Thursday, July 7, 2016

Real advances in blood technology

The ABCs of emergency medicine are changing.
I’m sorry, but this is going to be a long, complex discussion. Anything having to do with emergency care of your body would have to be. Before we’re done, you may find yourself making a list to carry in your wallet: TXA, FastClot, Perftec, Perflubron, Hemopure.
Anyway, the ABCs… Emergency responders have always been taught: Airway, Breathing, Circulation, in that order. But the decade-long war in the Middle East, horrific as it has been, has resulted in enormous advances in emergency medicine. Medics have learned that circulation – keeping your blood inside your body – is just as important, if not more important, than keeping you breathing. Here’s how their thinking is changing:

  • 1. Tourniquets.
For nearly a century medics were taught to avoid tourniquets. A WWI British field surgeon, Major Blackwood, called the tourniquet an ‘instrument of the devil’ after so many soldiers lost limbs because of them.

Blackwood was dealing with soldiers whose limbs had in some cases been tied off for days before further treatment. In most parts of the world today, treatment is only hours - or even minutes - away. Today’s medics know that a tourniquet can be left in place for up to 2 hours.
It isn’t about the tourniquet redesign; it’s the change in priorities. If a person has a large gash in their leg, for example, they likely have other things wrong as well. Previous thinking has been to FIRST get them breathing, then turn attention to the gash in the leg. But the medics in Afghanistan learned that during the several minutes it takes to get someone breathing properly they could bleed out.
“Tourniquets rapidly placed by the provider immediately, saved lives. The provider can then turn their attention to airway management, interventions to improve breathing… as well as IV placement and fluid administration.”
  • 2. Coagulants
Battlefield medics for the past 10 years have carried products like QuikClot, a finely ground mineral powder that helps wounds stop bleeding. More recent products feature gauze bandages impregnated with the mineral. While not too many EMTs carry this product yet, as more medics come back from the war with experience using QuikClot, its use in emergencies is growing. More recently, another coagulant bandage has hit the market. Called FastClot, this new invention is made by spinning dextran into fine threads like cotton candy, then attaching the body’s own clotting tool, fibrinogen, to the mesh.
The medic quoted above says:
“These specialized products have not been required often. However, these agents can be lifesaving, particularly in difficult-to-manage wounds, such as those of the groin or axilla. They provide effective hemorrhage control for wounds that aren’t amenable to other methods of hemorrhage control and which might otherwise be fatal.”
  • 3. Tranexamic acid (TXA)
In the previous column we mentioned TXA being used for a woman whose uterus wouldn't stop bleeding after delivery. In two recent studies – one of them in combat – TXA was shown to significantly improve the chances of survival of one out of seven patients. In some ERs it has become part of the routine to give TXA to all severely bleeding patients, or those with potential internal bleeding, if possible within 3 hours after injury.

Surgeons have begun administering TXA in many of their bloodiest operations – some heart surgeons even reportedly pouring it into the chest cavity before closing. Hospitals in some third world countries have likewise emptied a syringe of the stuff onto a gauze bandage and used it to stop otherwise unstoppable bleeding.

An Australian study in 2014 will see paramedics being equipped with TXA to be administered to accident victims.

  • 4. Permissive hypotension
In WWII, doctor Henry K. Beecher proposed that a relatively low systolic blood pressure of 85 was sufficient for a patient awaiting surgery. During the Vietnam era, with the ready availability of volume expanders medics began pumping their patients with bags of fluids to get blood pressure back up to acceptable numbers.

Turns out Beecher was right. What the Vietnam medics were inadvertently doing was disturbing the process of clot formation.

Back to the battlefield medic:
“The body’s natural response after trauma is to minimize hemorrhage by forming a fragile clot on the bleeding vessel. Excessive IV fluid administration can actually result in increased bleeding from the injured vessel… In a patient with penetrating trauma who is maintaining a systolic blood pressure at or above the 80–90 range or who has a radial pulse, IV access should be obtained with a saline lock but no IV fluid administered.”
He suggests that if the systolic BP falls below 80–90, or if the patient loses the radial pulse, then fluid should be given, just a quarter to a half unit at a time, and then the patient be reassessed.

  • 5. Artificial blood
As we saw in Part 2 of this series, blood is a marvelous creation. Coming up with a fluid that picks up oxygen from the lungs, releases it in the tissues, and doesn’t poison the body in the process, is a very tricky task.

20 years ago the most promising attempt at artificial blood was FluosolFluosol is a chemical called a perfluorocarbon (PFC), a liquid that can carry oxygen and carbon dioxide. While it was approved for emergency use in 1989, the FDA withdrew its approval in 1994, citing studies showing a higher incidence of stroke and heart attack in recipients.
Science is still working on PFCs. Perftoran, also called Perftec, is approved for human use in Russia and Mexico. It seems to have fewer side effects than Fluosol. A third generation PFC, Oxycyte, is in clinical trials in Switzerland and Israel. It is claimed to carry five times as much oxygen as hemoglobin, and also carries away CO2 to the lungs. Perflubron is a PFC that is an existing, approved medicine. It is given as a drink to patients about to have gastric pictures taken; it is also used to rinse the lungs of smoke-damaged patients as a product called LiquiVent. It is this secondary use, as an oxygen carrier, that has prompted its use in certain surgical procedures to avoid blood transfusion.

PHER-O2MP40XHemospan, and other blood replacements have come and gone. Hemospan was a product of a company called Sangart. It effectively passed phase II and phase III trials with few side effects. But Sangart has run through over a quarter of a billion investor dollars in the last couple years and, as of this writing, they seem to have disappeared off the face of the earth. Apparently coming up with a fluid to carry oxygen is easier, or at least less expensive, than getting approval from the FDA.

DxHb. Dextro-Sang started with a unique way of binding hemoglobin to dextran - a fluid already approved for transfusions. This combination promised oxygen delivery while protecting the kidneys. However, Dextro-Sang found southeast Asia to be an easier market than jumping through the regulatory hoops of the FDA, and dextran-hemoglobin might be hard to find in the U.S.

Hemopure is an HBOC approved for human use in South Africa but still being reviewed in the U.S. It has been given guarded approval for use in a few emergency situations by Jehovah’s Witness patients, so far with positive results. Hemopure starts with a sterilized hemoglobin molecule, a fraction derived from cow’s blood. As with human hemoglobin, it is good at grabbing onto oxygen and nitric oxide but not so good at letting go of them. So the Hemopure scientists take the molecule apart, turn half of it around and put it back together, making it less clingy with oxygen atoms. They also change the physical size of the molecule – it’s about 1/1000th the size of a red blood cell. It doesn’t do as good a job as your own blood in determining which tissues need oxygen the most. Nor does it carry away carbon dioxide as red blood cells do, but it does deliver oxygen. It breaks down and disappears in about 24 hours.

A doctor in Romania has approached the oxygen-transport problem from a completely different angle. Hemerythrin is neither a PFC nor an HBOC. It is a protein that transports oxygen in sea worms. Dr. Silaghi-Dumitrescu announced last month that he has successfully tested his Hemerythrin-based blood substitute on mice. He says human trials are about 2 years away.

Why all this work to change the transfusion landscape? Even though donated blood is “free,” it’s expensive to test, handle, store, and refrigerate; It has a short shelf life, even refrigerated; After storage it is an unreliable oxygen carrier; It carries antigens unique to the donor that can kill the recipient; It transmits disease; And study after study have shown that transfusion recipients, assuming they live, invariably leave the hospital with additional heart, respiratory, immune and other complications.

And that’s in a country where blood is given freely by kindhearted donors. In many parts of the globe, people don’t line up to give blood out of the goodness of their heart. They must be paid – or forced – to give blood. There are critical shortages, and the blood thus collected is even more problematic than in Europe and America. This is why countries like China and Thailand are throwing their financial resources into finding an acceptable blood substitute.
I’ve managed to get through four columns about blood with barely a mention of the Bible. Does the Bible have anything to do with blood? That will be the subject of the conclusion of this series. 

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