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BACKGROUND: The short shelf-life of liquid-stored platelets (LP) at 20-24°C poses shortage and wastage challenges. Cryopreserved platelets have significantly extended shelf-life, and were safe and efficacious for therapeutic transfusions of bleeding patients in the Afghanistan conflict and phase 2 randomized studies. Although hematology patients account for half of platelets demand, there is no randomized study on prophylactic cryopreserved platelet transfusions in them. METHODS: We performed a phase 1b/2a randomized cross-over study comparing the safety and efficacy of cryopreserved buffy coat-derived pooled platelets (CP) to LP in the prophylactic transfusions of thrombocytopenic hematology patients. RESULTS: A total of 18 adults were randomly assigned 1:1 to CP and LP for their first thrombocytopenic period (TP) of up to 28-days. A total of 14 crossed over to the other platelet-arm for the second TP. Overall, 17 subjects received 51 CP and 15 received 52 LP. CP-arm had more treatment emergent adverse event (29.4% vs. 13.3% of subjects, 9.8% vs. 3.8% of transfusions) than LP-arm but all were mild. No thromboembolism was observed. Both arms had similar bleeding rates (23.5% vs. 26.7% of subjects) which were all mild. Subjects in CP-arm had lower average corrected count increments than LP-arm (mean [SD] 5.6 [4.20] vs. 22.6 [9.68] ×109 /L at 1-4 h, p < .001; 5.3 [4.84] vs. 18.2 [9.52] ×109 /L at 18-30 h, p < .001). All TEG parameters at 1-4 h and maximum amplitude (MA) at 18-30 h improved from baseline post-CP transfusion (p < .05) though improvements in K-time and MA were lower than LP (p < .05). DISCUSSION: During shortages, CP may supplement LP in prophylactic transfusions of thrombocytopenic patients.
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Plaquetas , Transfusión Sanguínea , Adulto , Humanos , Estudios Cruzados , Transfusión de Plaquetas , Suplementos DietéticosRESUMEN
Current clinical practice guidelines lack explicit guidance on the indications and appropriate timing of venous ultrasound (US) in lower extremity deep vein thrombosis (DVT) follow-up. Moreover, abnormal findings reported on venous US in DVT follow-up or suspected recurrent DVT may be difficult for clinicians to interpret, which carries risk of harm from inappropriate use of anti- coagulation and increased healthcare resource utilization. Due to the above factors, over-use of ultrasound in diagnosis and follow-up of lower extremity DVT has been reported in western health systems. We have undertaken a case-based discussion and a scoping review of existing guidelines on the use of venousUS following prior diagnosis of DVT, to guide appropriate interpretation of commonly reported US abnormalities and provide our suggestions in the light of best available evidence on appropriate timing to perform follow-up US in management of lower extremity DVT.
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Sustained hypercoagulability and endotheliopathy are present in convalescent COVID-19 patients for up to 4 months from recovery. The hemostatic, endothelial, and inflammatory profiles of 39 recovered COVID-19 patients were evaluated up to 16 months after recovery from COVID-19. These values were compared with a control group of healthy volunteers (n = 124). 39 patients (71.8% males, median age 43 years) were reviewed at a mean of 12.7 ± 3.6 months following recovery. One patient without cardiovascular risk factors had post COVID-19 acute ischaemic limb. Elevated D-dimer and Factor VIII levels above normal ranges were noted in 17.9% (7/39) and 48.7% (19/39) of patients respectively, with a higher median D-dimer 0.34 FEU µg/mL (IQR 0.28, 0.46) (p < .001) and Factor VIII 150% (IQR 171, 203) (p = .004), versus controls. Thrombin generation (Thromboscreen) showed a higher median endogenous thrombin potential (ETP) of 1352 nM*min (IQR 1152, 1490) (p = .002) and a higher median peak height of 221.4 nM (IQR 170.2, 280.4) (p = 0.01) and delayed lag time 2.4 min (1.42-2.97) (p = 0.0002) versus controls. Raised vWF:Ag and ICAM-1 levels were observed in 17.9% (7/39) and 7.7% (3/39) of patients respectively, with a higher median VWF:Ag 117% (IQR 86, 154) (p = 0.02) and ICAM-1 54.1 ng/mL (IQR 43.8, 64.1) (p = .004) than controls. IL-6 was noted to be raised in 35.9% (14/39) of patients, with a higher median IL-6 of 1.5 pg/mL (IQR 0.6, 3.0) (p = 0.004) versus controls. Subgroup analysis stratifying patients by COVID-19 severity and COVID-19 vaccination preceding SARS-CoV-2 infection did not show statistically significant differences. Hypercoagulability, endothelial dysfunction, and inflammation are still detectable in some patients approximately 1 year after recovery from COVID-19.
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COVID-19 , Trombofilia , Adulto , COVID-19/complicaciones , Vacunas contra la COVID-19 , Factor VIII , Femenino , Humanos , Inflamación , Molécula 1 de Adhesión Intercelular , Masculino , SARS-CoV-2 , Trombina , Trombofilia/etiología , Factor de von WillebrandRESUMEN
BACKGROUND: There is an increasing frequency of oncology and hematopoietic stem cell transplant (HSCT) patients seen in the intensive care unit and requiring extracorporeal membrane oxygenation (ECMO), however, prognosis of this population over time is unclear. METHODS: MEDLINE, EMBASE, Cochrane and Web of Science were searched from earliest publication until April 10, 2020 for studies to determine the mortality trend over time in oncology and HSCT patients requiring ECMO. Primary outcome was hospital mortality. Random-effects meta-analysis model was used to obtain pooled estimates of mortality and 95% confidence intervals. A priori subgroup metanalysis compared adult versus pediatric, oncology versus HSCT, hematological malignancy versus solid tumor, allogeneic versus autologous HSCT, and veno-arterial versus veno-venous ECMO populations. Multivariable meta-regression was also performed for hospital mortality to account for year of study and HSCT population. RESULTS: 17 eligible observational studies (n = 1109 patients) were included. Overall pooled hospital mortality was 72% (95% CI: 65, 78). In the subgroup analysis, only HSCT was associated with a higher hospital mortality compared to oncology subgroup [84% (95% CI: 70, 93) vs. 66% (95% CI: 56, 74); P = 0.021]. Meta-regression showed that HSCT was associated with increased mortality [adjusted odds ratio (aOR) 3.84 (95% CI 1.77, 8.31)], however, mortality improved with time [aOR 0.92 (95% CI: 0.85, 0.99) with each advancing year]. CONCLUSION: This study reports a high overall hospital mortality in oncology and HSCT patients on ECMO which improved over time. The presence of HSCT portends almost a 4-fold increased risk of mortality and this finding may need to be taken into consideration during patient selection for ECMO.
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Oxigenación por Membrana Extracorpórea , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Neoplasias , Adulto , Niño , Oxigenación por Membrana Extracorpórea/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Unidades de Cuidados Intensivos , Neoplasias/etiología , Neoplasias/terapiaRESUMEN
Seated immobility thromboembolism syndrome (SIT) is the association of prolonged seated immobility with increased risk of venous thromboembolism (VTE). The advent of COVID-19 resulted in implementation of lockdowns to curb its spread. This resulted in compulsory work from home and minimization of outdoor activities. Consequently, this would have likely led to increased prolonged sitting and reduced mobility. Few case reports and studies have observed an increase in VTE incidence during the lockdown period. We likewise performed a clinical audit of our weekly thrombosis clinic cases and revealed three cases of VTE associated with prolonged sitting during Singapore's COVID-19 lockdown. Notably, all had other minor VTE risk factors in addition to prolonged sitting. All cases had intermediate-high risk pulmonary embolism and were given extended anticoagulation. With the pandemic still ongoing, periodic lockdown and quarantine measures may continue to be imposed. While the overall VTE risk conferred by prolonged seated immobility associated with lockdown measures is likely to be small, this risk can be easily mitigated and possibly prevented by simply staying mobile.
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COVID-19 , Embolia Pulmonar , Trombosis , Tromboembolia Venosa , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Humanos , Pandemias , Embolia Pulmonar/etiología , Embolia Pulmonar/prevención & control , Factores de Riesgo , Trombosis/complicaciones , Tromboembolia Venosa/complicaciones , Tromboembolia Venosa/prevención & controlRESUMEN
BACKGROUND: The procoagulant profile of platelet concentrates (PCs) following transfusion has been difficult to evaluate due to lack of specific markers. This study aimed to characterize procoagulant platelets in PCs and the effect of transfusion. STUDY DESIGN AND METHODS: Buffy coat-derived PCs from 12 donors were pooled, split, then stored conventionally, cold (2-6°C) or cryopreserved (-80°C). Procoagulant platelet profiles were assessed by flow cytometry (GSAO+ /P-selectin+ ), lactadherin-binding, and calibrated automated thrombogram, during storage, unstimulated, or after thrombin and collagen stimulation and compared with blood from healthy volunteers. Platelet activation (P-selectin) and procoagulant platelet formation potential were measured (flow cytometry) in patients receiving clinically indicated conventional PC transfusion. RESULTS: Independent of significant increases with storage, procoagulant platelet proportions with and without agonist stimulation were significantly blunted in conventionally stored PCs (stimulated day 5 conventional PC 4.2 ± 1.3%, healthy volunteer blood 11.1 ± 2.9%; p < .0001). Cryopreserved PCs contained the highest proportion of procoagulant platelets (unstimulated: cryopreserved 25.6 ± 1.8% vs. day 5 conventional 0.5 ± 0.1% vs. day 14 cold-stored 5.8 ± 1.0%, p < .0001), but demonstrated minimal increase with agonist. Transfusion of PCs was associated with an increase in procoagulant platelets (2.2 ± 1.4% vs. 0.6 ± 0.2%; p = .004) and reversal of the blunted agonist response (15.8 ± 5.9% vs. 4.0 ± 1.6%; p < .0001). Procoagulant responses post-transfusion were significantly higher than healthy controls, suggesting a priming effect. The P-selectin agonist response was not restored upon transfusion (79.4 ± 13.9% vs. 82.0 ± 2.5%). CONCLUSION: Storage blunts the procoagulant platelet response to agonist stimulation in PCs. Despite this, conventionally stored PCs have high procoagulant potential following transfusion, with a discordant, persistent reduction in P-selectin response.
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Plaquetas , Selectina-P , Conservación de la Sangre , Citometría de Flujo , Humanos , Selectina-P/análisis , Activación Plaquetaria , Transfusión de Plaquetas , Trombina/análisisRESUMEN
Management of adult patients with immune thrombocytopenia (ITP) is often unsatisfactory, due to variable efficacy of treatment, risk of life-threatening bleeding if disease control is poor, and side effects associated with treatment. Lack of data on the platelet count threshold associated with bleeding and infection risk associated with ITP treatment limits risk/benefit clinical decision making. We reviewed medical records of all ITP patients who were admitted to our hospital between 2012 and 2017 to evaluate the platelet count threshold for bleeding, infection burden associated with treatment, and real-world efficacy of second-line treatment. We demonstrated fair discrimination between platelet count and occurrence of bleeding, with 15 × 109/L being the optimal cut-off for predicting any bleeding while 20 × 109/L had the highest negative predictive value for severe bleeding. In multivariable analyses, patients who were treated with corticosteroids for at least 2 months were 5.3 times as likely to have an infection. In addition, rituximab response was strongly associated with response to frontline corticosteroids and infection was associated with older age ≥ 65 years and corticosteroid dependence. If corticosteroids are initiated, physicians should aim for the shortest duration of treatment before switching to effective second-line agents for hemostatic platelet counts.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/terapia , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Plaquetas/patología , Estudios de Cohortes , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Femenino , Estudios de Seguimiento , Hemorragia/sangre , Hemorragia/diagnóstico , Hemorragia/epidemiología , Hemorragia/etiología , Hospitalización/estadística & datos numéricos , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Infecciones/epidemiología , Infecciones/etiología , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Pronóstico , Púrpura Trombocitopénica Idiopática/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Rituximab/uso terapéutico , Singapur/epidemiología , Esplenectomía/estadística & datos numéricos , Resultado del TratamientoRESUMEN
BACKGROUND: Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients. METHOD AND RESULTS: This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16). CONCLUSIONS: Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.
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Non-transfusion-dependent thalassaemia (NTDT) is associated with a hypercoagulable state with thrombotic risk highest after splenectomy. Various mechanisms have been proposed. Although an antiplatelet agent is commonly recommended as thromboprophylaxis in NTDT, the role of platelets contributing to this hypercoagulable state is not well-defined. This study aims to evaluate the role of platelets contributing to hypercoagulability in NTDT patients using thrombin generation (TG). Platelet-rich (PRP) and platelet-poor plasma (PPP) were collected from NTDT patients (n = 30) and normal controls (n = 20) for TG measurement and compared. Controls had higher endogenous thrombin potential (ETP) in PPP (1204.97 nM.min vs 911.62 nM.min, p < 0.001) and PRP (1424.23 nM.min vs 983.99 nM.min, p < 0.001) than patients. Patients' mean normalized ETP ratio [{PRP ETP (patient)/PPP ETP (patient)}/{mean PPP ETP (controls)/mean PPP ETP (controls)}], demonstrated that the presence of platelet does not alter ETP (mean ratio 0.97, 95% CI 0.93-1.02, equivalence defined as 10%). Types of thalassaemia, splenectomy, and severity of liver iron overload did not significantly influence patients' ETP in PPP and PRP by multivariate analysis. Platelets did not increase the TG potential of NTDT patients. Instead of being hypercoagulable, our NTDT patients were hypocoagulable by ETP measurement, although this could not be conclusively demonstrated to correlate with their iron overloading state giving rise to reduced synthesis of coagulation factors. The guideline recommendations for thromboprophylaxis with antiplatelet agents in similar NTDT patients should be re-examined.
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Plaquetas/metabolismo , Talasemia/sangre , Trombina/metabolismo , Trombofilia/sangre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Sobrecarga de Hierro/sangre , Sobrecarga de Hierro/cirugía , Masculino , Persona de Mediana Edad , Plasma/metabolismo , Esplenectomía , Talasemia/cirugía , Trombofilia/cirugíaRESUMEN
BACKGROUND/OBJECTIVES: We compared the ex vivo haemostatic capacity of RTFP24 with FFP upon thawing and >24 h post-thaw. We included thrombin generation (TG) as few studies had compared global haemostatic function, and most did not directly compare RTFP24 with FFP >24 h post-thaw. MATERIALS/METHODS: Twenty units each of RTFP24 and FFP were measured for coagulation factors and thrombin generation upon thawing (D0) and 4 days post-thaw (D4). Labile factors were also measured from D1 to D3. 10 single cryoprecipitate units were each prepared from FFP and RTFP24, and measured for FXIII, FVIII and fibrinogen at D0. RESULTS: At D0, RTFP24 was comparable to FFP except for lower FV, protein S, endogenous thrombin potential (ETP) and higher FXIII. These differences were likely clinically insignificant since 95% and 80% of RTFP24 met our laboratory's reference ranges for FV/protein S and ETP, respectively. There were no differences between RTFP24- and FFP-derived cryoprecipitate. At D4, RTFP24 was comparable to FFP except for lower FV, ETP, and higher FXI and FXIII. More RTFP24 than FFP had ETP lower than our laboratory's reference range (45% vs 15%). Multiple coagulation factors and all TG parameters declined from their respective baselines. The percentage declines were comparable or less in RTFP24, except for protein C, fibrinogen and time to peak. CONCLUSION: RTFP24 and FFP, and their derived cryoprecipitate have comparable haemostatic capacity upon thawing. RTFP24 has poorer TG potential than FFP >24 h post-thaw, not supporting universal extension of RTFP24's shelf life except to facilitate urgent transfusions for massive haemorrhage.
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Conservación de la Sangre/métodos , Criopreservación/métodos , Plasma/metabolismo , Coagulación Sanguínea , Factores de Coagulación Sanguínea/metabolismo , Conservación de la Sangre/efectos adversos , Conservación de la Sangre/normas , Criopreservación/normas , Fibrinógeno/metabolismo , Humanos , Proteína S/metabolismo , Trombina/metabolismoAsunto(s)
Betacoronavirus , Infecciones por Coronavirus/sangre , Tiempo de Tromboplastina Parcial , Neumonía Viral/sangre , Trombofilia/sangre , Adulto , Proteína C-Reactiva/análisis , COVID-19 , Enfermedad Crítica , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Hiperlipidemias/sangre , Hiperlipidemias/complicaciones , Hipertensión/sangre , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Pandemias , Tiempo de Tromboplastina Parcial/estadística & datos numéricos , SARS-CoV-2 , Trombofilia/etiologíaRESUMEN
Introduction: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare haematologic disease characterised by intravascular haemolysis, thrombophilia and bone marrow failure. There is a lack of established clinical guidance on the screening, diagnosis and manage-ment of PNH in Singapore. A relatively low level of awareness among healthcare professionals regarding PNH manifestations further contributes to diagnostic delays. Additionally, limited access to complement inhibitors, like eculizumab, may delay treatment and impact patient outcomes. Method: Nine haematologists from different institu-tions in Singapore convened to formulate evidence-based consensus recommendations for optimising the diagnosis and management of patients with PNH and improving access to novel treatments. The experts reviewed the existing literature and international guidelines published from January 2010 to July 2023, focusing on 7 clinical questions spanning PNH screening, diagnostic criteria, investigations, treatment and monitoring of subclinical and classic disease, PNH with underlying bone marrow disorders, and PNH in pregnancy. A total of 181 papers were reviewed to formulate the statements. All experts voted on the statements via 2 rounds of Delphi and convened for an expert panel discussion to finetune the recommendations. Results: Sixteen statements have been formulated for optimising the screening, diagnosis and management of PNH. Upon confirmation of PNH diagnosis, individuals with active haemolysis and/or thrombosis should be considered for anti-complement therapy, with eculizumab being the only approved drug in Singapore. Conclusion: The current recommendations aim to guide the clinicians in optimising the screening, diagnosis and management of PNH in Singapore.
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Anticuerpos Monoclonales Humanizados , Hemoglobinuria Paroxística , Femenino , Humanos , Masculino , Embarazo , Anticuerpos Monoclonales Humanizados/uso terapéutico , Inactivadores del Complemento/uso terapéutico , Consenso , Técnica Delphi , Hemoglobinuria Paroxística/diagnóstico , Hemoglobinuria Paroxística/terapia , Complicaciones Hematológicas del Embarazo/diagnóstico , Complicaciones Hematológicas del Embarazo/terapia , Complicaciones Hematológicas del Embarazo/tratamiento farmacológico , SingapurRESUMEN
Thrombosis is one of the cardinal manifestations of myeloproliferative neoplasms (MPN). The mechanisms leading to a prothrombotic state in MPN are complex and remain poorly understood. Platelet mitochondria play a role in platelet activation, but their number and function have not been extensively explored in MPN to date. We observed an increased number of mitochondria in platelets from MPN patients compared with healthy donors. MPN patients had an increased proportion of dysfunctional platelet mitochondria. The fraction of platelets with depolarized mitochondria at rest was increased in essential thrombocythemia (ET) patients and the mitochondria were hypersensitive to depolarization following thrombin agonist stimulation. Live microscopy showed a stochastic process in which a higher proportion of individual ET platelets underwent mitochondrial depolarization and after a shorter agonist exposure compared to healthy donors. Depolarization was immediately followed by ballooning of the platelet membrane, which is a feature of procoagulant platelets. We also noted that the mitochondria of MPN patients were on average located nearer the platelet surface and we observed extrusion of mitochondria from the platelet surface as microparticles. These data implicate platelet mitochondria in a number of prothrombotic phenomena. Further studies are warranted to assess whether these findings correlate with clinical thrombotic events.
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Trastornos Mieloproliferativos , Neoplasias , Trombocitemia Esencial , Trombosis , Humanos , Plaquetas/metabolismo , Trombina/metabolismo , Trastornos Mieloproliferativos/metabolismo , Trombocitemia Esencial/metabolismo , Trombosis/metabolismo , Activación Plaquetaria , Neoplasias/metabolismo , MitocondriasRESUMEN
(1) Background: The activated partial thromboplastin time (APTT)- based clot waveform analysis (CWA) quantitatively extends information obtained from the APTT waveform through its derivatives. However, pre-analytical variables including reagent effects on the CWA parameters are poorly understood and must be standardized as a potential diagnostic assay. (2) Methods: CWA was first analysed with patient samples to understand reagent lot variation in three common APTT reagents: Pathromtin SL, Actin FS, and Actin FSL. A total of 1055 healthy volunteers were also recruited from seven institutions across the Asia-Pacific region and CWA data were collected with the Sysmex CS analysers. (3) Results: CWA parameters varied less than 10% between lots and the linear mixed model analysis showed few site-specific effects within the same reagent group. However, the CWA parameters were significantly different amongst all reagent groups and thus reagent-specific 95% reference intervals could be calculated using the nonparametric method. Post-hoc analysis showed some degree of influence by age and gender with weak correlation to the CWA (r < 0.3). (4) Conclusions: Reagent type significantly affects APTT-based CWA with minimal inter-laboratory variations with the same coagulometer series that allow for data pooling across laboratories with more evidence required for age- and gender-partitioning.
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Anticoagulantes/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Heparina/efectos adversos , Rivaroxabán/uso terapéutico , Trombocitopenia/inducido químicamente , Trombocitopenia/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trombocitopenia/diagnósticoRESUMEN
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a serious and life-threatening complication occurring after adenovirus-vector COVID-19 vaccines, and is rarely reported after other vaccine types. Herein, we report a case of possible VITT after the Pfizer-BioNTech mRNA vaccine booster, who presented with extensive lower limb deep vein thrombosis, severe thrombocytopenia, markedly elevated D-dimer and positive anti-PF4 antibody occurring 2 weeks post-vaccination, concurrent with a lupus anticoagulant. A complete recovery was made after intravenous immunoglobulin, prednisolone and anticoagulation with the oral direct Xa inhibitor rivaroxaban. The presenting features of VITT may overlap with those of antiphospholipid syndrome associated with anti-PF4 and immune thrombocytopenia. We discuss the diagnostic considerations in VITT and highlight the challenges of performing VITT confirmatory assays in non-specialized settings. The set of five diagnostic criteria for VITT is a useful tool for guiding initial management, but may potentially include patients without VITT. The bleeding risks of severe thrombocytopenia in the face of thrombosis, requiring anticoagulant therapy, present a clinical challenge, but early recognition and management can potentially lead to favorable outcomes.
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COVID-19 and metabolic syndrome, though seemingly different disorders, appear to share certain common pathogenic components, especially in the development of COVID-19-associated diabetes mellitus. The similarities include impairment in immunoendothelial, gastrointestinal, pancreatic, adipose and mitochondrial functions, with several critical micronutrients undergirding the intricate interactions among these dysfunctions. This discussion aims to highlight the parallels between COVID-19 and metabolic syndrome and to propose the possibility of SARS-CoV-2 being a prototype of an acquired etiological agent which can eventually lead to the development of classical metabolic syndrome. Based on the proposed model, the discussion will include the implication for early management of COVID-19 and metabolic syndrome.
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OBJECTIVES: Thrombin generation assays and activated partial thromboplastin time (aPTT)-based clot waveform analysis (CWA), are some examples of global coagulation assays. Each modality evaluates different aspects of the clot forming process to globally define haemostasis with exclusive measurement parameters. Data on CWA are emerging, but its performance against other haemostatic assays is yet to be ascertained. This study evaluates the correlation between aPTT-based CWA and CAT parameters across a range of INR in warfarin-treated patients. PATIENTS/METHODS: A prospective study consisting of patients on warfarin anticoagulation with varying INR levels. CWA and CAT were performed for the study subjects. RESULTS: 54 samples were included covering an INR range from 1.33-6.89, with a mean of 4.31 +/- 1.13. For CAT parameters, endogenous thrombin potential (ETP) and peak thrombin were assessed. Both unadjusted and adjusted (adjusted for final plateau transmittance) aPTT-based CWA were evaluated for parameters min1 (maximum velocity), min2 (maximum acceleration) and max2 (maximum deceleration). Peak thrombin showed significant correlation with all CWA parameters (min1: r = 0.435, P<0.001; min2: r = 0.485, P<0.001; max2: r = 0.578, P<0.001; adjusted min1: r = 0.734, P<0.001, adjusted min2: r = 0.693, P<0.001; adjusted max2: r = 0.751, P<0.001). ETP correlated significantly with all CWA parameters except unadjusted min1 (min1: r = 0.235, P = 0.087; min2: r = 0.326, P = 0.016; max2: r = 0.437, P<0.001; adjusted min1: r = 0.610, P<0.001, adjusted min2: r = 0.563, P<0.001; adjusted max2: r = 0.642, P<0.001). CONCLUSION: We demonstrated a modest correlation between CAT and CWA parameters. Adjusted CWA improved this correlation. These findings provide additional understanding of CWA and it's role in the evaluation of global haemostatic function.
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Pruebas de Coagulación Sanguínea/métodos , Coagulación Sanguínea/efectos de los fármacos , Trombina/efectos de los fármacos , Warfarina/uso terapéutico , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Warfarina/farmacologíaRESUMEN
The epidemiology of cancer associated thrombosis (CAT) in Asia is less well-studied and differs from that in the western countries. Here, we systematically examine population based and hospital-based studies reported between 1995 and 2020 to understand the epidemiology of CAT in Asia. From population-based studies, the estimated incidence of VTE in cancer patients was 1.85-9.88 per 1,000 person-years. The incidence of CAT in Asia is significantly higher than non-cancer associated VTE in the general population and cancer is perhaps the most important risk factor for VTE. Hospital-based studies were heterogeneous in study designs and reveal a wide range of prevalence of VTE among cancer patients at 0.5-44.6% while the cancer prevalence rates among VTE patients ranged from 6.1 to 65.5%. The cancer sites most associated with VTE and risk factors were similar between Asian and Western studies. CAT has a major impact on the survival of patients with cancer in Asia, but thromboprophylaxis is not commonly practiced and validated risk assessment tools are lacking. This study highlights the urgent need for large multinational epidemiological studies in Asia to establish the true burden of CAT and to guide appropriate prevention strategies.