For example, if there are two equivalent methods for generating factor Xa from factor X – meaning just as much thrombin is produced in factor Xa from factor VII – then why is factor VIII needed on the other side of the cascade? If the cascade reflected real-life biology, then hemophiliacs shouldn’t bleed. And why doesn’t factor XII matter? It leads to a prolonged partial thromboplastin time (PTT), but it doesn’t have any effect on biology.
Another sticking point: When heparin is used, it will block thrombin, inhibit factor Xa, and prolong the PTT and, to a lesser effect – the prothrombin time (PT). In a PT assay, heparinase is used, so heparin is degraded, and the effect on PT is understandable. However, this doesn’t explain why LMWH does not affect the PT and PTT times. LMWH inhibits thrombin-generating factor X; without factor X, thrombin is unable to turn fibrinogen into fibrin. Why doesn’t that affect the PT and PTT?
Hematology can be hard.
As hard as we might try to find an answer, there are certain facts that escape our understanding. We have to tell medical students something they never want to hear: “Even though we don’t understand this, you still have to know it.â€
This part is difficult for medical students, but acknowledging that roadblock, pointing at it and saying, “Yes, this part sucks,†is good. The important distinction to make is that no one understands it. Trust me, I have asked plenty of people, and no one can explain this to me.
How do we break this to students? Admit that it’s a mystery to all of us. Think about it this way: Can I explain the innerworkings of my car’s internal combustion engine? Do I know what a carburetor does? Not really, but I still drive my car. For all intents and purposes, it’s a miracle.
Why I Teach the Coagulation Cascade
Knowing the principles of the coagulation cascade helps explain test results, but it doesn’t explain what we see in patients with bleeding disorders. It is a frustrating concept – one that requires patience both to learn and to teach.
This is especially important when we, as hematologists, are answering questions from clinicians in other disciplines, such as anesthesiologists and cardiac surgeons. These specialists often send for PT and PTT tests, but they often don’t know how to interpret the results. So, if they gain a basic understanding about the coagulation cascade and can understand the results without calling for a hematologic consult, I’m satisfied.
For others who want a better and deeper understanding of coagulation, there’s the elegant cell-based model of hemostasis outlined by Hoffman and Monroe.1 It is a beautiful description that helps refine the theory and understanding of coagulation. I use it to explain coagulation to trainees who want more insight into biology.
The approach I developed may not provide a comprehensive understanding of the complexities of the coagulation pathways, but it helps people remember where the various coagulation factors fit into the cascade and identify abnormal test results associated with factor deficiencies. It’s slightly more than a passing familiarity and, as I like to tell people, knowing the coagulation cascade is guaranteed to help you on at least two board exam questions.
Reference
Hoffman M, Monroe DM 3rd. A cell-based model of hemostasis. Thromb Haemost. 2001;85:958-65.