Mar 03 2025 6 mins 8
Welcome back to the tasty morsels of critical care podcast.
Following on from the recent post on Heparin, today we’re going to talk about one of its more significant complications – Heparin Induced Thromboyctopaenia or HIT for short. In my notes I had it down as HITTS for hepain induced thrombotic thrombocytopaenia syndrome which I kind of liked as it included the important presence of thrombosis in the context of low platelets. But HIT is definitely snappier
There are incidentally 2 forms of HIT. Type 1 is an entirely benign phenomenon where the platelets transiently drop in the first few days of heparin exposure and spontaneously recover even with ongoing heparin use. There is no thrombosis associated and no doubt it happens all the time and we miss it.
From our perspective we’re only interested in type 2 HIT which is a serious immune phenomenon where the major concern is not bleeding but clotting despite the low platelet count.
Unsurprisingly a necessity for this condition is an exposure to heparin. This can be UFH or LMWH. It is an immune phenomenon so you don’t typically get it on the first exposure but it’s the ongoing or repeat exposure can cause the immune reaction. As part of normal heparin function it, at various points binds to something on platelets called PF4 – platelet factor 4. For reasons beyond the comprehension of this narrator, the body can produce IgG against this heparin-PF4 complex. The IgG has now labelled these platelets for destruction by macrophages hence the thrombocytopaenia. Again, for reasons beyond this narrator’s comprehension there is also activation of other platelets resulting in both arterial and venous thrombosis.
Incidence is estimated about 1-5% of those on UFH and <1% on those on LMWH. Interestingly the antibody reaction is quite common but even when present only ~10% of those with the antibody develop HIT properly.
The classic presentation is a fall in platelets somewhere 5-10 days following first heparin exposure. Counts usually are between 40 and 80 but 10% can be under 20. The 4T score has been developed as a means of establishing a pre-test probability for HIT.
I’ll outline the 4 categories briefly
- severity of the thrombocytopaenia. ie platelets of 10 or 120 make it unlikely while platelets of 50 are in the zone
- timing of the fall – 5-10 days being the sweet spot. The catastrophic fall in the first 48hrs of overwhelming sepsis for example would not be consistent with HIT
- presence of thrombosis. This can a bit equivocal as it can be difficult to find all the clot and a clotted CRRT filter maybe shouldn’t carry as much weight as a clotted femoral artery
- is presence of another reason for thromboyctopaenia likely – this is of course like the wells score very open to interpretation
A high 4T score usually prompts formal testing and usually a switch to an alternate anticoagulation regime pending the results. This is frequently misunderstood as it seems most are happy to stop heparin pending the test but disregard the fact that clotting is actually the problem so alternate anticoagulation is really needed.
Testing usually comes in 2 stages. The first is a more rapid easily available screening test which i believe is a PF4 immunoassay. This can be followed up by a fancier (checks notes) Heparin Induced Platelet Activation functional assay. I can attest that we have two tests available in our place but I wouldn’t swear they are the ones described above.
The main dilemma we’re left with, is when we suspect HIT but have not got a definitive test to confirm it. We need to make a probability and risk based decision on whether to commit to the diagnosis or not.
Let’s say we’ve decided it’s HIT and we need to anticoagulate. We have a few options, we can use direct thrombin inhibitors (DTIs) like bivalarudin or anti xa agents like fondaparinoux. In our place we reach for argatroban, one of the DTIs.
We will of course seek expert advice from our coagulation colleagues but the critical take homes here are suspicion of HIT, knowing the probability and tests and ensuring we anticoagulate despite the off putting low platelet count.
Reading
Shore-Lesserson, L. et al. The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines ∗ —Anticoagulation During Cardiopulmonary Bypass. Ann Thorac Surg 105, 650–662 (2018).
Lubnow, M. et al. Prevalence and outcomes of patients developing heparin-induced thrombocytopenia during extracorporeal membrane oxygenation. Plos One 17, e0272577 (2022).
