Vaccine-induced immune thrombotic thrombocytopenia: what do we know hitherto?

Vaccine-induced immune thrombotic thrombocytopenia (VITT), also known as thrombosis with thrombocytopenia syndrome, is a catastrophic and life-threatening reaction to coronavirus disease 2019 (COVID-19) vaccines, which occurs disproportionately in response to vaccination with non-replicating adenovirus vector (AV) vaccines. The mechanism of VITT is not well defined and it has not been resolved why cases of VITT are predominated by vaccination with AV vaccines. However, virtually all VITT patients have positive platelet-activating anti-platelet factor 4 (PF4) antibody titers. Subsequently, platelets are activated and depleted in an Fcγ-receptor IIa (FcγRIIa or CD32a)-dependent manner, but it is not clear why or how the anti-PF4 response is mounted. This review describes the pathogenesis of VITT and provides insight into possible mechanisms that prompt the formation of a PF4/polyanion complex, which drives VITT pathology, as an amalgam of current experimental data or hypotheses.

A case report of vaccine-induced immune thrombotic thrombocytopenia (VITT) with genetic analysis.

The emergence of the rare syndrome called vaccine-induced immune thrombocytopenia and thrombosis (VITT) after adenoviral vector vaccines, including ChAdOx1 nCov-19, raises concern about one's predisposing risk factors. Here we report the case of a 56-year-old white man who developed VITT leading to death within 9 days of symptom onset. He presented with superior sagittal sinus thrombosis, right frontal intraparenchymal hematoma, frontoparietal subarachnoid and massive ventricular hemorrhage, and right lower extremity arterial and venous thrombosis. His laboratory results showed elevated D-dimer, C-reactive protein, tissue factor, P-selectin (CD62p), and positive anti-platelet factor 4. The patient's plasma promoted higher CD62p expression in healthy donors' platelets than the controls. Genetic investigation on coagulation, thrombophilia, inflammation, and type I interferon-related genes was performed. From rare variants in European or African genomic databases, 68 single-nucleotide polymorphisms (SNPs) in one allele and 11 in two alleles from common SNPs were found in the patient genome. This report highlights the possible relationship between VITT and genetic variants. Additional investigations regarding the genetic predisposition of VITT are needed.

Whole Blood Procoagulant Platelet Flow Cytometry Protocol for Heparin-Induced Thrombocytopenia (HIT) and Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Testing.

Heparin-induced thrombocytopenia (HIT) is a well-characterized, iatrogenic complication of heparin anticoagulation with significant morbidity. In contrast, vaccine-induced immune thrombotic thrombocytopenia (VITT) is a recently recognized severe prothrombotic complication of adenoviral vaccines, including the ChAdOx1 nCoV-19 (Vaxzevria, AstraZeneca) and Ad26.COV2.S (Janssen, Johnson & Johnson) vaccines against COVID-19. The diagnosis of HIT and VITT involve laboratory testing for antiplatelet antibodies by immunoassays followed by confirmation by functional assays to detect platelet-activating antibodies. Functional assays are critical to detect pathological antibodies due to the varying sensitivity and specificity of immunoassays. This chapter presents a protocol for a novel whole blood flow cytometry-based assay to detect procoagulant platelets in healthy donor blood in response to plasma from patients suspected of HIT or VITT. A method to identify suitable healthy donors for HIT and VITT testing is also described.

Coagulopathies after vaccination against SARS-CoV-2: The sole solution might lead to another problem

The common reported adverse impacts of COVID-19 vaccination include the injection site's local reaction followed by various non-specific flu-like symptoms. Nevertheless, uncommon cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) and cerebral venous sinus thrombosis (CVST) following viral vector vaccines (ChAdOx1 nCoV-19 vaccine, Ad26.COV2 vaccine) have been reported. This literature review was performed using PubMed and Google Scholar databases using appropriate keywords and their combinations: SARS-CoV-2, adenovirus, spike protein, thrombosis, thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia (VITT), NF-kappaB, adenoviral vector, platelet factor 4 (PF4), COVID-19 Vaccine, AstraZeneca COVID vaccine, ChAdOx1 nCoV-19 COVID vaccine, AZD1222 COVID vaccine, coagulopathy. The s and titles of each article were assessed by authors for screening and inclusion English reports about post-vaccine CVST and VITT in humans were also collected. Some SARS-CoV-2 vaccines based on viral vector, mRNA, or inactivated SARS-CoV-2 virus have been accepted and are being pragmatic global. Nevertheless, the recent augmented statistics of normally very infrequent types of thrombosis associated with thrombocytopenia have been stated, predominantly in the context of the adenoviral vector vaccine ChAdOx1 nCoV-19 from Astra Zeneca. The numerical prevalence of these side effects seems to associate with this particular vaccine type, i.e., adenoviral vector-based vaccines, but the meticulous molecular mechanisms are still not clear. The present review summarizes the latest data and hypotheses for molecular and cellular mechanisms into one integrated hypothesis demonstrating that coagulopathies, including thromboses, thrombocytopenia, and other associated side effects, are correlated to an interaction of the two components in the COVID-19 vaccine.Copyright © 2022, Iranian Pediatric Hematology and Oncology Society. All rights reserved.

Anti-PF4 antibodies associated with disease severity in COVID-19.

Severe COVID-19 is characterized by a prothrombotic state associated with thrombocytopenia, with microvascular thrombosis being almost invariably present in the lung and other organs at postmortem examination. We evaluated the presence of antibodies to platelet factor 4 (PF4)-polyanion complexes using a clinically validated immunoassay in 100 hospitalized patients with COVID-19 with moderate or severe disease (World Health Organization score, 4 to 10), 25 patients with acute COVID-19 visiting the emergency department, and 65 convalescent individuals. Anti-PF4 antibodies were detected in 95 of 100 hospitalized patients with COVID-19 (95.0%) irrespective of prior heparin treatment, with a mean optical density value of 0.871 ± 0.405 SD (range, 0.177 to 2.706). In contrast, patients hospitalized for severe acute respiratory disease unrelated to COVID-19 had markedly lower levels of the antibodies. In a high proportion of patients with COVID-19, levels of all three immunoglobulin (Ig) isotypes tested (IgG, IgM, and IgA) were simultaneously elevated. Antibody levels were higher in male than in female patients and higher in African Americans and Hispanics than in White patients. Anti-PF4 antibody levels were correlated with the maximum disease severity score and with significant reductions in circulating platelet counts during hospitalization. In individuals convalescent from COVID-19, the antibody levels returned to near-normal values. Sera from patients with COVID-19 induced higher levels of platelet activation than did sera from healthy blood donors, but the results were not correlated with the levels of anti-PF4 antibodies. These results demonstrate that the vast majority of patients with severe COVID-19 develop anti-PF4 antibodies, which may play a role in the clinical complications of COVID-19.

COVID-19 vaccine affects neither prothrombotic antibody profile nor thrombosis in primary antiphospholipid syndrome: a prospective study.

OBJECTIVE: To explore whether inactivated COVID-19 vaccine influences the profile of prothrombotic autoantibodies and induces thrombotic events in primary antiphospholipid syndrome (APS) patients. METHODS: We enrolled 39 primary APS patients who received two doses of inactivated SARS-CoV-2 vaccine (BBIBPCorV, Sinopharm, Beijing, China) voluntarily in this prospective cohort. Prothrombotic autoantibodies were determined before vaccination and four weeks after the 2nd dose of vaccination. Thrombotic disorders were evaluated via hospital site visits and assessments. RESULTS: There was no significant difference in the presence of all eleven autoantibodies detected before and four weeks after vaccination: for aCL, IgG (14 vs. 16, P= 0.64), IgM (13 vs. 19, P= 0.34), IgA (2 vs. 3, P= 0.64); anti-ß2GP1, IgG (12 vs. 12, P= 1.00), IgM (5 vs. 8, P= 0.36), IgA (4 vs. 3, P= 0.69); aPS/PT IgG (13 vs. 16, P= 0.48), IgM (17 vs. 22, P= 0.26); LAC (22 vs. 28, P= 0.16); aPF4-heparin (0 vs. 0, P= 1.00), and antinuclear antibody (ANA) (23 vs. 26, P= 0.48). Notably, the distribution of aPL profile in pre- and post- vaccination cohort was not affected by SARS-CoV-2 vaccination: for patients with low-risk aPL profile (11 vs. 10, P= 0.799) and patients with high-risk aPL profile (28 vs. 29, P= 0.799), respectively. Furthermore, no case exhibited symptoms of the thrombotic disorder during a minimum follow-up period of 12 weeks. There was no adjustment to the ongoing treatment regimens following SARS-CoV-2 vaccination. CONCLUSIONS: Inactivated SARS-CoV-2 vaccine does not influence the profile of antiphospholipid antibodies and anti-PF4-heparin antibodies nor induces thrombotic events in primary APS patients.

Postmortem PF4 antibodies confirm a rare case of thrombosis thrombocytopenia syndrome associated with ChAdOx1 nCoV-19 anti-COVID vaccination.

We report a case of cerebral venous sinus thrombosis, bilateral adrenal hemorrhage, and thrombocytopenia in a 70-year-old man found dead. He had previously received the ChAdOx1 nCoV-19 vaccine (Vaxzevria®, AstraZeneca) 18 days before, and had since developed unspecific and undiagnosed characteristics of what proved to be a rare case of vaccine-associated thrombocytopenia with thrombosis syndrome (TTS). He was found dead 1 week after the beginning of symptoms (day 25 post-vaccine). Autopsy yielded venous hemorrhagic infarction with the presence of thrombi within dural venous sinuses, and extensive hemorrhagic necrosis of the central part of the adrenal glands. Antibodies against platelet factor 4 (PF4) were strongly positive in postmortem fluids, as measured with an enzyme-linked immunosorbent assay (ELISA). This difficult diagnosis is usually made during the patient's lifetime. After eliminating differential diagnoses, we concluded on a fatal case of vaccine-induced immune TTS with positive anti-PF4 antibodies in cadaveric blood, 3 weeks after ChAdOx1 nCoV-19 vaccination. Specific search for anti-PF4 antibodies in cadaveric blood appears therefore paramount to assess postmortem cases of TTS associated with anti-COVID vaccines.

No changes in hemostasis after COVID-19-heterologous vaccination schedule: A subanalysis of the phase 2 CombiVacS study.

Background: Several cases of unusual thrombotic events and thrombocytopenia were described after vaccination with recombinant adenoviral vectors encoding the spike protein antigen of SARS-CoV-2. Objectives: The objective of this study was to elucidate the impact of a COVID-19 heterologous vaccination schedule, including priming with adenovirus vaccine, on hemostasis profiles. Methods: The present study is a subanalysis of the CombiVacS clinical trial initiated in April 2021 that included adult participants previously vaccinated with a single dose of ChAdOx1-S. Between 8 and 12 weeks after vaccination, they were randomly assigned (2:1) to receive either BNT162b2 vaccine (intervention group, n = 99) or continue observation (control group, n = 50). Samples drawn before and 28 days after a vaccination with BNT162b2 were analyzed for platelet count and markers of hemostasis (D-dimer, anti-PF4 antibodies, cfDNA, PAI-1, thrombin generation, and serum capacity to activate platelets). Results: Platelet count from all participants after receiving BNT162b2 was within the normal range. Anti-PF4 antibodies were present in 26% and 18% of the subjects from the control and intervention groups, respectively, at day 28. In most cases, the levels of anti-PF4 antibodies were high before receiving BNT162b2. Serum from these participants did not activate platelets from healthy controls. There were no differences between the groups in PAI-1 and cfDNA plasma levels. According to the D-dimer plasma concentration, the thrombin generation test showed that none of the participants had a procoagulant profile. Conclusion: Our data suggest that the heterologous vaccination against COVID-19 with ChAdOx1-S and a second dose with BNT162b2 might be safe in terms of haemostasis.

Severe Thrombocytopenia, Thrombosis and Anti-PF4 Antibody after Pfizer-BioNTech COVID-19 mRNA Vaccine Booster-Is It Vaccine-Induced Immune Thrombotic Thrombocytopenia?

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.

Immunvermittelte Sinus- und Hirnvenenthrombosen: VITT und

In this review, we summarise the current knowledge on vaccine-induced immune thrombotic thrombocytopenia (VITT) and new insights into its underlying pathogenesis. VITT is characterised by severe thromboses occurring 5-20 days after vaccination with an adenoviral vector-based SARS-CoV-2 vaccine (AstraZeneca or Johnson & Johnson). Thromboses typically involve the cerebral sinus and venous system. Routine laboratory analyses show thrombocytopenia and high D-dimer levels. The pathogenesis is based on immunological processes similar to those in heparin-induced thrombocytopenia. Accordingly, VITT is associated with high-titre immunoglobulin G directed against platelet factor 4 (PF4). Interaction with adenoviral vector-based vaccines leads to modifications of PF4 allowing antibody-producing cells to identify PF4. Anti-PF4 antibodies activate platelets through Fc gamma IIa receptors. The detection of platelet-activating anti-PF4 antibodies confirms the diagnosis of VITT. Treatment is based on anticoagulation, which inhibits thrombin itself or thrombin formation, and high-dose intravenous immunoglobulin G, which inhibits cell activation via Fc gamma IIa receptors. In severe cases, plasma exchange could also be an option. In some patients, a pre-VITT syndrome precedes VITT. Pre-VITT patients typically present with severe headache before thromboses are manifest. The early identification of a pre-VITT syndrome allows for the prevention of thrombotic complications. The specific dynamics of the immune reaction in VITT correspond to a transient, secondary immune response. Current studies address how PF4 binds to different adenoviral proteins and investigate the functional role of other vaccine components. Some of these factors contribute to the induction of a pro-inflammatory "danger signal" that triggers the first stage of VITT pathogenesis. In the second stage, high-titre anti-PF4 antibodies activate platelets and granulocytes. In a process called NETosis ("neutrophil extracellular traps"), activated granulocytes release DNA. Anti-PF4 antibodies then bind to complexes of PF4 and DNA. This enhances further cell activation via Fc gamma receptors and consequently also the formation of thrombin. At the end of the article, we comment on how the current knowledge on VITT may influence global vaccination campaigns against SARS-CoV-2 and we address how anti-PF4 antibodies may be involved in recurrent arterial and venous thromboses not associated with VITT and HIT.

Central retinal vein occlusion post ChAdOx1 nCoV-19 vaccination - can it be explained by the two-hit hypothesis?

PURPOSE: To report a case of central retinal vein occlusion (CRVO) seven days following the first dose of ChAdOx1 nCoV-19 vaccine and propose a hypothesis for the possible underlying pathogenesis. OBSERVATION: A 31-year-old male presented with CRVO with cystoid macular edema, one week after receiving his first ChAdOx1 nCoV-19 vaccine dose. Apart from mild hyperhomocysteinemia, no major thrombophilic or systemic risk factors were found. Anti-platelet factor 4 antibodies, specific for vaccine-induced immune thrombotic thrombocytopenia, were also negative. However, he tested strongly positive (> 250 U/mL) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG spike antibodies, 2 weeks post the first dose - suggestive of a prior subclinical infection. CONCLUSION: COVID-19 is known to be associated with an altered host one-carbon metabolism resulting in hyperhomocysteinemia. We hypothesize that a prior subclinical infection with COVID-19, the first hit, may have led to hyperhomocysteinemia in our patient and vaccination must have been the second hit that triggered the thrombotic event. Further studies, including correlation of thrombotic complications with IgG antibody titres post-vaccination, are essential in order to better understand the pathogenesis of such events.

Thrombosis after SARS-CoV2 infection or COVID-19 vaccination: will a nonpathologic anti-PF4 antibody be a solution?-A narrative review.

The coronavirus disease 2019 (COVID-19) pandemic was triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a previously unknown strain of coronavirus. To fully understand the consequences and complications of SARS-CoV-2 infections, we have reviewed current literature on coagulation dysfunctions that are related to the disease and vaccination. While COVID-19 is more commonly considered as a respiratory illness, studies indicate that, in addition to respiratory illness, a coagulation dysfunction may develop in individuals after the initial infection, placing them at the risk of developing thrombotic events. Patients who died of COVID-19 had higher levels of D-dimer, a biomarker for blood clot formation and breakdown. Effective treatments for coagulation dysfunctions are critically needed to improve patient survival. On the other hand, antibodies against platelet factor 4 (PF4)/heparin may be found in patients with rare instances of vaccine-induced immunological thrombotic thrombocytopenia (VITT) following vaccination with adenovirus-based vaccines. VITT is characterized by atypical thrombosis and thrombocytopenia, similar to immune-mediated heparin-induced thrombocytopenia (HIT), but with no need for heparin to trigger the immune response. Although both adenovirus-based and mRNA-based vaccines express the Spike protein of SARS-CoV-2, VITT is exclusively related to adenovirus-based vaccines. Due to the resemblance with HIT, the use of heparin is highly discouraged against treating patients with thrombotic thrombocytopenia after SARS-CoV-2 infection or with VITT after vaccination. Intravenous immunoglobulin therapy coupled with anticoagulation is recommended instead. The well-studied anti-PF4 monoclonal antibody RTO, which does not induce pathologic immune complexes in the presence of heparin and has been humanized for a potential treatment modality for HIT, may provide a nonanticoagulant HIT-specific solution to the problem of increased blood coagulation after SARS-CoV-2 infection or the VITT after immunization.

[Heparin-induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia: novel insights on anti-platelet factor 4 antibodies].

The levels of anti-platelet factor 4 (PF4) antibodies, also known as anti-PF4 or heparin complex antibodies, are used to diagnose heparin-induced thrombocytopenia (HIT). In HIT, anti-PF4 antibodies induced by heparin exposure cause thrombocytopenia and thrombosis. However, anti-PF4 antibodies were recently reported to be associated with the development of fatal vaccine-induced immune thrombotic thrombocytopenia (VITT) after adenoviral vector vaccination for coronavirus disease 2019. HIT and VITT are caused by anti-PF4 antibodies and have similar pathological conditions. However, the severity of these conditions differs and the detection sensitivity of their antibodies varies depending on the assays used. Herein, we review HIT and VITT associated with anti-PF4 antibodies.

Vaccine-induced immune thrombotic thrombocytopenia: current evidence, potential mechanisms, clinical implications, and future directions.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) (also termed thrombosis with thrombocytopenia syndrome or vaccine-induced thrombotic thrombocytopenia or vaccine-induced immune thrombocytopenia) is characterized by (i) venous or arterial thrombosis; (ii) mild-to-severe thrombocytopenia; (iii) positive antiplatelet factor 4 (PF4)-polyanion antibodies or anti-PF4-heparin antibodies detected by the HIT (heparin-induced thrombocytopenia) ELISA; (iv) occurring 5-30 days after ChAdOx1 nCoV-19 (AstraZeneca) or Ad26.COV2.S (Johnson & Johnson/Janssen) vaccination. VITT's incidence is 1 per 100 000 vaccinated people irrespective of age and up to 1 in 50 000 for people <50 years of age with the AstraZeneca COVID-19 vaccine. The exact mechanism by which adenovirus-vectored COVID-19 vaccines trigger this syndrome is still unclear, as for the increased risk for acute cerebral sinus venous thrombosis and splanchnic vein thrombosis as compared to other locations of venous thrombotic events. VITT is associated with the detection of anti-PF4 antibodies, unrelated to previous use of heparin therapy. PF4 antibodies are thought to activate platelets via the platelet FcγRIIA receptors leading to further platelet activation that causes thrombosis and thrombocytopenia.

Case of Suspected SARS-CoV-2 Vaccine-induced Immune Thrombotic Thrombocytopenia: Dilemma for Organ Donation.

Several vaccines were developed and rolled out at an unprecedented rate in response to the coronavirus disease-2019 (COVID-19) pandemic. Most vaccines approved globally by WHO for emergency use to combat the pandemic were deemed remarkably effective and safe. Despite the safety, rare incidences of vaccine-induced thrombosis and thrombocytopenia (VITT), sometimes known as vaccine-induced prothrombotic thrombocytopenia (VIPIT), have been reported. We report a case of young female with prothrombotic conditions and suspected VITT who developed catastrophic cerebral venous sinus thrombosis (CVST) and progressed to brain death. We highlight hurdles of organ retrieval from a brain-dead patient with suspected SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia. There is limited data and lack of substantial evidence regarding transplantation of organs from brain-dead patients with suspected VITT. How to cite this article: Tiwari AM, Zirpe KG, Gurav SK, Bhirud LB, Suryawanshi RS, Kulkarni SS. Case of Suspected SARS-CoV-2 Vaccine-induced Immune Thrombotic Thrombocytopenia: Dilemma for Organ Donation. Indian J Crit Care Med 2022;26(4):514-517.

Retrospective review COVID-19 vaccine induced thrombotic thrombocytopenia and cerebral venous thrombosis-what can we learn from the immune response.

INTRODUCTION: Cerebral Venous Thrombosis (CVT), prior to the COVID pandemic, was rare representing 0.5 of all strokes, with the diagnosis made by MRI or CT venography.1-,3 COVID-19 patients compared to general populations have a 30-60 times greater risk of CVT compared to non-affected populations, and up to a third of severe COVID patients may have thrombotic complications.4-8 Currently, vaccines are the best way to prevent severe COVID-19. In February 2021, reports of CVT and Vaccine-induced immune thrombotic thrombocytopenia (VITT) related to adenovirus viral vector vaccines including the Oxford-AstraZeneca vaccine (AZD1222 (ChAdOx1)) and Johnson & Johnson COVID-19 vaccine (JNJ-78436735 (Ad26.COV2·S)), were noted, with a 1/583,000 incidence from Johnson and Johnson vaccine in the United States.11, 12 This study retrospectively analyzed CVT and cross-sectional venography at an Eastern Medical Center from 2018 to 2021, and presents radiographic examples of CVT and what is learned from the immune response. METHODS: After IRB approval, a retrospective review of cross-sectional CTV and MRVs from January 1st 2018 to April 30th 2021, at a single health system was performed. Indications, vaccine status, patient age, sex, and positive finding incidence were specifically assessed during March and April for each year. A multivariable-adjusted trends analysis using Poisson regression estimated venogram frequencies and multivariable logistic regression compared sex, age, indications and vaccination status. RESULTS AND DISCUSSION: From January 1, 2018 to April 30, 2021, (Fig. 1), a total of n = 2206 in patient and emergency room cross-sectional venograms were obtained, with 322 CTVs and 1884 MRVs. In 2018, 2019, 2020, respective totals of cross-sectional venograms were 568, 657, 660, compared to 321 cross-sectional venograms in the first four months of 2021. CTV in 2018, 2019, 2020, respective totals were 51, 86, 97, MRV totals were 517, 571, 563, compared to the 2021 first four month totals of 88 CTVs and 233 MRVs. March, April 2018, 2019, 2020, CTVs respectively were 6, 17, 11, compared to the 2021 first four months of 59 CTVs, comprising 63% of the total 93 CTVs, respective MRVs were 79, 97, 52, compared to 143 MRVs in the first four months of 2021 for 39% of the total 371 MRVs. In March, April 2020 during the pandemic onset, cross-sectional imaging at the East Coast Medical Center decreased, as priorities were on maintaining patient ventilation, high level of care and limiting spread of disease. In March/April 2021, reports of VITT and CVT likely contributed to increased CTVs and MRVs, of 39.65% [1.20-1.63] increase (P < 0.001) from prior. In March, April 2021 of 202 venograms obtained, 158 (78.2.%) were unvaccinated patients, 16 positive for CVT (10.1%), 44 were on vaccinated patients (21.7%), 8 specifically ordered with vaccination as a clinical indication, 2 positive for CVT (4.5%), (odds ratio = 0.52 [0.12-2.38], p = 0.200). CONCLUSION: CTV prior to the COVID pandemic, was rare, responsible for 0.5 of all strokes, at the onset of the pandemic in the East Coast, overall cross-sectional imaging volumes declined due to maintaining ventilation, high levels of care and limiting disease spread, although COVID-19 patients have a 30-60 times greater risk of CVT compared to the general population, and vaccination is currently the best option to mitigate severe disease. In early 2021, reports of adenoviral vector COVID vaccines causing CTV and VITT, led to at 39.65% increase in cross-sectional venography, however, in this study unvaccinated patients in 2021 had higher incidence of CVT (10.1%), compared to the vaccinated patients (4.5%). Clinicians should be aware that VITT CVT may present with a headache 5-30 days post-vaccination with thrombosis best diagnosed on CTV or MRV. If thrombosis is present with thrombocytopenia, platelets <150 × 109, elevated D-Dimer >4000 FEU, and positive anti-PF4 ELISA assay, the diagnosis is definitive.13 VITT CVT resembles spontaneous autoimmune heparin induced thrombocytopenia (HIT), and is postulated to occur from platelet factor 4 (PF4) binding to vaccine adenoviral vectors forming a novel antigen, anti-PF4 memory B-cells and anti-PF4 (VITT) antibodies.14-17.

A probable case of vaccine-induced immune thrombotic thrombocytopenia secondary to Pfizer Comirnaty COVID-19 vaccine.

The accelerated development of various vaccines against COVID-19 was a global effort to curb the COVID-19 pandemic. As a result, several unique vaccine-related adverse events were observed. Vaccine-induced immune thrombotic thrombocytopenia (VITT) has been recognised as a clinically distinct entity with a predisposition for thrombosis at unusual sites with laboratory features of consumptive coagulopathy in addition to anti-PF4 assay seropositivity. The majority of cases reported were associated with adenoviral-based vectors such as ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and Janssen Ad26.COV2.S (Johnson & Johnson). In our online search, we have not found any reports to date of VITT associated with Pfizer-BioNTech Comirnaty mRNA vaccine. We report a case of a previously healthy 76-year-old man who received his first-dose Pfizer Comirnaty vaccine on 11 October 2021 who developed left upper limb swelling on day 2 post-vaccination, which progressively worsened on day 4 post-vaccination. He was confirmed to have left axillary vein thrombosis on computer tomography arteriography/computed tomography venography of left upper limb on day 5 post-vaccination with new onset aphasia with unilateral limb weakness on day 8 post-vaccination. Magnetic resonance imaging/magnetic resonance angiography of the brain confirmed acute left middle cerebral artery thrombosis with infarction. Blood investigations showed thrombocytopenia, elevated D-dimer, hypofibrinogenemia in addition to his unusual sites of thrombosis involving both arterial and venous circulation. His IgG ELISA assay for anti-PF4 antibody was positive.