ResearchPad - Hematology https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Clinical, Laboratory, and Bone Marrow Findings of 31 Patients With Waldenström Macroglobulinemia]]> https://www.researchpad.co/product?articleinfo=Ncf03617d-0fcc-47fd-9e77-46f2747c453d

Background

Waldenström macroglobulinemia (WM) is a subset of lymphoplasmacytic lymphoma (LPL) with bone marrow (BM) involvement and an IgM monoclonal gammopathy of any level. We aimed to identify the clinical, laboratory, and BM findings of patients with WM and to evaluate the usefulness of CD154 for the diagnosis and prognosis of WM.

Methods

We reviewed the medical records and BM studies and/or flow cytometric immunotyping of 31 patients with untreated WM. Semiquantitative immunohistochemistry (CD20, CD138, tryptase, and CD154) of BM was performed.

Results

Only six patients presented with symptoms of hyperviscosity syndrome. Eleven patients had solid cancer and/or another hematologic malignancy. Mast cells (MC) increased in all samples, with some in close contact with tumor cells. Tryptase-positive MC (17.1/ high-power fields [HPF], 1.2–72.0/HPF) and CD154-positive MC (8.6/HPF, 0.1–31.1/HPF) were observed. The high CD154-positive MC (≥8.6/HPF) group showed a lower overall five-year survival rate than the low CD154-positive MC (<8.6/HPF) group (71.9% vs. 100.0%; P=0.012). Flow cytometric immunophenotyping of BM aspirates showed increased B lymphocytes and plasma cells with a normal phenotype (CD138+/CD38+/CD19+/CD45+/CD56).

Conclusions

Approximately one third of WM patients showed other malignancies and all patients had increased MC. Immunohistochemistry and flow cytometric immunophenotyping are useful for diagnosing WM, and increased CD154-positive MC can indicate poor prognosis.

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<![CDATA[Physicochemical and biological evaluation of JR-131 as a biosimilar to a long-acting erythropoiesis-stimulating agent darbepoetin alfa]]> https://www.researchpad.co/product?articleinfo=Na789b0ff-1b14-409c-afa6-0c7a70fc7c42

Renal anemia is predominantly caused by a relative deficiency in erythropoietin (EPO). Conventional treatment for renal anemia includes the use of recombinant human EPO (rhEPO) or a long-acting erythropoiesis-activating agent named darbepoetin alfa, which is a modified rhEPO with a carbohydrate chain structure that differs from native hEPO. We have developed a biosimilar to darbepoetin alfa designated JR-131. Here, we comprehensively compare the physicochemical and biological characteristics of JR-131 to darbepoetin alfa. JR-131 demonstrated similar protein structure to the originator, darbepoetin alfa, by peptide mapping and circular dichroism spectroscopy. Additionally, mass spectroscopic analyses and capillary zone electrophoresis revealed similar glycosylation patterns between the two products. Human bone marrow-derived erythroblasts differentiated and proliferated to form colonies with JR-131 to a similar degree as darbepoetin alfa. Finally, JR-131 stimulated erythropoiesis and improved anemia in rats similarly to darbepoetin alfa. Our data show the similarity in physicochemical and biological properties of JR-131 to those of darbepoetin alfa, and JR-131 therefore represents a biosimilar for use in the treatment of renal anemia.

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<![CDATA[Nocturnal hypercapnia with daytime normocapnia in patients with advanced pulmonary arterial hypertension awaiting lung transplantation]]> https://www.researchpad.co/product?articleinfo=Nacc6463a-eb28-4f4a-acf0-c81fc9df01f4

Background

Pulmonary arterial hypertension (PAH) is frequently complicated by sleep disordered breathing (SDB), and previous studies have largely focused on hypoxemic SDB. Even though nocturnal hypercapnia was shown to exacerbate pulmonary hypertension, the clinical significance of nocturnal hypercapnia among PAH patients has been scarcely investigated.

Method

Seventeen patients with PAH were identified from 246 consecutive patients referred to Kyoto University Hospital for the evaluation of lung transplant registration from January 2010 to December 2017. Included in this study were 13 patients whose nocturnal transcutaneous carbon dioxide partial pressure (PtcCO2) monitoring data were available. Nocturnal hypercapnia was diagnosed according to the guidelines of the American Academy of Sleep Medicine. Associations of nocturnal PtcCO2 measurements with clinical features, the findings of right heart catheterization and pulmonary function parameters were evaluated.

Results

Nocturnal hypercapnia was diagnosed in six patients (46.2%), while no patient had daytime hypercapnia. Of note, nocturnal hypercapnia was found for 5 out of 6 patients with idiopathic PAH (83.3%). Mean nocturnal PtcCO2 levels correlated negatively with the percentage of predicted total lung capacity (TLC), and positively with cardiac output and cardiac index.

Conclusion

Nocturnal hypercapnia was prevalent among advanced PAH patients who were waiting for lung transplantation, and associated with %TLC. Nocturnal hypercapnia was associated with the increase in cardiac output, which might potentially worsen pulmonary hypertension especially during sleep. Further studies are needed to investigate hemodynamics during sleep and to clarify whether nocturnal hypercapnia can be a therapeutic target for PAH patients.

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<![CDATA[Effects of amotosalen treatment on human platelet lysate bioactivity: A proof-of-concept study]]> https://www.researchpad.co/product?articleinfo=Ne8e94533-b9bd-43e3-83be-324d5eb7ad87

Background

Clinical application of mesenchymal stromal cells (MSCs) usually requires an in vitro expansion step to reach clinically relevant numbers. In vitro cell expansion necessitates supplementation of basal mammalian cell culture medium with growth factors. To avoid using supplements containing animal substances, human platelet lysates (hPL) produced from expired and pathogen inactivated platelet concentrates can be used in place of fetal bovine serum. However, globally, most transfusion units are currently not pathogen inactivated. As blood banks are the sole source of platelet concentrates for hPL production, it is important to ensure product safety and standardized production methods. In this proof-of-concept study we assessed the feasibility of producing hPL from expired platelet concentrates with pathogen inactivation applied after platelet lysis by evaluating the retention of growth factors, cytokines, and the ability to support MSC proliferation and tri-lineage differentiation.

Methodology/Principal findings

Bone marrow-derived MSCs (BM-MSCs) were expanded and differentiated using hPL derived from pathogen inactivated platelet lysates (hPL-PIPL), with pathogen inactivation by amotosalen/ultraviolet A treatment applied after lysis of expired platelets. Results were compared to those using hPL produced from conventional expired pathogen inactivated platelet concentrates (hPL-PIPC), with pathogen inactivation applied after blood donation. hPL-PIPL treatment had lower concentrations of soluble growth factors and cytokines than hPL-PIPC treatment. When used as supplementation in cell culture, BM-MSCs proliferated at a reduced rate, but more consistently, in hPL-PIPL than in hPL-PIPC. The ability to support tri-lineage differentiation was comparable between lysates.

Conclusion/Significance

These results suggest that functional hPL can be produced from expired and untreated platelet lysates by applying pathogen inactivation after platelet lysis. When carried out post-expiration, pathogen inactivation may provide a valuable solution for further standardizing global hPL production methods, increasing the pool of starting material, and meeting future demand for animal-free supplements in human cell culturing.

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<![CDATA[Isoniazid Induced Pure Red Blood Cell Aplasia]]> https://www.researchpad.co/product?articleinfo=Nb1c63667-9043-4dcf-8239-06ce9e59873c

Pure red blood cell aplasia (PRCA) is one of the uncommon causes of anemia. Drug-induced PRCA is even more infrequent. Only a few drugs are implicated in PRCA. Isoniazid is a widely used drug for the treatment of tuberculosis all over the world. It is known to cause hepatotoxicity, but in rare instances, it can lead to PRCA. 

A 72-year-old Caucasian male, who was started on isoniazid after the diagnosis of latent tuberculosis, presented two months later with episodes of syncope to primary care physician’s office. The initial blood work showed severe anemia. There were no signs of acute or chronic gastrointestinal blood loss, and the stool hemoccult test was negative. Iron, vitamin B12, folate, lactate dehydrogenase, bilirubin, transaminases, and erythropoietin were within normal limits. Peripheral blood smear showed normochromic and normocytic anemia. A reticulocyte count was less than 1,000 per microliter. Thymoma, human immunodeficiency virus, and parvovirus B19 were ruled out. Further work-up with bone marrow biopsy confirmed pure red blood cell aplasia. A detailed review of recently started medications revealed isoniazid as the offending drug. Isoniazid was stopped. Reticulocyte count and bone marrow recovered a few days after stopping with eventual improvement in hemoglobin level, thus confirming the diagnosis of isoniazid induced red blood cell aplasia.

Isoniazid is the first-line therapy for tuberculosis. Rarely, it can cause pure red blood cell suppression and severe anemia, an untoward effect, worth remembering.

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<![CDATA[Association of Blood Type With Postsurgical Mucosal Bleeding in Pediatric Patients Undergoing Tonsillectomy With or Without Adenoidectomy]]> https://www.researchpad.co/product?articleinfo=N94e7580b-d8ce-4c0c-8c33-3f9fa80b3a3f

Key Points

Question

Is blood type O associated with a higher prevalence hemorrhage in children after tonsillectomy with or without adenoidectomy?

Findings

In this cohort study of nearly 15 000 children who underwent tonsillectomy with or without adenoidectomy, the hemorrhage rate following surgery was 3.9%. In the cohort of children for whom a blood type was known, those with blood type O experienced bleeding as frequently as those with non-O types, despite having significantly lower baseline von Willebrand factor values.

Meaning

The findings of this study indicate that bleeding rates after tonsillectomy with or without adenoidectomy are similar in children with blood type O and those with non-O types.

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<![CDATA[Fusobacterium necrophorum Septicemia Leading to Lemierre’s Syndrome in an Immunocompetent Individual: A Case Report]]> https://www.researchpad.co/product?articleinfo=Naef1cec0-ed96-497d-8d22-318e0b032456

Lemierre syndrome is a life-threatening condition associated with infection by obligate anaerobes residing in oropharyngeal mucosa. The most common organism responsible is Fusobacterium necrophorum. We report a case in a 69-year-old gentleman. The man with past medical history of hypertension, anxiety and chronic alcohol abuse was brought in by his family for altered mental status and fever. He had a complicated stay with septic shock on multiple pressors, his blood cultures grew Fusobacterium necrophorum and neck ultrasound showed acute thrombus of the right internal jugular vein (IJV). The patient had received intravenous antibiotics throughout stay but had poor prognosis and eventually expired after a complicated hospital stay.

Lemierre syndrome is a rare syndrome usually associated with an acute oropharyngeal infection due to anaerobic bacteria leading to secondary septic thrombophlebitis of the internal jugular vein. The characteristic clinical picture noticed is a hematogenous progression to distant septic emboli. It is a life-threatening condition and a prompt diagnosis is critical for preventing fatal consequences.

The purpose of this case report is to increase awareness about this clinical condition among medical professionals.

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<![CDATA[Bone marrow transplantation for thalassemia]]> https://www.researchpad.co/product?articleinfo=N824f5c04-2e04-434a-842f-85bd6f9ef774

Early trials of allogeneic bone marrow transplantation (BMT) for homozygous beta-thalassemia and the analyses of results of transplantation in patients less then 16 years old have allowed us to identify three classes of risk using the criteria of degree of hepatomegaly, the degree of portal fibrosis and the quality of the chelation treatment given before the transplant. Patients for whom all three criteria were adverse constituted class 3, patients with none of the adverse criteria constituted class one and patients with one or various association of the adverse criteria formed Class 2. Most patients older than 16 years have disease characteristics that place them in class 3 with very few in class 2. For all the patients with an HLA identical donor we are actually using two Protocols for BMT to whom the patients are assigned on the base of the class they belong to at the time of BMT and independently on the age of the patient. For class 1, class 2 and for class 3 the probabilities of survival and of event-free-survival are respectively of 98% and 94%, 87% and 84%, 100% and 67%. For those patients that were older than 16 years at the time of the transplant, the probabilities of survival are 82% and the probabilities of event-free survival are 79%.

Bone marrow transplantation is a new form of radical treatment of thalassemia in those patients with an HLA identical donor.

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<![CDATA[Rosuvastatin Use Implicated in the Drug Reaction with Eosinophilia and Systemic Symptoms]]> https://www.researchpad.co/product?articleinfo=N6dcb7abc-ecc3-408b-abb7-e8dc20d57b5f

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a life-threatening drug-induced hypersensitivity reaction that is most closely associated with antiepileptics and antibiotics. While cases of DRESS are rare, here we present a case of DRESS in an adult male following administration of rosuvastatin who presented with fevers, generalized rash, and facial fullness. Vitals on presentation were temperature 102oF, pulse 95/min, blood pressure 95/47 mmHg, and respiratory rate of 14/min. His physical examination revealed scleral icterus, generalized blanching maculopapular rash, facial fullness, and right upper quadrant tenderness. Laboratory investigations found hemoglobin 10 gm/dl, white blood cell count 16.0 K/uL, peripheral eosinophil count 1,700 K/uL, alkaline phosphatase 2,501 U/L, aspartate transaminase 620 U/L, alanine transaminase 680 U/L, total bilirubin 13.2 mg/dl with a direct component of 9 mg/dl, blood urea nitrogen 66 mg/dl, creatinine 5.20 mg/dl, glomerular filtration rate 8 ml/min, and immunoglobulin E level 623 IU/mL. Serology for viral hepatitis, Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 was negative. Computed tomographic scan of chest, abdomen, and pelvis showed generalized lymphadenopathy. Over the next week, the patient deteriorated clinically with worsening transaminitis and oliguric acute renal failure requiring renal replacement therapy. As per the European Registry of Severe Cutaneous Adverse Reaction Criteria (RegiSCAR), the probability of rosuvastatin-induced DRESS syndrome was scored as “definite.” He was treated with systemic and topical glucocorticoids leading to a gradual improvement in his symptoms. Skin biopsy was suggestive of DRESS syndrome as well. Since DRESS carries such a significant risk of mortality between 10% and 20%, DRESS must be recognized and treated as soon as symptoms present. Clinicians should also be aware that statins, one of the most commonly prescribed drugs, are also a potential cause DRESS.

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<![CDATA[The Role of Blood Viscosity in Infectious Diseases]]> https://www.researchpad.co/product?articleinfo=N58238e42-440f-487e-977a-3cd53c206269

Blood viscosity is increased by elevated concentrations of acute phase reactants and hypergammaglobulinemia in inflammation. These increase blood viscosity by increasing plasma viscosity and fostering erythrocyte aggregation. Blood viscosity is also increased by decreased erythrocyte deformability, as occurs in malaria. Increased blood viscosity contributes to the association of acute infections with myocardial infarction (MI), venous thrombosis, and venous thromboembolism. It also increases vascular resistance, which decreases tissue perfusion and activates stretch receptors in the left ventricle, thereby initiating the systemic vascular resistance response. This compensates for the increased vascular resistance by vasodilation, lowering hematocrit, and decreasing intravascular volume. This physiological response causes the anemias associated with malaria, chronic inflammation, and other chronic diseases. Since tissue perfusion is inversely proportional to blood viscosity, anemia may be beneficial as it increases tissue perfusion when erythrocyte aggregating factors or erythrocytes with decreased deformability are present in the blood.

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<![CDATA[Iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood]]> https://www.researchpad.co/product?articleinfo=N9158e50b-6372-4968-9c34-a70f2648acea

Background

Iron overload is one of common complications of β-thalassemia. Systemic iron homeostasis is regulated by iron-regulatory hormone, hepcidin, which inhibits intestinal iron absorption and iron recycling by reticuloendothelial system. In addition, body iron status and requirement can be altered with age. In adolescence, iron requirement is increased due to blood volume expansion and growth spurt. Heterozygous β-globin knockout mice (Hbbth3/+; BKO) is a mouse model of thalassemia widely used to study iron homeostasis under this pathological condition. However, effects of age on iron homeostasis, particularly the expression of genes involved in hemoglobin metabolism as well as erythroid regulators in the spleen, during adolescence have not been explored in this mouse model.

Methods

Iron parameters as well as the mRNA expression of hepcidin and genes involved in iron transport and metabolism in wildtype (WT) and BKO mice during adolescence (6–7 weeks old) and adulthood (16–20 weeks old) were analyzed and compared by 2-way ANOVA.

Results

The transition of adolescence to adulthood was associated with reductions in duodenal iron transporter mRNA expression and serum iron levels of both WT and BKO mice. Erythrocyte parameters in BKO mice remained abnormal in both age groups despite persistent induction of genes involved in hemoglobin metabolism in the spleen and progressively increased extramedullary erythropiesis. In BKO mice, adulthood was associated with increased liver hepcidin and ferroportin mRNA expression along with splenic erythroferrone mRNA suppression compared to adolescence.

Conclusion

Our results demonstrate that iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood. The present study underscores the importance of the age of thalassemic mice in the study of molecular or pathophysiological changes under thalassemic condition.

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<![CDATA[Identification of key gene modules and hub genes of human mantle cell lymphoma by coexpression network analysis]]> https://www.researchpad.co/product?articleinfo=N430ea83f-4a22-409a-b9d1-a8aa4046804e

Purpose

Mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin lymphoma that is incurable with standard therapies. The use of gene expression analysis has been of interest, recently, to detect biomarkers for cancer. There is a great need for systemic coexpression network analysis of MCL and this study aims to establish a gene coexpression network to forecast key genes related to the pathogenesis and prognosis of MCL.

Methods

The microarray dataset GSE93291 was downloaded from the Gene Expression Omnibus database. We systematically identified coexpression modules using the weighted gene coexpression network analysis method (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were performed on the modules deemed important. The protein–protein interaction networks were constructed and visualized using Cytoscape software on the basis of the STRING website; the hub genes in the top weighted network were identified. Survival data were analyzed using the Kaplan–Meier method and were compared using the log-rank test.

Results

Seven coexpression modules consisting of different genes were applied to 5,000 genes in the 121 human MCL samples using WGCNA software. GO and KEGG enrichment analysis identified the blue module as one of the most important modules; the most critical pathways identified were the ribosome, oxidative phosphorylation and proteasome pathways. The hub genes in the top weighted network were regarded as real hub genes (IL2RB, CD3D, RPL26L1, POLR2K, KIF11, CDC20, CCNB1, CCNA2, PUF60, SNRNP70, AKT1 and PRPF40A). Survival analysis revealed that seven genes (KIF11, CDC20, CCNB1, CCNA2, PRPF40A, CD3D and PUF60) were associated with overall survival time (p < 0.05).

Conclusions

The blue module may play a vital role in the pathogenesis of MCL. Five real hub genes (KIF11, CDC20, CCNB1, CCNA2 and PUF60) were identified as potential prognostic biomarkers as well as therapeutic targets with clinical utility for MCL.

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<![CDATA[Agreement of stall‐side and laboratory major crossmatch tests with the reference standard method in horses]]> https://www.researchpad.co/product?articleinfo=Ne5c2f006-1372-403b-9633-cc73c039d7bd

Abstract

Background

Crossmatching is used to prevent life‐threatening transfusion reactions in horses. Laboratory methods are laborious and technically challenging, which is impractical during emergencies.

Hypothesis/Objectives

Evaluate agreement between a stall‐side crossmatch kit (KIT) and a laboratory method (LAB) in horses with known and unknown blood types.

Animals

Twenty‐four blood‐typed and alloantibody‐screened healthy adult horses (Aim 1) and 156 adult horses of unknown blood type (Aim 2).

Methods

Prospective, blinded study. Expected positive (n = 35) and negative (n = 36) crossmatches among 24 antibody and blood‐typed horses were used to determine sensitivity and specificity of KIT and LAB against the reference method. Agreement in 156 untyped horses was evaluated by reciprocal crossmatch (n = 156).

Results

Sensitivity (95% confidence interval [CI]) for LAB and KIT compared with expected reactions was 77.1% (59.9%‐90.0%) and 91.4% (77.0%‐98.2%), and specificity 77.8% (60.9%‐89.9%) and 73.5% (55.6%‐87.1%), respectively. The KIT was 100% sensitive for Aa reactions; LAB was 100% sensitive for Qab; and both were 100% sensitive for Ca. Cohen's κ agreement for LAB and KIT with expected positive and negative reactions (n = 71) was moderate (0.55 [0.36‐0.74]) and substantial (0.65 [0.47‐0.82]), respectively. Agreement was fair comparing LAB with KIT in Aim 1 (0.30 [0.08‐0.52]) and in untyped horses in Aim 2 (0.26 [0.11‐0.41]).

Conclusions and Clinical Importance

Agreement between KIT and LAB with expected reactions was blood type dependent. Performance of both methods depends on blood type prevalence.

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<![CDATA[Plasma disposition of gabapentin after the intragastric administration of escalating doses to adult horses]]> https://www.researchpad.co/product?articleinfo=Nc6ed3fd9-4440-4123-9313-e9287b824446

Abstract

Background

In humans, gabapentin an analgesic, undergoes non‐proportional pharmacokinetics which can alter efficacy. No information exists on the pharmacokinetics of dosages >20 mg/kg, escalating dosages or dose proportionality of gabapentin in horses.

Hypothesis and Objectives

Gabapentin exposure in plasma would not increase proportionally relative to the dose in horses receiving dosages ≥20 mg/kg. To assess the plasma pharmacokinetics of gabapentin after nasogastric administration of gabapentin at dosages of 10 to 160 mg/kg in adult horses.

Animals

Nine clinically healthy adult Arabian and Quarter Horses.

Methods

In a randomized blinded trial, gabapentin was administered by nasogastric intubation to horses at 10, 20 mg/kg (n = 3) and 60, 80, 120, 160 mg/kg (n = 6). Plasma was collected before and at regular times over 64 hours after administration of gabapentin. Gabapentin was quantified using a validated chromatographic method. Dose proportionality was estimated using a power model. Pharmacokinetic parameters were estimated using compartmental pharmacokinetic analysis.

Results

Plasma pharmacokinetics parameters of gabapentin were estimated after nasogastric administration at dosages of 10 to 160 mg/kg. Gabapentin plasma concentration increased with dose increments. However, the area under the concentration curve from zero to infinity and maximal plasma concentration did not increase proportionally relative to the dose in horses.

Conclusions and Clinical Importance

Gabapentin exposure in plasma is not proportional relative to the dose in horses receiving nasogastric dosages of 10 to 160 mg/kg.

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<![CDATA[Platelet aggregometry testing during aspirin or clopidogrel treatment and measurement of clopidogrel metabolite concentrations in dogs with protein‐losing nephropathy]]> https://www.researchpad.co/product?articleinfo=Nd5f2d8af-edf6-49d8-990d-6756b2faaae2

Abstract

Background

Dogs with protein‐losing nephropathy (PLN) are treated with antiplatelet drugs for thromboprophylaxis but no standardized method exists to measure drug response. It is also unknown if clopidogrel metabolite concentrations [CM] differ between healthy and PLN dogs.

Objectives

Assess response to aspirin or clopidogrel in PLN dogs using platelet aggregometry (PA) and compare [CM] between healthy and PLN dogs.

Animals

Six healthy and 14 PLN dogs.

Methods

Platelet aggregometry using adenosine diphosphate (ADP), arachidonic acid (AA), and saline was performed in healthy dogs at baseline and 1‐week postclopidogrel administration to identify responders or nonresponders. A decrease of ≥60% for ADP or ≥30% for AA at 1 or 3 hours postpill was used to define a responder. At 1 and 3 hours postclopidogrel, [CM] and PA were measured in healthy and PLN dogs. Platelet aggregometry was performed in PLN dogs at baseline, 1, 6, and 12 weeks after clopidogrel or aspirin administration.

Results

In PLN dogs receiving clopidogrel, PA differed from baseline at all time points for ADP but not for AA at any time point. Most dogs responded at 1 or both time points except for 1 dog that showed no response. For PLN dogs receiving aspirin, no differences from baseline were observed at any time point for either ADP or AA. No differences in [CM] were found at either time point between healthy and PLN dogs.

Conclusions and Clinical Importance

Platelet aggregometry may represent an objective method to evaluate response to clopidogrel or aspirin treatment and PLN dogs appear to metabolize clopidogrel similarly to healthy dogs.

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<![CDATA[Paraoxonase‐1 activity evaluation as a diagnostic and prognostic marker in horses and foals]]> https://www.researchpad.co/product?articleinfo=Nd5a6c708-3e5e-44cb-8d82-0b6591b89782

Abstract

Background

In several species, paraoxonase‐1 (PON‐1) decreases during inflammation, because of the presence of oxidative stress; its measurement recently has been validated in horses, but its role as a clinical biomarker is unknown.

Objectives

To evaluate sensitivity, specificity and likelihood ratio of PON‐1 activity to identify systemic inflammatory response syndrome (SIRS)‐positive horses or horses with a poor prognosis.

Animals

One hundred seventy‐two blood samples from 58 sick horses from 3 different veterinary hospitals.

Methods

In a cross‐sectional study, PON‐1 activity was measured upon admission and at 24‐hour intervals until discharge or death, and results were analyzed based on SIRS status and outcome.

Results

No statistically significant difference was found in median PON‐1 activity between SIRS and non‐SIRS cases or between survivors and non‐survivors except for mares, in which PON‐1 activity was significantly lower in SIRS‐positive horses (P = .05). The sensitivity of PON‐1 activity in identifying horses with SIRS or negative outcome was low (0.0%‐46.2% depending on the examined group) but its specificity was high (87.0%‐100.0%). However, when PON‐1 is low, the likelihood of death is 2.40‐3.89 times higher than the likelihood of survival. Repeated measurement of PON‐1 after treatment does not predict outcome.

Conclusions and Clinical Importance

Evaluation of PON‐1 activity in horses with inflammation might be advisable in the future, but only low activity at admission may be relevant in predicting SIRS or negative outcome.

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<![CDATA[Detection and dynamics of anti‐platelet antibodies in thrombocytopenic dogs with and without idiopathic immune thrombocytopenia]]> https://www.researchpad.co/product?articleinfo=Nce62046c-90b0-47d0-8b84-b8d8fca70b4c

Abstract

Background

Antiplatelet antibodies are detected in multiple diseases including primary immune thrombocytopenia (ITP). Dynamics of how these antibodies change over time in ITP is unknown in dogs.

Hypothesis/Objectives

Antiplatelet antibodies (APA) will be detected in thrombocytopenic dogs with multiple etiologies and dynamics of APA in dogs with ITP can be used to evaluate response to treatment and relapse. Determine APA at the time of diagnosis in thrombocytopenic dogs and serially in primary ITP dogs.

Animals

Seventy‐nine thrombocytopenic dogs and 28 primary ITP dogs.

Methods

Direct flow cytometry was performed in thrombocytopenic dogs at initial evaluation and serially in suspected primary ITP dogs. In primary ITP dogs, a 2‐tailed Fisher's exact test was performed comparing survival to discharge between dogs with and without melena and to relate response to treatment and relapse to changes in APA and platelet count (repeated measures analysis, Spearman correlation).

Results

Twenty percent (16/79) of thrombocytopenic non‐ITP dogs with infectious, neoplastic, or other diseases and all primary ITP dogs were positive for APA. Melena at initial evaluation was associated with decreased survival to discharge (odds ratio 0.06; P = .01). Persistence of APA was not associated with response to treatment, but recurrence of antibodies was associated with relapse (odds ratio 205.0; P < .01). There was no difference in percentage of APA or platelet count at initial diagnosis between dogs that did or did not respond to treatment.

Conclusions and Clinical Importance

Serial monitoring of APA in dogs with primary ITP appeared beneficial for determining relapse of disease.

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<![CDATA[Eltrombopag treatment of a dog with idiopathic aplastic pancytopenia]]> https://www.researchpad.co/product?articleinfo=N634a78cf-eb7c-4c4a-a5dc-7dec9f8b144d

Abstract

Idiopathic aplastic pancytopenia is an uncommon disease in dogs which results in pancytopenia and for which an immune‐mediated etiology is suspected. A small number of affected dogs reported in the veterinary literature have responded to immunosuppressive medication but the prognosis generally is considered poor with a reported mortality rate of 80%. Reported response rates to immunosuppression alone in affected people are low with overall and complete responses of 65 and 10%, respectively. With the addition of eltrombopag, an orally available thrombopoietin receptor agonist, reported overall and complete response rates in people increase to 94 and 58%, respectively. Herein, we report the use of eltrombopag in a dog with idiopathic aplastic pancytopenia. Eltrombopag was started after no response was seen to treatment with prednisolone and cyclosporine. Complete remission was achieved after the addition of eltrombopag and was sustained after stopping the medication.

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<![CDATA[Adult Hemophagocytic Lymphohistiocytosis in Sub-Saharan Area: A Retrospective Study of 26 cases]]> https://www.researchpad.co/product?articleinfo=Nf8da7507-d6ac-4ff9-9778-10f176c57daf

Introduction and background

Hemophagocytic lymphohistiocytosis (HLH) is a condition caused by inappropriate stimulation of macrophage cells with hemophagocytosis. This paper aims to describe its diagnostic specifics and etiology and seeks to identify the factors that affect its prognosis in the black African adult population.

Methods 

A retrospective multicentre study was carried out in three medical units in Senegal: Department of Internal Medicine at Pikine Teaching Hospital, and Department of Internal Medicine and Department of Nephrology at Aristide Le Dantec Teaching Hospital; the study covered the period from January 1, 2012 to March 30, 2015. This study included patients aged 18 years and older with a Hemophagocytosis Score (HScore) of ≥202 (with probabilities of acquired HLH of >90%). The data was obtained through medical records.

Results

In total, 26 patient files were included. The average age of the patients was 41 years, with a male-to-female ratio of 2.25:1. Fever and cytopenia were frequent. Other clinical signs included peripheral lymphadenopathy (69.2%), hepatomegaly (53.8%), splenomegaly (34.6%), neurological disorders (34.5%), and respiratory disorders (15.3%). Thrombocytosis was noted in three cases. Renal involvement was present in eight patients, with one case of collapsing glomerulopathy. The bone marrow aspirate revealed myelodysplasia in 12 patients. The dominant etiologies of HLH were hematological malignancies and infections. The mortality rate of HLH was 73%. Male gender and non-etiological targeted therapy were significantly associated with mortality. However, the age of <40 years in patients and current systemic disease in some cases were correlated with survival. The use of etoposide had no significant impact on the prognosis of our patients.

Conclusion

A high rate of male predominance, important central nervous system disorders, myelodysplasia, and paradoxical thrombocytosis were found to be the distinct features of adult HLH in our study population.

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<![CDATA[Kasabach-Merritt Syndrome in an Adult]]> https://www.researchpad.co/product?articleinfo=N33c6bc23-fb10-4074-8fb9-2d205cc52f4d ]]>