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1.
Platelets ; 35(1): 2363242, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38860550

ABSTRACT

Septic shock is a life-threatening disease worldwide often associated with thrombocytopenia. Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation, potentially influencing the course of the disease. However, there are few studies specifically evaluating the impact of thrombocytopenia on the prognosis of pediatric patients. Therefore, the study investigates effects of early thrombocytopenia in the prognosis of children with septic shock. Pediatric patients with septic shock from 2015 to 2022 were included monocentrically. Thrombocytopenia was defined as a platelet count of <100 × 109/L during the first 24 hours of septic shock onset. The primary outcome was the 28-day mortality. Propensity score matching was used to pair patients with different platelet counts on admission but comparable disease severity. A total of 419 pediatric patients were included in the analysis. Patients with thrombocytopenia had higher 28-day mortality (55.5% vs. 38.7%, p = .005) compared to patients with no thrombocytopenia. Thrombocytopenia was associated with reduced 28-PICU free days (median value, 0 vs. 13 days, p = .003) and 28-ventilator-free (median value, 0 vs. 19 days, p = .001) days. Among thrombocytopenia patients, those with platelet count ≤50 × 109/L had a higher 28-day mortality rate (63.6% vs. 45%, p = .02). Multiple logistic regression showed that elevated lactate (adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.04-1.17; P <0.001) and white blood cell (WBC) count (OR = 0.97; 95% CI: 0.95-0.99; p = .003) were independent risk factors for the development of thrombocytopenia. Thrombocytopenia group had increased bleeding events, blood product transfusions, and development of organ failure. In Kaplan-Meier survival estimates, survival probabilities at 28 days were greater in patients without thrombocytopenia (p value from the log-rank test, p = .004). There were no significant differences in the type of pathogenic microorganisms and the site of infection between patients with and without thrombocytopenia. In conclusion, thrombocytopenia within 24 hours of shock onset is associated with an increased risk of 28-day mortality in pediatric patients with septic shock.


What is the context? Septic shock is a life-threatening disease worldwide, leading to higher mortality.Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation.Although it is known that platelets are associated with prognosis, most studies have focused on adult populations. Limited data are available on the incidence of thrombocytopenia and its correlation with clinical outcomes , specifically, in pediatric patients with sepsis and septic shock. What is new? The present study suggests that thrombocytopenia within 24 hours of septic shock onset reflects a reliable tool for predicting the prognosis of septic shock in pediatric patients.Furthermore, elevated lactate and reduced white-blood-cell count were independent risk factors for the development of thrombocytopenia in pediatric patients with septic shock. What is the impact? This study suggests that thrombocytopenia within 24 hours of septic shock onset is associated with an increased risk of 28-day mortality and decreased ventilation-free, PICU-free days in pediatric patients with septic shock. In septic shock, thrombocytopenia is also associated with increased bleeding events, blood product transfusions, and organ dysfunction.


Subject(s)
Shock, Septic , Thrombocytopenia , Humans , Thrombocytopenia/complications , Thrombocytopenia/blood , Shock, Septic/complications , Shock, Septic/mortality , Shock, Septic/blood , Male , Female , Prognosis , Retrospective Studies , Child , Child, Preschool , Infant , Platelet Count/methods
2.
Ren Fail ; 46(1): 2359643, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38869010

ABSTRACT

INTRODUCTION: A reduction in platelet count in critically ill patients is a marker of severity of the clinical condition. However, whether this association holds true in acute kidney injury (AKI) is unknown. We analyzed the association between platelet reduction in patients with AKI and major adverse kidney events (MAKE). METHODS: In this retrospective cohort, we included AKI patients at the Hospital Civil of Guadalajara, in Jalisco, Mexico. Patients were divided according to whether their platelet count fell >21% during the first 10 days. Our objectives were to analyze the associations between a platelet reduction >21% and MAKE at 10 days (MAKE10) or at 30-90 days (MAKE30-90) and death. RESULTS: From 2017 to 2023, 400 AKI patients were included, 134 of whom had a > 21% reduction in platelet count. The mean age was 54 years, 60% were male, and 44% had sepsis. The mean baseline platelet count was 194 x 103 cells/µL, and 65% of the KDIGO3 patients met these criteria. Those who underwent hemodialysis (HD) had lower platelet counts. After multiple adjustments, a platelet reduction >21% was associated with MAKE10 (OR 4.2, CI 2.1-8.5) but not with MAKE30-90. The mortality risk increased 3-fold (OR 2.9, CI 1.1-7.7, p = 0.02) with a greater decrease in the platelets (<90 x 103 cells/µL). As the platelets decreased, the incidence of MAKE was more likely to increase. These associations lost significance when accounting for starting HD. CONCLUSION: In our retrospective cohort of patients with AKI, a > 21% reduction in platelet count was associated with MAKE. Our results are useful for generating hypotheses and motivating us to continue studying this association with a more robust design.


A reduction in platelet count in critically ill patients has been associated with a worse prognosis, but it is not yet known whether this relationship also exists in patients with acute kidney injury, who are more susceptible to platelet decrease due to the syndrome or due to the onset of hemodialysis. In our study of acute kidney injury patients, we found that those whose platelet count decreased >21% during the first days were more likely to experience a major kidney event. In addition, the greater the decrease in platelet count was, the more likely these events were to occur. The significance of this association was lost in patients who start hemodialysis. Our conclusions could serve to generate hypotheses about this interesting relationship.


Subject(s)
Acute Kidney Injury , Humans , Male , Retrospective Studies , Female , Acute Kidney Injury/blood , Acute Kidney Injury/mortality , Acute Kidney Injury/etiology , Middle Aged , Platelet Count , Mexico/epidemiology , Aged , Adult , Renal Dialysis , Critical Illness , Thrombocytopenia/blood , Risk Factors
3.
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
4.
Clin Immunol ; 264: 110252, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38744408

ABSTRACT

Children with Multisystem Inflammatory Syndrome in Children (MIS-C) can present with thrombocytopenia, which is a key feature of hemophagocytic lymphohistiocytosis (HLH). We hypothesized that thrombocytopenic MIS-C patients have more features of HLH. Clinical characteristics and routine laboratory parameters were collected from 228 MIS-C patients, of whom 85 (37%) were thrombocytopenic. Thrombocytopenic patients had increased ferritin levels; reduced leukocyte subsets; and elevated levels of ASAT and ALAT. Soluble IL-2RA was higher in thrombocytopenic children than in non-thrombocytopenic children. T-cell activation, TNF-alpha and IFN-gamma signaling markers were inversely correlated with thrombocyte levels, consistent with a more pronounced cytokine storm syndrome. Thrombocytopenia was not associated with severity of MIS-C and no pathogenic variants were identified in HLH-related genes. This suggests that thrombocytopenia in MIS-C is not a feature of a more severe disease phenotype, but the consequence of a distinct hyperinflammatory immunopathological process in a subset of children.


Subject(s)
Lymphohistiocytosis, Hemophagocytic , Systemic Inflammatory Response Syndrome , Thrombocytopenia , Humans , Lymphohistiocytosis, Hemophagocytic/blood , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphohistiocytosis, Hemophagocytic/genetics , Child , Male , Child, Preschool , Female , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/immunology , Thrombocytopenia/blood , Thrombocytopenia/immunology , Infant , Adolescent , Phenotype , Proteomics , COVID-19/immunology , COVID-19/blood , COVID-19/complications
5.
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
6.
J Vet Intern Med ; 38(3): 1512-1519, 2024.
Article in English | MEDLINE | ID: mdl-38619127

ABSTRACT

BACKGROUND: The immature platelet fraction (IPF), a parameter obtained by the Sysmex XN-1000V analyzer, is used in humans to differentiate between central (CEN) and peripheral (PER) thrombocytopenia (TP) but has not been evaluated in small animals. OBJECTIVES: Compare IPF between healthy, clinical non-TP and TP dogs and cats, study IPF in different causes of TP in dogs and cats and, establish IPF reference intervals (RIs), and study the effect of age and sex on IPF in healthy dogs and cats. ANIMALS: A total of 3281 dogs and 726 cats. METHODS: Retrospective review of medical records. Animals were classified as nonthrombocytopenic (healthy group and group of clinical patients without TP [NTP]) or TP. These latter animals were subclassified as pseudothrombocytopenia (PSE), CEN and PER, based on evaluation of platelet clumps, estimated platelet count in blood smears and final diagnosis. Blood samples were evaluated using a Sysmex XN-1000V with a specific platelet channel (PLT-F). RESULTS: The IPF was significantly different between each subtype of TP in both species. Immature platelet fractions <6.9% in dogs or 13.6% in cats, once PSE has been eliminated by review of blood smears, are indicative of CEN. Reference intervals for IPF were 0.5%-8% in healthy dogs and 1%-40.3% in healthy cats. CONCLUSIONS AND CLINICAL IMPORTANCE: We determined that IPF can differentiate between CEN and PER in dogs and cats, guiding additional testing and avoiding more invasive procedures (bone marrow sampling). A blood smear always should be evaluated to rule out platelet clumping.


Subject(s)
Cat Diseases , Dog Diseases , Thrombocytopenia , Animals , Dogs , Cats , Dog Diseases/diagnosis , Dog Diseases/blood , Thrombocytopenia/veterinary , Thrombocytopenia/diagnosis , Thrombocytopenia/blood , Cat Diseases/diagnosis , Cat Diseases/blood , Retrospective Studies , Female , Male , Diagnosis, Differential , Platelet Count/veterinary , Platelet Count/instrumentation , Blood Platelets , Reference Values
7.
Transfusion ; 64(6): 986-997, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38661229

ABSTRACT

BACKGROUND: Laboratory results are frequently abnormal in pregnant mothers. Abnormalities usually relate to pregnancy or associated complications. Hematological abnormalities and age in pregnancy may increase the likelihood for transfusion and mortality. STUDY DESIGN AND METHODS: Hematological profiles and transfusion history of pregnant mothers presenting to a tertiary hospital, were evaluated over 2 years. Age, anemia, leukocytosis and thrombocytopenia were assessed for transfusion likelihood. Iron deficiency and coagulation were assessed in transfused patients. Anemia, leukocytosis, thrombocytopenia, human immunodeficiency virus (HIV) and transfusion were assessed for mortality likelihood. RESULTS: There were 12,889 pregnant mothers included. Mothers <19-years-old had the highest prevalence of anemia (31.5%) and proportion of transfusions (19%). The transfusion likelihood was increased in mothers with anemia (odds ratios [OR] = 6.41; confidence intervals at 95% [95% CI] 5.46-7.71), leukocytosis (OR = 2.35; 95% CI 2.00-2.76) or thrombocytopenia (OR = 2.71; 95% CI 2.21-3.33). Mothers with prolonged prothrombin times received twice as many blood products as their normal counterparts (p = .03) and those with iron deficiency anemia five times more blood products (p < .001). Increased likelihood for mortality was seen in patients with anemia (OR = 4.15, 95% CI 2.03-8.49), leukocytosis (OR = 2.68; 95% CI 1.19-6.04) and those receiving blood transfusion (OR = 3.6, 95% CI 1.75-7.47). DISCUSSION: Adolescence, anemia, leukocytosis and thrombocytopenia expose mothers to a high risk for transfusion and/or mortality. These risk factors should promptly trigger management and referral of patients. Presenting hematological profiles are strong predictors of maternal outcome and transfusion risk.


Subject(s)
Blood Transfusion , Pregnancy Complications, Hematologic , Tertiary Care Centers , Humans , Female , Pregnancy , Adult , South Africa/epidemiology , Pregnancy Complications, Hematologic/blood , Pregnancy Complications, Hematologic/mortality , Pregnancy Complications, Hematologic/therapy , Pregnancy Complications, Hematologic/epidemiology , Thrombocytopenia/blood , Thrombocytopenia/mortality , Thrombocytopenia/etiology , Anemia/blood , Anemia/mortality , Anemia/etiology , Anemia/epidemiology , Young Adult , Adolescent , Risk Factors , Leukocytosis/mortality , Leukocytosis/blood
8.
Blood Adv ; 8(11): 2825-2834, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38588487

ABSTRACT

ABSTRACT: New analytical techniques can assess hundreds of proteins simultaneously with high sensitivity, facilitating the observation of their complex interplay and role in disease mechanisms. We hypothesized that proteomic profiling targeting proteins involved in thrombus formation, inflammation, and the immune response would identify potentially new biomarkers for heparin-induced thrombocytopenia (HIT). Four existing panels of the Olink proximity extension assay covering 356 proteins involved in thrombus formation, inflammation, and immune response were applied to randomly selected patients with suspected HIT (confirmed HIT, n = 32; HIT ruled out, n = 38; and positive heparin/platelet factor 4 [H/PF4] antibodies, n = 28). The relative difference in protein concentration was analyzed using a linear regression model adjusted for sex and age. To confirm the test results, soluble P-selectin was determined using enzyme-linked immunosorbent assay (ELISA) in above mentioned patients and an additional second data set (n = 49). HIT was defined as a positive heparin-induced platelet activation assay (washed platelet assay). Among 98 patients of the primary data set, the median 4Ts score was 5 in patients with HIT, 4 in patients with positive H/PF4 antibodies, and 3 in patients without HIT. The median optical density of a polyspecific H/PF4 ELISA were 3.0, 0.9, and 0.3. Soluble P-selectin remained statistically significant after multiple test adjustments. The area under the receiver operating characteristic curve was 0.81 for Olink and 0.8 for ELISA. Future studies shall assess the diagnostic and prognostic value of soluble P-selectin in the management of HIT.


Subject(s)
Biomarkers , Heparin , Proteomics , Thrombocytopenia , Humans , Heparin/adverse effects , Female , Proteomics/methods , Male , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombocytopenia/blood , Middle Aged , Aged , P-Selectin/blood , Platelet Factor 4 , Adult , Platelet Activation
9.
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
10.
Blood Adv ; 8(10): 2466-2477, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38513134

ABSTRACT

ABSTRACT: Sitosterolemia is a rare autosomal recessive genetic disorder in which patients develop hypercholesterolemia and may exhibit abnormal hematologic and/or liver test results. In this disease, dysfunction of either ABCG5 or ABCG8 results in the intestinal hyperabsorption of all sterols, including cholesterol and, more specifically, plant sterols or xenosterols, as well as in the impaired ability to excrete xenosterols into the bile. It remains unknown how and why some patients develop hematologic abnormalities. Only a few unrelated patients with hematologic abnormalities at the time of diagnosis have been reported. Here, we report on 2 unrelated pedigrees who were believed to have chronic immune thrombocytopenia as their most prominent feature. Both consanguineous families showed recessive gene variants in ABCG5, which were associated with the disease by in silico protein structure analysis and clinical segregation. Hepatosplenomegaly was absent. Thrombopoietin levels and megakaryocyte numbers in the bone marrow were normal. Metabolic analysis confirmed the presence of strongly elevated plasma levels of xenosterols. Potential platelet proteomic aberrations were longitudinally assessed following dietary restrictions combined with administration of the sterol absorption inhibitor ezetimibe. No significant effects on platelet protein content before and after the onset of treatment were demonstrated. Although we cannot exclude that lipotoxicity has a direct and platelet-specific impact in patients with sitosterolemia, our data suggest that thrombocytopenia is neither caused by a lack of megakaryocytes nor driven by proteomic aberrations in the platelets themselves.


Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 5 , Blood Platelets , Hypercholesterolemia , Intestinal Diseases , Lipid Metabolism, Inborn Errors , Phytosterols , Proteomics , Thrombocytopenia , Humans , Lipid Metabolism, Inborn Errors/diagnosis , Lipid Metabolism, Inborn Errors/genetics , Lipid Metabolism, Inborn Errors/blood , Lipid Metabolism, Inborn Errors/complications , Hypercholesterolemia/blood , Hypercholesterolemia/genetics , Hypercholesterolemia/complications , Phytosterols/adverse effects , Phytosterols/blood , Blood Platelets/metabolism , Blood Platelets/pathology , ATP Binding Cassette Transporter, Subfamily G, Member 5/genetics , Intestinal Diseases/blood , Intestinal Diseases/diagnosis , Intestinal Diseases/genetics , Intestinal Diseases/etiology , Intestinal Diseases/metabolism , Male , Thrombocytopenia/diagnosis , Thrombocytopenia/blood , Thrombocytopenia/etiology , Thrombocytopenia/metabolism , Female , Proteomics/methods , Pedigree , ATP Binding Cassette Transporter, Subfamily G, Member 8/genetics , Adult , Proteome , Adolescent , Lipoproteins
12.
Scand J Clin Lab Invest ; 84(2): 91-96, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38420711

ABSTRACT

BACKGROUND: The Immature Platelet Fraction (IPF) is an indicator of thrombopoiesis which is a useful parameter in thrombocytopenia. It demonstrates compensatory mechanisms in production of platelets, but currently not implemented in routine clinical practice. The aim of this study was to establish the reproducibility and stability of IPF, for both percentage (%-IPF) and absolute (A-IPF) measurements.Material/methods: A total of 71 samples, of which 45 for reproducibility and 26 for stability analysis, were assayed for full blood count using the Sysmex XN-10 analyser at room temperature (RT:19-25 °C). For reproducibility analysis, IPF measurements were analysed 11 times by different appraisers using the same sample, while for stability analysis, IPF was measured over fourteen hourly-intervals up to 24 h (n = 21) and then separately extended beyond the point of stability to 72 h (n = 5). RESULTS: Reproducibility analysis of %-IPF and A-IPF (n = 45) showed very reliable results, with the range of mean CV% values between 1.25-8.90% and 1.70-9.96%, respectively. On the other hand, overall, stability analysis of %-IPF and A-IPF (n = 21) at RT over 24 h showed reliable results, with pooled mean CV% values of 1.32% and 1.43%, respectively, with no significant difference between %-IPF and A-IPF (p = 0.767 and p = 0.821). All %-IPF and A-IPF values had exceeded the set acceptance criterion of stability (CV% ≥ 10.0%) before 72 h. CONCLUSIONS: Overall, %-IPF and A-IPF reproducibility and storage at RT for 24 h predominantly demonstrates the suitability of their usage for testing on the Sysmex XN-series analysers.


Subject(s)
Blood Platelets , Humans , Reproducibility of Results , Blood Platelets/cytology , Platelet Count/instrumentation , Platelet Count/methods , Thrombocytopenia/blood , Thrombocytopenia/diagnosis , Thrombopoiesis/physiology
13.
Arthritis Rheumatol ; 76(6): 928-935, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38225923

ABSTRACT

OBJECTIVE: While thrombosis and pregnancy loss are the best-known clinical features of antiphospholipid syndrome (APS), many patients also exhibit "extra-criteria" manifestations, such as thrombocytopenia. The mechanisms that drive APS thrombocytopenia are not completely understood, and no clinical biomarkers are available for predicting antiphospholipid antibody (aPL)-mediated thrombocytopenia. Calprotectin is a heterodimer of S100A8 and S100A9 that is abundant in the neutrophil cytoplasm and released upon proinflammatory neutrophil activation. Here, we sought to evaluate the presence, clinical associations, and potential mechanistic roles of circulating calprotectin in a cohort of primary APS and aPL-positive patients. METHODS: Levels of circulating calprotectin were determined in plasma by the QUANTA Flash chemiluminescent assay. A viability dye-based platelet assay was used to assess the potential impact of calprotectin on aPL-mediated thrombocytopenia. RESULTS: Circulating calprotectin was measured in 112 patients with primary APS and 30 aPL-positive (without APS criteria manifestations or lupus) patients as compared to patients with lupus (without APS), patients with unprovoked venous thrombosis (without aPL), and healthy controls. Levels of calprotectin were higher in patients with primary APS and aPL-positive patients compared to healthy controls. After adjustment for age and sex, calprotectin level correlated positively with absolute neutrophil count (r = 0.41, P < 0.001), positively with C-reactive protein level (r = 0.34, P = 0.002), and negatively with platelet count (r = -0.24, P = 0.004). Mechanistically, we found that calprotectin provoked aPL-mediated thrombocytopenia by engaging platelet surface toll-like receptor 4 and activating the NLRP3-inflammasome, thereby reducing platelet viability in a caspase-1-dependent manner. CONCLUSION: These data suggest that calprotectin has the potential to be a functional biomarker and a new therapeutic target for APS thrombocytopenia.


Subject(s)
Antiphospholipid Syndrome , Blood Platelets , Leukocyte L1 Antigen Complex , Thrombocytopenia , Humans , Antiphospholipid Syndrome/blood , Female , Leukocyte L1 Antigen Complex/blood , Male , Middle Aged , Adult , Thrombocytopenia/blood , Blood Platelets/metabolism , Biomarkers/blood , Toll-Like Receptor 4/blood , Antibodies, Antiphospholipid/blood
14.
Am J Hematol ; 99(6): 1168-1169, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38174980

ABSTRACT

A puzzling case of thrombocytopenia and giant unusual platelets in blood smear reveals a past diagnosis of Alport syndrome in 44-year-old woman with end-stage renal disease and abnormal CBC values.


Subject(s)
Blood Platelets , Nephritis, Hereditary , Thrombocytopenia , Humans , Nephritis, Hereditary/complications , Nephritis, Hereditary/diagnosis , Female , Thrombocytopenia/diagnosis , Thrombocytopenia/etiology , Thrombocytopenia/blood , Adult , Blood Platelets/pathology , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications
15.
Platelets ; 34(1): 2157383, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36683325

ABSTRACT

Circulating platelets maintain low cytosolic Ca2+ concentrations. At sites of vascular injury, agonist-induced Ca2+ release from platelet intracellular stores triggers influx of extracellular Ca2+, a process known as store-operated Ca2+ entry (SOCE). Stromal interaction molecule 1 (Stim1) senses reduced Ca2+ stores and triggers SOCE. Gain-of-function (GOF) mutations in Stim1, such as described for Stormorken syndrome patients or mutant mice (Stim1Sax), are associated with marked thrombocytopenia and increased platelet turnover. We hypothesized that reduced platelet survival in Stim1Sax/+ mice is due to increased Rap1/integrin signaling and platelet clearance in the spleen, similar to what we recently described for mice expressing a mutant version of the Rap1-GAP, Rasa3 (Rasa3hlb/hlb). Stim1Sax/+ mice were crossed with mice deficient in CalDAG-GEFI, a critical calcium-regulated Rap1-GEF in platelets. In contrast to Rasa3hlb/hlb x Caldaggef1-/- mice, only a small increase in the peripheral platelet count, but not platelet lifespan, was observed in Stim1Sax/+ x Caldaggef1-/- mice. Similarly, inhibition of αIIbß3 integrin in vivo only minimally raised the peripheral platelet count in Stim1Sax/+ mice. Compared to controls, Stim1Sax/+ mice exhibited increased platelet accumulation in the lung, but not the spleen or liver. These results suggest that CalDAG-GEFI/Rap1/integrin signaling contributes only minimally to accelerated platelet turnover caused by constitutive SOCE.


What do we know? Platelets are small blood cells which act to prevent blood loss, which circulate in a resting state but are rapidly activated upon exposure to ligands at the site of vascular injuryCalcium (Ca2+) is critical for platelet activation, especially for activation of integrins which support platelet­platelet interactionsIf platelet activation occurs in circulation, platelets can be prematurely cleared from blood and unable to function in hemostasisDisorders of Ca2+ dysregulation such as Stormorken syndrome are associated with reduced platelet counts (thrombocytopenia) and bleedingWhat did we discover? We used a mouse model expressing a mutation causing higher Ca2+ levels in cells including platelets (Stim1Sax), and investigated whether thrombocytopenia is due to stimulation of a specific pathway for integrin activation, mediated by a protein called Rap1 GTPaseWe crossed Stim1Sax mice with mice lacking an important activator of Rap1, the Ca2+-regulated protein CalDAG-GEFI, and saw no major improvement in thrombocytopeniaWe also observed more Stim1Sax platelets in the lung but not the liver or spleen, in contrast to mice with activation of platelet integrins in circulationWhat is the impact? Our results rule out activation of the CalDAG-GEFI/Rap1/integrin pathway as a major cause of thrombocytopenia in Stim1Sax miceOur findings help to narrow down potential causes of thrombocytopenia in disorders such as Stormorken syndrome.


Subject(s)
Blood Platelets , Calcium , Guanine Nucleotide Exchange Factors , Platelet Glycoprotein GPIIb-IIIa Complex , Animals , Mice , Blood Platelets/metabolism , Calcium/metabolism , Guanine Nucleotide Exchange Factors/metabolism , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism , Signal Transduction , Thrombocytopenia/blood , Thrombocytopenia/metabolism
16.
Ethiop J Health Sci ; 33(6): 955-962, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38784485

ABSTRACT

Background: Surgical treatment has transformed the course and outcome of congenital heart defects in high-income countries, but children with congenital heart diseases in sub-Saharan Africa, where access to cardiac surgery is limited, often experience the natural course of untreated lesions and their complications. The objective of this study was to determine the prevalence of hematologic derangements among Ethiopian children with unoperated cyanoticcongenital heart diseases, to identify factors associated with coagulopathy in this population, and to describe how these complications are managed in this setting. Methods: In this single-center cross-sectional study, we prospectively collected clinical and demographic data from children (<18 years) with cyanotic congenital heart diseases. Blood samples were collected to measure hematologic parameters. Polycythemia was defined as hematocrit >50% and thrombocytopenia as <150,000 per microliter. Results: Among 70 children recruited, the overall prevalence of polycythemia and thrombocytopenia was 63% (n=44) and 26% (n=18), respectively. On multivariate logistic regression analysis, hematocrit ≥65% (p-value=.024), and oxygen saturation <85% (p-value=.018) were independently associated with moderate or severe thrombocytopenia. Thirty-one (44%) patients had undergone therapeutic phlebotomy, and 84% (26/31) of these patients received iron supplementation. Conclusion: We report a high prevalence of polycythemia and thrombocytopenia in Ethiopian children with untreated cyanotic congenital heart diseases. There was variable implementation of iron supplementation and therapeutic phlebotomy, highlighting the need to optimize supportive management strategies in this population to mitigate the risk of life-threatening complications.


Subject(s)
Heart Defects, Congenital , Polycythemia , Thrombocytopenia , Humans , Ethiopia/epidemiology , Female , Heart Defects, Congenital/epidemiology , Heart Defects, Congenital/complications , Heart Defects, Congenital/blood , Male , Cross-Sectional Studies , Polycythemia/epidemiology , Polycythemia/blood , Polycythemia/etiology , Child, Preschool , Infant , Child , Thrombocytopenia/epidemiology , Thrombocytopenia/etiology , Thrombocytopenia/blood , Prevalence , Hematocrit , Cyanosis/epidemiology , Cyanosis/etiology , Cyanosis/blood , Adolescent , Prospective Studies , Phlebotomy/statistics & numerical data
17.
Saudi Med J ; 43(7): 723-729, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35830989

ABSTRACT

OBJECTIVES: To examine D-dimer, coagulation profile, and platelet count among patients hospitalized with coronavirus disease-19 (COVID-19) and compare them to findings from non-COVID-19 subjects. METHODS: The participants in this retrospective hospital-based observational study design included 112 confirmed diagnosed with COVID-19 who were admitted to King Khaled Hospital, Najran, Saudi Arabia, and another 112 non-COVID-19 subjects as a comparative group. Laboratory investigations, demographic and clinical records were obtained from participants' electronic indexed medical records. Coronavirus disease-19 diagnosis was confirmed according to positive real time polymerase chain reaction assay carried out at the hospital's central laboratory, where samples were extracted from a nasopharyngeal swab. Pneumonia related to COVID-19 is classified as critical, severe, moderate, mild, and asymptomatic whereas thrombocytopenia was marked when the platelet count was <150.00×109/L. Suitable statistical analysis was applied to determine possible differences between the findings from the 2 groups. RESULTS: The D-dimer and activated partial thromboplastin clotting time mean values were significantly elevated (p<0.001). The international normalized ratio and platelet count mean values confirmed a significant decrease (p<0.001). Thrombocytopenia was found 9 times in COVID-19 higher than in the non-COVID-19. D-dimer and prothrombin time mean values increased significantly among the COVID-19 patients with all patterns of symptoms on admission (p<0.001). CONCLUSION: D-dimer mean values increased significantly in deceased COVID-19 and in hospitalized intensive care unit (ICU) wards patients (p<0.001), indicating a potential predictive and prognostic severity marker, particularly among COVID-19 patients in the ICU.


Subject(s)
COVID-19 , Fibrin Fibrinogen Degradation Products , Thrombocytopenia , COVID-19/blood , COVID-19/diagnosis , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Prognosis , Retrospective Studies , Thrombocytopenia/blood , Thrombocytopenia/virology
18.
J Korean Med Sci ; 37(10): e75, 2022 Mar 14.
Article in English | MEDLINE | ID: mdl-35289136

ABSTRACT

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but life-threatening complication. VITT strongly mimics heparin-induced thrombocytopenia (HIT) and shares clinical features. Heparin is commonly used to prevent coagulation during hemodialysis. Therefore, nephrologists might encounter patients needing dialysis with a history of heparin exposure who developed thrombotic thrombocytopenia after vaccination. A 70-year-old male presented with acute kidney injury and altered mental status due to lithium intoxication. He needed consecutive hemodialysis using heparin. Deep vein thrombosis of left lower extremity and accompanying severe thrombocytopenia of 15,000/µL on 24 days after vaccination and at the same time, nine days after heparin use. Anti-platelet factor 4 antibody test was positive. Anticoagulation with apixaban and intravenous immunoglobulin (IVIG) infusion resolved swelling of his left calf and thrombocytopenia. There were no definitive diagnostic tools capable of differentiating between VITT and HIT in this patient. Although VITT and HIT share treatment with IVIG and non-heparin anticoagulation, distinguishing between VITT and HIT will make it possible to establish a follow-up vaccination plan in a person who has had a thrombocytopenic thrombotic event. Further research is needed to develop the tools to make a clear distinction between the clinical syndromes.


Subject(s)
ChAdOx1 nCoV-19/adverse effects , Heparin/adverse effects , Purpura, Thrombocytopenic, Idiopathic/etiology , Renal Dialysis/adverse effects , Thrombocytopenia/etiology , Aged , Anticoagulants/adverse effects , Autoantibodies/blood , Diagnosis, Differential , Humans , Immunoglobulin G/blood , Lithium/toxicity , Male , Platelet Count , Platelet Factor 4/immunology , Purpura, Thrombocytopenic, Idiopathic/blood , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Renal Dialysis/methods , Thrombocytopenia/blood , Thrombocytopenia/diagnosis
19.
PLoS One ; 17(2): e0264351, 2022.
Article in English | MEDLINE | ID: mdl-35213601

ABSTRACT

INTRODUCTION: Valproic acid (VPA) is a frequently prescribed anti-epileptic drug. Since its introduction side effects on hemostasis are reported. However, studies show conflicting results, and the clinical relevance is questioned. We aimed to determine the coagulopathies induced by VPA in patients who undergo high-risk surgery. The study results warrant attention to this issue, which might contribute to reducing bleeding complications in future patients. METHODS: Between January 2012 and August 2020, 73 consecutive patients using VPA were retrospectively included. Extensive laboratory hemostatic assessment (including platelet function tests) was performed before elective high-risk surgery. Patient characteristics, details of VPA treatment, and laboratory results were extracted from medical records. RESULTS: 46.6% of the patients using VPA (n = 73) showed coagulopathy. Mainly, platelet function disorder was found (36.4%). Thrombocytopenia was seen in 9.6% of the patients. Data suggested that the incidence of coagulopathies was almost twice as high in children as compared to adults and hypofibrinogenemia was only demonstrated in children. No association was found between the incidence of coagulopathies and VPA dosage (mg/kg/day). CONCLUSION: A considerable number of patients using VPA were diagnosed with coagulopathy, especially platelet function disorder. Further prospective studies are needed to confirm the need for comprehensive laboratory testing before elective high-risk surgery in these patients.


Subject(s)
Blood Coagulation Disorders , Hemostatics/administration & dosage , Thrombocytopenia , Valproic Acid/adverse effects , Adolescent , Adult , Aged , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/chemically induced , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Incidence , Infant , Male , Middle Aged , Platelet Function Tests , Retrospective Studies , Thrombocytopenia/blood , Thrombocytopenia/chemically induced , Thrombocytopenia/drug therapy , Thrombocytopenia/epidemiology , Valproic Acid/administration & dosage
20.
Viruses ; 14(2)2022 02 07.
Article in English | MEDLINE | ID: mdl-35215926

ABSTRACT

To clarify the predictive factors of significant platelet count improvement in thrombocytopenic chronic hepatitis C (CHC) patients. CHC patients with baseline platelet counts of <150 × 103/µL receiving direct-acting antiviral (DAA) therapy with at least 12-weeks post-treatment follow-up (PTW12) were enrolled. Significant platelet count improvement was defined as a ≥10% increase in platelet counts at PTW12 from baseline. Platelet count evolution at treatment week 4, end-of-treatment, PTW12, and PTW48 was evaluated. This study included 4922 patients. Sustained virologic response after 12 weeks post-treatment was achieved in 98.7% of patients. Platelet counts from baseline, treatment week 4, and end-of-treatment to PTW12 were 108.8 ± 30.2, 121.9 ± 41.1, 123.1 ± 43.0, and 121.1 ± 40.8 × 103/µL, respectively. Overall, 2230 patients (45.3%) showed significant platelet count improvement. Multivariable analysis revealed that age (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.99-1.00, p = 0.01), diabetes mellitus (DM) (OR = 1.20, 95% CI: 1.06-1.38, p = 0.007), cirrhosis (OR = 0.66, 95% CI: 0.58-0.75, p < 0.0001), baseline platelet counts (OR = 0.99, 95% CI: 0.98-0.99, p < 0.0001), and baseline total bilirubin level (OR = 0.80, 95% CI: 0.71-0.91, p = 0.0003) were independent predictive factors of significant platelet count improvement. Subgroup analyses showed that patients with significant platelet count improvement and sustained virologic responses, regardless of advanced fibrosis, had a significant increase in platelet counts from baseline to treatment week 4, end-of-treatment, PTW12, and PTW48. Young age, presence of DM, absence of cirrhosis, reduced baseline platelet counts, and reduced baseline total bilirubin levels were associated with significant platelet count improvement after DAA therapy in thrombocytopenic CHC patients.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/drug therapy , Aged , Female , Hepacivirus , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/drug therapy , Male , Middle Aged , Multivariate Analysis , Platelet Count , Retrospective Studies , Sustained Virologic Response , Thrombocytopenia/blood , Thrombocytopenia/drug therapy
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