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1.
Vet Parasitol Reg Stud Reports ; 51: 101027, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38772643

ABSTRACT

Canine tick-borne diseases, such as babesiosis, rangeliosis, hepatozoonosis, anaplasmosis and ehrlichiosis, are of veterinarian relevance, causing mild or severe clinical cases that can lead to the death of the dog. The aim of this study was detecting tick-borne protozoan and rickettsial infections in dogs with anemia and/or thrombocytopenia in Uruguay. A total of 803 domestic dogs were evaluated, and 10% were found positive (detected by PCR) at least for one hemoparasite. Sequence analysis confirmed the presence of four hemoprotozoan species: Rangelia vitalii, Babesia vogeli, Hepatozoon canis and Hepatozoon americanum, and the rickettsial Anaplasma platys. The most detected hemoparasite was R. vitalii, followed by H. canis and A. platys. This is the first report of B. vogeli in Uruguay and the second report of H. americanum in dogs from South America. The results highlight the importance for veterinarians to include hemoparasitic diseases in their differential diagnosis of agents causing anemia and thrombocytopenia.


Subject(s)
Anemia , Dog Diseases , Piroplasmida , Thrombocytopenia , Animals , Uruguay , Dogs , Dog Diseases/parasitology , Dog Diseases/diagnosis , Dog Diseases/epidemiology , Thrombocytopenia/veterinary , Thrombocytopenia/parasitology , Anemia/veterinary , Anemia/parasitology , Piroplasmida/isolation & purification , Piroplasmida/genetics , Female , Anaplasmataceae/isolation & purification , Anaplasmataceae/genetics , Male , Anaplasmataceae Infections/veterinary , Anaplasmataceae Infections/epidemiology , Anaplasma/isolation & purification , Anaplasma/genetics , Babesiosis/parasitology , Babesiosis/diagnosis , Coccidiosis/veterinary , Coccidiosis/parasitology , Eucoccidiida/isolation & purification , Eucoccidiida/genetics , Tick-Borne Diseases/veterinary , Tick-Borne Diseases/parasitology , Tick-Borne Diseases/microbiology , Tick-Borne Diseases/epidemiology , Babesia/isolation & purification , Protozoan Infections, Animal/parasitology , Protozoan Infections, Animal/epidemiology , Polymerase Chain Reaction/veterinary
2.
J Pak Med Assoc ; 74(5): 911-916, 2024 May.
Article in English | MEDLINE | ID: mdl-38783439

ABSTRACT

OBJECTIVE: To compare the extent of cytopenias and systemic immune inflammation index of hospitalised coronavirus disease-2019 patients during the first and second/third waves of the pandemic. Methods: The retrospective, cross-sectional study was conducted in October 2021 at Fatima Memorial Hospital, Lahore, Pakistan, and comprised data of hospitalised coronavirus disease-2019 patients regardless of age and gender from May 2020 to June 2021. Data was segregated into first wave that lasted from May to July 2020, second wave that lasted from early November to mid-December 2020, and third wave that ranged from mid-March to June 2021. For comparison purposes, the data of first wave was in group A, while data of second and third waves was pooled into group B. Age, gender, comorbidities, requirement of ventilator support and outcome of the patients was noted. Inflammatory markers were compared on the basis of complete blood count and systemic immune-inflammation index data. Data was analysed using SPSS 25. RESULTS: Of the 202 patients, 90(44.5%) were in group A and 112(55.4%) were in group B. There were 108(53.5%) males and 94(46.5%) females. The median age in males was 58 years (interquartile range: 21 years) and it was 56 years (interquartile range: 21 years) in females. Neutrophilia (p<0.001), leukocytosis (p<0.001) and lymphocytopenia (p<0.001) had direct association with increased systemic immune-inflammation. Raised systemic immune-inflammation also had an association with increased requirement of ventilator support (p=0.2) and increased mortality (p=0.001). There were more females, more critical patients, more patients with anaemia, leukopenia, lymphocytopenia and thrombocytopenia in group B compared to group A (p<0.05). Need for ventilator support and mortality were also higher in group B compared to group A (p<0.05). Conclusion: All the indicators analysed were worse during the second and third waves of coronavirus disease-2019 compared to the first wave of the pandemic.


Subject(s)
COVID-19 , SARS-CoV-2 , Thrombocytopenia , Humans , COVID-19/immunology , COVID-19/therapy , COVID-19/epidemiology , Male , Female , Middle Aged , Retrospective Studies , Cross-Sectional Studies , Pakistan/epidemiology , SARS-CoV-2/immunology , Adult , Aged , Thrombocytopenia/epidemiology , Thrombocytopenia/immunology , Hospitalization/statistics & numerical data , Leukopenia/epidemiology , Lymphopenia/immunology , Respiration, Artificial/statistics & numerical data , Inflammation/immunology , Cytopenia
3.
Saudi Med J ; 45(5): 495-501, 2024 May.
Article in English | MEDLINE | ID: mdl-38734423

ABSTRACT

OBJECTIVES: To investigate the prevalence of hematologic findings and the relationship between hemogram parameters and brucellosis stages in patients. METHODS: This multi-center study included patients older than 16 years of age who were followed up with a diagnosis of brucellosis. Patients' results, including white blood cell, hemoglobin, neutrophil, lymphocyte, monocyte, mean platelet volume, platelet and eosinophil counts were analyzed at the initial diagnosis. RESULTS: In this study 51.3% of the patients diagnosed with brucellosis were male. The age median was 45 years for female and 41 years for male. A total of 55.1% of the patients had acute brucellosis, 28.2% had subacute, 7.4% had chronic and 9% had relapse. The most common hematologic findings in brucellosis patients were anemia (25.9%), monocytosis (15.9%), eosinopenia (10.3%), and leukocytosis (7.1%). Pancytopenia occurred in 0.8% of patients and was more prominent in the acute phase. The acute brucellosis group had lower white blood cell, hemoglobin, neutrophil, eosinophil, and platelet counts and mean platelet volume, and higher monocyte counts compared to subacute and chronic subgroups. CONCLUSION: It was noteworthy that in addition to anemia and monocytosis, eosinopenia was third most prominent laboratory findings in the study. Pancytopenia and thrombocytopenia rates were low.


Subject(s)
Brucellosis , Humans , Brucellosis/epidemiology , Brucellosis/blood , Brucellosis/complications , Male , Female , Adult , Middle Aged , Turkey/epidemiology , Young Adult , Thrombocytopenia/epidemiology , Thrombocytopenia/blood , Adolescent , Aged , Anemia/epidemiology , Anemia/blood , Anemia/etiology , Blood Cell Count
4.
Zhonghua Zhong Liu Za Zhi ; 46(5): 419-427, 2024 May 23.
Article in Chinese | MEDLINE | ID: mdl-38742355

ABSTRACT

Objective: To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis. Methods: A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis. Results: The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P<0.001; 77.78% vs 16.84% for bone metastasis, P<0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs<111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant (P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups (P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs<111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage (HR=2.806, 95%CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH (HR=1.841, 95%CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS (HR=2.538, 95%CI:1.169-5.512, P=0.019). Conclusions: Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.


Subject(s)
Bone Marrow , Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Small Cell Lung Carcinoma/pathology , Lung Neoplasms/pathology , Prognosis , Bone Marrow/pathology , Prospective Studies , Female , Male , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Bone Neoplasms/secondary , Middle Aged , Bone Marrow Neoplasms/secondary , Survival Rate , Bone Marrow Cells , Aged , Thrombocytopenia , Proportional Hazards Models , Kaplan-Meier Estimate , Clinical Relevance
5.
Int J Mol Sci ; 25(9)2024 May 01.
Article in English | MEDLINE | ID: mdl-38732176

ABSTRACT

Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low platelet counts are referred to as thrombosis with thrombocytopenia syndrome, including heparin-induced thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia, paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, thrombotic microangiopathy (TMA), and disseminated intravascular coagulation. TMA includes thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (HUS), and atypical HUS. Patients with these pathologies present with thrombosis and consumptive thrombocytopenia associated with the activation of platelets and the coagulation system. Treatment varies from disease to disease, and many diseases have direct impacts on mortality and organ prognosis if therapeutic interventions are not promptly implemented. Underlying diseases and the results of physical examinations and general laboratory tests as part of a thorough workup for patients should promptly lead to therapeutic intervention before definitive diagnosis. For some diseases, the diagnosis and initial treatment must proceed in parallel. Utilization of not only laboratory tests but also various scoring systems is important for validating therapeutic interventions based on clinical information.


Subject(s)
Thrombocytopenia , Thrombosis , Humans , Thrombocytopenia/diagnosis , Thrombosis/etiology , Blood Platelets/metabolism , Platelet Count , Heparin/therapeutic use , Thrombotic Microangiopathies/diagnosis , Thrombotic Microangiopathies/etiology , Thrombotic Microangiopathies/blood
7.
Sci Rep ; 14(1): 11262, 2024 05 17.
Article in English | MEDLINE | ID: mdl-38760419

ABSTRACT

With its increasing use in the treatment of thrombocytopenia, avatrombopag's associated adverse events (AEs) pose a major challenge to its clinical application. This study aims to comprehensively study AEs associated with avatrombopag by using real-world evidence. We curated AE reports for avatrombopag from the first quarter of 2018 to the fourth quarter of 2023 in the US Food and Drug Administration's Adverse Event Reporting System (FAERS) database. AEs were coded using the Medical Dictionary for Regulatory Activities of Preferred Terms and System Organ Classes. The reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item Gamma-Poisson Shrinker were used to investigate the relationship between avatrombopag and AE reports. Among 9,060,312 reported cases in the FAERS database, 1211 reports listed avatrombopag as "primary suspected" drug. Disproportionality analysis identified 44 preferred terms across 17 organ systems met the criteria for at least one of the four algorithms. The most commonly reported AEs were platelet count decreased (20.2%), headache (16.7%), platelet count increased (11.9%), platelet count abnormal (6.3%), contusion (2.7%), pulmonary embolism (2.3%), and deep vein thrombosis (2.1%). Unexpected AEs such as seasonal allergy, rhinorrhea, antiphospholipid syndrome, ear discomfort, and photopsia were also observed. Excluding the other serious outcomes, hospitalization (34.6%) was the most frequently reported serious outcome, followed by death (15.4%). Most reported AEs occurred within the first 2 days of initiating avatrombopag therapy, and the median onset time was 60 days. We identified new and unexpected AEs with clinical use of avatrombopag, and our results may provide valuable information for clinical monitoring and identifying risks associated with avatrombopag.


Subject(s)
Adverse Drug Reaction Reporting Systems , Data Mining , Pharmacovigilance , United States Food and Drug Administration , Humans , United States/epidemiology , Retrospective Studies , Male , Female , Middle Aged , Aged , Adult , Thrombocytopenia/chemically induced , Thrombocytopenia/epidemiology , Databases, Factual , Thiazoles/adverse effects , Young Adult , Adolescent , Child , Thiophenes
8.
PLoS One ; 19(5): e0301359, 2024.
Article in English | MEDLINE | ID: mdl-38787838

ABSTRACT

BACKGROUND: Thrombosis with thrombocytopenia syndrome (TTS) is a very rare prothrombotic disorder that is a safety concern for some COVID-19 vaccines. We aimed to devise a case definition to estimate the incidence of thrombosis with thrombocytopenia as a proxy for TTS in a national insurance claims database. METHODS: We conducted a retrospective observational study using the National Health Insurance Research Database (NHIRD) in Taiwan over the three-year period prior to the SARS-COV-2 pandemic (2017-2019). Our case definition was all patients with newly diagnosed thrombosis co-occurring with a diagnosis of thrombocytopenia within seven days before or after the thrombosis diagnosis. Cases were identified using International Classification of Disease-10 codes. FINDINGS: We identified 2010 patients with newly diagnosed thrombosis co-occurring with thrombocytopenia during the study period. The mean age was 64.71 years; female:male ratio 1:1.45. The most frequent thrombotic events were coronary artery disease (18.81%), cerebral infarction (16.87%), and disseminated intravascular coagulation (13.13%). Cerebral venous sinus thrombosis was rare (<0.1%). The average annual incidence rate of co-occurring new diagnoses of thrombosis and thrombocytopenia was 2.84 per 100 000 population. Incidence rates were higher in men than women, except in 20-39 year-olds (higher in females). 20.6% of patients died within the first month after diagnosis. INTERPRETATION: We observed that the demographic and clinical characteristics of thrombosis with co-occurring thrombocytopenia using our case definition is different from that of TTS. Further research is needed to refine the case definition of TTS in the post-COVID-19 vaccination period.


Subject(s)
COVID-19 , Thrombocytopenia , Thrombosis , Humans , Female , Male , Middle Aged , COVID-19/complications , COVID-19/epidemiology , Thrombocytopenia/epidemiology , Thrombocytopenia/complications , Incidence , Thrombosis/epidemiology , Thrombosis/etiology , Thrombosis/complications , Aged , Retrospective Studies , Taiwan/epidemiology , Adult , SARS-CoV-2/isolation & purification , Young Adult , Aged, 80 and over , Databases, Factual , Adolescent , Pandemics
9.
Medicine (Baltimore) ; 103(21): e38304, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38788032

ABSTRACT

RATIONALE: Miller-Fisher syndrome (MFS) is a rare subtype of Guillain-Barre syndrome with classic features of ataxia, areflexia, and ophthalmoplegia that can be caused by a preceding infection including COVID-19. We present a current, asymptomatic thrombocytopenic COVID-19 infection as a cause of MFS in a 60-year-old male with a concurrent chronic immune neuropathy. PATIENT CONCERNS: A 60-year-old male presenting with acute symptoms of MFS including ataxia, areflexia, and ophthalmoplegia on a chronic immune neuropathy for at least 1 year and concurrent asymptomatic COVID-19 positive infection. DIAGNOSIS: MFS suspected secondary to a current thrombocytopenic COVID-19 infection. INTERVENTIONS: Five days of intravenous immune globulin with continued monthly intravenous immune globulin as an outpatient, follow-up long-term in a neuromuscular clinic, electromyography as an outpatient, and continued physical therapy. OUTCOMES: The patient significantly improved after initial treatment. LESSONS: The full effect of COVID-19 on the various Guillain-Barre syndrome subtypes is unknown, although it clearly can be a cause of the various variants including being caused by a current, asymptomatic infection.


Subject(s)
COVID-19 , Immunoglobulins, Intravenous , Miller Fisher Syndrome , Humans , Miller Fisher Syndrome/diagnosis , Miller Fisher Syndrome/immunology , Male , COVID-19/complications , COVID-19/immunology , Middle Aged , Immunoglobulins, Intravenous/therapeutic use , SARS-CoV-2 , Thrombocytopenia
11.
Clin Lab ; 70(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38747921

ABSTRACT

BACKGROUND: Pseudothrombocytopenia (PTCP) can be caused by anticoagulants or pre-analytical issues. The authors present a case of PTCP attributed to pre-analytical issues in a 68-year-old male patient. METHODS: The platelet count results were obtained using both the impedance and fluorescence channels of Sysmex XN-10. The blood film was scanned using both Cellavision DM96 and a microscope. RESULTS: The flag for PLT-Clumps and the scattergram from the PLT-F channel indicated the presence of platelet aggregation. Fibrin could be observed at the feathered end of the blood film. A diagnosis of PTCP resulting from pre-analytical issues was made. CONCLUSIONS: The presence of fibrin in a blood film is a critical indicator for diagnosing PTCP due to pre-analytical issues.


Subject(s)
Fibrin , Thrombocytopenia , Humans , Male , Aged , Thrombocytopenia/blood , Thrombocytopenia/diagnosis , Fibrin/metabolism , Fibrin/analysis , Platelet Count/methods , Anticoagulants , Platelet Aggregation , Blood Platelets
12.
J Cardiothorac Surg ; 19(1): 219, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627820

ABSTRACT

OBJECTIVES: Thrombocytopenia following Perceval aortic valve replacement has been described previously with variable outcome. Studies have lacked a robust analysis of platelet fluctuation and factors affecting it. We aimed to statistically describe the trend in thrombocyte variability as compared with conventional aortic valve replacement, and to assess predictors as well as impact on associated outcomes. METHODS: One hundred consecutive patients with first-time Perceval were retrospectively compared to 219 patients after Perimount Magna Ease valve replacement. The primary outcome was the serial thrombocyte count on day 0-6. Generalized estimating equations were used to analyse the data using fixed-effect models: for the effect of the post-operative day on platelet count, and random-effect models estimating both time-variant (platelets) and time in-variant variables (valve type, age, LV function, pre-op platelet level). RESULTS: Perceval patients were older (72 ± 1 vs 68 ± 1 years, p < 0.01) with higher NYHA status (3(2-3) vs 2(1-2), p < 0.001). Mean platelet count in the sutureless group was lowest on day 2 (91.9 ± 31.6 vs 121.7 ± 53.8 × 103 µl-1), and lower on day 4 (97.9 ± 44) and 6 (110.6 ± 61) compared to the conventional group (157.2 ± 60 and 181.7 ± 79) but did not result in a higher number of transfusions, bleeding or longer hospital stay (p > 0.05). Reduced platelet count was a strong predictor of red cell transfusion in the conventional (p = 0.016), but not in the sutureless group (p = 0.457). Age (Coef -1.025, 95%CI-1.649--0.401, p < 0.001) and CPB-time (Coef 0.186, 95%CI-0.371--0.001, p = 0.048) were predictors for lower platelet levels. CONCLUSION: Considering the older patient profile treated with Perceval, postoperative thrombocytopenia does not impact on outcome in terms of transfusions, complications or hospital stay.


Subject(s)
Aortic Valve Stenosis , Bioprosthesis , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Thrombocytopenia , Humans , Aortic Valve/surgery , Retrospective Studies , Heart Valve Prosthesis Implantation/adverse effects , Aortic Valve Stenosis/surgery , Treatment Outcome , Bioprosthesis/adverse effects , Prosthesis Design , Heart Valve Prosthesis/adverse effects , Thrombocytopenia/etiology , Risk Factors , Disease Progression
13.
Sci Rep ; 14(1): 9705, 2024 04 27.
Article in English | MEDLINE | ID: mdl-38678158

ABSTRACT

The primary triggers that stimulate the body to generate platelet antibodies via immune mechanisms encompass events such as pregnancy, transplantation, and blood transfusion. Interestingly, our findings revealed that a subset of male patients with hepatocellular carcinoma (HCC), despite having no history of transplantation or blood transfusion, has shown positive results in platelet antibody screenings. This hints at the possibility that certain factors, potentially related to the tumor itself or its treatment, may affect antibody production. To delve the causes we initiated this study. We employed a case-control study approach to analyze potential influential factors leading to the positive results via univariate and multivariate regression analysis. We utilized Kendall's tau-b correlation to examine the relationship between the strength of platelet antibodies and peripheral blood cytopenia. Antitumor medication emerged as an independent risk factor for positive results in HCC patients, and the strength of platelet antibodies positively correlated with the severity of anemia and thrombocytopenia. Without history of blood transfusion, transplantation, pregnancy, those HCC patients underwent recent tumor medication therapy are experiencing peripheral erythrocytopenia or thrombocytopenia, for them platelet antibody screenings holds potential clinical value for prevention and treatment of complications like drug-immune-related anemia and/or bleeding.


Subject(s)
Blood Platelets , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/immunology , Liver Neoplasms/blood , Liver Neoplasms/immunology , Male , Female , Middle Aged , Blood Platelets/immunology , Case-Control Studies , Thrombocytopenia/blood , Thrombocytopenia/immunology , Thrombocytopenia/etiology , Aged , Adult , Autoantibodies/blood , Autoantibodies/immunology , Anemia/blood , Anemia/immunology , Risk Factors , Cytopenia
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(4): 410-413, 2024 Apr 15.
Article in Chinese | MEDLINE | ID: mdl-38660906

ABSTRACT

The first patient, a 10-year-old girl, presented with pancytopenia and recurrent epistaxis, along with a history of repeated upper respiratory infections, café-au-lait spots, and microcephaly. Genetic testing revealed compound heterozygous mutations in the DNA ligase IV (LIG4) gene, leading to a diagnosis of LIG4 syndrome. The second patient, a 6-year-old girl, was seen for persistent thrombocytopenia lasting over two years and was noted to have short stature, hyperpigmented skin, and hand malformations. She had a positive result from chromosome breakage test. She was diagnosed with Fanconi anemia complementation group A. Despite similar clinical presentations, the two children were diagnosed with different disorders, suggesting that children with hemocytopenia and malformations should not only be evaluated for hematological diseases but also be screened for other potential underlying conditions such as immune system disorders.


Subject(s)
Abnormalities, Multiple , Humans , Female , Child , Abnormalities, Multiple/genetics , Pancytopenia/etiology , Pancytopenia/genetics , DNA Ligase ATP/genetics , DNA Ligase ATP/deficiency , Thrombocytopenia/genetics , Thrombocytopenia/etiology , Cytopenia
15.
Biomolecules ; 14(4)2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38672505

ABSTRACT

Thrombopoietin, the primary regulator of blood platelet production, was postulated to exist in 1958, but was only proven to exist when the cDNA for the hormone was cloned in 1994. Since its initial cloning and characterization, the hormone has revealed many surprises. For example, instead of acting as the postulated differentiation factor for platelet precursors, megakaryocytes, it is the most potent stimulator of megakaryocyte progenitor expansion known. Moreover, it also stimulates the survival, and in combination with stem cell factor leads to the expansion of hematopoietic stem cells. All of these growth-promoting activities have resulted in its clinical use in patients with thrombocytopenia and aplastic anemia, although the clinical development of the native molecule illustrated that "it's not wise to mess with mother nature", as a highly engineered version of the native hormone led to autoantibody formation and severe thrombocytopenia. Finally, another unexpected finding was the role of the thrombopoietin receptor in stem cell biology, including the development of myeloproliferative neoplasms, an important disorder of hematopoietic stem cells. Overall, the past 30 years of clinical and basic research has yielded many important insights, which are reviewed in this paper.


Subject(s)
Blood Platelets , Thrombopoietin , Thrombopoietin/metabolism , Humans , Blood Platelets/metabolism , Animals , Receptors, Thrombopoietin/metabolism , Receptors, Thrombopoietin/genetics , Thrombopoiesis , Thrombocytopenia/metabolism , Megakaryocytes/metabolism , Megakaryocytes/cytology
16.
J Stroke Cerebrovasc Dis ; 33(6): 107310, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38636321

ABSTRACT

OBJECTIVES: Heparin-induced thrombocytopenia is a known complication of heparin exposure with potentially life-threatening sequelae. Direct thrombin inhibitors can be substituted for heparin in patients with heparin-induced thrombocytopenia that require anticoagulation. However, the use of direct thrombin inhibitors as a substitute for heparin has not been widely reported in the neuroendovascular literature. MATERIALS AND METHODS: Here we report the first use of the direct thrombin inhibitor bivalirudin in a neuroendovascular procedure as a substitute for heparin in a patient with a ruptured pseudoaneurysm and heparin-induced thrombocytopenia, and review the literature on the use of bivalirudin and argatroban for such patients. RESULTS: Bivalirudin was safely and effectively used in the case reported, with no thrombotic or hemorrhagic complications. Our literature review revealed a paucity of studies on the use of heparin alternatives, including bivalirudin, in neuroendovascular procedures in patients with heparin-induced thrombocytopenia. CONCLUSIONS: Heparin-induced thrombocytopenia is an important iatrogenic disease process in patients undergoing neuroendovascular procedures, and developing protocols to diagnose and manage heparin-induced thrombocytopenia is important for healthcare systems. While further research needs to be done to establish the full range of anticoagulation options to substitute for heparin, our case indicates bivalirudin as a potential candidate.


Subject(s)
Anticoagulants , Antithrombins , Heparin , Hirudins , Peptide Fragments , Recombinant Proteins , Thrombocytopenia , Humans , Male , Middle Aged , Aneurysm, False/surgery , Aneurysm, False/drug therapy , Aneurysm, Ruptured/surgery , Aneurysm, Ruptured/diagnostic imaging , Anticoagulants/adverse effects , Antithrombins/adverse effects , Antithrombins/therapeutic use , Drug Substitution , Endovascular Procedures/adverse effects , Heparin/adverse effects , Intracranial Aneurysm/surgery , Intracranial Aneurysm/drug therapy , Peptide Fragments/therapeutic use , Peptide Fragments/adverse effects , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Recombinant Proteins/administration & dosage , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombocytopenia/drug therapy , Treatment Outcome
17.
Biochem Biophys Res Commun ; 715: 150004, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38678784

ABSTRACT

Megakaryopoiesis and platelet production is a complex process that is underpotential regulation at multiple stages. Many long non-coding RNAs (lncRNAs) are distributed in hematopoietic stem cells and platelets. lncRNAs may play important roles as key epigenetic regulators in megakaryocyte differentiation and proplatelet formation. lncRNA NORAD can affect cell ploidy by sequestering PUMILIO proteins, although its direct effect on megakaryocyte differentiation and thrombopoiesis is still unknown. In this study, we demonstrate NORAD RNA is highly expressed in the cytoplasm during megakaryocyte differentiation. Interestingly, we identified for the first time that NORAD has a strong inhibitory effect on megakaryocyte differentiation and proplatelet formation from cultured megakaryocytes. DUSP6/ERK1/2 pathway is activated in response to NORAD knockdown during megakaryocytopoiesis, which is achieved by sequestering PUM2 proteins. Finally, compared with the wild-type control mice, NORAD knockout mice show a faster platelet recovery after severe thrombocytopenia induced by 6 Gy total body irradiation. These findings demonstrate lncRNA NORAD has a key role in regulating megakaryocyte differentiation and thrombopoiesis, which provides a promising molecular target for the treatment of platelet-related diseases such as severe thrombocytopenia.


Subject(s)
Blood Platelets , Cell Differentiation , Dual Specificity Phosphatase 6 , Megakaryocytes , Mice, Knockout , RNA, Long Noncoding , Thrombopoiesis , Megakaryocytes/metabolism , Megakaryocytes/cytology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Animals , Thrombopoiesis/genetics , Blood Platelets/metabolism , Mice , Dual Specificity Phosphatase 6/metabolism , Dual Specificity Phosphatase 6/genetics , MAP Kinase Signaling System , Thrombocytopenia/genetics , Thrombocytopenia/metabolism , Thrombocytopenia/pathology , Humans , Mice, Inbred C57BL , Cells, Cultured
18.
Clin Drug Investig ; 44(5): 357-366, 2024 May.
Article in English | MEDLINE | ID: mdl-38684605

ABSTRACT

BACKGROUND: Chemotherapy-induced thrombocytopenia is often a use-limiting adverse reaction to gemcitabine and cisplatin (GC) combination chemotherapy, reducing therapeutic intensity, and, in some cases, requiring platelet transfusion. OBJECTIVE: A retrospective cohort study was conducted on patients with urothelial cancer at the initiation of GC combination therapy and the objective was to develop a prediction model for the incidence of severe thrombocytopenia using machine learning. METHODS: We performed receiver operating characteristic analysis to determine the cut-off values of the associated factors. Multivariate analyses were conducted to identify risk factors associated with the occurrence of severe thrombocytopenia. The prediction model was constructed from an ensemble model and gradient-boosted decision trees to estimate the risk of an outcome using the risk factors associated with the occurrence of severe thrombocytopenia. RESULTS: Of 186 patients included in this study, 46 (25%) experienced severe thrombocytopenia induced by GC therapy. Multivariate analyses revealed that platelet count ≤ 21.4 (×104/µL) [odds ratio 7.19, p < 0.01], hemoglobin ≤ 12.1 (g/dL) [odds ratio 2.41, p = 0.03], lymphocyte count ≤ 1.458 (×103/µL) [odds ratio 2.47, p = 0.02], and dose of gemcitabine ≥ 775.245 (mg/m2) [odds ratio 4.00, p < 0.01] were risk factors of severe thrombocytopenia. The performance of the prediction model using these associated factors was high (area under the curve 0.76, accuracy 0.82, precision 0.68, recall 0.50, and F-measure 0.58). CONCLUSIONS: Platelet count, hemoglobin level, lymphocyte count, and gemcitabine dose contributed to the development of a novel prediction model to identify the incidence of GC-induced severe thrombocytopenia.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Cisplatin , Deoxycytidine , Gemcitabine , Thrombocytopenia , Humans , Deoxycytidine/analogs & derivatives , Deoxycytidine/adverse effects , Deoxycytidine/administration & dosage , Thrombocytopenia/chemically induced , Thrombocytopenia/epidemiology , Thrombocytopenia/diagnosis , Cisplatin/adverse effects , Cisplatin/administration & dosage , Male , Female , Retrospective Studies , Aged , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Urologic Neoplasms/drug therapy , Platelet Count , Risk Factors , Machine Learning
20.
In Vivo ; 38(3): 1243-1252, 2024.
Article in English | MEDLINE | ID: mdl-38688620

ABSTRACT

BACKGROUND/AIM: Capecitabine plus oxaliplatin (CapeOX) therapy is used as an adjuvant chemotherapy regimen for patients with colorectal cancer (CRC). Although oxaliplatin induces thrombocytopenia, the risk factors for thrombocytopenia in oxaliplatin-treated patients with CRC are not well established. We aimed to investigate the risk factors for thrombocytopenia in CapeOX-treated patients with CRC. In addition, we evaluated platelet counts and non-invasive liver fibrosis indices, specifically the aspartate aminotransferase-to-platelet ratio index (APRI) and the fibrosis-4 index (FIB-4), during CapeOX therapy in these patients. PATIENTS AND METHODS: Between July 2017 and June 2020, we enrolled CapeOX-treated patients with high-risk stage II or stage III CRC at seven hospitals collaborating with the Division of Oncology, Aichi Prefectural Society of Hospital Pharmacists (Aichi prefecture, Japan). In this retrospective study, we investigated patients' backgrounds, laboratory data, concomitant medications, number of cycles of CapeOX and oxaliplatin, cumulative dose of oxaliplatin, and administration period. The cut-off values were calculated using receiver operating characteristic analysis of platelet counts and APRI and FIB-4 scores. RESULTS: Fifty-five patients without thrombocytopenia and 44 patients with thrombocytopenia were enrolled. During CapeOX therapy, the thrombocytopenia group showed a significant decrease in platelet count and a significant increase in APRI and FIB-4 scores compared to the non-thrombocytopenia group. Baseline albumin level ≤3.5 g/dl and platelet count ≤238×103/µl were independently associated with ≥grade 2 thrombocytopenia in CapeOX-treated patients. CONCLUSION: Baseline albumin level and platelet count may be useful for predicting thrombocytopenia in CapeOX-treated patients with high-risk stage II or stage III CRC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Capecitabine , Colorectal Neoplasms , Oxaliplatin , Thrombocytopenia , Humans , Capecitabine/adverse effects , Capecitabine/administration & dosage , Thrombocytopenia/chemically induced , Male , Female , Oxaliplatin/adverse effects , Oxaliplatin/administration & dosage , Colorectal Neoplasms/drug therapy , Aged , Middle Aged , Risk Factors , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Platelet Count , Retrospective Studies , Aged, 80 and over , Adult
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