Organ Donation From a Brain Dead Donor With Vaccine-induced Immune Thrombotic Thrombocytopenia After Ad26.COV2.S: The Risk of Organ Microthrombi.

Vaccine-induced immune thrombotic thrombocytopenia (VITT), which is a complication of vector-based severe acute respiratory syndrome coronavirus 2 vaccines, has a high mortality.[1] Since affected individuals are relatively young and usually have no concomitant disease, they are particularly suitable as organ donors.[2] There are concerns regarding the safety of organ donation from deceased donors with VITT.[3,4] We report herein the pretransplantation evaluation and preparations for transplantation of an organ donor with VITT and what surprising findings emerged after the pathologic workup despite unremarkable standard diagnostics.

A 50-y-old female developed VITT with severe thrombocytopenia and thrombosis of the cerebral arteries and venous sinuses 12 d after the Ad26.COV2.S (Johnson & Johnson) vaccine. A computed tomography (CT) scan showed extensive ischemia of both cerebral hemispheres and incipient entrapment of the brain stem. CT angiography revealed occlusion of the middle cerebral artery on both sides, as well as sinus vein thrombosis of the superior sagittal sinus and transverse sinus on both sides. No intracranial hemorrhage was detected. Initial platelet count was 55 x 109/L, and d-dimer level was 31 µg/mL. Activated partial thromboplastin time (22 s) and fibrinogen (378 mg/dL) were within a normal range. Antiplatelet factor 4 (anti-PF4)/heparin antibodies were detected (3.48 optical density [OD] units; negative <0.3 OD). Modified heparin-induced platelet activation assay was positive. The patient received IVIG therapy and argatroban. Brain death was determined on day 3 of hospitalization. After multidisciplinary discussion, we decided to evaluate the patient for organ donation. A standard assessment of the suitability of the patient as an organ donor including chest radiography, bronchoscopy, transthoracic echo, abdominal sonography, and standard laboratory diagnostics was undertaken. Despite a slightly increased creatinine level of 79.2 µmol/L (reference ≤70.4 µmol/L) diagnostic findings were normal; abdominal sonography especially showed no significant findings. Therefore, a further CT scan was not performed. The donor was reported to Eurotransplant. The recipient centers showed reluctance because of the VITT diagnosis. Finally, matched recipients were identified for the heart, liver, and kidneys. The patient underwent a multiple organ allograft recovery with argatroban infusion immediately before aortic cross-clamping. At the back table, a tumor-suspected lesion at the left kidney and an infarction at the right kidney were noticed. Pathologic workup using frozen sections revealed an angiomyolipoma in the left kidney and fresh infarction in the right kidney. Further investigation depicted platelet and fibrin depositions in the glomeruli of the left kidney (Figure 1). In the liver, a hemangioma and a segment with an arterial thrombosis were detected. The kidneys and the liver were refused by the respective transplantation centers. Only the heart was transplanted. The recipient of the heart did not develop thrombosis or thrombocytopenia. Anti-PF4 antibodies remained negative 3 wks after transplantation (0.270 OD).

FIGURE 1.

Morphological and immunophenotypical findings in the kidneys. Left kidney parenchyma (A–D) next to an angiomyolipoma showing glomerular fibrin deposition and right kidney (E and F) with fresh infarction. A, Overview with normal-looking kidney parenchyma with inconspicuous glomeruli and tubuli (H&E staining, x100 original magnification). Some glomeruli show intravascular fibrin deposits (asterisk) (B, Masson trichrome staining, x200 original magnification), containing platelets shown by CD61 staining (C, immunoperoxidase, x400 original magnification) and fibrin shown by fibrin staining (D, immunoperoxidase, x400 original magnification). E, Totally necrotic kidney parenchyma with hypereosinophilia and loss of nuclear staining infiltrated by many neutrophilic granulocytes as a reaction to the necrosis (H&E staining, x200 original magnification). F, PAS stain also shows the necrotic parenchyma (x200 original magnification). H&E, hematoxylin and eosin; PAS, Periodic acid–Schiff.

Organ donation from deceased donors with VITT is associated with some risks, such as the presence of retained thrombi in the transplanted organ and the transmission of VITT to the recipient.[3,5] Although our patient had normal biochemical parameters and ultrasonography of the kidneys was normal, we detected an infarction and microthrombi during further diagnostics. Furthermore, an intraluminal blood clot was detected in the liver after organ procurement. A thorough radiologic assessment of the organs with multiphase CT angiography before organ retrieval could be useful to detect hypoperfusion or infarct in organs. The extent of microthrombi and organ function should be carefully assessed before deciding whether the organ is suitable for transplantation or not.

The risk of passenger lymphocyte syndrome, which is the production of antibodies in the naive recipient by transplanted immune cells of the donor, is higher for organs with a high immune cell content, such as the lung, liver, pancreas, and small bowel.[5] So far, 1 patient was reported who developed anti-PF4 antibodies (2.3 OD) and severe thrombocytopenia after liver transplantation from a donor with VITT.[4] Platelet count recovered after IVIG therapy, and the recipient was discharged with a functioning graft.[4] Another study detected anti-PF4/heparin antibodies in 3 liver recipients; of these, 1 developed thrombosis without allograft loss.[3] Posttransplantation follow-up of the recipient should include platelet count, d-dimer, fibrinogen, and anti-PF4 antibodies.[5]

Lastly, because of the prothrombotic state in patients with VITT, the donor should receive a nonheparin anticoagulant, and platelet transfusions should be avoided.

In conclusion, VITT patients should not be completely excluded as organ donors, but a thorough pretransplantation evaluation of potential risks and functionality of the organs, as well as close monitoring of the recipient during and after transplantation, is necessary.