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Hemostasis: Maintaining the Right Numbers Is Crucial


Editor's note: Physicians have a special place among the thinkers who have elaborated the argument for intelligent design. Perhaps that's because, more than evolutionary biologists, they are familiar with the challenges of maintaining a functioning complex system, the human body. With that in mind, Evolution News & Views is delighted to present this series, "The Designed Body." For the complete series, see here. Dr. Glicksman practices palliative medicine for a hospice organization.

So far in this series, we have seen that evolutionary biologists can only speculate on how complex systems within the body came into being. As for the body knowing how to make sure it has the right amounts of oxygen, carbon dioxide, hydrogen ion, hemoglobin, iron, water, sodium, and potassium, the evolution of such a wonder similarly remains a black box.

The same applies to hemostasis, the process by which the body forms fibrin clots to stop bleeding and allow it to heal. Without this, a minor injury would be lethal. As noted previously, hemostasis involves mainly three processes, which are triggered when blood vessel damage occurs. Those are vasoconstriction, platelet aggregation, and activation of the clotting factors. However, since the presence of clots within a major vessel, like an artery sending blood to the heart, the brain, or the lungs, can result in sudden death, hemostasis must turn on only when it's needed and turn off and stay off when it's not.

In previous articles I've shown that chemicals released by the endothelium (the tissue lining the inside of the blood vessel), with the help of specific anti-clotting factors produced in the liver, combine normally to prevent clotting unless an injury takes place. The total absence of platelets, or any one of most of the clotting or anti-clotting factors, would have disrupted this delicate balance, making it impossible for our earliest ancestors to live long enough to reproduce. As with iron, potassium, and blood pressure, not having enough can be deadly, but so can having too much.

An Analogy from Nature

Consider Beavers build dams across streams to form large enough ponds in which to build their homes. When nature or a predator creates an opening in the dam, the beavers must quickly patch up the damage or lose their home. To prevent further leakage, the patch must seal the opening and be strong enough to withstand the force of water against it. Solid logs, flexible branches, and soft leaves packed together with lots of soft mud are the usual materials used by beavers to construct and repair dams. The size of the opening determines how much material must be used to complete the job properly. Even beavers "know" that real numbers have consequences for life. So too the body must have enough material to prevent traumatic blood loss through hemostasis.

Due to the laws of nature, like friction, momentum, sheer, pressure, and gravity, the body experiences thousands of small vascular injuries every day. These trigger vasoconstriction and platelet aggregation to form a platelet plug. The body must have enough platelets to begin the process of hemostasis. Thrombopoietin is a hormone produced mainly in the liver and kidneys that controls platelet production in the bone marrow. The normal platelet count is 150,000-450,000 per microliter (uL = mm3) of blood. Platelet counts below 20,000/uL, and in particular, less than 10,000/uL, often result in moderate or severe spontaneous bleeding, which can be life-threatening if it occurs in the brain or the gastrointestinal system.

But having too many platelets isn't good for the body either. Platelets are cell-like structures that float in the bloodstream. Just like having too many food particles in the kitchen can clog the drain, so having too many platelets in the circulation can slow blood flow, particularly in the small arteries and arterioles, which can compromise organ and tissue function. Platelet counts above 750,000/uL can result in a heart attack, a stroke, or blood clots in other areas of the body. Thus, not just any number of platelets is needed to have controlled hemostasis. It looks like most of the time, the system that the body uses knows what it's doing.

During platelet aggregation, fibrinogen molecules attach to them and activation of the clotting factors takes place. The coagulation cascade involves several clotting factors using two different chemical pathways to form prothrombinase. Prothrombinase converts prothrombin into thrombin, which then converts fibrinogen into fibrin so a fibrin clot can form to seal the damaged site. In addition, the endothelium secretes chemicals that not only prevent platelet aggregation but also ones (heparan sulfate and thrombomodulin) that work with others from the liver (antithrombin and protein C) to prevent activation of the clotting factors.

When blood vessel damage takes place, these inhibitors of clotting are no longer present in sufficient amounts to prevent the clotting cascade from taking over to form a fibrin clot. Since the endothelium on either side of the injury site is functioning normally, these anti-clotting chemicals make sure that the clot only forms where it's supposed to, and doesn't propagate up or down the blood vessel. This is how the body is able to control hemostasis so that it turns on when it's needed and turns off and stays off when it isn't.

Thousands of Small Vessel Injuries Every Day

The liver produces most of the clotting and some of the anti-clotting factors, but as with most things made in the liver, medical science has very little understanding of how they are controlled. As noted above, thousands of small vessel injuries take place every day. This means that to prevent blood loss and promote healing, hemostasis is always working and, by necessity, is continually using the clotting factors. For hemostasis to function properly, it is not only important for all of the clotting factors to be present, but there must be enough of each of them to get the job done right

When there isn't enough of any one clotting factor, this puts the body at risk for excessive and sometimes spontaneous bleeding. These are called hemorrhagic or bleeding disorders. The normal blood level of fibrinogen is about 3,000 units, but if it drops below 1,000 units, excessive bleeding can take place with limited injury because there just isn't enough to go around. The normal blood level of prothrombin is about 100 units and if it drops below 30 units, the same thing happens.

For Factor V, the normal and critical numbers are 10 units and 2.5 units, for Factor VII, 0.5 units and 0.125 units, for Factor VIII, 0.1 units and 0.04 units (Hemophilia A), for Factor IX, 5 units and 1.5 units (Hemophilia B), for Factor X, 10 units and 2 units, for Factor XI, 5 units and 1.5 units and for Factor XIII, 30 units and 1.5 units.

Too Much of a Good Thing

But having too much of a good thing can cause problems as well. Prothrombin 20210 is an inherited gene mutation that occurs in about 1 percent of the U.S. population, when the liver produces about 30 percent more prothrombinthan normal. Having too much prothrombin significantly increases the risk of clotting and can cause what are known as prothombotic or hypercoagulable states. These conditions can often lead to thromboembolism in which a clot forms, usually in a leg vein, and then breaks off and travels to the right side of the heart and then to the lungs. Pulmonary embolism is a medical emergency that can quickly lead to death because the blood flowing to the lungs to pick up oxygen and drop off carbon dioxide is compromised.

Another mechanism that can cause a hypercoagulable state is a deficiency in the amount or function of the anti-clotting factors. Deficiencies of antithrombin and protein C are relatively rare, while their total absence is considered to be incompatible with life. However, the commonest inherited prothrombotic condition is Factor V Leiden. This occurs in about 5 percent of the U.S. population and may be responsible for up to 30 percent of the cases of thromboembolic disease.

Normal endothelium secretes thrombomodulin, which joins to thrombin to activate protein C. Activated Protein C (APC) then deactivates Factors V and VIII, both of which are very important for clot formation. However, the amino acid structure of Factor V Leidenis such that it is resistant to being broken down by APC. This results in an increase in the presence of activated Factor V and the accumulation of more thrombin than usual. Having more thrombin can often lead to clots forming not only in the veins, but less frequently in the arteries as well. So a person with this condition is not only at risk for leg clots and pulmonary embolism but also heart attack and stroke.

The foregoing shows that the body's ability to prevent itself from bleeding to death from injury, while making sure it has enough blood flow to its trillions of cells, is a very delicately balanced process. The process, hemostasis, involves both pro- and anti-clotting factors. Not having enough pro-clotting compared to anti-clotting factors results in a bleeding disorder, like hemophilia, with its risk of hemorrhagic death (cerebral or gastrointestinal bleed). Not having enough anti-clotting compared to pro-clotting factors, like Factor V Leiden, results in a hypercoagulable state with its risk of a thromboembolic death (heart attack, stroke, pulmonary embolism).

Evolutionary biology speculates on how the many pro- and anti-clotting factors came into existence. But it never addresses how they could have worked together to allow an organism to survive long enough to reproduce. For that requires not only that an organism has all the parts of this irreducibly complex system, but that it also has the natural survival capacity to produce the right amounts of each.

Although medical science remains in the dark about such evolutionary mysteries, this does not stop some biologists from telling the public and teaching children otherwise. It takes a lot of imagination to believe that the ultra-complex and delicately balanced process of hemostasis came about by chance and the laws of nature alone. Advocates of intelligent design, who see the design seen in nature as real rather than an illusion, are on firmer ground, supported by what is already known about what it takes for life to survive under the laws of nature. In the next few articles in this series, I will look at how the body protects itself from invasion and what happens when its defenses break down.

Image credit: Alf van Beem (Own work) [CC0], via Wikimedia Commons.