Vaccine-induced thrombosis and thrombocytopaenia with widespread abdominal venous thrombosis, venous ischaemia and bowel oedema

Background

The introduction of vaccines has been the most important countermeasure against the COVID-19 pandemic. Over a short period of time (December 2020 to March 2021), the European Medicines Agency has approved four vaccines, which include Pfizer, Moderna, AstraZeneca and Johnson & Johnson. In February 2021, a new disease had been documented in association with the AstraZeneca vaccine, known as vaccine-induced thrombotic thrombocytopaenia (VITT).1

VITT involves a constellation of thrombosis and thrombocytopenia observed in patients after vaccination with the AstraZeneca vaccine. It is a rare documented complication of the vaccine; in the UK, more than 20 million people have been vaccinated with AstraZeneca, of which 79 cases of rare blood clots with low platelets as well as 19 deaths have been reported. This equates to approximately one case per 250 000 people vaccinated and one death per million.2

We present below a case of AstraZeneca-induced VITT, which presented at a district general hospital and required the involvement of a multidisciplinary team to provide appropriate management. As it is a rare and novel disease, our aim of this case report is to raise awareness of its presentation, investigation and management.

Case presentation

A 49-year-old woman presented to the accident and emergency department of a district general hospital with a 2-day history of central abdominal pain, vomiting and diarrhoea.

On admission, she had passed approximately 600 mL of blood per rectally. She became unstable and immediately was resuscitated with intravenous fluids. On examination, there was tenderness throughout the abdomen, more markedly in the umbilical and left iliac fossa. On auscultation, her bowel sounds were sluggish.

Her previous medical history included mild asthma and uterine fibroids. She had no regular medications or drug allergies. She had received the first dose of the AstraZeneca vaccine 13 days previously.

Investigations

Investigation results were available in the following order: the venous blood gas showed lactate of 3.4 mmol/L, base excess –8 mmol/L and haemoglobin 109 g/L.

A CT mesenteric angiogram (figure 1) showed massive venous thrombosis of the visceral vessels (portal vein, splenic vein and superior mesenteric vein), resulting in venous ischaemia. There was also suggestion of ischaemic colitis, evidenced by marked stranding of the adjacent viscera, and a possible abdominal haematoma with a feeding vessel superior to the bladder (figure 2).

Blood investigations revealed a severe thrombocytopaenia with a platelet count of 6×10⁹/L; fibrinogen levels of 0.6 g/L and d-dimer that could not be analysed despite four attempts, therefore advised by the laboratory to treat as maximum (>128 000 ng/mL). Furthermore, her coagulation profile was raised: international normalised ratio of 1.9, prothrombin time of 24.0 s and an activated partial thromboplastin time of 36.0 s. Her renal functions showed a severe acute kidney injury. Liver function tests, however, were within normal parameters.

Her COVID-19 PCR testing via nasopharyngeal swab returned negative.

Based on her deranged blood parameters, urgent discussion with the haematology consultant ensued; a presumed diagnosis of VITT and resultant disseminated intravascular coagulation were made.

Treatment

Her immediate management as advised by the local haematology consultant consisted of intravenous immunoglobulins (IVIG) at a dose of 1 g/kg, methylprednisolone at 500 mg intravenously and transfusion with two units of red cells and two units of cryoprecipitate. Due to the ongoing internal bleeding, the decision to not anticoagulate was made. Once stabilised, she was further discussed and immediately reviewed by the surgical, medical and intensive care team.

Outcome and follow-up

The decision was made to transfer the patient to a tertiary centre within 7 hours of initial presentation, where she went on to have a prolonged inpatient stay (approximately 3 months). A platelet factor 4 (PF-4) antibody assay (ELISA) was later performed, concluding VITT as the diagnosis.

On day 1, she underwent a transjugular intrahepatic portosystemic shunt procedure and thrombolysis for the portomesenteric thrombosis. This was repeated again on day 3; CT showed full recanalisation of the portal vein and >70% recanalisation of the superior mesenteric and splenic veins.

She was commenced on further IVIG at a dose of 0.5 mg/kg over 3 days (days 2–4 following admission). She was also treated with plasma exchange, where she received a total of five sessions (days 2–8 of admission). Pulsed methylprednisolone was also given on day 2–3 of admission at a dose of 500 mg intravenously followed by a weaning course of oral prednisolone. Rituximab at a dose of 100 mg was given on days 4 and 8. She was initiated on a argatroban infusion during the initial 13 days, which was later changed to fondaparinux. By day 14 of admission, her thrombocytopaenia had resolved.

CT head was also performed during admission, which showed a non-occlusive thrombus, affecting the left internal carotid artery, left transverse sinus and posterior aspect of the superior sagittal sinus. She was monitored closely, and her neurology remained intact throughout her admission.

Almost a month later, the patient’s condition deteriorated further. An urgent CT abdomen and pelvis revealed a pneumoperitoneum and peritoneal fluid suggesting bowel perforation. She underwent an emergency laparotomy, which identified multiple small bowel perforations; subsequent bowel resection and stoma formation were performed. She was diagnosed with small bowel syndrome and initiated on parenteral nutrition.

The patient was eventually discharged with haematology (2 weeks), gastroenterology and nutrition clinic follow-up (6 weeks). Fondaparinux injections were to be continued until her next haematology appointment. Entecavir for a total of 6 months was initiated to mitigate the low risk of hepatitis B reactivation following rituximab administration.