolytic anemia (MAHA) and low ADMS13:AC at our institution. Methods: In this retrospective study, after IRB approval, electronic medical records (EMR) of institutional patients who had ADMS13:AC and inhibitor profile performed in our special coagulation laboratory between 2018 and July 17, 2023, were reviewed. Eligible patients had ADMS13:AC ≤20% were ≥ 18 years and had evidence of liver injury at time of ADMS13. Liver injury was defined as ALT or AST elevations greater than two times the upper level of normal within one month prior to ADMS13:AC testing, history of end stage liver disease or cirrhosis, or liver transplant with evidence of graft dysfunction. Details regarding clinical presentation, management and outcomes were extracted from the EMR. PLASMIC and ISTH DIC scores were retrospectively calculated. Results: 70 patients had at least one ADMS13:AC < 20% during the study period. 28/70 patients met liver injury inclusion criteria and 20/28 had TCP and MAHA. Of those 20 patients, median age at initial ADMS13:AC was 56.5 years (29-85). Most patients (n=14) had ADMS13:AC of 10-20%. ADMS13:AC was < 5% and 5-10% in 3 patients each. Eleven patients had a positive inhibitor with a median Bethesda titer of 1.85 BU (0.5-3.9). Etiology of liver included: ischemic hepatopathy (n=8), liver graft failure (n=4), liver metastasis (n=3), cirrhosis (n=2), alcoholic hepatitis (n=1), unknown (n=2). Median hemoglobin and platelet (plt) count at time of ADMS13 was 7 g/dL (6.4-13.2) and 30 x10 9/L (3-98), respectively. 7/20 patients had a PLASMIC score of ≥5; PLASMIC score was ≥5, in 2/6 patients with ADMS13:AC <10%. 16/18 patients had an ISTH DIC score ≥5. 18/20 patients had a creatinine > 2 mg/dL or were receiving renal replacement therapy the time of ADMS13: AC. 7/20 patients had total or direct bilirubin of >30mg/dL. Eight/20 patients were treated with plasma exchange (PEX) for a median duration of 7 days (2-13). 66.7% of pts with ADMS13:AC <10% received PEX. Glucocorticoids and Rituximab were used with the intent to treat TTP in 7 and 3 patients, respectively. Caplacizumab was used in 2 patients. 3/8 (37.5%) patients receiving PEX demonstrated normalization of MAHA. One of these patients demonstrated improvement but not normalization of plts (Table 1B, case 5). All patients had recurrence of hematologic abnormalities after PEX was stopped. One patient was treated with plasma infusion with stabilization in plt count. There were 13 and 15 deaths within 1 and 6 months of first ADMTS13:AC, respectively. One death was potentially attributable to management of TTP (Table 1B, case 1). There was no difference in time to death or mortality with the use of PEX. Repeat ADMS13:AC remote from PEX, TCP and MAHA was available for 1/5 surviving patients. This patient (Table1, case 2) had normalization of ADMS:AC after undergoing liver transplant. Conclusion: The differential diagnosis of TCP and MAHA in patients with liver injury includes hepatic dysfunction, DIC and TMA. In the current cohort, 89% of evaluable patients met criteria for overt DIC per ISTH criteria. Due to a low ADMTS13:AC, 40% of patients underwent a trial of PEX with 37.5% demonstrating improvement in MAHA that was not sustained upon discontinuation of PEX due to persistent liver dysfunction. Six-month mortality was 75% and use of PEX did not affect mortality. Given the high mortality, further studies evaluating which patients with TMA and liver injury are more likely to benefit from therapies typically used to treat TTP are necessary.

Role of Platelet Indices and Thrombopoietin (TPO) Serum Levels in the Differential Diagnosis of Thrombocytopenia

Background: The differential diagnosis of an isolated thrombocytopenia may be challenging, especially when it comes to differentiate immune thrombocytopenia (ITP) and an isolated thrombocytopenia in the context of bone marrow (BM) failure, in particular myelodysplastic syndromes (MDS); in such cases a BM examination is usually performed. It is known that thrombopoietin (TPO) serum levels are low in patients with ITP, while they are increased in case of amegakaryocytic thrombocytopenia. Furthermore, some platelet indices such as immature platelet fraction (IPF) may help to discriminate between hyporigenerative and consumption thrombocytopenia. Aim: The aim of this study was to compare TPO serum levels and platelet indices in patients with thrombocytopenia of different etiologies. Based on pathogenesis, we chose 3 groups of patients: ITP, amegakaryocytic thrombocytopenia (aplastic anemia (AA) or post-chemotherapy (CHT)) and thrombocytopenia in MDS and acute myeloid leukemia (AML). Although the diagnosis of amegakaryocytic thrombocytopenia and AML is straightforward with BM examination, we included patients with these diseases as a proof of concept and training set for our findings. Methods: This was a monocentric, retrospective, explorative study. Blood samples of patients with a platelet count < 100x109/L were collected. IPF, mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), platelet large cell ratio (P-LCR) were obtained using Sysmex XN-1000 hemocytometer (Sysmex Corporation). TPO serum levels were measured with a quantitative sandwich ELISA (R&D Systems). Microsoft Excel software was used for descriptive statistical analysis. Anova and Student's t-test were used for comparisons between groups. A p-value <0.05 was considered statistically significant. Results: We enrolled 84 patients: 50 ITP, 22 AML/MDS (13 AML, 9 MDS), 12 AA/post-CHT (4 AA, 8 post-CHT). Results are reported in Table 1. Neither mean platelet count (p=0.20) nor PCT (p=0.44) were significantly different between the three groups. Mean TPO serum levels were higher in patients with AA/post-CHT compared to ITP and AML/MDS groups (p<0.001). All patients in AA/post-CHT group had a TPO serum level >500 pg/mL, this value was never reached in patients with ITP and AML/MDS. TPO serum levels were higher in AML/MDS patients compared to ITP patients (p<0.001). While TPO serum levels were available for all patients, platelet indices were not, due to technical issues. IPF was available in 46/50 ITP patients, 20/22 AML/MDS and 8/12 AA/post-CHT, and it was higher in ITP patients if compared to AA/post-cht (p=0.021) and AML/MDS (p=0.0045). MPV, PDW and P-LCR were available in 27/50 ITP patients, 12/22 AML/MDS and 9/12 AA/post-CHT: they were higher in ITP patients than in the other groups (AML/MDS p=0.0185, AA/post-CHT p=0.017). In our cohort, patients with TPO ≥250 pg/mL and IPF <12% had a higher probability to belong to AML/MDS group (TPO: OR 0.08, 95% CI 0.02-0.32; IPF: OR 0.19, 95% CI 0.06-0.59). These findings were confirmed by multivariate analysis (IPF: p-value = 0.0185, CI 0.8647-0.9868; TPO: p-value = 0.004, CI 1.002-1.011). The other platelet indices were not included in this analysis due to the paucity of data. No correlation was found between platelet count, TPO and IPF in ITP patients. Of note, no differences were observed in terms of platelet count, TPO serum levels ad IPF between patients with AML and MDS. Conclusions: Our findings confirm that, in patients with the same platelet count, those with consumptive thrombocytopenia have higher IPF and lower TPO levels, while patients with amegakaryocytic thrombocytopenia have higher TPO levels and lower IPF. While TPO levels alone can distinguish amegakaryocytic thrombocytopenia from other etiologies, these preliminary data suggest that by combining IPF and TPO, patients with consumptive thrombocytopenia can be distinguished from MDS patients. This could be useful to spare BM examination in selected cases, or as an additional tool when the diagnosis remains uncertain also with BM examination. These data need to be confirmed in larger cohorts. The role of the other platelet indices, and the technical issues in their determination, needs further studies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Use of PLT-F channel and immature platelet fraction parameters in differential diagnosis of thrombocytopenia

Establishing the true causes of thrombocytopenia is of paramount importance, since the tactics of managing patients depend on it. Obtaining information about the activity of thrombocytopoiesis until recently was possible only after examining the bone marrow, but modern laboratory diagnostic capabilities make it possible to evaluate thrombocytopoiesis by a comprehensive clinical blood test performed on a hematological analyzer using a fluorescent optical method (PLT-F). At the same time, in addition to the number of platelets in peripheral blood, information is available on the number of immature platelets (IPF) in absolute and relative terms. Objective: to evaluate the possibility of using the PLT-F channel and IPF parameters in the differential diagnosis of thrombocytopenia. We reviewed three clinical cases with different pathogenetic variants of thrombocytopenia (immune thrombocytopenia, thrombocytopenia in DIC and thrombocytopenia associated with bone marrow damage). In all cases, a clinical blood test was performed on a Sysmex XN 1000 hematological analyzer using the PLT-F channel. When using the PLT-F channel, parameters are available to differentiate thrombocytopenia according to the mechanism of pathogenesis. The absolute value of IPF is a criterion for the activity of thrombocytopoiesis in the bone marrow, while the relative value of IPF, namely the increase in this parameter, is a criterion for the loss of platelets in the peripheral bloodstream (destruction or increased consumption of platelets). The availability of obtaining diagnostic information about the activity of thrombocytopoiesis and loss of platelets in the peripheral bloodstream using a clinical blood test using the PLT-F channel on Sysmex XN hematological analyzers is of great clinical importance, since a clinical blood test, being a routine study, does not require special conditions for sampling biomaterial, and can be performed not only at the stage of diagnosis, but also during therapy monitoring.

Importance of platelet indices in the establishment of etiopathological categorization of thrombocytopenia in children

BACKGROUND: Evaluation of thrombocytopenia requires thorough clinical history, examination, complete hemogram, including platelet indices and bone marrow study whenever indicated. The etiopathogenetic mechanism decides patient management. Platelet-derived indices have a well-established correlation with the differential diagnosis of thrombocytopenia in adult-based research. These indices include mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large cell ratio. The aim of the present study is to evaluate the variation and relationship of platelet indices in hypoproductive and hyperdestructive thrombocytopenia in children. MATERIALS AND METHODS: A prospective, observational study for a period of 1 year was done on children with thrombocytopenia. Platelet count (PLT), PDW, MPV, and platelet-large cell ratio (PLCR) along with relevant clinical details of the thrombocytopenic patients were collected and tested for the statistical significance by the unpaired t-test. RESULTS: This study included 80 patients of thrombocytopenia who were classified into hypoproductive (40 cases) and hyperdestructive (40 cases). The mean PLT in hypoproduction group is 49.3 ± 27.8 × 109/l and in hyperdestruction group is 45.7 ± 35.4 × 109/l with a P value of 0.548. The MPV in hypoproduction group is 9.3 ± 0.5 fl and in hyperdestruction group is 12.5 ± 1.7 fl, with a statistically significant P value of 0.002. The mean PDW in hypoproduction group is 16.3 ± 2.3 fl and in hyperdestruction group is 17.7 ± 2.8 fl with a P value of 0.055. The PLCR in hypoproduction group is 27.57% ±3.57% and in hyperdestruction group is 39.65% ±3.53% with a P value of 0.0003. CONCLUSION: Platelet indices may provide useful information in discriminating the hypoproductive and hyperdestructive thrombocytopenia in children too. Interpretation of platelet indices can help the thrombocytopenic children in the initial management and can avoid invasive investigations.

Clinical Significance of Platelet Parameters in the differential diagnosis of thrombocytopenia

Clinical Significance of Platelet Parameters in the differential diagnosis of thrombocytopenia

Variation of Platelet Indices in Differential Diagnosis of Thrombocytopenia – An Observational Study in a Tertiary Care Centre

Variation of Platelet Indices in Differential Diagnosis of Thrombocytopenia – An Observational Study in a Tertiary Care Centre

Reticulated platelets and immature platelet fraction: Clinical applications and method limitations.

So-called "reticulated" or "immature platelets," which are newly released into the circulation, are more reactive than mature platelets, contain more RNA, and can be counted using flow cytometry after staining with thiazole orange or using some fully automated hematology analyzers, albeit with numerical disagreement. This review provides an overview of the state of the art of available technology for measuring immature or reticulated platelets (RP) with preanalytical (time stability, biological variation), analytical (methods, imprecision), and postanalytical (reference range) limitations. We also analyzed the clinical conditions in which immature/RP can be considered a diagnostic or prognostic tool (ie, differential diagnosis of thrombocytopenia, recovery after bone marrow or stem cell transplantation, risk assessment in cardiovascular diseases, response to antiplatelet drugs). They might also be of clinical utility in other settings but with lower evidence. The lack of a specific reference method and universal control material, as well as dependency of results on the measurement technique used, calls for different reference intervals and compromises comparison between clinical studies carried out using different analytical methods. To obviate lack of agreement between methods, more specific RNA dyes are necessary and the impact of the platelet size on the fluorescence signal defined. In the harmonization age, also in nomenclature field, a new definition instead of "reticulated" or "immature" platelets would be useful, and "young platelets" might be a more appropriate definition taking into account both the age and the functionality of this platelet fraction.

Reticulated platelets – clinical application and future perspectives

Abstract Reticulated platelets are immature platelets freshly released from the bone marrow into the circulation and contain vestigial amounts of ribonucleic acid. Thus, they can serve as an indicator for the activity of thrombopoiesis. Despite the current lack of a standardized reference method, two types of hematology analyzers have incorporated a fully automated measurement of reticulated platelets. The “immature platelet fraction” (IPF; Sysmex XE-/XN-series) has some clinical utility in the differential diagnosis of thrombocytopenia. This is less clear for “reticulated platelets” (retPLT; Abbott CELL-DYN Sapphire/Alinity HQ). The usefulness of these parameters in the prediction of platelet recovery after chemotherapy or stem cell transplantation and as a decision aid for platelet transfusions has not been unequivocally confirmed. Recent findings have shown an association of reticulated platelets with an adverse risk in patients with coronary artery disease and stroke as well as resistance to anti-platelet therapy. Furthermore, a role of reticulated platelets for the prediction of sepsis was indicated. However, validation in larger prospective trials is necessary to establish the clinical benefit of reticulated platelets in these conditions. This review gives an overview of the available analytical methods and summarizes the current knowledge regarding the clinical application of reticulated platelets.

Immature platelet fraction related parameters in the differential diagnosis of thrombocytopenia

The pathogenesis of thrombocytopenia can be divided into increased destruction (ID) of platelets in the peripheral blood and decreased production (DP) of platelets in the bone marrow. This study aimed to analyze the efficacy of immature platelet fraction (IPF) related parameters, including the IPF count (IPF#), IPF percentage (IPF%) and highly fluorescence IPF percentage (H-IPF%), measured by XN-9000, in the differential diagnosis of thrombocytopenia. One hundred and twenty healthy volunteers were enrolled in the healthy control (HC) group, and 180 thrombocytopenia patients were grouped into either the increased destruction (ID) group or the decreased production (DP) group according to their final diagnosis. IPF# was significantly lower in the DP group than in the ID and HC groups (P < .01). Among the three groups, the ID group had the highest IPF% and H-IPF%, and the HC group had the lowest IPF% and H-IPF%. The differences between the three groups were all statistically significant (P < .01). In differentiating the ID patients from the DP patients, the areas under the operating characteristics curve of IPF#, IPF% and H-IPF% were 0.859, 0.944 and 0.930, respectively. False positive rates were below 0.04 when IPF#, IPF% and H-IPF% were above 2.65, 7.55 and 2.35, respectively. IPF related parameters showed high efficacy in the differential diagnosis of thrombocytopenia. However, due to the small numerical values of the IPF related parameters in some thrombocytopenia patients, the fluctuations of IPF% and H-IPF% should also be taken into consideration. Though H-IPF% is a new parameter, its effectiveness in the differential diagnosis of thrombocytopenia is not better than IPF%’s.

Differential diagnosis of thrombocytopenia in pregnancy

Differential diagnosis of thrombocytopenia in pregnancy

Immature Platelet Fraction Based Diagnostic Predictive Model for Immune Thrombocytopenic Purpura

IntroductionImmune thrombocytopenic purpura (ITP) is known as an acquired, immune-mediated disease characterized by isolated thrombocytopenia. Many studies have asserted that a diagnosis of ITP does not require a routine bone marrow examination. However, bone marrow examination is necessary in many cases because the diagnosis of ITP requires exclusion of other diseases including bone marrow disease. As both physicians and patients are reluctant to perform an invasive bone marrow examination, other parameters, including the immature platelet fraction (IPF, %), have been incorporated into the differential diagnosis of thrombocytopenia. In this study, we assessed its usefulness of IPF as a diagnostic marker and developed a diagnostic predictive model for ITP.MethodsWe retrospectively analyzed 330 patients with thrombocytopenia (platelet count < 100 x 109/L) who presented to Korea University Guro hospital between April 2013 and December 2017. We classified patients into 2 groups: those diagnosed with ITP (ITP group) and those without ITP (non-ITP group). ITP was diagnosed on the basis of clinical manifestations and laboratory results according to International Working Group diagnostic criteria. Non-ITP group included thrombocytopenia due to bone marrow disease, infection, drug, liver disease, etc.We used an automated hematologic analyzer (Sysmex XE-2100) to quantify the IPF and estimated other laboratory variables, including hemoglobin, platelet, white blood cell counts, reticulocytes, protein, albumin, bilirubin, pro-thrombin, activated partial thromboplastin time, ferritin, lactate dehydrogenase, blood urea nitrogen, creatinine, and C-reactive protein.All data were statistically analyzed using SPSS version 20. Logistic regression analysis was performed with the laboratory variables to access their diagnostic contribution. We used receiver-operating characteristic (ROC) and the point with the highest sum of sensitivity and specificity on the ROC curve was determined as the cut-off value of each variables. P-values < 0.05 were considered statistically significant.ResultsA total of 103 and 227 patients were diagnosed as ITP and non-ITP. The median IPF is significantly higher in ITP group, with a value of 10.5% (1.3-48%) vs. 5.9% (0.7-31.5%) in the non-ITP group, and cut-off value for differentiation of ITP was 7.0% with a sensitivity of 64.8% and a specificity of 65.2%. Since ITP remains a diagnosis of exclusion, some patients who did not undergo a bone marrow examination might have been misclassified into the ITP group. To exclude the possibility of misclassification, we conducted a subgroup analysis of only patients who had undergone a bone marrow examination (BM group). A total of 162 patients performed bone marrow examination, 47 and 115 were classified into the ITP and non-ITP group. The median IPF was significantly higher in ITP group, with a value of 13.6% (4.3-38.5%) vs. 4.7% (0.7-31.5%) for the non-ITP group. The cut-off value was 9.25%, with a sensitivity of 78.7% and a specificity of 78.3%. The median IPF was higher in this subgroup and the sensitivity and specificity of the cut-off value were also higher than the former group. (Figure 1)We confirmed that IPF could be a useful parameter for diagnosing ITP, but since IPF alone could not diagnose ITP, we also evaluated other laboratory variables by the logistic regression analysis. Hemoglobin, ferritin showed statistical significance, and the optimal cut-off value was 12 g/dl and 175 mg/ml. To adequately reflect sensitivity and specificity, we divided patients into 3 groups according to IPF; IPF<5, ≥5 and <10, ≥10. We developed simple diagnostic predictive model with these variables. Our model gave point to each of variables; 1 to high hemoglobin level (>12g/dl), low ferritin level (<175ng/ml) and IPF ≥5 and <10, 2 to IPF ≥10. The final score was obtained by summing the points. We demonstrated that ITP could be highly predicted in patients with score 3-4 (80% in all patients group, 89% in BM group) and could be excluded in patients with score 0-1 (95% in all patients group, 97% in BM group). (Table 1)ConclusionsThe results showed that IPF could be a good diagnostic marker for ITP. We suggested the diagnostic predictive model for ITP using IPF, hemoglobin and ferritin. This model could diagnose ITP with high probability and avoid a bone marrow examination. Further studies would be needed to refine and validate this predictive model. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Novel Cycs Missense Mutation in the α-Helix of the Cycs C-Terminal Domain Causes Non-Syndromic Thrombocytopenia

We report a patient with thrombocytopenia from a Japanese family with hemophilia A spanning four generations. Various etiologies of thrombocytopenia, including genetic, immunological, and hematopoietic abnormalities, determine the prognosis for this disease. The CYCS gene (MIM123970) encodes cytochrome c, somatic, a small heme protein localized in the inner membrane of mitochondria. Cytochrome c is an electron carrier in the mitochondrial respiratory chain as well as a key initiator of apoptosis (Cell Death Differ. 2018;25(1):46-55). To date, only three families with CYCS missense variants have been reported: a large New Zealander family (p.Gly42Ser), an Italian family (p.Tyr49His), and a white/mixed British family (p.Ala52Val) (Nat Genet. 2008;40(4):387-9, Biochim Biophys Acta. 2014;1842(2):269-74, Haematologica. 2016;101(10):1170-1179). These patients were affected by an autosomal dominant phenotype characterized by low platelet count without extra-hematological findings. Moreover, these patients' peripheral blood cell morphologies, including platelet size, were all normal.In this study, we identified a novel heterozygous mutation in CYCS using whole exome sequencing. This variant (c.301_303del:p.Lys101del) is located in the α-helix of the cytochrome c (CYCS) C-terminal domain. In silico structural analysis suggested that this mutation results in protein folding instability. By the deletion mutation, the Ala102 position is considered to be replaced with the neighboring Thr103, which would impair the hydrophobic core and destabilize protein folding. All three reported missense mutations are clustered within the highly conserved Ω-loop (Biochim Biophys Acta. 2014;1842(2):269-74, Sci Rep. 2016, 27;6:30447, Biophys Chem. 2017;230:117-126). Previous structural analyses also showed that two mutations in the Ω-loop (p.Gly42Ser and p.Tyr49His) of CYCS disrupted hydrogen bonds (Sci Rep. 2016, 27;6:30447, Biophys Chem. 2017;230:117-126). Although in silico analysis suggested the significant structural impact of p.Lys101del, it is arguable that a one amino acid in-frame deletion outside the Ω-loop would have a mild or neutral effect. To verify the pathogenicity of this variant in the less characterized C-terminal region, we used the fission yeast Schizosaccharomyces pombe as a model system (Biosci Biotechnol Biochem. 2013;77(7):1548-55). Using the yeast model system, we clearly demonstrated that this one amino acid deletion (in-frame) resulted in significantly reduced cytochrome c protein expression and functional defects in the mitochondrial respiratory chain, indicating that the loss of function of cytochrome c underlies thrombocytopenia. Similar deleterious effects in terms of mitochondrial respiratory function were reported for two other pathogenic mutations, p.Gly42Ser and p.Tyr49His in CYCS (Biochim Biophys Acta. 2014;1842(2):269-74). The clinical features of known CYCS variants have been reported to be confined to mild or asymptomatic thrombocytopenia, as was observed for the patient in our study. Hence, we suggest that loss-of function variants in CYCS cause non-syndromic thrombocytopenia.In conclusion, our findings provide further support for CYCS mutations being causative for pure isolated thrombocytopenia. In a clinical setting, differential diagnosis of thrombocytopenia is important for evaluating the risk of developing hematological malignancies. Genetic testing complemented with the relevant functional studies should be considered part of appropriate patient care.The study protocol was approved by Institutional Review Boards of Yokohama City University School of Medicine and the Gunma University Graduate School of Medicine. Written informed consent was obtained from all participants. DisclosuresHanda:Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau.

Thrombocytopenia in pregnancy

Thrombocytopenia develops in 5% to 10% of women during pregnancy or in the immediate postpartum period. A low platelet count is often an incidental feature, but it might also provide a biomarker of a coexisting systemic or gestational disorder and a potential reason for a maternal intervention or treatment that might pose harm to the fetus. This chapter reflects our approach to these issues with an emphasis on advances made over the past 5 to 10 years in understanding and managing the more common causes of thrombocytopenia in pregnancy. Recent trends in the management of immune thrombocytopenia translate into more women contemplating pregnancy while on treatment with thrombopoietin receptor agonists, rituximab, or mycophenylate, which pose known or unknown risks to the fetus. New criteria to diagnose preeclampsia, judicious reliance on measurement of ADAMTS13 to make management decisions in suspected thrombotic thrombocytopenic purpura, new evidence supporting the efficacy and safety of anticomplement therapy for atypical hemolytic uremic syndrome during pregnancy, and implications of thrombotic microangiopathies for subsequent pregnancies are evolving rapidly. The goals of the chapter are to help the hematology consultant work through the differential diagnosis of thrombocytopenia in pregnancy based on trimester of presentation, severity of thrombocytopenia, and coincident clinical and laboratory manifestations, and to provide guidance for dealing with some of the more common and difficult diagnostic and management decisions.

The differential diagnosis of thrombocytopenia in neonates

The article discusses the causes and mechanisms of development of thrombocytopenia in neonates, the algorithm of diagnostic search in case of thrombocytopenia, is an example of clinical observation of the newborn diagnosed with von Willebrand disease.

The Differential Diagnosis of Thrombocytopenia in Pregnancy.

Thrombocytopenia is, after anemia, the second most common abnormality of the complete blood count in pregnancy, with a reported frequency of 6.6% to 11.2%. It has many causes. Thrombocytopenia should be diagnostically evaluated as early as possible in pregnancy, so that the obstetrical management can be accordingly planned to minimize harm to the mother and child. As the various underlying diseases share clinical features and laboratory findings, the differential diagnosis is often a difficult interdisciplinary challenge. In this article, we review pertinent literature (2000-January 2015) retrieved by a selective search in PubMed. Gestational thrombocytopenia is the most common type, accounting for 75% of cases, followed by severe pre-eclampsia/HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count) in 15-22% and autoimmune thrombocytopenia (ITP) in 1-4%. Gestational thrombocytopenia and ITP differ in the bleeding history, the severity of thrombocytopenia, the frequency of neo - natal thrombocytopenia, and the rate of normalization of the platelet count after delivery. The HELLP syndrome and rarer microangiopathic hemolytic anemias (e.g., thrombotic thrombocytopenic purpura) can be differentiated on the basis of their main clinical features, such as hypertension/proteinuria and upper abdominal pain, the severity of hemolysis and thrombocytopenia, the degree of transaminase elevation, and the rapidity of postpartum remission of the clinical and laboratory findings. A stepwise diagnostic procedure should be followed to distinguish further causes, e.g., to differentiate thrombocytopenia due to infection, autoimmune disease, or drugs from thrombocytopenia due to a rare hereditary disease. The early interdisciplinary evaluation of thrombocytopenia in pregnancy is a prerequisite for the optimal care of the mother and child. The development of evidence-based recommendations for interdisciplinary management should be a goal for the near future.

Evaluation of the diagnostic performance of platelet-derived indices for the differential diagnosis of thrombocytopenia in pediatrics

&lt;p&gt;Background. Platelet-derived indices have a well-established correlation with the differential diagnosis of thrombocytopenia in adult-based research. These indices include mean platelet volume, platelet distribution width, and platelet-large cell ratio.&lt;/p&gt;&lt;p&gt;Objective. To determine the values of platelet-derived indices in a pediatric population with diagnoses of thrombocytopenia and their etiologic correlation.&lt;/p&gt;&lt;p&gt;Materials and methods. Analytic observational diagnostictest study. The population for this analytical study was pediatric patients between 6 months and 18 years of age who had thrombocytopenia (&amp;lt;100x109/L). The study period was 18 months long.&lt;/p&gt;&lt;p&gt;Results. Of 54 subjects, 18 (33.3%) were diagnosed with idiopathic thrombocytopenic purpura, and 36 (66.7%) were diagnosed with acute leukemia. Mean age was 7.4 years and 6.8 years for immune thrombocytopenic purpura and acute leukemia, respectively. Mean platelet distribution width values for immune thrombocytopenic purpura and acute leukemia were 15.08 fL and 10.73, respectively. Mean MPV for immune thrombocytopenic purpura and acute leukemia was 11.7 fL and 9.8 fL, respectively. Mean platelet-large cell ratio was 38.26% and 24.97% for idiopathic thrombocytopenic purpura and acute leukemia, respectively. Differences in these three distinct platelet indices between idiopathic thrombocytopenic purpura and acute leukemia were statistically significant (p=0.00). The area under the ROC curve for platelet-derived indices showed that they were adequate for defining the causes of thrombocytopenia. MPV and platelet-large cell ratio had an area under the curve of 0.89 and 0.88, respectively, while platelet size deviation width had an area under the curve of 0.903.&lt;/p&gt;&lt;p&gt;Conclusions. Platelet-derived indices could be useful in the initial approach for the differential diagnosis of pediatric patients with thrombocytopenia.&lt;/p&gt;

An Intriguing Case of Anaemia and Splenomegaly

Objectives : Thrombocytopenia and splenomegaly are common features in several haematological disorders. Gaucher disease (GD) is a rare lysosomal storage disorder frequently characterized by thrombocytopenia and splenomegaly, which represents a clinical challenge for haematologists and internists. Case : We describe the case of a 37-year-old patient with a diagnosis of spherocytosis since childhood, who developed hepatic failure and presented striking features of GD including hepatosplenomegaly, bone fractures and post-partum bleeding. We reconsidered the diagnosis of spherocytosis and investigated Gaucher disease. Conclusion : GD should be considered in the differential diagnosis of thrombocytopenia and splenomegaly.

Novel heterozygous c.798C&gt;G and c.1040T&gt;G mutations in the GBA1 gene are associated with a severe phenotype of Gaucher disease type 1

Novel heterozygous c.798C&gt;G and c.1040T&gt;G mutations in the GBA1 gene are associated with a severe phenotype of Gaucher disease type 1

Differential Diagnosis of Thrombocytopenia in Hematopoietic Stem Cell Transplant Patients

Thrombocytopenia has remained a major concern in post-haematopoietic stem cell transplant patients. It is a strong negative indicator for survival and is often seen in patients with advanced acute and chronic Graft versus host disease (GVHD). The pathogenesis of thrombocytopenia varies from impaired thrombopoiesis to increased turnover of platelets. The dose of CD34+ cells and that of megakaryocyte specific lineage cells (CD34+ /CD41+ and CD34+ / CD61+ ) has a positive effect on thrombopoiesis. Conditions like bone marrow fibrosis, CMV infection and ganciclovir administration affect the bone marrow environment leading to ineffective thrombopoiesis. Increased destruction of platelets is seen with GVHD, drugs, infections, thrombotic microangiopathy and platelet refractoriness due to alloimmunization. The management of thrombocytopenia includes treating the underlying conditions and supportive care with platelet transfusion. Platelet refractoriness is managed using ABO matched platelets, HLA-matched platelets or cross-matched platelets for transfusion depending on the underlying cause. Some of the recent studies have concentrated on the effect on thromobopoiesis due to maturation of megakaryocytes or ploidy and the effect of cytokines on bone marrow microenvironment. Further studies are needed to incorporate these parameters as part of routine laboratory investigation in thromobocytopenic patients along with estimation of anti-platelet antibodies for better diagnosis and management of these patients.

SP0037 Two difficult SLE patient cases

Case 1 is a woman who was referred for pregnancy counselling in 1993 (age 29 years). She had antiphospholipid syndrome (APS) based on a history with DVT, 2 early spontaneous...