Of Clot, Tofu, and Cheese

The process of clotting is something vascular surgeons take for granted, but patients may have a hard time understanding what a clot is because in most people’s experience, it is rare for someone to see enough blood to form clot. How many patients or even health care providers have seen a tube or a basin of blood clot? So how do we describe clot to patients? I think the solution lies in food.

Most people who know me will say that I propose food as the answer for most things but hear me out. In describing clot, food is particularly salient. Clot is protein made insoluble, and there are many foods that have similar properties. Tofu, jello, and cheese and their making can give context where the word “clot” cannot.

All are made by taking a solution of protein and allowing them to form clumps that cause them to fall out of solution. It may require an acid, as in the case of tofu and cheese, but mere time and cooling may be sufficient as in the case of jello. And like these, clot may take on a soft crumbly quality when it is fresh clot, to a tenacious formed clump when given enough time. The difference is like silken or soft tofu and firm tofu. Or fresh ricotta cheese before it has time to set in its mold and the firmer cheese you get after weeks of curing.
With enough time, you get a hard substance that you can slice with a knife, like a dry cheddar or Parmesan. That is how I think of clot. It can be soft and formless like early jello before it is ready to eat. Or it can be hard and formed like mature dry cheese. The softer it is, the easier it is to dissolve or suck out via gadget or catheter, but there is a time factor to this softness -thing of your jello setting and hardening in your fridge. The harder the thrombus is, the less likely it is you can remove it with catheters and more likely you will have success with an operation as in the first picture. The harder stuff in fact crumbles well like a parmesan cheese and is harder to remove.

Burrata, handmade in Calabria is similar to the kind of semi-mature clot that deforms well but is tenacious and difficult to break up and remove except in one piece.

There are several things to draw from this with regard to devices designed to retrieve clot. Clot can occlude catheters as much as they can occlude arteries. Clot retrieval depends on net output of fresh clot that deforms well and flows well but fails in the hardened brittle clot that is well organized and adherent. Retrieving these crusty dried clot matter may be impossible for a device that depends on clot deformability or a maximum particle size, and these clots are the ones that are more partial to crumbling and embolizing. All devices must accept the fact that the unclogging is done in a flowing circulatory system where items swept downstream have the consequence of killing tissues whose arteries are blocked by emboli. There is always embolism with minimally invasive approaches. These devices make sense for hard to access circuits like the brain, but make far less sense in circuits like the extremities where surgical control is relatively low risk and results in reversal of blood flow -like in TCAR. Each of these devices can cost several thousand dollars. The fact is, operations can be faster and safer because embolism can be controlled and a wider range of clots, and larger amounts of it, can be removed at a lower cost. The first picture shows the results of a popliteal cut down and tibial thrombectomy where inflow was first restored in the below knee popliteal artery, and clot retrieved from each of the three tibial vessels (misleadingly, the tibial thrombus is all lined up), and a simultaneous 4 compartment fasciotomy performed, all under 90 minutes with no use of contrast. Unfortunately, open thrombectomy is a bit of a lost art in that many of the maneuvers and steps required to revascularize a limb successfully with no preoperative imaging requires experience. A younger patient with an arrthymia related embolism and normal soft arteries is approached far differently from an older person with atherosclerosis and diabetes, where open thrombectomy is better suited for the first, and catheter based approaches better for the latter.

Diagnostic and Therapeutic

The open surgical exploration of the extremity arteries is fast becoming a lost art along with the physical examination. In the setting of acute limb ischemia, the first decision in my mind is: was this an embolism? The presence of arrrhythmias, cardiac shunts, and aneurysms may suggest this, the next question is did this patient have a prodrome of limb ischemia related symptoms and history of atherosclerosis. The fact is, you have about 4-6 hours to return blood flow before irreversible neuromuscular damage sets in, maybe less if important collaterals are lost. Choice of procedure then devolves to choices about the most expedient methods for returning blood flow to the extremity, and between endovascular procedures and open surgery, it is rarely possible to manage significant clot burden with endovascular methods without adding the burden of procedural time. These considerations are balanced by patient risk. If the patient cannot tolerate general anesthesia, it is still possible to operate under local anesthesia. Otherwise, one is faced with choices like stenting across clot or common femoral artery. The algorithm is simple -ensure inflow, thrombectomize outflow, check for backbleeding, restore flow, check flow, repeat as necessary downstream. Fasciotomy as needed and close the skin if you can.

Endovascular options deal with the basic physics of trying to pull clot of varying consistency through a small lumen over a long length while not pushing emboli. The needs are simple -a low profile, cheap, over the wire solution for evacuating clot without embolizing nor injuring the patient on a 100cm and 150cm length catheter. Cost wise, open surgery always beats any endovascular option if wound complications of open surgical exposure are avoided. Both methods can’t cover themselves if open fasciotomy wounds keep the patient in the hospital for weeks. The fact is, we already have this magic system in the catheters that we already have on the wall, albeit, they don’t work particularly well if you are dealing with Parmesan, but none of the systems do. I recently declotted a graft fistula with just 6F sheaths, a regular #3 Fogarty ballon, 6mg of tissue plasminogen activator, and was able to salvage the blood and return to the patient.

Conclusion

Vascular surgeons should have as many words for clot as Eskimos purportedly do for snow. There is no one solution to a problem, but all the tools must be available to the vascular surgeon. Ironically, only the simplest are needed most of the time.

The shunt as temporary bypass -a modest proposal

The rise of cardiopulmonary bypass life support has also given a rise to the need to keep large, obstructive cannulas in femoral arteries. ECMO cannulas are often kept in for days, and it is not uncommon to discover limb ischemia and infarction relatively late. This can be avoided by placing a distal perfusion cannula to shunt blood to the leg early in the ECMO process. The ECMO cannulas have a convenient side port to send a little flow to a 6F sheath placed in the femoral or popliteal artery. This is an established technique (reference 1, sketch below), and it works despite the modest flows achieved because it does not take much to keep the leg alive. These patients are not walking, nor are they need to heal leg wounds, so just enough blood flow means something just a little more than what they get when the common femoral artery is completely occluded by the life support cannulas. What is fascinating to me is that these shunts can pptentially help to save limbs when used as temporary extracorporeal bypasses when definitive vascular surgical care is not immediately available.

brachial to femoral shunt sketch

 

When I was a medical student, I took on a research project after my first year where I had a Langendorff preparation of a rat heart (below).

langendorff prep in MRI
an isolated, perfused, beating rat heart placed in a superconducting magnet for NMR spectra acquisition 

My project was to take a rat heart and keep it alive, beating, and even working, through a perfusion apparatus and place this inside a superconductive magnet to obtain Phosphorus nuclear magnetic resonance spectra -intracellular metabolism data including concentration of ATP, intracellular pH, and ATP/ADP ratio. While the project was successful -I am quite proud to have been the only person at Columbia to have successfully acquired NMR-S data with living beating heart, I moved on to other interests and took away this concept: with oxygenated, glucose enriched, isoosmolar fluid perfused at arterial pressure, any organ can be kept alive, possibly indefinitely, including a brain which only recently others have found possible (reference 2) in reputable scientific circles, but the the Nature publishing Yalies were scooped by the Simpsons decades ago (below), and maybe Mary Shelley centuries before,

simpsons head

This is the simple idea. Revascularization is keeping the target vascular bed alive by delivering oxygenated blood. With a shunt, it could be little, it could be a lot, but it certainly is better than zero, and even a little can buy you time.

The breakthrough that I had was several years ago, a patient arrived from another hospital with an Impella pump which did not have a side port like an ECMO cannula. It is a large catheter that augments cardiac output and in the patient that I was asked to see this patient as their leg was cold and pulseless. Their cardiac output was very poor, and they were sustaining an augmented systolic pressure in the 90’s. There was no way to get this patient to the operating room for a revascularization of any sort. It did strike me that the patient had the misfortune of having catastrophic heart failure in the absence of significant athersclerosis and had normal brachial arteries. After discussing the ramifications with the ICU and family, I placed a brachial artery 5F cannula, and connected it to a 5F sheath I placed in the superficial femoral artery below the occlusive common femoral sheath (figure below). A doppler on the tubing connecting the two cannulas confirmed flow and the patient’s left hand maintained a pulsatile oximetry waveform. The leg pinked up and eventually there was a signal in the foot. This managed to perfuse the leg which did better than the patient who succumbed to multiorgan failure from heart failure. The leg did great.

Which leads me to these thoughts. Most hospitals are good at diagnosing large vessel occlusion via CTA. Most hospitals have doctors who can place arterial lines with ultrasound guidance. In the instance of aortoiliac occlusion or femoral occlusion from thromboemboliem, time is a critical limiting factor to limb salvage. Many hospitals do not have vascular surgeons. Many hospitals transfer these patients with a heparin drip but in the ischemic condition. Transfer arrangements may take hours. Why not ameliorate this situation by having an appropriate physician -an anesthesiologist, an intensivist, an EM physician, place an ultrasound guided radial or brachial arterial line, connect to arterial line tubing to a dorsalis pedis arterial line. Tape it all down on the patient after confirming flow (crude sketch below). This would be better than the three extra hours of ischemia the patient gets hit with on transfer. No one would transport a donor kidney without adequate perfusion and protection, but dying legs get transferred all the time with established warm ischemia. If done well, it might turn an emergency procedure into an urgent, semi-elective one. Have the vascular surgeon video conference in to confirm the absence of blood flow and appropriateness of temporary shunting.

radial to dp shunt
radial artery to dorsalis pedis artery shunt

If we are to live in  a world with less vascular surgeons, then the radius of survival has to be extended with use of technology and simple ideas such as this. Comments are welcome.

Reference
1. Foltan M, Philipp A, Göbölös L, Holzamer A,
Schneckenpointner R, Lehle K, Kornilov I, Schmid C, Lunz D. Quantitative assessment of peripheral limb perfusion using a modified distal arterial cannula in venoarterial ECMO settings. Perfusion. 2019 Mar 13:267659118816934. doi: 10.1177/0267659118816934.

2. Vrselja, Z., Daniele, S. G., Silbereis, J., Talpo, F., Morozov, Y. M., Sousa, A. M. Mario, S., Mihovil, P., Navjot, K., Zhuan, Z. W., Liu, Z., Alkawadri, R., Sinusas, A. J., Latham, S.R., Waxman, S. G., & Sestan, N. (2019). Restoration of brain circulation and cellular functions hours post-mortem. Nature, 568(7752), 336–343.