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Interactive Learning : HealthCast Transcripts

Episode 26 : Thrombophilia

Release Date: August 5, 2008

Dr. David Meyerson: Hi, I'm Dr. David Meyerson, Cardiologist at Johns Hopkins, and your host for this edition of  this edition of Vascular Disease Foundation's HealthCast. We're very excited to be able to bring you excellent, easy to understand science  on all topics relating to heart and blood vessel diseases as a public service.

As a public education forum, the Vascular Disease Foundation is made up of representative groups of the premier medical and science advisory groups in the country that relate to vascular diseases.  These are groups that use peer reviewed science to verify that the information you are getting is nationally recognized as the very best and most reliable data available. We have a very special guest today; it's Dr. John Bartholomew, also known as Jerry.  He has been at the Cleveland Clinic since 1988.  He is currently Section Head for Vascular Medicine in the Department of Cardiovascular Medicine there.

We're going to be talking about thrombophilia and hypercoagulable states.  It's our goal on the VDF HealthCast to bring you things that you haven't heard enough of before.  Ideas in medicine and science that he patient and the patient's family should be more well conversant in so that you can be asking your doctor about it, so that you can understand what is going on with you if you have any one of the heart and/or blood vessel diseases that we talk about. Dr. Bartholomew is the Section Head for Vascular Medicine in the Department of Cardiovascular Medicine at the Cleveland Clinic.  He actually even did his hematology fellowship here at Johns Hopkins and knows many of the same people that Dr. Kerry Stewart and I know.  He's a Fellow of the Society of Vascular Medicine, a Fellow of the International Academy of Clinical and Applied Thrombosis and Hemostasis.  A lot of big words which we'll talk about in just a moment, and a Fellow in the American College of Cardiology and I'm told incidentally, he's a hell of a guy. Dr. Bartholomew, Jerry, thanks for being with us today.

Dr. Jerry Bartholomew: Thank you Dr. Meyerson and Dr. Stewart.

Dr. David Meyerson: You feel free, of course, to call me David.

Dr. Jerry Bartholomew:  Okay, thanks.

Dr. David Meyerson:  So thrombophilia, these are, thrombophilia in general is an increased propensity to develop blood clots?

Dr. Jerry Bartholomew: That is correct. Some people have used the term hypercoagulable states, but many scientists are now, prefer to use the term thrombophilia or a tendency to form blood clots more readily than the average person.

Dr. David Meyerson:  Now thrombophilia would be different than thrombocytosis generally means an increase in the platelet count, the cells that help us to form blood clots and in reality if you have too many platelets, you may be predisposed to a blood clot, but again these are different terms. Thrombophilia generally implies blood clots of the veins or the lungs and again thrombocytosis just too many platelets.

Dr. David Meyerson:  Excellent.  Now, let me then take us one step backwards so that our listeners don't get lost.  Red cells carry oxygen.  White blood cells fight infection.  Tell us just a little bit more about the platelets.

Dr. Jerry Bartholomew: Well the platelets help us to form a blood clot that's really generally a very good blood clot.  For example, if you cut yourself, one of the first things that help us to stop bleeding are platelets which combine together or grow together to form a clot and again, this is a good type of a blood clot or --

Dr. David Meyerson:  So a blood clot, Jerry, a blood clot sitting on a stomach ulcer preventing it from bleeding is your best friend.

Dr. Jerry Bartholomew: That's correct.

Dr. David Meyerson: While a blood clot going to the lung or in the artery that nourishes the heart muscle causing a heart attack is anything but.

Dr. Jerry Bartholomew: That's absolutely correct.

Dr. David Meyerson: Okay.  So then the platelets initiate the blood clotting in areas that were cut, or also what if the inner lining of a blood vessel wall is damaged in some way?  Don't platelets congregate there?

Dr. Jerry Bartholomew: Absolutely.  That's another one of the things that they do and that's again, it's a very important part and you know, many years ago, these things when they were looked at under a microscope were just felt to be [indecipherable], so now we know that they play many, many roles.

Dr. David Meyerson: All right.  So that helps us with platelets and if we want to make platelets less sticky, we have some medicines that we use commonly in cardiology.  One would be aspirin, another one would be Plavix.  Is that right?

Dr. Jerry Bartholomew: That's correct.

Dr. David Meyerson: So, but how does that tie in, our listeners, I can tell that they're trying to get into their own minds.  What's the difference between that and coumadin or warfarin and a blood thinner and what I want to also have them understand is that a blood thinner doesn't mean the difference between 5W30 oil and 10W40, but it's something different.  Tell us.

Dr. Jerry Bartholomew: Right.  Well, warfarin or coumadin as it's often known is the blood thinner that affects part of the coagulation cascade. It's a little bit different than the platelets.  This medication, warfarin again, inhibits several vitamin K dependant factors known as two, seven, nine and ten. By this mechanism, they thin the blood and prevent blood from clotting.  And these agents, or this agent warfarin, is used in situations as we mentioned earlier like deep vein thrombosis or pulmonary embolism, but it's also used in your patient population with atrofibrillation.

Dr. David Meyerson: Absolutely.  And again, for our listeners, coumadin is a brand name of a medicine called warfarin.  They are one in the same generally.

Dr. Jerry Bartholomew: That's correct.

Dr. David Meyerson: So then let's -- so if we understand this correctly then, platelets begin the blood clotting process, but also there are other factors in blood which begin a blood clotting process in a totally different non-platelet dependent way.

Dr. Jerry Bartholomew: That's right and these factors are generally in the plasma and they are often referred to as the coagulation cascade.

Dr. David Meyerson: Excellent.  So that, in fact, when as clinicians, we try to interrupt a disease process or prevent a disease process, we try to understand whether the platelet issues are the bigger issues, or the blood clotting issues are the greater danger.

Dr. Jerry Bartholomew: That's correct and in cardiology, it's often the platelets whereas in my speciality more of hematology, it's often the plasma proteins.

Dr. David Meyerson: So and that's -- I wanted to get that far so that our listeners really get their mind around what we're talking about.  So Jerry if you would, then tell me a little bit more about what are the clinical manifestations of thrombophilia?  What diseases do you see commonly?

Dr. Jerry Bartholomew: Well, the clinical findings generally are again, the deep vein thrombosis or DVT as it's known, also pulmonary embolism or PE as many people refer to it and if you have a blood clot in the leg known as a deep vein thrombosis, generally your leg will swell, you'll have pain, you may have erythema or redness in the leg and if that blood clot is one that goes to your lungs, it can cause shortness of breath, chest pain that's often described as pleuritic, that means very sharp pain when you take in a deep breath or if you move suddenly, but you can also even have a problem with coughing up blood and, of course, shortness of breath.

Dr. David Meyerson: And of course, people can certainly die from pulmonary embolis so this is a very important thing for us to recognize and to treat.

Dr. Jerry Bartholomew: Yes actually I think pulmonary embolism is the third most common cause of cardiovascular death after myocardial infarction and stroke.

Dr. David Meyerson: Uh-huh [affirmative] and to our listeners, if you are listening to this podcast, then you can easily when you're done with this, go back and look at our previously posted ones because we do have at least a couple talking about deep vein thrombosis and the prevention of pulmonary emboli and you'll understand a little bit more when you listen to both. So Jerry, pulmonary emboli and lower extremity or deep vein thrombosis of the legs are not the only diseases that you see.  Sometimes you can see perhaps a portal vein or hepatic vein thrombosis of the veins in the liver or perhaps kidney or other thrombosis, don't you?

Dr. Jerry Bartholomew: That's correct.  We often are called to see a patient, perhaps post- operatively for a portal vein thrombosis, or something in the intestines known as a mesenteric vein thrombosis and we do see cerebral vein thrombosis which are clots in the veins of the brain and as you pointed out, renal vein thrombosis or kidney thrombosis and then we also see patients with superficial vein thrombosis which generally involve the veins on the surface, such as the saphenous vein for example.

Dr. David Meyerson: And on occasion in the hospital, we see somebody with an upper extremity, with an arm that's swollen dramatically beyond what we would think would be normal or acceptable.  Do you see vein thrombus forming in upper extremities?

Dr. Jerry Bartholomew: Oh absolutely.  This is becoming a much more common as you well know, David, especially with the use of pacemakers and central venous lines and other upper extremity access.  But another common finding or another commonly seen patient, maybe not so commonly, but is the young individual who is athletic who develops an upper arm deep vein thrombosis or upper extremity thrombosis in one of the larger veins and they will often present with pain and swelling.  We see this occasionally in baseball players or weight lifters and a whole host of different people.

Dr. David Meyerson: Does this come from overuse or something?  What would be the ideology?

Dr. Jerry Bartholomew: Well, that's one of the thought is that there is repetitive trauma to the vein by elevated the arm, but sometimes these individuals have an extra rib or an extra cervical -- well, cervical rib is what it's called -- or other bony structure abnormalities.

Dr. David Meyerson: So any time, what -- to our listeners -- what Dr. Bartholomew's already pointed out is that when we have areas of the body which squeeze or compromise a vein, whenever blood does not flow freely, blood has a potential to clot and that is one of those issues, so if there's a mechanical compression or as Dr. Bartholomew said just moments ago, sometimes if there is a wire or a lead or some medical device that's being used, once in a while, this can also predispose to clot formation. And so but Jerry, our listeners are very aware of the difference between arterial thrombosis and vein thrombosis because we've gone over that several times before.  So far, everything you've told us about has been in the veins, hasn't it?

Dr. Jerry Bartholomew: That's correct.

Dr. David Meyerson: And does thrombophilia also affect the arteries?

Dr. Jerry Bartholomew: It can as well and you know, we see people that are of a younger age, for example, we often think of thrombophilia if you have someone young who's had a stroke for example, or even a blood clot in one of the arteries of the lower extremity for example.  Although it's much less common.

Dr. David Meyerson: So would it be likely -- there must be an enormous work-up that's possible in somebody like this, a lot of things to test for.

Dr. Jerry Bartholomew: Well you know the first rule of thumb is to do an excellent history and physical and oftentimes patients with thrombophilia will have a strong family history, perhaps a mother or a sister or a father or a grandparent will have had a history of blood clots.  So getting a history is extremely important and then there are a number of other factors that can also precipitate a venous thrombosis.

Dr. David Meyerson: Not wanting to scare our patients, but do you see these thrombosis happening in a greater extent in people with cancers?

Dr. Jerry Bartholomew: Oh absolutely.  This is certainly one area that is extremely common.  Any type of cancer can lead to a deep vein thrombosis or pulmonary embolism or even an arterial event, as I mentioned earlier.  So this is certainly a precipitating factor.

Dr. David Meyerson: So if you saw a patient that had an isolated, they went on a long plane ride, they sat in one position for six or seven hours, and they ended up with swelling and discomfort in their left leg and you did a, one of the doppler studies that we've discussed on this program before, and you saw a blood clot in the deep vein of the leg, you would go ahead and treat them with coumadin for a period of time, but would that be enough to undertake one of the more sophisticated evaluations that hematology would require?

Dr. Jerry Bartholomew: You know, this is a very interesting and kind of a difficult question to answer simply because, you know, the question always is, who should I test?  And there are medical reasons to test people and then there are non-medical reasons and this might be one of those reasons that are kind of right in the middle.  The recent chest guidelines which, as you well know, are published by the American College of Chest Physicians, has suggested that patients are at risk for a long airplane trip as you pointed out, if they are flying more than seven or eight hours, but more commonly we see these blood clots in shorter flights, so this is a tough question to answer and I think again, you go back to your history and your physical examination to try and answer it. And one of the reasons though --

Dr. David Meyerson: And certainly for a recurrent episode.

Dr. Jerry Bartholomew: One of these reasons that we're often faced with or that patient and families expect it, you know, somebody else has had a blood clot and gee they did all these laboratory tests which are quite expensive and many times when we see these individuals, referring doctors expect us to do a thrombophilia testing survey.

Dr. David Meyerson: Let me, one more perhaps slightly simpler example.  I guess if you saw something similar happening in someone who's had recent orthopedic surgery to their leg, for example --

Dr. Jerry Bartholomew: Right.  In that situation, I think they have a good reason and we would not take up an extensive study of why they formed the blood clot because we would think that the main reason was the surgery itself or injury to the vein that occurs when the surgery takes place.

Dr. David Meyerson: So now we're taking our listeners into an area that they've never been before Jerry and I'm very grateful for you being here today specifically for this. So when blood clots form for no other apparent reason, we don't have a mechanical compromise of a vessel, we don't have an injury to a vessel that we're aware of, they don't have a cancer that we're aware of and yet they haven't been on a plane ride or had an orthopedic surgery, or been at bed rest for any extensive length of time and they still develop venous thrombosis, then we begin to look at some very interesting things that many clinicians don't know a lot about.  Could you tell us about what factor five leiden might be?

Dr. Jerry Bartholomew: Sure. This and a number of other tests are hereditary clotting factors that have been really only identified in the last fifteen even twenty years.  In fact, when I did my training, we didn't know about factor five leiden or prothrombin gene mutation.  Again, these are genetic inherited thrombophilia conditions that occur, at least for factor five leiden, may be present in as many as five to six percent of the Caucasian population in the United --

Dr. David Meyerson: And are there any similar numbers for African-American, Hispanic, etcetera?

Dr. Jerry Bartholomew: Not really.  It's much less common in these two groups at least as we've been able to identify to date.

Dr. David Meyerson: And so factor five leiden, I believe as you mentioned, it was reported I think probably in the early like 1993 or `94.

Dr. Jerry Bartholomew: That's correct.

Dr. David Meyerson: So it hasn't been around all that long, but when you find someone who is beginning to clot, is there -- there is a -- what does the work-up consist of?

Dr. Jerry Bartholomew: Well as you pointed out, in the person that you have no other real good reason for developing a blood clot, we actually order something called a thrombophilia or a hypercoagulable panel as it's known here at the Cleveland Clinic and that consists of a number of different tests in addition to the looking for factor five leiden or the prothrombin gene mutation, we look for something that used to be known as anti-thrombin three and now is called anti-thrombin.  We look for other protein deficiencies, protein C and protein S and then there are a few other studies that we will also obtain, one being the lupus anticoagulant and another one being anticardiolipin antibodies.

Dr. David Meyerson: And those are the antiphospholipid antibodies?

Dr. Jerry Bartholomew: That's correct.

Dr. David Meyerson: So what are the, what's the clinical implication of this?  Is it to identify someone who is more likely to clot, to know how to properly treat the clot that they have currently and of course, to prevent the next series of clots?

Dr. Jerry Bartholomew: Well that's certainly one reason.  But it's also always very helpful to be able to identify a genetic defect because one of the concerns every patient has is gee do I have an underlying cancer that is going to show up at a later date and when you can identify, for example, that they have an inherited thrombophilia condition, that does put them somewhat at ease, but it also --

Dr. David Meyerson: You know, it's funny, but our patients could indeed say, "Thank God I don't have a cancer."

Dr. Jerry Bartholomew: That's correct.

Dr. David Meyerson: Or said another way, thank God I have an inheritable disorder of coagulation."  Which most people wouldn't welcome, but if you had to compare that to having a cancer, I guess you'd pick the former.

Dr. Jerry Bartholomew: And that's absolutely correct, but it also is helpful to you once you identify this in taking care of that patient for an extended period of time and just because you have one of these genetic defects, that doesn't mean you always need to be on lifelong anticoagulation.  It really depends on the presentation of the blood clot itself.

Dr. David Meyerson: Which type of anticoagulation, because remember we mentioned the platelet inhibition with aspirin and perhaps Plavix and medicine similar to that.

Dr. Jerry Bartholomew: Uh-huh [affirmative].

Dr. David Meyerson: Or do they need the warfarin, the so-called blood thinner, that inhibits the vitamin K dependent clotting cascade?

Dr. Jerry Bartholomew: Well for the number of tests that we were, the tests that we were just discussing, warfarin is the mainstay of long-term therapy and then we have other agents as you well know, like heparin or the low molecular weight heparin preparations or the NI10A  inhibitors, so there are several new medications that are available, but for the long treatment, we still use coumadin or warfarin.

Dr. David Meyerson: Is there anything coming down the path soon that would be an oral equivalent of coumadin or warfarin that might be a little bit easier to take and not have to monitor so often?

Dr. Jerry Bartholomew: Well we hope so and I'm sure you're aware of many of those.  Unfortunately the latest agent that didn't make it was a few years ago in Ximelagatron, but there are some new NI10A's which when I say NI10A, it's part of that coagulation cascade we mentioned earlier, that if we can inhibit that area then it will thin someone's blood and then there are some direct thrombid inhibitors of which we have agents that are intravenously available, but not anything orally available that are now being looked at as well, so again another part of that coagulation cascade that we talked about earlier.

Dr. David Meyerson: Excellent Jerry.  Listen in the few minutes that we have left, I'd like to kind of open the forum to you instead of responding to the questions, I'd like you to have a moment to tell our listeners any last things that you would want them to know.  Any questions that you would -- would you want them, for example, to say to their doctor have you looked for other reasons why blood clots or what else would you like to pass along to our listeners?

Dr. Jerry Bartholomew: Well I think that although we've identified many of these coagulation defects or thrombophilia factors as you've pointed out, factor five leiden, and prothrombin gene mutation, patients are still often frustrated that we don't have the exact cause of why they formed a blood clot and we refer to that as an idiopathic event and I think that they, many people again are frustrated that we can't exactly put a finger on why they formed their blood clot, but as you pointed out in 1992 or `93, the factor five leiden was identified and then prothrombin gene mutation at a later date and then more recently, I think we think that factor eight which if you don't have enough factor eight, you have hemophilia, a bleeding problem, but if you have too much factor eight, some people feel that you have the thrombophilia and a clotting condition so we're still identifying factors on a regular basis and I think that again that should help to reassure the patients that we're still looking for these clotting abnormalities.

Dr. David Meyerson: Are there any foods or natural products that ought to be either encouraged for use or discouraged?

Dr. Jerry Bartholomew: Well if you're on coumadin or warfarin, you have to be careful in eating green leafy vegetables.  That can really affect your, the medication itself and so that is an area that you need to discuss with your physician and most people that are put on that medication get a handout that describes the agents that you should and shouldn't be taking especially foods, so that's one area that I would caution individuals on.

Dr. David Meyerson: And I'm sure you'll agree, what we caution our patients here at Hopkins very often is that if they are on coumadin or warfarin for any reason and someone, another physician wants to give them an additional medication, an antibiotic for example, we must be very cautious to know which antibiotic is being given and whether or not it's compatible with coumadin because for example, if somebody takes a medicine called Bactrim which is an excellent antibiotic when used by itself for many reasons, but if you give that to someone who is on coumadin, three days from then their anticoagulant level could be three times what it's supposed to be.

Dr. Jerry Bartholomew: Oh that's absolutely right and the patient should get a booklet about coumadin as it's called as you pointed out, or warfarin and look through that very carefully and they also have to follow the advice of their physician and have their blood checked on a regular basis and the last thing I advise all my patients is to have identification on their person at all times that they are on this medication in case they are in an accident or knocked unconscious and you know, they need to have emergency attention.

Dr. David Meyerson: Excellent advice.  I'd like to thank my very special guest, John Bartholomew, also known as Jerry.  He is the Section Head for Vascular Medicine of the Department of Cardiovascular Medicine at the Cleveland Clinic.  He did his fellowship in hematology right here at Johns Hopkins and as I said at the beginning and I'm told incidentally, he's a hell of a guy and I think he is. I think he's given us wonderful, wonderful information. Jerry I thank you so much for being with us today.

For the Vascular Disease Foundation --

Dr. Jerry Bartholomew: Thank you David, it's been my pleasure and Kerry as well.

Dr. David Meyerson: For the Vascular Disease Foundation then, for my colleague Dr. Kerry Stewart who is at the electronic controls today, for Dr. Bartholomew in Cleveland and for myself, I'm Dr. David Meyerson, thank you so much for listening, until next time.


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