Q. I understand that hemophilia is caused by factor VIII or IX deficiency and both factors work in the intrinsic pathway. But in patients who are missing factors VIII or IX, isn’t there still the extrinsic pathway that can activate factor X to convert fibrinogen to fibrin? Please help.
A. Great question!
You are absolutely correct: the extrinsic pathway does, in fact, convert factor X to Xa, which then converts prothrombin to thrombin, which leads to fibrin formation. So why can’t you just use that side of the pathway?!
It turns out that you actually need both the intrinsic and extrinsic pathways in your body. In a test tube, you can form fibrin along either pathway. But in the body, the pathways are intertwined in such a way that if you’re missing something on either the extrinsic or intrinsic side, you won’t be able to clot properly.
In our bodies, the thing that kicks off the clotting cascade is tissue factor “exposure.” Tissue factor is not floating around in the blood normally – or at least, it isn’t normally “visible” to the blood (it might be in little membrane fragments, but it’s not active until it’s needed). When you need to form a clot, tissue factor appears, and together with factor VIIa (which happens to be just floating around in the blood) it converts factor X to Xa (which then converts prothrombin to thrombin, which converts fibrinogen to fibrin). So: clotting initially begins along the extrinsic pathway.
The weird thing, though, is that as soon as we make a little Xa, that Xa (along with the aptly-named tissue factor pathway inhibitor) turns off the extrinsic pathway! A little thrombin is formed, though, before the pathway gets turned off – and that thrombin kicks off the intrinsic pathway (the other side of the cascade, with factors VIII and IX). Fibrin formation then proceeds along this pathway until it’s no longer needed.
The bottom line is: you need both the intrinsic and extrinsic pathways to form fibrin in vivo. If you don’t have factors VIII or IX, you can’t utilize the intrinsic pathway – and you’ll have a very hard time forming fibrin!
- Monica Austin said Very helpful. Thank you.
- Jean said Amazing explanation, already had an idea, well elaborated and segmented to maximize understanding. G...
- Christine said This is a fantastic review for the ASCP MLS exam! Thank you!
- Cyndi said Your blog is great! I’m a fellow in pulmonary & critical care and LOVE this site 🙂
- kabelo said that was great explanation
- Callistus said Thanks a lot. I want to learn more.
- Montez said My husband has AML and as you can imagine, some articles are extremely hard for the layman to under...
- Daniel said Thanks so much…..was really helpful for my seminar work……
- Oneyda Julissa Ramìrez Medina said Thanks, Let’s learn pathology
- Lizzy said Extremely helpful. Thank you!!
- Maureen said It was quite explicit & useful. Thanks.
- Manpreet said Thank you….it’s useful