Surprisingly, HIT occurred not only in patients with heparin exposure, but also in several heparinnave patients. == 4. learnt about the insidious disease E3330 that COVID19 represents, including autoimmune outcomes in affected patients. Keywords:COVID19, heparininduced thrombocytopenia, platelet factor 4/heparin antibodies == 1. INTRODUCTION == COVID19 (coronavirus disease 2019) is a recognized global pandemic caused by infection with SARSCoV2 (severe acute respiratory syndrome coronavirus 2). This infectious disease is thought to have E3330 originated in Wuhan, China, in late 2019, and at time of writing has infected over 141 million people and caused over 3 million deaths.1Severe COVID19 reflects primarily a prothrombotic disorder, with thrombosis appearing in various forms.2,3,4For example, a recent metaanalysis has indicated a venous thromboembolism (VTE) rate, including deep vein thrombosis (DVT) and pulmonary thrombosis (PE), of close to 30% in patients with severe COVID19.5Acute myocardial ischaemia (infarction) and cerebrovascular accidents may also develop in as many as 8% and 3% of COVID19infected patients needing intensive care,6whilst systemic coagulopathy and disseminated intravascular coagulation (DIC) may occur in as many as 7% of such patients.7Evidence of microthrombosis in multiple organs including lungs, kidneys and liver, also occurs, although only identifiable on autopsy in patients who have died due to COVID19.8,9,10,11Indeed, COVID19 appears to affect all facets of haemostasis, including primary haemostasis (ie platelets, von Willebrand factor, endothelium), secondary haemostasis and fibrinolysis.12,13,14,15In addition, thromboses may arise from disturbances in immune response, creating cytokine disturbance (socalled cytokine storm), according to immunothrombosis/endotheliitis type mechanisms.2 Perhaps unsurprisingly, then, a series of autoimmune events have also been reported in patients with COVID19, including for example the presence of antiphospholipid antibodies potentially associated with antiphospholipid syndrome.16Of relevance to the current narrative review is that there have been several reports of platelet factor 4/heparin (PF4/H) antibodies being present in COVID19infected patients. Accordingly, we critically appraise this literature to answer the question: is heparininduced thrombocytopenia (HIT) a feature of COVID19? == 2. MATERIALS AND METHODS == This is a narrative review. The PubMed database (https://pubmed.ncbi.nlm.nih.gov) was searched as required for both background information on PF4/H antibodies and HIT as well as specific papers related to COVID19. For the latter, we primarily used the search term (heparin AND (antibodies OR thrombocytopenia OR thrombocytopaenia OR HIT)) AND (COVID OR SARS)). An initial search performed on 24 March 2021 was later updated to be current as of 1 April 2021. Of 102 separate articles identified by this specific search, we then excluded general reviews and commentaries (ie not presenting original data), HNRNPA1L2 and papers otherwise found to be irrelevant to the topic. == 3. RESULTS == == 3.1. Background information on platelet factor 4/heparin antibodies vs HIT == PF4/H antibodies develop in some individuals after exposure to heparin, primarily unfractionated heparin (UFH), but in some cases also to low E3330 molecular weight heparin (LMWH).17These antibodies can be detected immunologically via a wide range of assays, including ELISA (enzymelinked immunosorbent E3330 assays), LIA (latex immunoassay), CLIA (chemiluminescence immunoassays) and particle/lateral flowbased methods.18,19There is some considerable interassay variability regarding the detection of these PF4/H antibodies. For example, ELISA assays tend to detect a proportionally greater number of PF4/H antibodies than does CLIA.20Irrespective, the presence of these PF4/H antibodies in themselves does not identify pathological E3330 HIT, which also requires resultant activation of platelets.21This represents a functional event detected by functional assays, such as SRA (serotonin release assay) and HIPA (heparininduced platelet aggregation).22,23Only a small proportion of detected PF4/H antibodies will cause platelet activation, and thus positivity in the functional assays, and therefore, the anticipated pathological consequence of thrombosis.21,24There is also an association between the level of detected PF4/H antibodies and the likelihood of positivity in a functional assay. For example, an ELISA OD >1.0 or a CLIA value >10 U/mL may be characterized as more likely associated with functional assay positivity.18,20,21,24However, it is generally accepted that a.