Post-mortem findings in vaccine-induced thrombotic thombocytopenia

Italy, August 2021, Pomara et al, Haematologica

Summary

Case reports of detailed post-mortem macroscopic and microscopic findings in two similar cases of VITT that occurred in the Italian region of Sicily.

Patient 1 was a 50-year-old man (body weight 90 kg) with abdominal pain that developed 10 days after vaccination with ChAdOx1 nCoV-19. He presented with severe thrombocytopenia, low plasma fibrinogen and very high D-dimer. Computed tomography (CT) showed portal vein thrombosis with smaller thrombi in the splenic and upper mesenteric veins. Clinical conditions deteriorated and a new CT scan showed massive intracerebral hemorrhage. Treated with multiple transfusions of platelet concentrates that failed to control bleeding the patient died 4 days after the onset of symptoms and 16 days after vaccination. A serum sample obtained before nadroparin showed the presence of anti PF4/polyanion complex IgG antibodies by enzyme-linked immunosorbent assay (ELISA).

Patient 2, a 37-year old previously healthy woman (61 kg) with a negative history for significant disease and drug intake developed 10 days after the administration of the same vaccine first low back pain and then a strong headache. She became progressively drowsy and ultimately unconscious, and was, therefore, admitted to the emergency room of her local hospital. With laboratory tests similar of those of patient 1 (Table 1), a CT scan showed an occlusive thrombus in the superior sagittal venous sinus and a very large hemorrhage in the frontal cerebral lobe. Transported comatose by helicopter to a larger hub hospital she underwent craniotomy in order to control intracranial hypertension and remove the frontal lobe hemorrhage. She survived the operation but remained comatose and died 10 days after the first hospital admission and 23 days after vaccination. Anti- PF4/polyanion complex antibody reactivity was detected by ELISA and confirmed in a stored serum sample.

Autopsy Findings

The main macroscopic finding was that venous thrombosis was much more widespread and catastrophic than diagnosed by imaging during life.  In both cases the sites of venous thrombosis identified by imaging were confirmed, coupled with dramatic pictures of cerebral hemorrhages. While case 1 was confirmed to have had portal and mesenteric thrombosis with extension into the splenic vein, case 2 showed besides cerebral sinus thrombosis a massive thrombosis of the whole venous tree of the left upper limb extending from the hand to the axillary vein, with symmetric lesions in the veins of the right hand and the right axillary vein. In addition, the superficial veins of both feet appeared to be thrombosed. The histological evaluation revealed the presence of vascular thrombi associated with hemorrhagic phenomena localized in the meningeal space and focally involving the brain. The thrombotic phenomena also involved small- and medium- sized vessels.

Microscopic findings showed vascular thrombotic occlusions occurring in the microcirculation of multiple organs and increased inflammatory infiltrates. Immunohistochemical analyses highlighted the vascular and peri-vascular expression of adhesion molecules such as VICAM1, as well as the presence of CD66b+, CD163+ and CD61+ activated inflammatory cells, also expressing C1r. These findings indicate that the activation of the innate immune system and complement pathway promote the inflammatory process leading to the microvascular damage of multiple organs.

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