https://evolutionnews.org/2023/08/the-incredible-design-of-vertebrate-blood-clotting/

"Thus, the formation of this platelet plug (and the injury itself) initiates the coagulation cascade.

***

"Vertebrate blood coagulation is best understood by focusing first on the ultimate objective of the cascade, which is the formation of a fibrin gel that reinforces the initial platelet plug, thereby strengthening the clot. The clot itself is made of fibers composed of the protein fibrin, which circulates in an inactive form (fibrinogen) in the blood plasma.

***

'The cleavage of fibrinopeptides exposes new binding sites on the fibrin molecule, allowing the individual fibrin molecules to polymerize into a clot.8 The fibrin molecules further aggregate and form a mesh-like network, which is stabilized by the enzyme factor XIIIa.9 Factor XIIIa catalyzes the crosslinking of fibrin molecules through the formation of covalent bonds between specific amino acid residues, creating a stable fibrin clot. The resulting fibrin clot, together with the platelets, provides a physical barrier at the site of injury, preventing further blood loss. It also serves as a scaffold for other components of the clotting process, which aggregate on the fibrin network to form a stable blood clot.

"If the pathway consisted only of fibrinogen and thrombin, thrombin would constantly cleave fibrinogen, and the consequence would be uncontrolled and excessive clotting throughout the bloodstream. To avoid this, it is essential that the process be carefully regulated. Blood clotting involves the use of proenzymes, which are enzymes that are retained in an inactive state and need to be converted into active enzymes through specific cleavage by proteases such as thrombin.

***

"Once activated, factor Va plays a critical role in the amplification of the coagulation process by enhancing the activity of factor X and promoting the production of more thrombin. This makes the coagulation cascade autocatalytic, since the activation of clotting factors leads to the activation of more of the same proteins.

***

"To prevent excess clotting and ensure that the clotting cascade remains localized to the site of injury, there are several regulatory mechanisms.16 Antithrombin III (ATIII) is a natural anticoagulant that inhibits the activity of thrombin and several other coagulation factors, including factor Xa and factor IXa. It achieves its anticoagulant effects through a mechanism called “serpin” inhibition.17 Serpins (serine protease inhibitors) are a class of proteins that regulate the activity of proteases, including those involved in blood clotting. ATIII binds to Thrombin’s active site, effectively blocking its ability to cleave fibrinogen into fibrin. By inhibiting thrombin, antithrombin III indirectly helps regulate the activation of factor V and thereby prevents excessive clotting.

***

"To prevent excess clotting and ensure that the clotting cascade remains localized to the site of injury, there are several regulatory mechanisms.16 Antithrombin III (ATIII) is a natural anticoagulant that inhibits the activity of thrombin and several other coagulation factors, including factor Xa and factor IXa. It achieves its anticoagulant effects through a mechanism called “serpin” inhibition.17 Serpins (serine protease inhibitors) are a class of proteins that regulate the activity of proteases, including those involved in blood clotting. ATIII binds to Thrombin’s active site, effectively blocking its ability to cleave fibrinogen into fibrin. By inhibiting thrombin, antithrombin III indirectly helps regulate the activation of factor V and thereby prevents excessive clotting.

***

"After the clot is formed, it undergoes retraction, which involves the contraction of fibrin by platelets within the clot, resulting in the clot becoming denser.21 This process helps to reduce the size of the clot and brings the edges of the wound closer together. Eventually, as the wound heals, the clot needs to be dissolved to restore normal blood flow. Plasmin, a proteolytic enzyme, breaks down the fibrin meshwork into soluble fragments, leading to the dissolution of the clot.22 Plasmin is generated from plasminogen by tissue plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-Pa), among other molecules.

***

"Several of the proteins discussed here depend upon vitamin K for their synthesis — these are prothrombin, factors VII, IX, and X, as well as proteins C and S (i.e., the anticoagulant proteins that serve to inhibit excessive clot formation). Vitamin K is essential for the post-translational modification of these clotting factors. Without adequate vitamin K, these proteins cannot undergo the necessary chemical changes, which would impair their ability to function properly in the coagulation process."

comment: this enormous process contains more than 25-6 steps. (see diagram) I've boiled down an enormous article which discusses every intricacy in detail. Earlier forms before vertebrates on land had simpler systems from which this developed, but the jump to this sophistication was enormous, irreducibly complex and not explained by Darwinism. Designer always fits.

https://www.sciencedaily.com/releases/2021/06/210607202208.htm

"Blood clotting is actually a physics-based phenomenon that must occur to stem bleeding after an injury," said Wilbur A. Lam, W. Paul Bowers Research Chair in the Department of Pediatrics and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. "The biology is known. The biochemistry is known. But how this ultimately translates into physics is an untapped area."

And that's a problem, argues Lam and his research colleagues, since blood clotting is ultimately about "how good of a seal can the body make on this damaged blood vessel to stop bleeding, or when this goes wrong, how does the body accidentally make clots in our heart vessels or in our brain?"

The workhorses to stem bleeding are platelets -- tiny 2-micrometer cells in the blood in charge of making the initial plug. The clot that forms is called fibrin, which acts as a glue scaffold that the platelets attach to and pull against. Blood clot contraction arises when these platelets interact with the fibrin scaffold. To demonstrate the contraction, researchers embedded a 3-millimeter mold with millions of platelets and fibrin to recreate a simplified version of a blood clot.

"What we don't know is, 'How does that work?' 'What's the timing of it so all these cells work together -- do they all pull at the same time?' Those are the fundamental questions that we worked together to answer," Lam said.

***

"The simulations showed that the platelets work best when they're not in total sync with each other," Lam said. "These platelets are actually pulling at different times and by doing that they're increasing the efficiency (of the clot)."

This phenomenon, dubbed by the team asynchronous mechanical amplification, is most pronounced "when we have the right concentration of the platelets corresponding to that of healthy patients," Alexeev said.

Comment: Clotting is a cascade of about 20 steps starting with platelets. we are still trying to understand it fully. Obviously the clot must be confined to the region it is needed and never massive. Activation in brain or coronary vessels is thought to be the result of leaking chemicals from cracked arteriosclerotic plaques. My question is how did unguided evolution invent such a critical but totally controlled process?

https://medicalxpress.com/news/2017-11-blood-clots.html

"Blood clotting is the "Jekyll and Hyde" of biological processes. It's a lifesaver when you're bleeding, but gone awry, it causes heart attacks, strokes and other serious medical problems.

"If a clot grows too big, pieces dislodged by blood flow (emboli) can block downstream blood vessels in the lungs or brain, leading to life-threatening complications such as pulmonary embolism or ischemic stroke. Therefore, once a clot forms, even for beneficial reasons, it must shrink and disappear after wound healing starts to maintain normal blood flow.

"While scientists know a lot about how blood clots form, relatively little was known about how they contract—a slow process that takes an hour to complete.

***

"As a result of injury or inflammation, platelets in blood get activated, become sticky, and bind together and with a stringy protein called fibrin to form a mesh-like plug (the blood clot) that stops bleeding into tissue. Platelets play a central role in clot contraction, but, until now, scientists haven't been able to show exactly how they accomplish this.

"As described in the paper, clot shrinkage occurs when platelets form hand-like protrusions called filopodia. These filopodia then attach to fibrin fibers and reel them in using the same hand-over-hand action used by a person pulling on a rope. The platelets retain the fibrin in tiny, tightly wound bundles, therefore remodeling the fibrin mesh to make it more dense and stiff. The reeling action also brings platelets and clusters of platelets closer together, reducing the overall volume of the clot followed by complete dissolution by fibrinolytic enzymes.

***

"Alber said the findings highlight a new role for filopodia, which were previously thought to help cells move around and sense their environment.

"'Until now, we knew very little about how individual platelets or small clusters of platelets exert a contractile force on fibrin fibers and how this tension collapses a clot's structure and reduces its size," Alber said. "Through this research, we have revealed a novel function for filopodia, which is their ability to re-arrange the fibrin matrix to cause clot shrinkage."

Comment: Multicellular Life could not continue to survive, unless a protective mechanism was present from the beginning to protect the circulatory blood system from leaks. This is the sort of system hat is so complex it had to begin in tact all at once, again implying design by God. No way to develop it step by step through multiple coordinated mutations.


> David: First problem with considering evolution inventing this is the mechanism obviously must have a controlled start and a controlled stop. This cannot be invented by hunt and peck; it must work from the beginning. After this stage the clotting factors appear and there are over 17 of them, all in beautiful coordination. I can't think of anything but design. In organisms with a blood/circulatory system this is a 'must' for life to survive.- Another article further describing the mechanism. It is this sort of complex arrangement that leads to my belief in God:-http://www.evolutionnews.org/2015/11/clotting_contro101231.html-"To prevent serious injury or death, the body had to come up with a mechanism that could apply a substance strong enough to stop the blood loss. -"This innovation is called hemostasis and involves three actions; vasoconstriction, platelet aggregation, and activation of the clotting factors. Hemostasis ultimately forms a fibrin clot, stops the bleeding, and allows healing to take place. However, since heart attacks and strokes occur due to clotting, the body must be able to control hemostasis so that it only turns on when it's needed and turns off and stays off when it's not. In other words, controlled hemostasis is a delicate balance between the forces that promote and prevent clotting. -***-"So, in summary, the clottingfactors in the blood remain inactive until blood vessel injury takes place to turn on the coagulation cascade. Meanwhile, the liver and the endothelium combine to produce anti-clotting factors that together work to turn off hemostasis and allow it to stay off when it's not needed. It is this delicate balance of clotting and anti-clotting factors that allows the body to normally be able to stop bleeding when injured, while at the same time allowing blood to flow freely to the tissues. Moreover, the total absence of fibrinogen, or prothrombin, or Tissue Factor, or Factor V, or Factor VII, or Factor VIII, or Factor IX, or Factor X, or Factor XI, or Factor XIII, or antithrombin, or protein C or TFPI would have made it impossible for our earliest ancestors to live long enough to reproduce. -"Michael Behe has described a system where the absence of any one part renders it non-functional as being irreducibly complex. It certainly looks like hemostasis is irreducibly complex, because if any one of the many clotting or anti-clotting factors were absent life would be impossible."-Comment: If you kept count there are 17 or so various factors acting to promote and to stop clotting. I can't think of a Darwinian just-so story to make this happen by chance or by itty-bitty steps by innovation.


> I'm still not fully convinced... the year this happened I had a mouth FULL of metal. (Braces, headgear... the whole scary lot!) The only thing that keeps me skeptical is that I never had this happen more than once. -My radio event involving the tee shirt soaked in tea was a one time thing,but it happened. My wife is recurrent, less as she grows older with me. Your event is like the one I experienced and my wife has. 
 
> Agreed. Your book has at least done a better job of pulling my attention into these areas that I typically have ignored due to their necessarily subjective nature.-That is all I intended. I think something is in that realm, but more than that, who knows? 
> > 
> > My view of consciousness is that it is an emergent phenomenon from a brain, the most complex item in the universe, and is related to the UI indirectly or directly.
> 
> Disembodied consciousness necessitates that there are two fundamental substances in the universe, mind and matter. I'm not discounting you here, but presenting you with the most direct challenge to your thought that you should consider in order to refine it. In what way can your thinking answer the challenges posed to Cartesian Dualism? I don't think it would be a fruitless exercise for either of us. -Here you are very much acting like my editor, and I appreciate it. My current concept is the UI is a part of everything, Spinoza-like: the information in plants and animals that aids their living state. Our individual minds are part of the UI but without a full connection. We have free will, the UI doesn't control us, but we tend to have all those religions that assume a greater power.
The theologic philosophers refer to the UI as a necessary being. I'll give it more thought. And thank you.


> Next, you discuss an instance (page 148) where you attempt to explain a "psychic" event. 
> 
> Do you have any metal fillings? -Only two gold inlays. -> Once, when I was... about 14 or 15, I wrote the lyrics to the song "Closer," from "Nine Inch Nails," a full two years before I ever heard the song... when I first heard the song and felt the amazing "deja vu," I attributed it to grabbing radio waves that morning when the song first played. The song was first released May 1994, and I recall hearing it (without listening to the radio) for the first time sometime that summer. I hated the band when it first appeared... it wasn't until I heard THIS song for the first time that I realized there was a connection here... Maybe the youth of the country had an unconscious event then...?-Yours is a great example of a psychic event. Believe it. I know it when I hear about it. My wife has had several that I have observed
> 
> The only other negative from this chapter involves your idea of the collective unconscious...-Rupert Sheldrake has done some interesting stuff, you can't deny that. Just keep your mind open. One day we may know a great deal about such phenomena. I don't really 'know'. I wonder, however.
> 
> At what point can you deride dualism and advocate its existence as you do on pages 160, 167, 170, 172, and 173? -I don't know that these examples support dualism. They are just psychic events.
> 
> If you claim that mind and body are separate as you seem to do in all but in one portion where you attribute the entire body as conscience--as I subscribe to--how do you defeat the arguments against Cartesian dualism?-My view of consciousness is that it is an emergent phenomenon from a brain, the most complex item in the universe, and is related to the UI indirectly or directly.
> 
> Finally, on page 173 you argue that "science is silent theologically..." How can you you possibly argue this without a discussion of what science is, what it does, and its implicit assumption of methodological materialism? 
> 
> Before I print one word to the positive of this chapter, I require you to respond to at least THAT QUESTION...-I thought I covered the methodological materialism in chapter one. Should I have repeated it?

I will begin with negatives instead of positives this time, because overall, this chapter has introduce a new level of doubt within me that never existed a priori. 
> 
> First, you cite a study concerning fertility in 2001 on page 177. This study was discredited by finding that one study leader, "Daniel Wirth, a.k.a. John Wayne Truelove, is not an M.D. but an M.S. in parapsychology who has since been indicted on felony charges for mail fraud and theft, committed apparently at the time the study was claimed to be conducted." -When I cited the study I had no idea it was fake. book came out in early 2004.
Chapter was written in early 2003. 
> I shan't use this to discredit all such studies, but I would further draw attention to the MANTRA Study. "A 2005 MANTRA (Monitoring and Actualisation of Noetic Trainings) II study conducted a three year clinical trial led by Duke University comparing intercessory prayer and MIT (Music, Imagery, and Touch) therapies for 748 cardiology patients.-Again 2005 is after my book 
> "The STEP project" (2005) resulted in more negative effects of prayer, resulted in a comment by Dawkins, "It seems more probable that those patients who knew they were being prayed for suffered additional stress in consequence..."
> 
> This is the one that I tried to find previously that resulted in those being prayed for, suffering worse results than those who were NOT prayed for. 
> 
> I will search for further negatives, and then move on to the postives.-You need only look before 2003. I know about the fraudulent study I cited. If I ever get to a revision, all can be changed.


> Don't mistake the forest for the trees.... I find Aeschylus and Shakespeare more divinely inspiring than science, in regards to human intellect! But the main reason this argument feels weak to me is that it more or less says "we were designed because WE are so smart..."
> 
> Unless I oversimplified it, it makes me cringe! (Sorry! :-/ )-Don't be sorry. I have appreciated all of your comments, and I again repeat a statement from before. I wish you and dhw had been my editors. I found Adler's book, 'The Difference' about two years after writing that chapter 5 (It was from 1967). I could have made the chapter stronger with that background. I still think Adler has a major point. You are a much more exacting thinker than I am with your philosophy background, too exacting in some areas! Like odds against chance life. :>)) Our Hat Size Is (Still) Too Big for Darwin. But now try Chapter 6, a really fuzzy area.


> I really, really hate that you're blowing my idea off: How long does it take before humans are aware that they are aware? How long before they notice that their best hunters are begot by their best hunters, and their smartest shamans beget smarter shamans? How long before they select for the prettiest girls?-Arranged marriages, which is part of your proposal, usually is ranking status, money, etc. Not IQ
> 
> Consider Plato's republic. Have you considered how strongly it models Spartan society? Sparta's policy of infanticide turns noses to modern morality, but I hardly think that they were the first group of humans to engage in the practice.-The chinese are doing this now by sex. Same thing has gone on in India. If you are going to knock off stupid when do you recognize stupid. Not at birth but perhaps 7-10 year later. Hitler wanted to create aa master race, and had a program, but I don't see much evidence of it now. All the electricity from wind farms, not nuclear. And sort of fell for global warming hysteria. But, Merkel is obviously the brightest crayon in the EU box.-> When I said a couple years back that in order to infer a UI you first must be able to differentiate between human and nonhuman intelligence--this is EXACTLY what I had in mind.- The UI may be just like ours without the emotion. This is one area of possible difference, but we can understand the laws of physics, and unwrap the codes in biology, made by that UI. I think I can infer it from the evidence at hand.

David begins to go for the jugular rather early, combining what I suspect is his Adlerian background into building a case that we're smarter than we need to be.
> > 
> > My reading is early and very preliminary, but I have a simple question to ask:
> > 
> > Could it not be the case that as soon as our primitive ancestors--under pressure from the Ice Age you discuss--began to identify their geniuses and began a program of selection of their own? 
> 
> Cute start to your comments. But(!), H sapiens is in Africa, and not as cold. Attraction to sex is still attraction to sex. No one in the Rift Valley is thinking about IQ.-I really, really hate that you're blowing my idea off: How long does it take before humans are aware that they are aware? How long before they notice that their best hunters are begot by their best hunters, and their smartest shamans beget smarter shamans? How long before they select for the prettiest girls?-We've done this with dogs for millenia, and if you prepare a revision for your book, though you don't agree, I implore you to consider the role of artificial selection: it is the strongest challenge to the idea of a UI, simply because as I said once a long time ago--it creates a tapestry that is impossible to unwind! But we KNOW man has done this to himself!-Consider Plato's republic. Have you considered how strongly it models Spartan society? Sparta's policy of infanticide turns noses to modern morality, but I hardly think that they were the first group of humans to engage in the practice; and if you consider that it took only 12,000 years to go from the wolf to the Chihuahua, the wall of your argument begins cracking. -When I said a couple years back that in order to infer a UI you first must be able to differentiate between human and nonhuman intelligence--this is EXACTLY what I had in mind.

David begins to go for the jugular rather early, combining what I suspect is his Adlerian background into building a case that we're smarter than we need to be.
> 
> My reading is early and very preliminary, but I have a simple question to ask:
> 
> Could it not be the case that as soon as our primitive ancestors--under pressure from the Ice Age you discuss--began to identify their geniuses and began a program of selection of their own? -Cute start to your comments. But(!), H sapiens is in Africa, and not as cold. Attraction to sex is still attraction to sex. No one in the Rift Valley is thinking about IQ.