A rare case of COVID-19 vaccine-induced thrombotic thrombocytopenia in a young patient
A rare case of COVID-19 vaccine-induced thrombotic thrombocytopenia in a young patient

A rare case of COVID-19 vaccine-induced thrombotic thrombocytopenia in a young patient

Pulmonary SARS-Cov-2 syndrome resulted in significant morbidity and mortality, with new variants spreading rapidly. COVID-19 prevention vaccines have been developed to minimize efficacy and severity; however, side effects of the vaccine have been documented in several studies. In our case, we report a case of a young woman who came to the emergency room with fever, dizziness, headache, vomiting, blurred vision, numbness, and weakness in the left upper and lower limbs. This weakness developed rapidly to all limbs within two hours associated with altered behavior and visual hallucinations. The family reported a history of the patient receiving his first dose of COVID-19 AstraZeneca vaccine 18 days before admission. Based on her clinical picture and examination, she was diagnosed with vaccine-induced immune thrombotic thrombocytopenia (VITT). She was successfully treated with intravenous immunoglobulin (IVIG) and direct oral anticoagulant apixaban.

At a time when there is a strategic goal of vaccinating the global population of COVID-19 to inhibit the spread of infection and reduce hospitalization, this particular clinical scenario underscores the need for all clinicians to remain vigilant in the face of rare complications. of the COVID-19 vaccination.

Introduction

Recently, in late February 2021, a very rare prothrombotic disorder in combination with thrombocytopenia has been reported following vaccination with the adenovirus vector-based vaccines ChAdOx1 nCoV-19 from AstraZeneca / Oxford (marketed as Vaxzevria and Covishield) and recently Ad.26.COV2 . S from Janssen (Johnson & Johnson) [1]. This new disorder, known as vaccine-induced immune thrombotic thrombocytopenia (VITT), is associated with high titers of immunoglobulin G class antibodies directed against the cationic platelet chemokine, platelet factor 4 (PF4; CXCL4) [2]. These antibodies activate potent platelets via platelet FcγIIa receptors, with platelet activation greatly enhanced by PF4 [2,3].

VITT syndrome, which mimics autoimmune heparin-induced thrombocytopenia (AHIT), has a characteristic feature of thrombosis in unusual sites, including splanchnic veins, adrenal glands, and cerebral and ophthalmic veins. Arterial thrombosis including ischemic stroke and peripheral arterial occlusion have also occurred, often in people with venous thrombosis. Women and those under the age of 55 are considered to be at higher risk [3,4].

WHITE, with its high mortality and morbidity, should be suspected when a patient develops symptoms such as severe headache, blurred vision, vomiting, altered sensorium, focal neurological deficits, abdominal pain, leg pain and / or swelling or dyspnoea, four to thirty days after vaccination [1,4]. Awareness of VITT, identification of early warning signs and symptoms, with proper handling is essential [4].

In this case study, we report a case of a young woman with life-threatening cerebral venous thrombosis who showed good improvement when appropriate treatment of anticoagulation with a non-heparin direct oral anticoagulant and intravenous immunoglobulin (IVIG) was initiated.

Case presentation

Our patient was a 23-year-old woman who came to the emergency room with fever, dizziness, headache, vomiting, blurred vision, numbness, and weakness in the left upper and lower limbs. This weakness developed rapidly to all limbs within two hours, associated with altered behavior and visual hallucinations. The family reported that the patient received his first dose of COVID-19 AstraZeneca vaccine 18 days before admission. She was a known case of prolactinoma on cabergoline tablet 0.25 mg twice a week.

On examination she was conscious and oriented, but quite irritable, with heart rate 88 / min, respiratory rate 20 / minute, blood pressure 109/70 mmHg, temperature 38 degrees Celsius, oxygen saturation 96% on room air, a normal Glasgow coma scale score and normal students. There was hypertension in all limbs, force was 3/5 and 2/5 on right and left upper and lower limbs respectively. Reflexes were excessive and the plantar response decreased bilaterally. Cranial nerve and meningeal signs were roughly intact. While awaiting laboratory results, an initial brain computed tomography (CT) scan showed no major abnormality.

A possible post-vaccination meningoencephalitis diagnosis was made and treatment was started accordingly, including a small dose of dexamethasone 6 mg injection per day and a prophylactic dose of enoxaparin 40 mg s / c twice daily with close neuromonitoring in the intensive care unit (ICU). .

Lab results revealed pronounced thrombocytopenia; platelet count was 59 x 109 / l with extremely elevated d-dimer of 12600 ng / ml (normal range 70-500 ng / ml), fibrinogen level of 1.8 gm / l (normal range 1.50-4.00 g / l) and other normal pro-coagulating reprocessing. A VITT diagnosis was established. A venogram CT scan of the brain and cerebral sinuses was performed promptly, showing extensive superior sagittal sinus thrombosis with bilateral frontal parietal infarcts (Figure 1). Due to the high degree of suspension of VITT, an enzyme-linked immunosorbent assay (ELISA) test for platelet factor-4 antibody (anti PF4 antibody) was sent to a higher center.

Based on the critical clinical picture of the patient, laboratory results, radiological findings and without waiting for the results of the anti-PD4 antibody, an interdisciplinary decision immediately started IVIG 1 g / kg once daily for two days. Enoxaparin was switched to a non-heparin anticoagulant, direct oral anticoagulant (apixaban 5 mg twice daily) with close observation of platelet levels. As expected, the results of anti-PF4 antibody were positive. A significant improvement in the patient’s neurological condition was evident in a few days. Headache, blurred vision and weakness were markedly improved. On day 10 of admission, the patient was able to walk freely without support. Her platelet count returns to normal.

Discussion

With the rapid development and distribution of vaccines to control the COVID-19 pandemic, trials showed reassuring safety signals, and many received approval [3,4]. Recently, however, a rare, catastrophic hypercoagulative syndrome associated with thrombocytopenia following vaccination with the adenovirus-based vaccines has been reported. This syndrome has been designated as WHITE [2].

The frequency of VITT after the AstraZeneca vaccine varies widely, with most cases occurring in young adults (typically <60 years), especially young women, with no obvious risk factors or known thrombophilia. [3,5]. Although the pathogenesis of VITT is uncertain, many laboratory findings support the theory that the mechanism of thrombocytopenia and thrombosis is similar to the mechanism of autoimmune HIT / T, in that the anti-PF4 antibody is induced by polyanions in bacterial surface nucleic acids, including lipid A. instead of heparin. . Some vaccine components have been suggested as significant aspects that may cause PF4 release and anti-PF4 antibody production in VITT, such as adenovirus DNA, nail protein and / or neoantigen caused by the vaccine [3,6].

Most patients with VITT have an unusual thrombosis site as cerebral veins, splanchnic system, portal and hepatic veins, pulmonary veins, cerebral artery and other systemic sites have been reported [7,8]. The incidence of cerebral venous thrombosis is higher with neurological symptoms, including chronic and severe headaches, vision problems, nausea, seizures, focal neurological deficits, multifocal symptoms, and changes in mental status. Consistent abdominal pain, dyspnoea and / or edema in leg pain are some of the other symptoms [4,7].

In our case, the young woman with no previous thrombosis or family history of thrombophilia presented a new onset of worsening headache, dizziness, and vomiting and signs of increased intracranial pressure 18 days after ChAdOx1 nCov-19 vaccination. Due to the significant mortality and morbidity associated with VITT, a number of guidelines have been rapidly developed with the aim of helping physicians diagnose and manage this rare complication. Successful treatment requires a multidisciplinary approach, as in this case, which involved intensive care, hematology, neurology and neurosurgery.

Any newly vaccinated patient with symptoms suggestive of VITT should have their platelet count, d-dimer, prothrombin time, partial thromboplastin time, and fibrinogen serially evaluated. Any abnormal results should be followed up with an ELISA anti-PF4 assay. A positive anti-PF4 test is significant, whereas a negative test in a patient with a high index of suspected VITT can be examined further without delaying intervention [6].

Many guidelines call for IVIG treatment to be started immediately in all cases where VITT is suspected. Thrombosis is a rare side effect of immunoglobulin, but it is still a necessary treatment to limit the development of the disease [9].

A multicenter cohort study of cerebral venous thrombosis following vaccination against COVID-19 in the United Kingdom by Perry et al., Has shown that the consequences of VITT-associated cerebral venous thrombosis are worse than in other forms of cerebral venous thrombosis. They found that the proportion of patients with VITT who died or were dependent on others for their care at the end of hospitalization was significantly lower in those receiving IVIG and non-heparin anticoagulation compared to those , which was not [10]. This supports our approach to our patients, whose clinical picture, laboratories and radiology results all largely indicated VITT. Although the results of anti-PF4 antibodies were pending, immediate treatment with IVIG and direct oral anticoagulant apixaban, a non-heparin-based drug, markedly restored her general neurological symptoms and platelet count. [9].

We compared our case with other cases that received the AstraZeneca vaccine, which showed neurological symptoms and showed that the duration after exposure was different, high suspicion of VITT, and early intervention can improve the result (Table 1).

Previously comparable VITT published cases Our case
Age / Gender 32 years / woman 26 years / woman 64 years / man 23 years / woman
Clinical presentation Headache, blurred vision, dizziness and left hemiparesis. Severe headache. Drowsiness malaise and vague abdominal pain. fever, dizziness, headache, vomiting, blurred vision, numbness and weakness in the left upper and lower limbs.
Vaccine received Covishield AstraZeneca AstraZeneca AstraZeneca
Duration from vaccination to VITT 11 days 8 days 7 days 18 days
Platelets 120 × 109/ L 22 × 109 / L 20 x 109 / L 59 x 109/ L
d-dimer 1105 ng / ml 9452 ng / ml 36900 ng / ml 12600 ng / ml
Fibrinogen 2.6 mg / dl 173.8 mg / dl 400 mg / dl 180 mg / dl
Treatment Mannitol, 3% saline, Intravenous levetiracetam, enoxaparin 40 mg twice daily subcutaneously, right parietal decompressive hemicraniectomy with evacuation of the intracranial hematoma and IVIG. IVIG, dexamethasone and Apixaban. argatroban infusion and IVIG. Dexamethasone, Prophylactic dose of enoxaparin, IVIG and apixaban.
Forecast Printing after 17 days Printing after 6 days Printing after 14 days Printing after 10 days
Reference Kotal et al. [1] Khuhapinant et al. [11] Al Rawahi et al. [12] Our patient

Conclusions

Regardless of the fact that COVID-19 vaccination can cause this unusually serious complication, experts recommended that the benefits outweigh the risks. Our case report highlights the importance of increasing physicians’ awareness and early detection of warning signs of VITT following COVID-19 vaccination in highly probable cases. Rapid treatment with IVIG and non-heparin anticoagulation can significantly improve the patient’s outcome. Because VITT has such a high mortality rate, treatment should start before the anti-PF4 antibody ELISA test confirms a positive result. To understand the underlying mechanism of VITT, more research collaboration is needed.


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