COVID 19: Vaccine induced immune thrombotic thrombocytopenia (VITT)

Hi friends,

This post is regarding one of the rarer side effects of COVID 19 vaccine.

Last year, with the onset of COVID pandemic, we were all eagerly looking for a solution and it was vaccine. Now we have so many vaccines, available from different brands, and they have been proven to be highly safe and effective.

In late February 2021, a prothrombotic syndrome was observed in a small number of individuals who received certain adenoviral vector-based vaccines to COVID 19

Implicated vaccines:

Ø  ChAdOx1 CoV- 19 vaccine (AstraZeneca, University of Oxford and Serum Institute of India)

Ø  Ad26.COV2.S vaccine (Janssen;Johnson & Johnson)

This syndrome was named as vaccine –indced immune thrombotic thrombocytopenia(VITT).

The other names are

-      thrombosis with thrombocytopenia syndrome (TTS) and

-      vaccine- indced prothrombotic  immune thrombocytopenia(VIPIT)

We shall talk about the salient features of VITT in this post

Pathophysiology: 

VITT is caused by antibodies of IgG class which recognize platelet factor 4 (PF4) bound to platelets.

We are aware that heparin induced thrombocytopenia(HIT) is also caused by antibodies to PF4.

Then what is the difference between antibodies in HIT and VITT?

The major difference is that HIT antibodies are heparin dependent but the antibodies in VITT is not heparin dependent (not induced by heparin exposure, do not require heparin for detection in vitro platelet activation assays).

The mechanism how these implicated vaccines trigger vaccine development is unknown however initial theories suggest that components of the vaccine including virus proteins and free DNA bind to PF4 and generate a neo-antigen.

Incidence of VITT is unknown but it appears to be exceedingly rare.

Risk factors for VITT are unknown.

Clinical features:

VITT strongly resembles autoimmune heparin-induced thrombocytopenia (aHIT).

VITT likely begins 5 to 10 days post vaccination.

The main clinical features are

·         Thrombocytopenia – typical platelet count is in between 10,000-100,000/microL.

·         Thrombosis

·         Coagulation abnormalities/DIC

·         Bleeding

The distinctive feature of this syndrome is thrombosis in unusual sites but the reasons for this are unknown.

-      Splanchnic (splenic, portal, mesenteric) veins.

-      Adrenal veins

-      Cerebral veins

-      Ophthalmic veins

Of course, the most common Pulmonary embolism and deep vein thrombosis of the leg also can occur.

Arterial thrombosis has also occurred in patients with venous thrombosis.

Evaluation:

When to suspect?

The mneumonic VITT can be used:

V- Vaccine given

I- Interval 5-30 days post vaccine

T- Thrombosis

T-Thrombocytopenia

Laboratory testing:

1)    Complete blood count

2)   Cogulation tests: Prothrombin time, activated Partial thromboplastin time, fibrinogen and D-dimer

3)   PF4 antibody testing

4)   Imaging to diagnose thrombosis

Differential diagnosis:

Other causes of thrombosis and thrombocytopenia should be considered such as immune thrombocytopenia and thrombotic thrombocytopenic purpura.

Treatment of VITT (Documented or high suspicion)

1)    Avoid all heparins

2)   Avoid platelet transfusions unless critical bleeding

3)   Avoid Vitamin K antagonists until stably anticoagulated and platelet count normalized

4)   Treat thrombosis with a non-heparin anticoagulant (a DOAC is preferred)

5)   Treat with IvIg

Monitoring:

1.     Daily CBC, PT/INR,aPTT, fibrinogen and d-dimer while in patient.

2.    Continue monitoring with the above mentioned tests after discharge less frequently.

                                      Stay home, Take care...

                                                                                               By Dr.Priyavadhana B

References:

1.   https://www.uptodate.com/contents/covid-19-vaccine-induced-immune-thrombotic-thrombocytopenia.

2.Greinacher A, Thiele T, Warkentin TE, et al. Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. N Engl J Med 2021; 384:2092.

3.Schultz NH, Sørvoll IH, Michelsen AE, et al. Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination. N Engl J Med 2021; 384:2124.

4. Muir KL, Kallam A, Koepsell SA, Gundabolu K. Thrombotic Thrombocytopenia after Ad26.COV2.S Vaccination. N Engl J Med 2021; 384:1964.