RESUMO
Severe COVID-19 patients demonstrate hypercoagulability, necessitating thromboprophylaxis. However, less is known about the haemostatic profile in mild COVID-19 patients. We performed an age and gender-matched prospective study of 10 severe and 10 mild COVID-19 patients. Comprehensive coagulation profiling together with Thromboelastography and Clot Waveform Analysis were performed. FBC, PT, APTT, D-dimer, fibrinogen and CWA were repeated every 3 days for both groups and repeat TEG was performed for severe patients up till 15 days. On recruitment, severe patients had markers reflecting hypercoagulability including raised median D-dimer 1.0 µg/mL (IQR 0.6, 1.4) (p = 0.0004), fibrinogen 5.6 g/L (IQR 4.9, 6.6) (p = 0.002), Factor VIII 206% (IQR 171, 203) and vWF levels 265.5% (IQR 206, 321). Mild patients had normal values of PT, aPTT, fibrinogen and D-dimer, and slightly elevated median Factor VIII and von Willebrand factor (vWF) levels. Repeated 3-day assessments for both groups showed declining trends in D-dimer and Fibrinogen. CWA of severe COVID-19 group demonstrated hypercoagulability with an elevated median values of aPTT delta change 78.8% (IQR 69.8, 85.2) (p = 0.001), aPTT clot velocity (min1) 7.8%/s (IQR 6.7, 8.3) (p = 0.001), PT delta change 22.4% (IQR 19.4, 29.5) (p = 0.004), PT min1 7.1%/s (IQR 6.3, 9.0) (p = 0.02), PT clot acceleration (min 2) 3.6%/s2 (IQR 3.2, 4.5) (p = 0.02) and PT clot deceleration (max2) 2.9%/s2 (IQR 2.5, 3.5) (p = 0.02). TEG of severe patients reflected hypercoagulability with significant increases in the median values of CFF MA 34.6 mm (IQR 27.4,38.6) (p = 0.003), CRT Angle 78.9° (IQR 78.3, 80.0) (p = 0.0006), CRT A10 67.6 mm (IQR 65.8, 69.6) (p = 0.007) and CFF A10 32.0 mm (IQR 26.8, 34.0) (p = 0.003). Mild COVID-19 patients had absent hypercoagulability in both CWA and TEG. 2 severe patients developed thromboembolic events while none occurred in the mild COVID-19 group. Mild COVID-19 patients show absent parameters of hypercoagulability in global haemostatic tests while those with severe COVID-19 demonstrated parameters associated with hypercoagulability on the global haemostatic tests together with raised D-Dimer, fibrinogen, Factor VIII and vWF levels.
Assuntos
COVID-19 , Hemostáticos , Trombofilia , Trombose , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , COVID-19/complicações , Fator VIII , Fibrinogênio/análise , Humanos , Estudos Prospectivos , Tromboelastografia , Trombofilia/diagnóstico , Trombofilia/etiologia , Trombose/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Fator de von WillebrandRESUMO
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.
RESUMO
Patients with COVID-19 are known to be at risk of developing both venous, arterial and microvascular thrombosis, due to an excessive immuno-thrombogenic response to the SARS-CoV-2 infection. Overlapping syndromes of COVID-19 associated coagulopathy with consumptive coagulopathy and microangiopathy can be seen in critically ill patients as well. Blood was collected from 12 Intensive Care Unit (ICU) patients with severe COVID-19 who were on either mechanical ventilation or on high flow oxygen with a PaO2/FiO2 ratio of <300 mmHg. Laboratory tests were performed for parameters of haemostasis, clot waveform analysis and anti-phospholipid antibodies. CWA parameters were raised with elevated aPTT median Min1 (clot velocity) 9.3%/s (IQR 7.1-9.9%/s), elevated PT median Min1 10.3%/s (IQR 7.1-11.1%/s), elevated aPTT median Min2 (clot acceleration) 1.5%/s2 (IQR 1.0-1.6%/s2), elevated PT median Min2 5.2%/s2 (3.6-5.7%/s2), elevated aPTT median Max2 (clot deceleration) 1.3%/s2 (IQR 0.8-1.4%/s2) elevated PT median Max2 3.8%/s2 (IQR 2.6-4.2%/s2), increased aPTT median Delta change (decreased light transmission due to increased clot formation) 87.8% (IQR 70.2-91.8%) and PT median Delta change 33.0%. This together with raised median Factor VIII levels of 262.5%, hyperfibrinogenemia (median fibrinogen levels 7.5 g/L), increased median von Willebrand factor antigen levels 320% and elevated median D-dimer levels 1.7 µg/dl support the diagnosis of COVID-19 associated coagulopathy. A lupus anticoagulant was present in 50% of patients. Our laboratory findings further support the view that severe SARS-CoV-2 infection is associated with a state of hypercoagulability.
Assuntos
Coagulação Sanguínea , COVID-19/sangue , Trombofilia/virologia , Adulto , Testes de Coagulação Sanguínea , COVID-19/complicações , COVID-19/fisiopatologia , Estado Terminal , Feminino , Humanos , Inibidor de Coagulação do Lúpus/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombofilia/sangueAssuntos
Betacoronavirus , Infecções por Coronavirus , Mycoplasma pneumoniae , Pandemias , Pneumonia Viral , Adulto , Anticorpos Antibacterianos/sangue , COVID-19 , Coinfecção , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Humanos , Masculino , Mycoplasma pneumoniae/imunologia , Mycoplasma pneumoniae/isolamento & purificação , Pneumonia por Mycoplasma/complicações , Pneumonia Viral/sangue , Pneumonia Viral/complicações , SARS-CoV-2Assuntos
Anemia/etiologia , Betacoronavirus , Transfusão de Sangue/estatística & dados numéricos , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Injúria Renal Aguda/etiologia , Adulto , Idoso , Anemia/terapia , Bancos de Sangue/estatística & dados numéricos , COVID-19 , Doenças Cardiovasculares/complicações , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Evolução Fatal , Feminino , Gastroenteropatias/complicações , Hemorragia Gastrointestinal/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Pandemias , Plasma , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Utilização de Procedimentos e Técnicas , Síndrome do Desconforto Respiratório/etiologia , SARS-CoV-2 , Choque Séptico/complicações , SingapuraAssuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Adulto , Fatores Etários , Antígenos CD/sangue , COVID-19 , China , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Lactato Desidrogenases/sangue , Linfopenia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/fisiopatologia , SARS-CoV-2 , Singapura , TrombocitopeniaAssuntos
Arteriopatias Oclusivas/diagnóstico , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Hemostasia , Isquemia/diagnóstico , Extremidade Inferior/irrigação sanguínea , Pneumonia Viral/diagnóstico , Tromboelastografia , Tromboembolia/diagnóstico , Adulto , Anticoagulantes , Arteriopatias Oclusivas/sangue , Arteriopatias Oclusivas/terapia , Arteriopatias Oclusivas/virologia , COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Procedimentos Endovasculares , Hemostasia/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Humanos , Isquemia/sangue , Isquemia/terapia , Isquemia/virologia , Masculino , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Valor Preditivo dos Testes , SARS-CoV-2 , Tromboembolia/sangue , Tromboembolia/terapia , Tromboembolia/virologia , Fatores de Tempo , Resultado do Tratamento , Fluxo de TrabalhoRESUMO
The underlying immunological mechanisms of immediate-type hypersensitivity reactions (HSR) to COVID-19 vaccines are poorly understood. We investigate the mechanisms of immediate-type hypersensitivity reactions to the Pfizer BNT162b2 vaccine and the response of antibodies to the polyethylene glycol (PEG)ylated lipid nanoparticle after two doses of vaccination. Sixty-seven participants, median age 35 and 77.3% females who tolerated two doses of the BNT162b2 vaccine (non-reactors), were subjected to various blood-sampling time points. A separate group of vaccine reactors (10 anaphylaxis and 37 anonymised tryptase samples) were recruited for blood sampling. Immunoglobulin (Ig)G, IgM and IgE antibodies to the BNT162b2 vaccine, biomarkers associated with allergic reaction, including tryptase for anaphylaxis, complement 5a(C5a), intercellular adhesion molecule 1 (ICAM-1) for endothelial activation and Interleukin (IL)-4, IL-10, IL-33, tumour necrosis factor (TNF) and monocyte chemoattractant protein (MCP-1), were measured. Basophil activation test (BAT) was performed in BNT162b2-induced anaphylaxis patients by flow cytometry. The majority of patients with immediate-type BNT162b2 vaccine HSR demonstrated raised C5a and Th2-related cytokines but normal tryptase levels during the acute reaction, together with significantly higher levels of IgM antibodies to the BNT162b2 vaccine (IgM 67.2 (median) vs. 23.9 AU/mL, p < 0.001) and ICAM-1 when compared to non-reactor controls. No detectable IgE antibodies to the BNT162b2 vaccine were found in these patients. The basophil activation tests by flow cytometry to the Pfizer vaccine, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol (DMG-PEG) and PEG-2000 were negative in four anaphylaxis patients. Acute hypersensitivity reactions post BNT162b2 vaccination suggest pseudo-allergic reactions via the activation of anaphylatoxins C5a and are independent of IgE-mechanisms. Vaccine reactors have significantly higher levels of anti-BNT162b2 IgM although its precise role remains unclear.