An Unusual Case of Combined Thrombosis and Amegakaryocytopenia Resembling Thrombosis With Thrombocytopenia Syndrome Following COVID-19 Infection in an Unvaccinated Patient.

As a global community, we have learned that the manifestations of severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2), infection, or coronavirus disease 2019 (COVID-19), extends far beyond respiratory compromise. Thrombocytopenia is thought to occur secondary to increased platelet consumption. Platelet activation and platelet-mediated immune inflammation contribute towards the thromboembolic complications seen in COVID-19 patients. In this report, the authors present the unusual case of a 75-year-old female with a history of COVID-19 infection who presented with a transient ischemic attack, thrombocytopenia, and amegakaryocytopenia.

Acute limb ischemia secondary to vaccine-induced thrombotic thrombocytopenia.

Vaccine-associated thrombosis has previously been described in patients presenting with cerebral sinus thrombosis, deep venous thrombosis/pulmonary embolism, or mesenteric venous thrombosis. Only recently has arterial thrombosis gained attention. A new entity known as vaccine-induced thrombotic thrombocytopenia (VITT) has been associated with the coronavirus disease of 2019 (COVID-19) vaccines produced by AstraZeneca and Johnson & Johnson. We describe a case series of three patients who presented with acute limb ischemia with vaccine-associated arterial occlusions, one of whom was diagnosed with VITT.

Pituitary apoplexy and COVID-19 vaccination: a case report and literature review.

A 50-year-old man was admitted to our hospital for vomit, nausea, diplopia, and headache resistant to analgesic drugs. Symptoms started the day after his third COVID-19 mRNA vaccine (Moderna) whereas SARS-CoV-2 nasal swab was negative. Pituitary MRI showed recent bleeding in macroadenoma, consistent with pituitary apoplexy. Adverse Drug Reaction was reported to AIFA (Italian Medicines Agency).A stress dexamethasone dose was administered due to the risk of adrenal insufficiency and to reduce oedema. Biochemistry showed secondary hypogonadism; inflammatory markers were elevated as well as white blood cells count, fibrinogen and D-dimer. Pituitary tumour transsphenoidal resection was performed and pathology report was consistent with pituitary adenoma with focal haemorrhage and necrosis; we found immunohistochemical evidence for SARS-CoV-2 proteins next to pituitary capillaries, in the presence of an evident lymphocyte infiltrate.Few cases of pituitary apoplexy after COVID-19 vaccination and infection have been reported. Several hypotheses have been suggested to explain this clinical picture, including cross-reactivity between SARS-CoV-2 and pituitary proteins, COVID-19-associated coagulopathy, infection-driven acutely increased pituitary blood demand, anti-Platelet Factor 4/heparin antibodies development after vaccine administration. Ours is the first case of SARS-CoV-2 evidence in pituitary tissue, suggesting that endothelial infection of pituitary capillaries could be present before vaccination, possibly due to a previous asymptomatic SARS-CoV-2 infection. Our case underlines that SARS-CoV-2 can associate with apoplexy by penetrating the central nervous system, even in cases of negative nasal swab. Patients with pituitary tumours may develop pituitary apoplexy after exposure to SARS-CoV-2, therefore clinicians should be aware of this risk.

A Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia.

This report discusses a case of a 37-year-old female who developed vaccine-induced thrombotic thrombocytopenia (VITT) after receiving the Johnson and Johnson COVID-19 vaccination. The patient first presented to the ED with complaints of a worsening headache. Labs were significant for thrombocytopenia with a platelet count of 22,000, and the patient was admitted to the inpatient unit for monitoring. The day after admission, the patient was found to have a right common femoral artery embolus, left distal popliteal trifurcation embolism, a small pulmonary embolism in the right lower lobe, and a mural thrombus of the infrarenal abdominal aorta. Following these findings, the patient underwent emergent thrombectomy of the common and superficial femoral arteries. Over the hospital course of six days, the patient received steroids and IV immunoglobulin (IVIG), which led to the resolution of the thrombocytopenia. The patient was given argatroban followed by apixaban for anticoagulation. She was instructed to follow up with hematology within one to two weeks post-discharge for monitoring of anticoagulation and thrombus surveillance. This case report outlines the clinical course, diagnosis, and treatment of a case of VITT, which will assist physicians in early recognition and adequate treatment of this condition as the COVID-19 pandemic continues.

Vaccine-Induced Thrombotic Thrombocytopenia: A Case of Splanchnic Veins Thrombosis.

Vaccines have been vital in preventing and curbing the spread of SARS-CoV-2 infection. Adenoviral vector-based vaccines, namely the ChAdOx1-S vaccine (AstraZeneca, Cambridge, UK) and Ad26.COV2.S (Janssen; Johnson & Johnson, New Brunswick, NJ, USA), have been associated with a possibly fatal adverse event known as vaccine-induced thrombotic thrombocytopenia (VITT), wherein thrombi form in unusual sites, mainly the cerebral and splanchnic veins. With the female gender predominantly affected, patients present with headache, abdominal pain, neurological symptoms and fever. It is hypothesized that certain components of the vaccine, including the adenovirus vector, may trigger the formation of antibodies against platelet factor 4 (PF4). The antigen-antibody complexes that form thereafter then activate a cascade of reactions eventually leading to the consumptive coagulopathy. This pathogenesis closely resembles a well-understood complication of heparin, known as heparin-induced thrombocytopenia. The lab results in VITT are reflective of its proposed pathophysiology: low platelets, low fibrinogen and high D-dimer, in addition to elevated anti-PF4 titers are classic findings. Treatment mainly includes non-heparin anticoagulants, intravenous immune globulin (IVIG) and plasma exchange. There is some role for surgical intervention, such as mechanical thrombectomy. Mortality due to VITT is usually caused by cerebral hemorrhage. We describe a case of a 36-year-old female who presented with epigastric pain two weeks after receiving her first dose of the AstraZeneca vaccine, and upon workup, was subsequently found to have thrombosis of her right portal and right common iliac vein.

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.

Thrombotic Complications after COVID-19 Vaccination: Diagnosis and Treatment Options.

Coronavirus disease 2019 (COVID-19) vaccines were developed a few months after the emergence of the pandemic. The first cases of vaccine-induced thrombotic complications after the use of adenoviral vector vaccines ChAdOx1 nCoV-19 by AstraZeneca, and Ad26.COV2.S by Johnson & Johnson/Janssen, were announced shortly after the initiation of a global vaccination program. In these cases, the occurrence of thrombotic events at unusual sites-predominantly located in the venous vascular system-in association with concomitant thrombocytopenia were observed. Since this new entity termed vaccine-induced thrombotic thrombocytopenia (VITT) shows similar pathophysiologic mechanisms as heparin-induced thrombocytopenia (HIT), including the presence of antibodies against heparin/platelet factor 4 (PF4), standard routine treatment for thrombotic events-arterial or venous-are not appropriate and may also cause severe harm in affected patients. Thrombotic complications were also rarely documented after vaccination with mRNA vaccines, but a typical VITT phenomenon has, to date, not been established for these vaccines. The aim of this review is to give a concise and feasible overview of diagnostic and therapeutic strategies in COVID-19 vaccine-induced thrombotic complications.

Case Report: Hypergranular Platelets in Vaccine-Induced Thrombotic Thrombocytopenia After ChAdOx1 nCov-19 Vaccination.

BACKGROUND: Vaccine-induced thrombotic thrombocytopenia (VITT) post SARS-CoV-2 vaccination is characterized by thrombocytopenia and severe thrombosis. Platelet function during patient recovery in the medium-/long-term has not been investigated fully. Here, we undertook a 3-month study, assessing the recovery of a VITT patient and assessing platelet morphology, granule content and dense-granule release at two distinct time points during recovery. CASE PRESENTATION: A 61 year-old female was admitted to hospital 15 days post ChAdOx1 nCov-19 vaccination. Hematological parameters and peripheral blood smears were monitored over 3 months. Platelet morphology and granule populations were assessed using transmission electron microscopy (TEM) at two distinct time points during recovery, as was agonist-induced platelet dense-granule release. Upon admission, the patient had reduced platelet counts, increased D-dimer and high anti-PF4 antibodies with multiple sites of cerebral venous sinus thrombosis (CVST). Peripheral blood smears revealed the presence of large, hypergranular platelets. Following treatment, hematological parameters returned to normal ranges over the study period. Anti-PF4 antibodies remained persistently high up to 90 days post-admission. Two days after admission, VITT platelets contained more granules per-platelet when compared to day 72 and healthy platelets. Additionally, maximal ATP release (marker of dense-granule release) was increased on day 2 compared to day 72 and healthy control platelets. CONCLUSION: This study highlights a previously unreported observation of platelet hypergranularity in VITT which may contribute to the thrombotic risk associated with VITT. Optimal approaches to monitoring recovery from VITT over time remains to be determined but our findings may help inform therapeutic decisions relating to anticoagulation treatment in this novel pathology.

Bilateral Thalamic Stroke: A Case of COVID-19 Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) or a Coincidence Due to Underlying Risk Factors?

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but potentially life-threatening side effect that has only been observed in adenovirus-based vaccines for coronavirus disease 2019 (COVID-19). VITT is an immune-mediated condition that generally presents within five to 10 days post-vaccination with thrombosis, thrombocytopenia, and coagulation abnormalities. A diagnosis of VITT is made clinically and through laboratory testing. Although VITT is an important differential to consider, it is believed that more emphasis should be placed on vaccination due to the safety and efficacy in overcoming COVID-19.

Review and evolution of guidelines for diagnosis of COVID-19 vaccine induced thrombotic thrombocytopenia (VITT).

Coronavirus disease 2019 (COVID-19) is a life-threatening infectious disease caused by Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). In response to the still ongoing pandemic outbreak, a number of COVID-19 vaccines have been quickly developed and deployed. Although minor adverse events, either local (e.g., soreness, itch, redness) or systematic (fever, malaise, headache, etc.), are not uncommon following any COVID-19 vaccination, one rare vaccine-associated event can cause fatal consequences due to development of antibodies against platelet factor 4 (PF4), which trigger platelet activation, aggregation, and possible resultant thrombosis, often at unusual vascular sites. Termed thrombosis with thrombocytopenia syndrome (TTS) by reporting government agencies, the term vaccine-induced (immune) thrombotic thrombocytopenia (VITT) is more widely adopted by workers in the field. In response to increasing reports of VITT, several expert groups have formulated guidelines for diagnosis and/or management of VITT. Herein, we review some key guidelines related to diagnosis of VITT, and also provide some commentary on their development and evolution.

COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia: A Case Series.

Vaccine-induced thrombotic thrombocytopenia is a life-threatening prothrombotic syndrome that has been associated with two adenoviral vector-based coronavirus disease 2019 (COVID-19) vaccines. Although it remains a rare disorder with relatively low incidence, awareness of this condition is crucial given the ongoing vaccination programs of millions around the world. In this case series, we report four cases of vaccine-induced thrombotic thrombocytopenia, diagnosed at Queen Alexandra Hospital, Portsmouth, United Kingdom. We also review the mechanism of this syndrome, its clinical presentation, diagnosis, and course of treatment with emphasis on the role of therapeutic plasma exchange.

Mechanisms of Immunothrombosis in Vaccine-Induced Thrombotic Thrombocytopenia (VITT) Compared to Natural SARS-CoV-2 Infection.

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.