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1.
Swiss Med Wkly ; 151: w30084, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1573820

ABSTRACT

We report the occurrence of immune thrombocytopenia (ITP) in a 77-year-old man a few days after receiving the first dose of the COVID-19 mRNA vaccine tozinameran (Comirnaty®). The patient was treated with systemic corticosteroids, intravenous immunoglobulins and eltrombopag. He elected to proceed with the second dose of tozinameran 14 weeks after the first and his platelet count remained stable under a tapered eltrombopag dose. To our knowledge, this is the first case in which a second tozinameran dose has been administered to a patient who developed presumed secondary ITP after the first vaccination. We also report global pharmacovigilance data for the occurrence of ITP after vaccination with tozinameran.


Subject(s)
COVID-19 , Purpura, Thrombocytopenic, Idiopathic , Aged , COVID-19 Vaccines , Humans , Pharmacovigilance , Purpura, Thrombocytopenic, Idiopathic/chemically induced , SARS-CoV-2 , Vaccines, Synthetic
2.
J Korean Med Sci ; 36(43): e306, 2021 Nov 08.
Article in English | MEDLINE | ID: covidwho-1566642

ABSTRACT

Immune thrombocytopenia (ITP) is an autoimmune condition characterized by platelet destruction through antibody-mediated mechanism. ITP is one of the manifestations of a coronavirus disease, as well as an adverse event occurring after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several cases of ITP have been described after vaccination with two mRNA-based vaccines-BTN162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)-against SARS-CoV-2. Herein, we report a case of ITP occurring after vaccination with ChAdOx1 adenovirus vector nCoV-19 (AstraZeneca) vaccine in Korea. A 66-year-old woman presented with multiple ecchymoses on both upper and lower extremities and gingival bleeding, appearing 3 days after receiving the first dose of ChAdOx1 nCoV-19. Her laboratory results showed isolated severe thrombocytopenia without evidence of combined coagulopathy. She was diagnosed with ITP and successfully treated with high-dose dexamethasone and intravenous immunoglobulin. Clinical suspicion to identify vaccine-related ITP is important to promptly initiate appropriate treatment.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Ecchymosis/etiology , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Vaccination/adverse effects , Aged , COVID-19/epidemiology , COVID-19 Vaccines/adverse effects , Dexamethasone/therapeutic use , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Periodontal Index , Purpura, Thrombocytopenic, Idiopathic/drug therapy , SARS-CoV-2
3.
J Korean Med Sci ; 36(43): e306, 2021 Nov 08.
Article in English | MEDLINE | ID: covidwho-1506220

ABSTRACT

Immune thrombocytopenia (ITP) is an autoimmune condition characterized by platelet destruction through antibody-mediated mechanism. ITP is one of the manifestations of a coronavirus disease, as well as an adverse event occurring after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several cases of ITP have been described after vaccination with two mRNA-based vaccines-BTN162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)-against SARS-CoV-2. Herein, we report a case of ITP occurring after vaccination with ChAdOx1 adenovirus vector nCoV-19 (AstraZeneca) vaccine in Korea. A 66-year-old woman presented with multiple ecchymoses on both upper and lower extremities and gingival bleeding, appearing 3 days after receiving the first dose of ChAdOx1 nCoV-19. Her laboratory results showed isolated severe thrombocytopenia without evidence of combined coagulopathy. She was diagnosed with ITP and successfully treated with high-dose dexamethasone and intravenous immunoglobulin. Clinical suspicion to identify vaccine-related ITP is important to promptly initiate appropriate treatment.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Ecchymosis/etiology , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Vaccination/adverse effects , Aged , COVID-19/epidemiology , COVID-19 Vaccines/adverse effects , Dexamethasone/therapeutic use , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Periodontal Index , Purpura, Thrombocytopenic, Idiopathic/drug therapy , SARS-CoV-2
5.
Vaccine ; 39(48): 7052-7057, 2021 11 26.
Article in English | MEDLINE | ID: covidwho-1487997

ABSTRACT

Emerging evidence suggest a possible association between immune thrombocytopenia (ITP) and some formulations of COVID-19 vaccine. We conducted a retrospective case series of ITP following vaccination with Vaxzevria ChadOx1-S (AstraZeneca) and mRNA Comirnaty BNT162b2 COVID-19 (Pfizer-BioNTech) vaccines and compare the incidence to expected background rates for Victoria during the first six months of the Australian COVID-19 vaccination roll-out in 2021. Cases were identified by reports to the Victorian state vaccine safety service, SAEFVIC, of individuals aged 18 years or older presenting with thrombocytopenia following COVID-19 vaccination without evidence of thrombosis. Twenty-one confirmed or probable cases of ITP were identified following receipt of AstraZeneca (n = 17) or Pfizer-BioNTech (n = 4) vaccines. This translates to an observed incidence of 8 per million doses for AstraZeneca vaccine, twice the expected background rate of 4.1 per million. The observed rate for Pfizer-BioNTech was consistent with the expected background rate. The median time to onset for the cases post AstraZeneca vaccination was 10 days (range 1-78) and median platelet nadir 5 × 109/L (range 0-67 × 109/L). Hospital presentations or admissions for management of symptoms such as bleeding occurred in 18 (86%) of the cases. The majority of cases (n = 11) required intervention with at least 2 therapy modalities. In conclusion, we observed a substantially higher than expected rate of ITP following AstraZeneca vaccination. ITP is the second haematological adverse event, distinct from that of thrombosis with thrombocytopenia syndrome (TTS), observed following AstraZeneca vaccination.


Subject(s)
COVID-19 , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Vaccines , COVID-19 Vaccines , Humans , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Retrospective Studies , SARS-CoV-2 , Vaccination , Victoria/epidemiology
7.
BMJ Case Rep ; 14(9)2021 Sep 27.
Article in English | MEDLINE | ID: covidwho-1440813

ABSTRACT

A 40-year-old man with no cardiac history presented with central chest pain 8 days after receiving the ChAdOx1 nCov-19 vaccine against COVID-19. Initial blood tests demonstrated a thrombocytopaenia (24×109 µg/L) and a raised d-dimer (>110 000 µg/L), and he was urgently transferred to our tertiary referral central for suspected vaccine-induced immune thrombocytopaenia and thrombosis (VITT). He developed dynamic ischaemic electrocardiographic changes with ST elevation, a troponin of 3185 ng/L, and regional wall motion abnormalities. An occlusion of his left anterior descending coronary artery was seen on CT coronary angiography. His platelet factor-4 (PF-4) antibody returned strongly positive. He was urgently treated for presumed VITT with intravenous immunoglobulin, methylprednisolone and plasma exchange, but remained thrombocytopaenic and was initiated on rituximab. Argatroban was used for anticoagulation for his myocardial infarction while he remained thrombocytopaenic. After 6 days, his platelet count improved, and his PF-4 antibody level, troponin and d-dimer fell. He was successfully discharged after 14 days.


Subject(s)
COVID-19 , Myocardial Infarction , Purpura, Thrombocytopenic, Idiopathic , ST Elevation Myocardial Infarction , Thrombocytopenia , Thrombosis , Vaccines , Adult , COVID-19 Vaccines , Electrocardiography , Humans , Male , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Purpura, Thrombocytopenic, Idiopathic/drug therapy , SARS-CoV-2 , ST Elevation Myocardial Infarction/etiology
9.
Front Immunol ; 12: 728513, 2021.
Article in English | MEDLINE | ID: covidwho-1394762

ABSTRACT

VITT is a rare, life-threatening syndrome characterized by thrombotic symptoms in combination with thrombocytopenia, which may occur in individuals receiving the first administration of adenoviral non replicating vectors (AVV) anti Covid19 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) is characterized by high levels of serum IgG that bind PF4/polyanion complexes, thus triggering platelet activation. Therefore, identification of the fine pathophysiological mechanism by which vaccine components trigger platelet activation is mandatory. Herein, we propose a multistep mechanism involving both the AVV and the neo-synthetized Spike protein. The former can: i) spread rapidly into blood stream, ii), promote the early production of high levels of IL-6, iii) interact with erythrocytes, platelets, mast cells and endothelia, iv) favor the presence of extracellular DNA at the site of injection, v) activate platelets and mast cells to release PF4 and heparin. Moreover, AVV infection of mast cells may trigger aberrant inflammatory and immune responses in people affected by the mast cell activation syndrome (MCAS). The pre-existence of natural antibodies binding PF4/heparin complexes may amplify platelet activation and thrombotic events. Finally, neosynthesized Covid 19 Spike protein interacting with its ACE2 receptor on endothelia, platelets and leucocyte may trigger further thrombotic events unleashing the WITT syndrome.


Subject(s)
Antibodies/adverse effects , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Purpura, Thrombocytopenic, Idiopathic/physiopathology , Adenoviridae/genetics , Animals , Blood Platelets/immunology , Blood Platelets/pathology , COVID-19 Vaccines/immunology , Disease Models, Animal , Genetic Vectors , Humans , Mice , Platelet Activation/immunology , Platelet Factor 4 , Rabbits
10.
J Autoimmun ; 121: 102662, 2021 07.
Article in English | MEDLINE | ID: covidwho-1385817

ABSTRACT

Herein, we consider venous immunothrombotic mechanisms in SARS-CoV-2 infection and anti-SARS-CoV-2 DNA vaccination. Primary SARS-CoV-2 infection with systemic viral RNA release (RNAaemia) contributes to innate immune coagulation cascade activation, with both pulmonary and systemic immunothrombosis - including venous territory strokes. However, anti-SARS-CoV-2 adenoviral-vectored-DNA vaccines -initially shown for the ChAdOx1 vaccine-may rarely exhibit autoimmunity with autoantibodies to Platelet Factor-4 (PF4) that is termed Vaccine-Induced Thrombotic Thrombocytopenia (VITT), an entity pathophysiologically similar to Heparin-Induced Thrombocytopenia (HIT). The PF4 autoantigen is a polyanion molecule capable of independent interactions with negatively charged bacterial cellular wall, heparin and DNA molecules, thus linking intravascular innate immunity to both bacterial cell walls and pathogen-derived DNA. Crucially, negatively charged extracellular DNA is a powerful adjuvant that can break tolerance to positively charged nuclear histone proteins in many experimental autoimmunity settings, including SLE and scleroderma. Analogous to DNA-histone interactons, positively charged PF4-DNA complexes stimulate strong interferon responses via Toll-Like Receptor (TLR) 9 engagement. A chain of events following intramuscular adenoviral-vectored-DNA vaccine inoculation including microvascular damage; microbleeding and platelet activation with PF4 release, adenovirus cargo dispersement with DNA-PF4 engagement may rarely break immune tolerance, leading to rare PF4-directed autoimmunity. The VITT cavernous sinus cerebral and intestinal venous territory immunothrombosis proclivity may pertain to venous drainage of shared microbiotal-rich areas of the nose and in intestines that initiates local endovascular venous immunity by PF4/microbiotal engagement with PF4 autoantibody driven immunothrombosis reminiscent of HIT. According to the proposed model, any adenovirus-vectored-DNA vaccine could drive autoimmune VITT in susceptible individuals and alternative mechanism based on molecular mimicry, vaccine protein contaminants, adenovirus vector proteins, EDTA buffers or immunity against the viral spike protein are secondary factors. Hence, electrochemical DNA-PF4 interactions and PF4-heparin interactions, but at different locations, represent the common denominator in HIT and VITT related autoimmune-mediated thrombosis.


Subject(s)
Autoantibodies/immunology , COVID-19/immunology , Purpura, Thrombocytopenic, Idiopathic/immunology , SARS-CoV-2/immunology , Thrombosis/immunology , Vaccines/adverse effects , COVID-19/pathology , COVID-19/prevention & control , Humans , Platelet Activation/immunology , Platelet Factor 4/immunology , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Purpura, Thrombocytopenic, Idiopathic/pathology , Thrombosis/chemically induced , Thrombosis/pathology , Vaccines/immunology
12.
J Stroke Cerebrovasc Dis ; 30(11): 106072, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1377775

ABSTRACT

Recently cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) and thrombosis following the adenoviral vector vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were reported. A mechanism similar to heparin-induced thrombocytopenia was proposed with antibodies to platelet factor 4 (PF4). Vaccine related arterial thrombosis in the brain is rare but life-threatening and optimal treatment is not established. We report clinical, laboratory, imaging findings and treatment in a 51-year-old female presenting with acute left middle cerebral artery (MCA) occlusion 7 days after the first dose of ChAdOx1 nCoV-19 vaccine. Due to low platelet count and suspicion of VITT she was not eligible for intravenous thrombolysis (IVT) and proceeded to mechanical thrombectomy (MER) with successful recanalization four hours after onset of symptoms. Treatment with intravenous immunoglobulin (IVIG) and heparin pentasaccharide fondaparinux was initiated. Presence of anti-PF4 antibodies was confirmed. The patient improved clinically with normalization of platelet count. Clinicians should be alert of VITT in patients with acute ischemic stroke after ChAdOx1 nCov-19 vaccination and low platelet counts. MER showed to be feasible and effective. We propose considering MER in patients with VITT and large vessel occlusion despite thrombocytopenia. High-dose IVIG should be started immediately. Alternative anticoagulation to heparin should be started 24 hours after stroke onset unless significant hemorrhagic transformation occurred. Platelet transfusion is contraindicated and should be considered only in severe hemorrhagic complications. Restenosis or reocclusion of the revascularized artery is possible due to the hypercoagulable state in VITT and angiographic surveillance after the procedure is reasonable.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Infarction, Middle Cerebral Artery/chemically induced , Ischemic Stroke/chemically induced , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Anticoagulants/therapeutic use , COVID-19/immunology , COVID-19/virology , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Infarction, Middle Cerebral Artery/diagnostic imaging , Infarction, Middle Cerebral Artery/immunology , Infarction, Middle Cerebral Artery/therapy , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/immunology , Ischemic Stroke/therapy , Middle Aged , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Purpura, Thrombocytopenic, Idiopathic/immunology , Purpura, Thrombocytopenic, Idiopathic/therapy , Thrombectomy , Treatment Outcome
13.
J Obstet Gynaecol Res ; 47(11): 4077-4080, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1367347

ABSTRACT

Over 26 million cases of coronavirus disease 2019 (COVID-19) have been reported in the United States with over 440 000 deaths. Despite COVID-19 vaccine approval, pregnant women were excluded from clinical trials. We report a case of immune thrombocytopenia in the first trimester, which occurred 13 days after initiating the COVID-19 vaccination series. Thorough evaluation, including hematology consultation, established the diagnosis. High-dose oral corticosteroids were started, and she was discharged home with significant improvement in platelet count on her fourth day of hospitalization with no subsequent complications. We advocate that the benefits of COVID-19 vaccination outweigh the risk of infection in pregnancy and that pregnant women should be included in clinical trials. Closer post-vaccination surveillance may be warranted in the pregnant population pending further data.


Subject(s)
COVID-19 , Purpura, Thrombocytopenic, Idiopathic , COVID-19 Vaccines , Female , Humans , Pregnancy , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Purpura, Thrombocytopenic, Idiopathic/diagnosis , SARS-CoV-2 , United States , Vaccination
16.
Nat Commun ; 12(1): 4663, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1338537

ABSTRACT

Vaccine-induced thrombotic thrombocytopenia with cerebral venous thrombosis is a syndrome recently described in young adults within two weeks from the first dose of the ChAdOx1 nCoV-19 vaccine. Here we report two cases of malignant middle cerebral artery (MCA) infarct and thrombocytopenia 9-10 days following ChAdOx1 nCoV-19 vaccination. The two cases arrived in our facility around the same time but from different geographical areas, potentially excluding epidemiological links; meanwhile, no abnormality was found in the respective vaccine batches. Patient 1 was a 57-year-old woman who underwent decompressive craniectomy despite two prior, successful mechanical thrombectomies. Patient 2 was a 55-year-old woman who developed a fatal bilateral malignant MCA infarct. Both patients manifested pulmonary and portal vein thrombosis and high level of antibodies to platelet factor 4-polyanion complexes. None of the patients had ever received heparin in the past before stroke onset. Our observations of rare arterial thrombosis may contribute to assessment of possible adverse effects associated with COVID-19 vaccination.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/immunology , Cerebral Infarction/chemically induced , Purpura, Thrombocytopenic, Idiopathic/chemically induced , SARS-CoV-2/immunology , Thrombosis/chemically induced , Autoantibodies/blood , Autoantibodies/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Cerebral Infarction/diagnostic imaging , Computed Tomography Angiography/methods , Female , Humans , Magnetic Resonance Imaging/methods , Middle Aged , Platelet Factor 4/immunology , Purpura, Thrombocytopenic, Idiopathic/diagnostic imaging , SARS-CoV-2/physiology , Thrombosis/diagnostic imaging , Tomography, X-Ray Computed/methods , Vaccination/adverse effects , Venous Thrombosis/chemically induced , Venous Thrombosis/diagnostic imaging
19.
J Thromb Haemost ; 19(9): 2263-2267, 2021 09.
Article in English | MEDLINE | ID: covidwho-1297836

ABSTRACT

BACKGROUND: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) following the administration of the AstraZeneca (AZ) ChAdOx1 nCOV-19 vaccine has recently been reported. The associated clinical and laboratory features have included thrombosis at unusual sites, thrombocytopenia, and raised D-dimers with positivity for IgG anti-platelet factor 4 (PF4) antibodies. OBJECTIVES: A UK National External Quality Control Assessment Scheme external quality control exercise was carried out by distributing liquid and lyophilized samples from a subject with VITT, a pool of samples from subjects with classical heparin-induced thrombocytopenia (HIT), and a non-VITT/non-HIT case to 85 centers performing HIT testing. METHODS: Participating centers employed their locally validated testing methods for HIT assays. RESULTS: The lyophilized and liquid samples were found to be commutable for the ELISA assays used in the detection of anti-PF4 antibodies. The Aeskulisa, Stago, Hyphen, and LIFECODES anti-PF4 ELISA assays successfully detected the VITT antibody, whereas the Acustar HIT, Werfen LIA, and the Stago STIC assays did not. CONCLUSION: It is important that clinical and laboratory teams are aware of the limitations of some anti-PF4 assays when using them to aid diagnosis of VITT syndrome.


Subject(s)
Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Thrombosis , Vaccines , COVID-19 Vaccines , Heparin/adverse effects , Humans , Platelet Factor 4 , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , United Kingdom
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