ResearchPad - Hematology https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Clinical and Biochemical Assessment of Liver Function Test and Its Correlation with Serum Ferritin Levels in Transfusion-dependent Thalassemia Patients]]> https://www.researchpad.co/article/elastic_article_11605 Aims

The aim of our study was to correlate liver function tests with serum ferritin levels in multi-transfused thalassemia patients.

Methods 

This was a descriptive cross-sectional study conducted in the department of hematology, Khyber Medical University, from January 2018 to December 2018. Thalassemia patients of either sex dependent on transfusion ≥ 1 year and having a confirmatory report of the disease were included in our study. The nonprobability convenience sampling technique was used. The Pearson correlation coefficient was applied to observe the correlation between serum ferritin level and liver function tests. A p-value of ≤0.05 was considered statistically significant. SPSS version 23 (SPSS Inc., Chicago, Illinois) was used for data analysis.

Results

A total of 138 subjects of age range 2-23 years, with a mean age of 12.08 ± 6.02 years, were included in our study. The mean serum ferritin of patients in our study was 3278.64 ng/ml with the lowest of 285.2 ng/mL and the highest of 10940.2 ng/ml. With the increase in serum ferritin levels, a rapid increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels was seen. When serum ferritin levels were correlated with total bilirubin level, the bilirubin level remains static with a further increase in serum ferritin levels.

Conclusion

It was deduced that iron deposition is the ultimate reason for increased liver enzymes. There was a positive correlation between serum ferritin and ALT, AST, and ALP while a weak connection was found between serum ferritin and bilirubin levels.

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<![CDATA[Recurrent Venous Thromboembolism in a Patient with Klippel-Trenaunay Syndrome Despite Adequate Anticoagulation with Warfarin]]> https://www.researchpad.co/article/elastic_article_11582 Klippel-Trenaunay syndrome (KTS) is a rare genetic condition defined by capillary malformation, venous malformation, and soft tissue and bony overgrowth. Due to venous malformations, individuals are predisposed to intravascular coagulopathy leading to thrombosis and thromboembolism. However, anticoagulating these patients long-term remains a challenge because of the presence of capillary malformations that increase bleeding risk. We present a rare case of a 30-year-old Caucasian male with KTS and history of gastrointestinal bleeding who has been on anticoagulation since the age of 7 and has had three different inferior vena cava filters placed during his lifetime. At presentation, he had dyspnea with stable vital signs. His prothrombin time/international normalized ratio was 37.3 and 3.2, respectively and chest computed tomography showed bilateral segmental pulmonary embolism (PE). He was treated with heparin drip and his home anticoagulation was switched from warfarin to apixaban at the time of discharge for better anticoagulation optimization. KTS is a condition associated with venous thromboembolic complications that can be difficult to manage. PE should remain on the top of the list of differential diagnoses in patients with KTS presenting with dyspnea even if laboratory findings suggest an alternate diagnosis.

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<![CDATA[Argatroban Treatment and Decreased Fibrinogen in a Septic Patient]]> https://www.researchpad.co/article/elastic_article_11578 Disseminated intravascular coagulation (DIC) is a consumptive coagulopathy associated with multiple conditions. Diagnosis is based upon clinical and laboratory findings with assessment of fibrinogen, platelets, D-dimer, prothrombin time/international normalized ratio and activated partial thromboplastin time. Herein, we report a case of a 39-year-old female patient diagnosed with endocarditis complicated by pulmonary septic emboli. For anticoagulation, the patient initially was treated with a heparin drip, but the patient remained subtherapeutic despite increasing dosage. The patient was transitioned to argatroban and developed an acute drop in the fibrinogen level. With concern for possible DIC, argatroban was held with a repeat panel six hours later revealing a significantly improved fibrinogen level. It was discovered that the Clauss method, which measures the capability of fibrinogen to form a clot after a high concentration of thrombin is added to diluted plasma, was used to measure fibrinogen at our institute. Argatroban may falsely reduce measured fibrinogen levels in vitro, caused by this method.

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<![CDATA[Administration of lower doses of radium-224 to ankylosing spondylitis patients results in no evidence of significant overall detriment]]> https://www.researchpad.co/article/elastic_article_11232 The use of low doses of radium-224 (224Ra) chloride for the treatment of ankylosing spondylitis was stopped following the discovery that patients treated with it had a higher than control incidence of leukaemia and other cancers. This was so even though the treatment resulted in decreased pain and increased mobility–both of which are associated with decreased mortality. It was decided to re-analyze the epidemiological data looking at all causes of death. The risk of leukaemia, solid cancer, death from non-cancer causes and from all causes in a study populations of men that received either the typical dose of 5.6 to 11.1 MBq of 224Ra, any dose of 224Ra or no radium were compared using the Cox proportional hazard model. For patients that received the typical dose of 224Ra agreed with the excess cancer was similar to that reported in previous studies. In contrast, these patients were less likely to die from non-cancer diseases and from all causes of death than the control patients. No excess mortality was also found in the population of all males that received the radionuclide. It is concluded that 224Ra treatment administered at low doses to patients with ankylosing spondylitis did not impact mortality from all causes. The study demonstrates the need to consider all causes of death and longevity when assessing health impacts following irradiation.

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<![CDATA[Hyperhomocysteinemia and Pulmonary Embolism in a Young Male]]> https://www.researchpad.co/article/elastic_article_10531 The association of hyperhomocysteinemia with thrombosis has provoked debate in the medical literature. Although studies have found associations between moderate homocysteine elevations and thrombotic events, others dispute this relationship. We present herein the case of a 24-year-old male who presented with unprovoked bilateral submassive pulmonary emboli. Extensive hypercoagulability workup was notable for an elevated homocysteine level, in addition to low vitamin B12 and folate levels. Of note, the patient had a history of small bowel resection after trauma, which may have contributed to the aforementioned metabolic derangements, potentially increasing his risk for thrombosis and interfering with the efficacy of his anticoagulation.

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<![CDATA[Complete Molecular Response in Chronic Myeloid Leukemia After Six Months of Imatinib: A Single Center Experience]]> https://www.researchpad.co/article/elastic_article_10506 Introduction: The hallmark of chronic myeloid leukemia (CML) is the development of the fusion gene, BCR-ABL which has unopposed tyrosine kinase activity. The first tyrosine kinase inhibitor (TKI) imatinib is claimed to have superior efficacy and side effect profile as compared to traditional treatment options. This study was conducted to see our patients’ molecular response to imatinib treatment. The objective of this study was to determine the frequency of complete molecular response in patients after six months of imatinib therapy.

Methods: A descriptive case series was designed and conducted in Oncology department, Jinnah hospital Lahore (May-November 2016). Newly diagnosed patients of CML aged between 20 and 65 years were enrolled. They were prescribed 400 mg imatinib daily and complete molecular response was assessed after six months of treatment.

Results: Mean age was 39.76 ± 9.072 years. Some 66 of them were males while 69 were females. Some 40 patients (29.6%) were found to be in complete molecular response after six months of imatinib therapy.

Conclusion: Imatinib at a dose of 400 mg/day is optimal as the primary therapy for CML.

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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/article/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[The Role of Blood Viscosity in Infectious Diseases]]> https://www.researchpad.co/article/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[Rosuvastatin Use Implicated in the Drug Reaction with Eosinophilia and Systemic Symptoms]]> https://www.researchpad.co/article/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[Paraoxonase‐1 activity evaluation as a diagnostic and prognostic marker in horses and foals]]> https://www.researchpad.co/article/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[Plasma disposition of gabapentin after the intragastric administration of escalating doses to adult horses]]> https://www.researchpad.co/article/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[Detection and dynamics of anti‐platelet antibodies in thrombocytopenic dogs with and without idiopathic immune thrombocytopenia]]> https://www.researchpad.co/article/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[Platelet aggregometry testing during aspirin or clopidogrel treatment and measurement of clopidogrel metabolite concentrations in dogs with protein‐losing nephropathy]]> https://www.researchpad.co/article/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[Eltrombopag treatment of a dog with idiopathic aplastic pancytopenia]]> https://www.researchpad.co/article/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[Clinical, Laboratory, and Bone Marrow Findings of 31 Patients With Waldenström Macroglobulinemia]]> https://www.researchpad.co/article/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/article/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[Effects of amotosalen treatment on human platelet lysate bioactivity: A proof-of-concept study]]> https://www.researchpad.co/article/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[Nocturnal hypercapnia with daytime normocapnia in patients with advanced pulmonary arterial hypertension awaiting lung transplantation]]> https://www.researchpad.co/article/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[Isoniazid Induced Pure Red Blood Cell Aplasia]]> https://www.researchpad.co/article/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/article/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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