key: cord-1049628-9th9mm7e
authors: Guditi, Dr Swarnalatha; Setty, Mr Girish; Verma, Dr Manish; Reddy, Dr Ram; Devraj, Dr Rahul; Raju, Bhushan; Gokhale, Gopal Krishna
title: A case report of vaccine induced thombotic thrombocytopenia due to COVID 19 vaccine as a deceased donor
date: 2021-11-12
journal: Transplant Proc
DOI: 10.1016/j.transproceed.2021.11.002
sha: bc1e8d8aca76f3e172bc0f56f7a86639f845f7db
doc_id: 1049628
cord_uid: 9th9mm7e

With rapid massive vaccination campaign against COVID 19 across the globe, there are increasing reports of thrombotic complications with various COVID 19 vaccines like Pfizer–BioNTech mRNA vaccine and Moderna mRNA vaccine, AstraZeneca Oxford (serum institute) and Johnson & Johnson/ Janssen. We report a case of successful organ donation form an 18-year- old girl, who presented with cerebral venous thrombosis due to VITT following 1st dose of COVID 19 vaccine (AstraZeneca, University of Oxford, and Serum Institute of India), causing brain death. Four recipients received 5 organs, kidneys (2), liver (1) and combined heart and lung (1). All four recipients had normal graft function without any thrombotic complication after 16 weeks of transplantation. This is first such case being reported from Asian countries

With rapid massive vaccination campaign against COVID 19 across the globe, there are increasing reports of thrombotic complications with various COVID 19 vaccines like Pfizer-BioNTech mRNA vaccine and Moderna mRNA vaccine, AstraZeneca Oxford (serum institute) and Johnson & Johnson/ Janssen. We report of case successful organ donation form an 18-year-old girl, who presented with cerebral venous thrombosis due to vaccine induced thrombotic thrombocytopenia (VITT) following 1 st dose of COVID 19 vaccine (AstraZeneca, University of Oxford, and Serum Institute of India), causing brain death.

An 18-year old female presented to hospital on 9th June 2021 with complaints of headache and fever of three days duration, vomiting and swaying while walking of one day and one episode of seizure on the day of presentation. She received 1 st dose of COVID 19 vaccine (AstraZeneca, University of Oxford, and Serum Institute of India) on 30/5/21. She had no previous co-morbidities like hypertension, diabetes, coagulation abnormality and features suggestive of connective tissue disorder. She was not on any medication and never used heparin. On examination at presentation, vitals were stable but GCS was 3.

She was immediately intubated and connected to mechanical ventilator in view of poor GCS.

Neuroimaging studies showed extensive cerebral venous thrombosis with right frontal hemorrhage and surrounding peri-lesional edema and mass effect with midline shift and intraventricular extension of hemorrhage. Neurosurgery consultation was taken and right frontotemporal decompressive craniotomy was done on the same day of admission. Further investigation revealed anemia Hb 8.6 g/dl (12 -15 g/dl) , leukocytosis with total leukocyte count of 17,940/mm 3 (4300 -10,800/mm 3 ), thrombocytopenia plate count 50 ,000 /mm 3 (1,50,000 -450,000/mm 3 ) and folate-3.5nmol/L ( 6.12 -38.52nmol/L) and vitamin B12 -37pmol/L (118-701pmol/L) deficiency. PT 15 , INR 1.5 , plasma fibrinogen 250 mg/dl, Liver function tests; bilirubin 0.8mg/dl, AST 45U/L, ALT 35 U/LALP 170U/L and renal function tests; urea 45 mg/dl, creatinine1.2 mg/dl were normal. D Dimer 14360 ng/ml (100-250ng/ml) was elevated. Vasculitis and connective tissue disorder work up were negative; ANA dsDNA, C-ANCA, P-ANCA, APLA profile.

Infection workup was also negative; malaria, dengue, viral markers, scrub typhus, leptospira, chikungunya and COVID-19 RTPCR. HITT test were also negative. Her sensorium worsened and gradually developed hypotension. She was treated with vasopressors; noradrenaline and dopamine infusions 5ml/hour, single donor platelet trasnfuisons, PRBC transfusions, Heparin 5000 unit 8 th hourly, Inj levetiracetam 500 mg infusion twice daily, Inj Piperacillin tazobactum 500 mg thrice a day, Inj Mannitol 100 mg infusion/24 hrs, Tab folvite 10 mg daily, Inj B12 once daily and supportive care.

Tracheostomy was done after a week and continued on mechanical ventilation. In view of thrombocytopenia, increased D Dimer and thrombotic complication with history of COVID vaccine a

week before presentation and no other cause to explain her condition, a possibility of VITT was considered. However, an antibody against PF4 was negative. On 19/6/21, patient condition worsened, pupils bilateral dilated with 6 mm and fixed and absent brain stem reflexes. EEG showed isoelectric activity consistent with electro cerebral silence, without any discernible activity while recording at a sensitivity of 2uV. Apnea test was performed to confirm the diagnosis of brain death, both the apnea tests done 6 hrs apart were positive, confirming the diagnosis of brain death. Brainstem death declaration was done on 19-06-2021. Parents were counseled regarding the organ donation to which they readily agreed.

But the challenges then for deceased donor transplantation organization were, whether to accept VITT case as a organ donor?, what are the formalities to be fulfilled to report to the state and central authorities as adverse event following immunization (ADFI) before donation process? and would the recipients have a change of recurrence of thrombotic thrombocytopenia after transplantation?.

After thorough consultation with the state and central vaccination authorities, appropriate documentation was done with respect to adverse events following immunization and after completing the legal formalities heart, lungs, liver and two kidneys were retrieved. The post mortem examination was also performed by forensic department from government general hospital. The organs were allocated as per the regional allocation policy. Post mortem examination showed extensive thrombosis and hemorrhage in the brain but no evidence of disseminated intravascular coagulation in any of the visceral organs.

Heart and lung recipient was 26-years-old girl waiting in the list since June 2018 for heart and lung failure secondary to VSD. She had a long waiting period due to non-availability of size matched donor.

Combined heart and lung transplant was done with informed consent. She had a smooth postoperative course and was extubated within 24 hours. She had stable platelet count and did not face any untoward haematological consequences.

Liver recipient was a 64 year old lady with decompensate liver disease, with no history portal vein thrombosis or variceal bleed in the last two weeks and no history of vaccination in last 4 weeks. Liver transplant was done after informed consent. She had uneventful post operative course except mild elevation in D Dimer from 385 ng/dl (100-250ng/ml) on day one postoperative period to maximum of 3182 (100-250ng/ml) on Day 8 th , and platelets least reported was 60,000/cumm (1,50,000 -450,000/mm 3 ) on day 7 th . She received Inj Arixtra 2.5 mg for a week followed by tab ecosprin 75 mg a day along with triple immunosuppression of prednisolone, tacrolimus and mycofenolate mofitil. Her LFT normalized by 5 th day and was discharged after 2 weeks.

Kidney-1 recipient was 31-year-old female, on waiting list for 3 years, with diagnosis of presumed chronic interstitial nephritis, end stage renal disease and on maintenance hemodilaysis for the past 4 years. Kidney transplantation was done after informed consent. She was given ATG as induction and triple immunosupression (prednisolone, tacrolimus and mycofenolate mofiltil as maintenance therapy. she The incidence of VITT, was estimated, to be 1 case per 100,000 exposures. 6 The sites of thromboses in majority were cerebral venous sinus thrombosis, splancnic thrombosis and rarely pulmonary embolism. The risk factors identified were young age and female sex.

Approximately 40% of the patients died and common cause of death being ischemic brain injury, superimposed hemorrhage, or both conditions, often after anticoagulation. Hence it's quite common to encounter brain death in VITT patients giving scope for organ donation.

While considering VITT patient as a brain dead donor, there are several challenges, which needs to be addressed;1. The legalities of documentation and reporting as an adverse events following immunization (ADFI) to the concerned national authorities, particularly during a mass immunization program as part of global pandemic and the conduct of post mortem examination with preservation of specimens to ascertain the cause of death, 2. Viability of the organs, as these organs could be damaged by hematological complications, and 3. Despite organs being functional and structurally normal, what would be the change of the recurrence of hematological complications and graft thrombosis in the recipient after transplantation?

We report successful organ donation from a case of VITT, following COVID 19 vaccination with AstraZeneca Oxford (Serum Institute of India) in an 18 year old girl who presented with cerebral venous thrombosis superimposed with right frontal hemorrhage evolving into brain death. All the four recipients; combined heart and lung (1), liver (1) and kidney (2) No recipient had detectable anti-PF4 antibodies Leonardo Centonze et al reported successful liver transplantation from a 32-y-old female brain death (DBD) donor with CVST and hepatic veins thrombosis after ChAdOx1 nCov-19 vaccination to a 69-yold female recipient with multifocal hepatocellular carcinoma and HCV-cirrhosis.

There have been no reports of deceased donation from VITT following COVID19 vaccine from developing countries.

Despite sparse literature, VITT following COVID 19 vaccine, can still be accepted as a deceased donor, considering the fact that; 1. There is significant reduction in deceased donation and transplantation during the COVID pandemic increasing the organ shortage, particularly in developing countries where deceased donation is miniscule. 2. The mortality rate on waiting list has increased and 3. There has been increasing reports of VIIT with COIVID 19 vaccine, the most common site being cerebral venous thrombosis, and with ongoing massive vaccination programme across the worldwide; it's possible that we see more cases of deceased donor secondary to VITT in coming days. However, necessary precaution should be taken before considering VITT as deceased donor. All the required documentation should be done with respect to ADFI in additional to legal documentation of brain death and informed consent. 

Considering the organ shortage, suspected or proven VITT secondary to COVID vaccination can be accepted as a deceased donor gauging the risk and benefit to the recipient. And the following precaution should be taken, thorough evaluation and optimization of the donor and meticulous selection, informed consent before transplantation and close post operative monitoring of the recipient after transplantation 

Death of Florida doctor after receiving COVID-19 vac-cine under investigation. USA Today

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SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia

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Organ transplantation from deceased donors with vaccine-induced thrombosis and thrombocytopenia

François Kerbaul. Solid organ procurement and transplantation from deceased donors with vaccine-induced thrombosis and thrombocytopenia

Successful Liver Transplantation From a Deceased Donor With Vaccine-Induced Thrombotic Thrombocytopenia Causing Cerebral Venous Sinus and Hepatic Veins Thrombosis After ChAdOx1 nCov-19 Vaccination