THROMBOSIS AND HAEMOSTASIS
antibodies has the ability to identify or rule out vaccine-induced immune thrombocytopenia. While death rates remain high, earlier diagnosis would enable potential treatment pathways to be initiated as quickly as possible.
References 1 Pavord S, Scully M, Hunt BJ. Clinical
features of vaccine-induced immune thrombocytopenia and thrombosis. N Engl J Med 2021 Aug 11. doi: 10.1056/ NEJMoa2109908. Online ahead of print.
Alongside its Asserachrom HPA assay (pictured), Stago has developed Asserachrom HPIA-IgG, a highly sensitive and specific ELISA for detecting H-PF4 antibodies of the IgG class.
PF4 antibodies was performed with various techniques used locally for HIT testing at individual medical centres. In many cases, HIT testing with a chemiluminescence assay was negative, while testing of the same sample with an ELISA was found to be positive.
VITT guidelines from NICE All the patients investigated had low or normal fibrinogen levels and elevated D-dimer, with no evidence of thrombophilia or causative precipitants. The need to have the right diagnostic tools to identify VITT was evident, with the study flagging up that platelet transfusion had to be avoided faced with these clinical manifestations and coagulation abnormalities. Instead, patients could be given a non-heparin anticoagulant and intravenous immunoglobulin.
Based on these expert findings, there
are now recommended haematology protocols for investigating VITT in patients who present with acute thrombosis and thrombocytopenia or an isolated low platelet count (Table 3). The recently issued 2021 NICE guidelines COVID-19 rapid guideline: vaccine-induced immune thrombocytopenia and thrombosis (VITT)2 reinforce the value of further confirmatory testing once thrombocytopenia is confirmed, or a strong clinical suspicion of VITT remains.
The panel advises that while D-dimer
results alone are not sufficient, when accompanied by thrombocytopenia this would give a strong indication of VITT.
It further advises that other factors such as normal PT and APTT levels and the fibrinogen level would give a more complete clinical picture. Ruling out VITT is also covered in the guidelines, with the panel advising that the side effect was unlikely in people with: n no thrombocytopenia n thrombocytopenia without thrombosis, and D-dimer at or near normal and normal fibrinogen
n thrombosis without thrombocytopenia, and D-dimer that is raised (but not the high and very high levels seen in VITT) and normal fibrinogen.
Highly specific Asserachrom assays While functional assays rely on the ability of the H-PF4 antibody to activate platelets in the presence of heparin, ELISAs confirm the presence of the antibody without consideration for its ability to cause platelet activation. In addition to the existing Asserachrom HPIA, Stago has developed Asserachrom HPIA-IgG, a highly sensitive and specific ELISA for detecting H-PF4 antibodies of the IgG class. In clinical studies performed on more than 400 samples, Asserachrom HPIA-IgG demonstrated the same high sensitivity of the poly-specific Asserachrom HPIA (100%), with enhanced specificity (92.3%). Its strip format makes it possible for a laboratory to run the assay to analyse small quantities. The kit can be adapted to run on automated ELISA systems.
The evidence is mounting that only an ELISA with the specificity to detect H-PF4
UK NEQAS Coagulation has now issued guidance to its participating laboratories that confirms best practice would be to run an ELISA
34
2 National Institute for Health and Care Excellence. COVID-19 rapid guideline: vaccine-induced immune thrombocytopenia and thrombosis (VITT). London: NICE, 2021 (
www.nice.org.uk/guidance/ng200/resources/ covid19-rapid-guideline-vaccineinduced- immune-thrombocytopenia-and-thrombosis- vitt-pdf-51036811744).
3 Makris M, Pavord S, Lester W, Scully M, Hunt B. Vaccine-induced immune thrombocytopenia and thrombosis (VITT). Res Pract Thromb Haemost 2021; 5 (5): e12529. doi: 10.1002/rth2.12529. eCollection 2021 Jun.
4 Schultz NH, Sørvoll IH, Michelsen AE et al. Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination. N Engl J Med 2021; 384 (22): 2124–30. doi: 10.1056/NEJMoa2104882.
5 Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med 2021; 384 (22): 2092–101. doi: 10.1056/NEJMoa2104840.
6 Scully M, Singh D, Lown R et al. Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination. N Engl J Med 2021; 384 (23): 2202–11. doi: 10.1056/NEJMoa2105385.
7 Medicines and Healthcare products Regulatory Agency. Coronavirus vaccine – weekly summary of yellow card reporting. 2021 (
www.gov.uk/government/ publications/coronavirus-covid-19 -vaccine- adverse-reactions/coronavirus -vaccine- summary-of-yellow-card -reporting).
8 Platton S, Bartlett A, MacCallum P et al. Evaluation of laboratory assays for anti- platelet factor 4 antibodies after ChAdOx1 nCOV-19 vaccination. J Thromb Haemost 2021; 19 (8): 2007–13. doi: 10.1111/jth.15362.
Dr Alex Stephenson-Brown is Product Manager, Reagents and Scientific Affairs, Diagnostica Stago.
Further information is available from: Diagnostica Stago UK Theale Lakes Business Park 12 Moulden Way, Sulhamstead Reading RG7 4GB Tel: +44 (0)845 054 0614 Web:
www.stago-uk.com
SEPTEMBER 2021
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