Abstract

Thrombotic thrombocytopenic purpura (TTP) is a potentially fatal consumptive coagulopathy that requires prompt diagnosis and treatment. It is characterized by microangiopathic hemolytic anemia and thrombocytopenia, with microthrombosis.

COVID-19 vaccination is proven to reduce disease morbidity and mortality. Vaccines have been hypothesized to link to certain autoimmune diseases.

We present the case of a 43-year-old man with no personal or family history of hematologic diseases who admitted with a chief complaint of fever and icterus 15 days after vaccination with the second dose of COVID_19 AstraZeneca (ChAdOx1-S). Clinical and Laboratory data (increased LDH, decreased haptoglobin, and indirect hyperbilirubinemia) was suspicious of TTP. We confirm the diagnosis of TTP With low ADAMTS13. To our knowledge, this is the first Iranian case of vaccine-induced TTP that has been reported.

In conclusion, for accurate diagnosis of patients with clinical symptoms of thrombocytopenia after COVID-19 vaccination, clinicians should be alert to the possibility of acquired TTP.

Keywords: thrombocytopenic purpura; COVID-19; Vaccination.

Citation: Amiri BS, Radkhah H, Taslimi R, Shahbazi Z, Khadembashiri MM. Thrombotic thrombocytopenic purpura a new threat of a savior: A case report. J Clin Images Med Case Rep. 2022; 3(10): 2111.

Introduction

As a potentially fatal consumptive coagulopathy, Thrombotic Thrombocytopenic Purpura (TTP) requires immediate diagnosis and treatment [1].

It is characterized by microangiopathic hemolytic anemia and thrombocytopenia, with microthrombosis as a result of critically decreased activity of the von Willebrand factor-cleaving protease ADAMTS13 and ensuing end-organ damage [1].

ADAMTS132 mutations that are passed down hereditarily can cause TTP. It also can be acquired by an autoantibody inhibitor (which accounts for 95% of cases) [2]. AntiADAMTS13 antibodies can be caused by various factors, including malignancies, pregnancy, medicine, viral infections, and vaccines [3].

An important aspect of preventative medicine is vaccination, and COVID-19 vaccination has been established to reduce morbidity and mortality due to the disease [4].

Recently, after vaccination with the viral vector-based COVID-19 vaccines, alarming hematological abnormalities of rare thromboembolic events were discovered [3].

The correlation between vaccinations and microangiopathic thrombotic issues remains unclear; nevertheless, vaccines have previously been postulated to play a role in initiating certain autoimmune diseases [5].

In this article, we report the first Iranian instance of TTP (Thrombotic thrombocytopenic purpura) following the second dosage of the oxford AstraZeneca vaccination without any underlying condition.

Case report

A 43-year-old man, 15 days after receiving the covid-19 vaccination, was presented to our hospital with a fever and icterus as his chief complaint.

Four days after receiving the second dose of the Covid-19 AstraZeneca vaccine, he complained of epigastric pain and nausea (ChAdOx1-S).

After that, he had a rash relieved by antihistamines (chlorpheniramine).

He was admitted to the hospital a day later with dyspnea and fever.

After four days, he was discharged from the hospital due to normal chest lung CT angiography for pulmonary thromboembolism and negative Covid-19 PCR testing.

According to his discharge sheet, he had normal lab results.

His new symptoms began two days after discharge with arthralgia, severe joint pain accompanied by severe weakness, continuous fever after 5 days, icterus and dark urine, and drowsiness.

His personal and family medical histories were ordinary in terms of thrombotic episodes and autoimmune diseases.

He developed a fever and myalgia for two days after receiving his first vaccination 10 weeks earlier.

In physical examination, he was drowsy but oriented and answered pertinent questions.

When he inhaled ambient air, his oxygen saturation level was 90%, and when he used nasal oxygen, it was 98%.

His temperature was 38,7, Pulse rate: 100/min, Blood pressure: 110/70.

His sclera and skin were icterus. Tenderness in his hand, foot, wrist, and fingers was present, but there was no redness or any symptoms of active arthritis.

Examination of the lung, abdomen and nervous system was otherwise normal.

Table 1 shows his first lab results.

The patient had a 3-minute tonic-clonic seizure on day 3 of his admission, which was brought under control with midazolam after the post-ictal phase, the patient was conscious without any focal neurological deficit, then he became tachypneic in an hour.

Table 1: The course of the patient’s lab tests during admission and discharge data.

Table 2: The main differences betweenThrombocytopenia after covid vaccination, Vaccine-induced TTP, and VITT [17].

He was admitted to the intensive care unit, and the following day, he was intubated due to status epilepticus. His brain CT scan and chest X-ray were also normal during that time.

His new laboratory results revealed progressive thrombocytopenia, anemia, increased creatinine, and a high LDH (Lactate Dehydrogenase) level, all of which were consistent with hemolytic anemia. His PBS (Peripheral Blood Smear) revealed schistocytes, supporting the diagnosis of microangiopathic hemolytic anemia.

Plasmapheresis and dexamethasone were initiated immediately in response to his high plasmic score, and diagnostic lab tests for thrombotic thrombocytopenic purpura and rheumatologic diseases were sent.

After five days of plasmapheresis, plasmapheresis was scheduled twice a day and rituximab was added to the treatment plan because his platelet count did not increase adequately.

TTP was definitively diagnosed based on a decrease in ADAMTS 13 activity (< 10%) and a high ADAMTS 13 inhibition antibody level.

Evaluation for rheumatologic diseases was negative. His plasmapheresis was discontinued when his platelet count returned to normal, as well as his LDH level.

Extubation was accomplished by increasing the patient’s level of consciousness.

His laboratory data from the time he was discharged is on the table. He was discharged with weekly rituximab for 4 weeks.

Discussion

Vaccine-associated autoimmunity is caused by two main mechanisms: Molecular mimicry and an increase in the cascade of immune events leading to abnormal activation of the innate and acquired immune systems. Molecular mimicry is attributed to cross-reactivity between antigens [2]. Type 1 interferon activation and nuclear translocation of transcription factors nuclear factor-kappa B NF-kB contribute to the abnormal activation of the immune system. When it comes to the Pfizer-BioNTech COVID-19 vaccine (mRNA vaccine), the situation is complicated further by the nucleic acid formulation’s accelerated development process and the emergency pandemic situation [2].

After vaccination with the viral vector-based COVID-19 vaccines ChAdOx1 nCoV-19 (Astra Zeneca) and Ad26.COV2.S (Johnson & Johnson), a concerning hematological phenomenon of abnormal thromboembolic events and concurrent thrombocytopenia (dubbed VIPIT/VITT) has been observed [3].

TTP is caused by a quantitative or functional ADAMTS131 deficit that can be passed hereditarily or acquired.

TTP results from an inherited or acquired quantitative or functional deficiency in ADAMTS13 [1]. Acquired TTP is characterized by severe ADAMTS13 deficiency (activity < 10 percent due to inhibitors and autoantibodies against ADAMTS13); patients with inherited ADAMTS13 mutations are said to have inherited TTP [1]. The main differences between thrombocytopenia after covid vaccination, Vaccine-induced TTP, and VITT (Table 2) [8].

The causal relationship between acquired TTP and vaccination is primarily supported by temporal correlations rather than by the identification of cross-reactive epitopes between antigens in these vaccines and ADAMTS13 [6].

Some reports attribute this development to the development of other vaccines, most notably those against influenza viruses [6]. Additionally, TTP occurred following vaccination with the 23-valent pneumococcal polysaccharide [6]. These onset times following COVID-19 vaccination are consistent with those following other vaccinations [6].

TTP is characterized by thrombocytopenia, mechanical hemolysis, anemia, renal failure, neurological dysfunction, and fever [6].

ADAMTS13 detection typically takes days and is thus not a practicable measure but rather a confirmation test. Acute diagnosis is made based on clinical findings and laboratory data [1].

Thrombocytopenia, microangiopathic hemolytic anemia (anemia associated with laboratory values of cytolysis: Increased LDH, decreased haptoglobin, and indirect hyperbilirubinemia), reticulocytosis, and schistocytes in peripheral blood cell smears, and renal failure are all included in the laboratory data [1].

The PLASMIC score is used to predict disease severity and the ability to respond to plasmapheresis [1].

In our case, due to a high PLASMIC score, hemolytic anemia with thrombocytopenia, and neurological symptoms, we initiated plasmapheresis without waiting for the ADAMTS13 level to be determined. We confirm the diagnosis of TTP by assessing the patient’s ADAMTS13 level, which was checked prior to plasma exchange.

The brain MRI was not performed because the neurological symptoms resolved completely and temporarily once the underlying cause was corrected.

Plasmapheresis, steroids, and rituximab are the primary treatments for vaccine-induced TTP [1]. Plasma exchange removes autoantibodies from the circulation while also providing functionally active ADAMTS131. Steroids suppress the immune system [1]. Rituximab is a monoclonal anti-CD20 antibody that depletes B cells and has been shown to reduce the rate of TTP relapse [1].

Caplacizumab, an anti-VWF antibody fragment, has been shown to normalize platelet counts more quickly, with fewer plasma exchanges and a composite of mortality, recurrence, and major thromboembolism compared to placebo. Incident rates are lower [1]. The addition of caplacizumab to Plasmapheresis (PEX) and steroids resulted in a similarly rapid response to that reported in the HERCULES study [7].

Plasmapheresis, corticosteroids, and rituximab were used to treat our case with a rapid and excellent response. Given the clinical presentation, laboratory findings, and absence of thrombosis, Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT) is unlikely, and TTP associated with COVID-19 vaccination is the most likely diagnosis. To our knowledge, this is the first report of an Iranian case of vaccine-induced TTP.

Conclusion

Patients who develop clinical symptoms (such as shortness of breath, neurological symptoms, petechia, or spotting) following COVID-19 vaccination should be encouraged to seek prompt medical attention. Additionally, clinicians should be aware of the possibility of acquired TTP in order to make an early and accurate diagnosis of patients with clinical symptoms of thrombocytopenia following COVID-19 vaccination.

There are some limitations to this interpretation of the association between TTP development and COVID-19 vaccination. First, despite the mass vaccination of millions of people worldwide, only a small number of TTP cases have been reported following COVID-19. Second, although no clinical data were available prior to vaccination, COVID-19 vaccination may have exacerbated pre-existing TTP. Third, the mechanism by which the vaccine induces the generation of new anti-ADAMTS13 antibodies is unknown. Further biological studies are needed to verify when and how inhibitors (antibodies) against ADAMTS13 are produced during the immune response to vaccines such as COVID-19.

Acknowledgment: The authors thank the patient.

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