Last week, we talked about hypertension. This week… it’s blood clots! Or, more precisely, Venous Thromboembolism/Deep Vein Thrombosis (VTE/DVT).
A Venous Thromboembolism is the new catch-all term for blood clots generally originating in the lower extremities- also known as a Deep Vein Thrombosis. Technically, you can't have the "embolism" part until the clot breaks off and travels somewhere, so in a rare display of not letting pedanticism get in the way of an idea, the VTE moniker has come to refer to clots in general, whether or not they've broken off.
Now, what is a clot? It's normally a good thing. It's a collection of blood platelets, red blood cells, and polymorphonuclear lymphocytes that aggregate at the site of an injury to keep you from bleeding to death in the event of tissue damage, whether that damages arises from direct trauma, infection, cancer, or another process. Where we run into problems is when this inital stimulus sets off a very normal, helpful process, but then something else "tips the scale" and makes things run amok. And, indeed, this is exactly what happens with most people that get VTE/DVTs; they're doing just fine, even if they have risk factors for a DVT/VTE, and might go their whole lives without ever getting a DVT/VTE, until that scale gets tipped.
And the more things "tipping the scale", the higher likelihood that you'll get a DVT/VTE. Have only one risk factor? You might have a below 1% risk of developing a DVT/VTE. But combine five such risk factors, even if they're small on their own, and you can confer an almost 100% risk of developing a DVT/VTE on yourself.
Of course, that begs the question- what are the things that "tip the scale"? For that, we look to a fancy thing called Virchow's Triad. Virchow's Triad consists of the three states that lead to dysfunctional clot formation- venous stasis, endothelial damage, and hypercoaguability states.
VENOUS STASIS
Venous stasis is pretty simple; a lack of good venous blood return to the heart. When you can't make your blood circulate effectively, and it has a chance to "pool" more, even in otherwise normal circumstances, you dramatically increase your risk of clotting. This is why we most often see blood clots form in the lower extremities, like the calves (or, less often, the thighs), forming in major vessels or the inferior vena cava, the large vein that feeds blood from the lower extremity vascular bed back into the heart. You've already got blood working against gravity, and so it doesn't take much to throw the system off.
Venous stasis can arise from a number of different things- immobilization, such as after surgery; prolonged limb dependency, ie, standing for long periods and not moving (think something like a cashier or assembly line worker); dehydration; obesity; and loss of the normal "venous pump" of one-way valves and muscles. See, your venous system has lots of one-way valves. Your body wants that de-oxygenated blood to go back to the heart, and ONLY back to the heart. Your heart beating, supplemented in the legs by your leg muscles, help to "milk" that blood back up to where it needs to be. Any of the things listed above can cause a dysfunction of that process, but there's one in particular that probably causes the most problems- the next part of Virchow's Triad.
ENDOTHELIAL DAMAGE
Endothelial damage! Otherwise known as damage to the vein walls. This doesn't have to be severe damage, either; anything from subtle cellular changes to inflammation to direct, massive trauma can cause endothelial damage enough to put one at risk for developing a DVT/VTE. Having a site of "trauma" in the vein wall encourages clots to form there in order to heal it. Now, normally, the endothelium of your vein walls have the ability to secrete anticoagulant and vasodilating compounds. That's because, again, clots are a normal part of the healing process, and your body recognizes they're only good for a little bit; it doesn't want them to hang around longer than necessary. So your veins have the ability to dissolve those clots and then open themselves up to make sure they go away. Trauma interrupts that second process- the clots can form, but then can't dissolve properly.
This is a perfect example of what we were referring to before by a normal, helpful process that's hijacked or set out-of-whack by other events. We also discussed, in reference to the venous return system, that things like dehydration and obesity affect your venous return. They do, mechanically- but the other side of that coin is that they also directly damage the endothelium. Why? Because they're both inflammatory states, and inflammation is a major cause for trauma in vein walls. Paradoxically, inflammation isn't necessarily a bad thing. In fact, we can't heal without it. As mentioned before, inflammation helps fight off pathogens by flooding us with white blood cells, keeps our veins constricted so we don't bleed to death, and goes after anything that damages us. But it's not meant to be a long-term process; you're supposed to have inflammation for a little bit, and then it goes away. When we inflict long-term inflammatory states on ourselves, it tips the balance to the bad side.
Clearly, any trauma we sustain- particularly of the lower extremities- puts us at risk for clots. Trauma patients, such as those who've been in a car accident or similar circumstances, are at huge risk of developing DVT/VTEs, as are any surgical patients whatsoever. Some forms of trauma can confer an almost 100% risk of DVT/VTE formation; we find that particularly in patients with a traumatic brain injury, and those that are on mechanical ventilation.
With surgical patients, even if not on the lower extremities, we've got someone who has a disorder of some sort going on that requires surgery in the first place, which will up your risk of DVT/VTE, no matter how small. Then we're cutting them open to fix it, which inflicts trauma and puts the body into an inflammatory state. Then, lots of times, we immobilize the patients afterwards- and there we've just inflicted three major risk factors for DVT/VTE development on someone in the name of making them better! Heh.
Back in the day, surgeons used to say, "Ten days of bed rest!" after major surgery. But we found then that after twenty-four hours had passed, the number one cause of death in these patients was DVT/VTE; a clot formed, broke off, then traveled to their lungs or heart or brain. Now we've gone to almost the other end of the spectrum, to a “whip and drive!” initiative of getting patients up and moving very quickly after major surgery, and making a huge emphasis on prevention of these clots from forming, whether it's from compression stockings patients can wear in the bed, to medicines we can give to thin the blood.
Another cause of endothelial trauma is cancer. Cancer patients have a huge risk of developing DVT/VTEs. As mentioned before, a major component of inflammation is clotting- and cancer is a major, systemic inflammatory state. Oftentimes, cancer patients lose weight, are in constant pain, and have the associated cancer problems going on top of that. Effectively, the longer you have cancer, the more likely you are to develop a clot.
The "big three" cancers for danger of DVT/VTE are ovarian, brain, and pancreatic cancer. Pancreatic cancer confers an almost 100% risk of DVT/VTE development. In fact, since cancer is so often diagnosed by secondary findings or associated factors- people rarely get diagnosed with cancer without there having been something different that prompted diagnostic tests- we need to include DVT/VTE on the list of factors where we should consider cancer as a cause. That is, if someone comes in and presents with a DVT/VTE, and they don't have any other risk factors or mitigating events, cancer should be something to ponder.
HYPERCOAGUABILITY
The final leg of Virchow's Triad is hypercoagulability. Hypercoaguability refers to your body being in a state, generally genetic or metabolic in nature, that destroys or disrupts the normal balance between clotting and "lysis", or un-clotting. Cancer can also go in this category, alongside other things like anemia, liver disease, disseminated intravascular coagulation (the result of things like septic shock, transfusion reactions, etc), oral contraception, pregnancy, hormone replacement therapy, or smoking.
The most common genetic factor in hypercoaguability is something called a Factor V Liden mutation. 20% of patients who present with a DVT/VTE will end up testing positive for this condition, and it's in about 4.8% of the American population as a whole. However, most people with a Factor V Liden mutation will go their entire lives without any complication or having a DVT/VTE, until something happens to trigger it- like getting pregnant, starting on oral contraceptive medicine, taking a plane flight to Japan, etc.
Oddly enough, for reasons that we're not able to readily discern, most people with Factor V Liden mutations will only get deep vein thromboses; it generally doesn't progress into a pulmonary embolism. For that reason, people with Factor V Liden mutations are often treated solely with aspirin, as opposed to more aggressive anti-coagulants like warfarin or heparin, since their risk is just of a DVT, and not a VTE/PE. DVTs are bad, but not nearly as bad as PE/VTEs.
We mentioned earlier that cancer was most frequently diagnosed in the wake of associated findings; we find the same is true for thrombophillic findings like Factor V Liden deficiency. For instance, a woman who has multiple miscarriages may be suffering from thrombophilia as the root cause for this.
As an example of all of the above, if you had a 32-year old healthy female who comes into your clinic saying she recently became pregnant and had one-sided swelling of her lower leg, you'd be very concerned she had a DVT, and possibly something like Factor V Liden mutations.
A more recent aside, insofar as hypercoaguability states go, we have NSAIDS- non-steroidal anti-inflammatory drugs, like ibuprofen, aleve, and toradol. They present us with a bit of a conundrum. The way NSAIDs work is they interrupt the inflammatory process, specifically the very end of the inflammatory process where a lot of the pain chemicals and enzymes are expressed. But they're kind-of a blunt weapon, which is why people get ulcers and such from overuse of the drugs, because they're not very selective about how they work. When they did research into what enzymes in particular mediate pain and inflammation, they found one called the COX-2 enzyme, and so they developed medications that went after this enzyme in particular. It blocked pain and inflammation, but that's it- no other side effects, no ulcers, etc. So unlike ibuprofen, which hits a variety of enzymes including COX-2, these ONLY went after the COX-2 enzyme. And they actually worked really well!
If you remember medications called Vioxx and Celebrex, then you'll know that they were taken of the market abruptly because they were killing people left and right. It turns out that while inhibiting the COX-2 enzyme did prevent pain and inflammation, and kept people from getting stomach ulcers, it also caused an imbalance between anti-thrombotic prostacyclins and thromboxane- basically, it jacked with the clotting process, and these people died horribly, mostly from PE/VTEs.
While we knew that other NSAIDs like ibuprofen and aleve also act on the COX-2 enzyme, if not as specifically as Vioxx or Celebrex, just this year studies have come out suggesting there's a pooled risk ratio of developing DVT/VTEs 1.8 times greater among people who regularly used NSAIDs than those that don't. In fact, the only NSAID that doesn't give you an increased risk of heart attack or DVT/PE is aspirin, which works solely on the COX-1 enzyme.
So, obviously, there's a conundrum here. This doesn't mean we should just knee-jerk stop using these NSAIDs altogether. Useage of NSAIDs has also been linked to a significantly reduced risk for breast and colon cancer. People with chronic arthritis, are we just going to tell them hey, sorry, you're just gonna have to tough it out? No. We need to be able to understand what these medications do, so we can make better choices about what we suggest to our patients, the therapies we put them on and advice we give them.
PATHOPHYSIOLOGIC CONESEQUENCES OF DVT
There are a number of things that can happen if you get a DVT/VTE, the most serious of which is obviously that it'll take on the pedantic function of the name venous thromboEMBOLISM, and break off and travel to your lungs. It's a common misconception, but DVTs cannot break off and travel to your brain or heart unless you have another sort-of heart dysfunction- which is actually much more common than we previously realized. When you're a fetus, and up until you're about six months old, there is a "hole" in your heart called the foramen ovale. It's used to help shunt blood from the placenta through a fetus' heart in utero. Once you're born, you've no need for it, and so it closes up over the first six months of your life. New research suggests, however, that as many as one in every four people have a patent foramen ovale, meaning that hole never closes completely. If that's the case, then having a pulmonary embolism puts you at a significant risk for a heart attack or stroke.
When you block a blood vessel, you build up pressure behind it. That's why oftentimes we associate DVTs with swelling in the lower legs; that blood's got nowhere to go, so it backflows into the vessels or vascular bed around it. Now, everyone probably gets clots in their lower legs at some point in their life, but if your system is working like it's supposed to, even big ones that might cause temporary swelling will simply kind-of go away; the body engages it's ability to induce "lysis" and kill the clot. But if their big enough to cause swelling behind them, they'll damage that balance in the veins, as discussed before, which makes it harder for venous blood to return to the heart in the future, which then puts you at more of a risk of clotting, etc, etc.
But that begs the question- how do you recognize the physical signs of a DVT or a VTE?
The answer much of the time, unfortunately, is... you don't. Far too often, there simply aren't any physical signs of a DVT, which is why knowing the patient's history is of the utmost importance. But there are a few physical signs that are common, the most important of which is pain. If you have deep lower-extremity pain in the absence of any other pertinent findings- as in, say, a sports or overuse injury- it should be a red flag. Note thats DEEP pain. DVT pain is deep, and rarely superficial. Unilateral leg swelling is the most reliable sign of a DVT. Swelling often begins at the medial malleolus, which is the "boney bump" on either side of your ankle. If you look at that bone, there's a little pocket there, around where your heel and achilles tendon are located- if you had a DVT, you might see that spot filled up or a little bit swollen.
As far as measurements go, measuring leg circumference is the best way to determine is one side is more swollen than the other. If you pick a spot, say the bottom of the kneecap, go down about 10cm (4in) or so and measure both sides at the same level. A small difference between legs, particularly between the dominant and non-dominant leg, is not uncommon, but a difference of 3cm (1.2in) in diameter or greater in the calf is a warning sign. Speaking of the calf, it can also present with tenderness, which is usually most prominent on deep palpation. You can g ahead and squeeze the leg to see if it's tender, you're very unlikely to be able to squeeze it hard enough or in the right way to dislodge the clot, and if you're having pain from it, you probably won't be able to squeeze very hard because of the pain.
Sometimes you'll even see varicose veins; a sudden onset of someone having varicose veins should be a big warning sign they might have a clot, because that would suggest the clot is causing backpressure and that blood is trying to go somewhere to get back to the heart- like through more superficial veins that can't handle that pressure, ergo they bulge and distend.
The old standard for testing for presence of DVT was to analyze a patient's Homan's Sign, where the doctor would manipulate your leg to provoke pain on flexion of your foot; the problem was, there was only about a 10% sensitivity as to whether the test was right or wrong, and a 0% percent specificity, meaning that even if you provoked a "positive" Homan's sign, there's so many different things it could be it was worthless as a diagnostic tool. But it doesn't really hurt the patient, so you'll get plenty of folks who still do it- no harm, no foul.
Long story short, DVTs are VERY hard to diagnose clinically; there's often no or vague symptoms, and there are so many other things that can cause DVT-like symptoms that it's almost impossible to diagnose with 100% certainty by physical symptoms alone. The problem is that it's hard to simply ignore DVT-like symptoms, because even if there's a chance they're caused by other things, DVTs can break off and turn into PEs in a big damn hurry- so you have to act quickly.
There's a few ways to diagnostically look for blood clots. One of them is a blood test called a d-dimer. So, one of the things that gets made when your body makes a clot is a "dimer" of two different molecules. Your body is constantly trying to lyse, or dissolve, clots as their being made, and even if the clot is significant enough that your body can't get it done all the way, it'll keep trying to- which floods your bloodstream with this fibrin-degredation product called a "d-dimer". It's an extremely sensitive test, but not a very specific one, which means if your d-dimer is negative, you don't have a clot. But if your d-dimer is positive, it's not necessarily from a clot, as there's a variety of other reason a d-dimer might be elevated.
The number one diagnostic tool, which is about 99% sensitive and specific to finding blood clots, are compression ultrasound of the part of the body suspected of having a clot. Easy to do, non-invasive, can even do it at the bedside of a sick patient. There are some more exotic ways to do it; new methods such as digital photoplethysmography, which is similar to that cute red light they put on the end of your finger to measure your blood oxygen level, or CT veinography. In some pregnant patients, they'll even do an MRI in some instances. Back in the day, they used to do "venography", which was to plunk an IV catheter into a vein on the foot, and then take a bunch of xrays to look for filling deficits, but that used enormously less nowadays because we don't want to make the foot and leg any worse than it is.
So we really want to emphasize prophylaxis and prevention of DVTs. We want to identify people who are at risk, and utilize prophylactic measures before a clot forms, instead of treatments after the fact- an ounce of prevention vs a pound of cure and such. Thigh-high compression stockings have been found to be very effective in lowering the risk of DVT in at-risk patients. In surgical or hospitalized patients, we want to encourage the use of compression stockings and devices in particular, alongside early ambulation and, if necessary, the use of low-molecular weight heparin, like enoxaparin. LMWH is good because it doesn't have a side-effect profile as aggressive as unfractionated heparin, which requires very careful usage, monitoring of blood values, and a variety of other steps before use. High-risk patients will still often use warfarin, which is a very aggressive, long-term anticlotting agent that also requires monitoring, or sometimes even have a filter implanted in their inferior vena cava that stops large clots from reaching the lungs.
A fancy new way of getting rid of clots is catheter-directed thrombolysis, where we either go into the vein with a catheter and spray the clot with clot-busting drugs directly, or we grind the thing up and suck it out. Pretty cool, and it works great- but it's not very cost effective. Alas.
Sequelae (long-term consequences) of DVTs
With the long-term consequences of DVTs, you have to consider the recurrence rates, which can be up to twenty percent in some patients, and weigh that against the consequences of long-term aggressive anti-coagulation usage with therapies like warfarin, which is a pain for everyone involved. You also need to worry about post-thrombotic/phlebitic syndrome, which occurs in about 1 out of every 3 DVT patients. Venous stasis ulcers, which are large areas of skin breakdown which comes from insufficient oxygen flow to the lower extremities, are particularly troublesome for patients with diabetes, too.
The key takeway from DVTs is that up to 50% of them WILL result in the patient getting a pulmonary embolism without treatment!
Which leads us to our next topic- Pulmonary embolisms!
Pulmonary embolisms are what you get when a clot breaks off from it's location, particularly in a lower extremity, and then travels to and lodges in your lung. These are less likely to result from a clot in your calf, but much more likely from one in the thigh or pelvis. As for risk factors, well... they're exactly the same as the risk factors for DVT, because with only a couple exceptions, a PE will originate from a DVT.
My pathology professor always used to say we can often trace the genesis of pulmonary embolisms to a condition called “iatrogensis imperfecta profunda”, which translates to "We did it really badly". This is because often times, things we do will increase the risk of PE dramatically (like improper immobilization after surgery). Embolisms aren't just from blood clots, however; they can be anything that blocks the venous or pulmonary arterial system. Pieces off of IV catheters, air bubbles that are big enough, fat (happens a lot with broken legs, you can get a fat embolism from the trauma), et cetera.
So, what happens is the material travels from it's point of origin, goes from the inferior vena cava to the right side of the heart, where it's pumped into the lungs (along with all de-oxygenated blood)... and there it gets lodged in one of the pulmonary arteries. This keeps your lung from getting enough oxygen; hypoxia is a finding in up to 90% of patients with pulmonary embolism.
The reason that hypoxia isn't a 100% finding, and why you might have a pulmonary embolism with only subtle signs, is because often other blood supplies (such as from the bronchial arteries) can pick up some of the slack. But if the pulmonary artery is blocked at one of the first junctions after it's exit from the heart to the lung, you can have right-sided heart failure because of the backflow that puts into the lungs.
HOW DOES THIS RELATE TO POLITICS?
Because you need a provider that can put hands on their patient- see them IN PERSON- to be able to determine whether or not someone potentially has a blood clot, or any other number of competing things going on with them. Particularly in rural communities, like mine, where folks might have to drive an hour each way (or more!) to reach one of the urban centers to go see a doctor.
You need someone who knows your history, knows your family history and risk factors. Maybe you're a young woman, newly on contraceptives, and had a skiing injury recently. Or you're older, and have had a history of heart failure, and now found a lump in your breast. Or you've been diagnosed with a clot, but we can send you home on low-molecular weight heparin, like enoxaparin, you just need someone to check in with near where you live every once and awhile.
We need primary care providers to be able to attend to these folks in the communities they live in. And right now, the old-time country docs, those staples of Americana, are leaving primary care... and not getting back into it. And the folks in Richmond, in the general assembly building, sure aren't doing a dang thing about it.
That's why we need to flip the House of Delegates here in Virginia. We need to get people in Richmond willing to fight to make sure we can address these health conditions before they become problems, and life-threatening ones.