Case 147 summary: VITT

Many thanks for following our case this week of a young patient with VITT – a syndrome which emerged in Spring 2021 and offered significant challenges to treat

Following extensive roll-out of vaccines to protect against SARS-CoV-2, concerns arose around cases of thrombosis at unusual sites and thrombocytopenia. There were several case reports assimilated in different countries associated with the ChAdOx1 nCoV-19 (Oxford–AstraZeneca) vaccine. In the UK, an expert panel was convened to offer advice on the investigation and management of these patients and clinical experience quickly grew. The condition was termed Vaccine-induced immune thrombocytopenia and thrombosis (VITT).

Key clinical features (Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis | NEJM):

  • Onset of symptoms 5 – 30 days after vaccination (median 14 days)
  • Thrombosis (cerebral venous sinus thrombosis, DVT/PE and splanchnic vein thrombosis for the most part)
  • Thrombocytopenia (any level below lower limit of normal) – median 47 per cubic millimeter
  • Elevated D-dimer – median level 24,000
  • Anti-PF4 antibodies by ELISA

Investigations for thrombosis should be guided by clinical symptoms

Cases should be reported to the MHRA’s COVID-19 Yellow Card scheme

Management (COVID-19 rapid guideline: vaccine-induced immune thrombocytopenia and thrombosis (VITT) (magicapp.org))

  • Anticoagulation
    • Start as soon as benefit outweighs risk of bleeding using a non-heparin drug. Local experience in high bleeding-risk situations has been to use argatroban, and then fondaparinox or a DOAC once bleeding risk has reduced
    • Platelet transfusion or fibrinogen replacement may need to be considered for surgical intervention/bleeding
  • Managing the immune response
    • IVIg 1 g/kg – consider 2nd dose at 48h – 72h depending on response
    • Consider corticosteroids if response to IVIg is insufficient
    • Consider plasma exchange with fresh frozen plasma (1 volume exchange a day) as an alternative to a second dose of intravenous immunoglobulin – continue for up to 5 days, or until platelets recover
    • Consider rituximab for people with VITT that has not responded to a second dose of intravenous immunoglobulin or plasma exchange – 375 mg/m2 for 4 weekly doses

There are a group of high risk patients for whom prognosis is very poor: CVST with secondary bleeding, low platelets (<30) and/or thrombosis at multiple sites. These patients will likely benefit from more intensive treatment with plasma exchange and steroids up front

Ongoing management

Guidance states to continue anticoagulation for at least 3 months, and when anti-PF4 antibodies are no longer detected. This will likely be an individualised decision based on site of thrombosis and patient factors

In terms of second vaccine against SARS-CoV-2, the consensus is to give an alternative, mRNA vaccine once clotting has stabilised and at least 12 weeks has elapsed from the implicated dose.

Aetiology

The mechanism that links the vaccines and VITT is still uncertain. The detection of anti-PF4 antibodies suggests a similar process to HITT but without heparin as a trigger. The most likely hypothesis is that some element of the vaccine is binding to PF4 and triggering an immune response.

References/further reading:

Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis | NEJM

COVID-19 rapid guideline: vaccine-induced immune thrombocytopenia and thrombosis (VITT) (magicapp.org)

Greenbook COVID-19 chapter 14a (publishing.service.gov.uk)

vitt_patient_information_v4-20210420.pdf (b-s-h.org.uk)

Thrombosis UK | The Thrombosis Charity wishes to increase awareness of thrombosis among the public and health professionals and to raise research funds to improve patient care. Helping people who suffer from VTE, DVT, PE and clots.COVID vaccines and blood clots: what researchers know so far (nature.com)

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