Welcome back to the tasty morsels of critical care podcast.
This week we’ll make a fly by at part of Oh Chapter 100 looking at haemostatic failure. The understanding of the haemostatic system seems a little like the universe at times with our knowledge, and the gaps in our knowledge expanding away from us quicker than can we track. As a result this summary will be necessarily superficial, brief and likely inaccurate.
The traditional understanding of haemostasis was centred on circulating coagulation factors, the modern understanding holds that coagulation takes place mostly on the surface of activated or damaged cells. However, I think it still holds true that the core of haemostasis involves vascular constriction, platelet plugging with fibrin clot formation to seal the deal.
I was reared with the idea of two pathways towards clotting in the old fashioned clotting cascade – the intrinsic and the extrinsic pathway. These appear to have been renamed in the interim with the intrinsic pathway (always on the left hand side in the diagrams i can visualise from memory) being renamed the contact activation pathway and the extrinsic pathway (being on the right side of the diagram) now renamed the tissue factor pathway. It seems that most coagulation activation occurs via this latter tissue factor pathway where the protein tissue factor is exposed by tissue injury beginning the process. Platelet plugging (or primary haemostasis) results with subsequent fibrin formation by the action of thrombin on fibrinogen, to complete the process. (secondary haemostasis)
Though to say the process is now completed is to neglect the presence of native anticoagulant processes which to be fair are rarely measured. This consists of several types of inhibitory proteins such as protein C and S to give a couple of well known examples. These act as a sort of brakes on the system to ensure everything is held in balance.
We have various tests we can apply to the haemostatic system but the more you look into this the more you realise you’re not measuring one thing but the test really reflects the activity of potentially multiple factors and an abnormal result cannot simply be used as a surrogate for any given coagulation factor but instead reflects the blended result of upset of multiple different factors.
Platelet number is relatively easy to measure but tells us very little about platelet function which can be affected by things like vWF or the aspirin they took 3 days ago. Platelet function is a little bit of a holy grail that we have not quite nailed down yet.
Prothrombin time measures the extrinsic or tissue factor pathway and is most obviously prolonged in people on vitamin K antagonists such as warfarin where it is expressed in the INR. In the critically ill it can also reflect vitamin K deficiency or deficiency of any number of factors in that pathway say from liver dysfunction. You can distinguish between vitamin K dependant causes using an Echis time. This fascinating test involves adding snake venom from Echis carinatus multisquamatus, an Asian viper to a sample of blood. If the prolonged INR is vit k dependant it should normalise, whereas if it is factor deficient it will remain prolonged.
The APTT is felt to reflect the intrinsic or contact activation pathway. it is most commonly used for measuring heparin activity (which is a post in itself) but if the APTT is raised in in the absence of heparin then it might reflect factor deficiency (eg one of the thrombophilias) where it should correct to normal with a mixing study where normal plasma is added. A long APTT in the absence of heparin may also reflect the presence of some kind of inhibitor with the commonest example being the lupus anticoagulant.
Of course we have the viscoelastic assays which are likely a more functional assay of global haemostasis than our traditional tests but they remain fairly niche in their use in critical care (as opposed to anaesthesia) in Ireland so far. They are due their own post in due course.