In this episode of PodMD, American trained haematologist and oncologist Dr Jean Connors will be discussing the topic of thrombosis, including what thrombosis is, how a patient with thrombosis would typically present, the treatment options, any warning signs to look out for, when to refer and more.
Please note this is a machine generated transcription and may contain some errors.
*As always, all in this PODMD podcast is intended for health professionals and the comments are of a general nature. Information given is not intended as specific medical advice pertaining to any given patient. If you have a clinical issue with one of your patients please seek appropriate advice from a colleague with expertise in the area.
Today I’d like to welcome to the PodMd studio Dr Jean Connors.
Dr. Jean Connors is an American trained haematologist and oncologist, with a special interest in transfusion medicine.
Dr. Connors is the U.S. spokesperson for the World Thrombosis Day campaign; a hematology attending physician at Brigham and Women’s Hospital and Dana Farber Cancer Institute in Boston, USA; medical director of the anticoagulation management services and the Hemostatic Antithrombotic Stewardship Program; and an associate professor of medicine at Harvard Medical School.
She received a medical degree from The Johns Hopkins University in Baltimore, Maryland, completed her residency in internal medicine at Beth Israel Deaconess Medical Center in Boston, Massachusetts, as well as fellowships in transfusion medicine and hematology and oncology from Brigham and Women’s Hospital. She is the associate editor of the Journal of Thrombosis and Haemostais and a member of many professional societies including the American Society of Hematology and the International Society on Thrombosis and Haemostasis.
Today, we’ll be discussing the topic of Thrombosis
*We do hope you enjoy this podcast but please remember that the advice here is of a general nature and is not intended as specific advice about a given patient. The views and opinions expressed in this podcast are those of the doctor, not PodMD.
If you do have a patient on whom you require specific advice, then please seek advice from a colleague with appropriate expertise in that area.
Jean thanks for talking with us on Pod MD today.
Jean: Thank you for having me.
The topic of today’s discussion is thrombosis. Jean, Can you give us a brief overview about thrombosis?
Jean: So thrombosis is a blood clot that forms when blood clots aren’t needed. So if you have surgery, for example and you have a cut or bruise or something along those lines, you need a blood clot to stop the bleeding. But thrombosis is when you have a blood clot in a vessel, either a vein or an artery, but primarily veins, where it forms when it’s really not supposed to, there’s no bleeding. There’s no hole in the blood vessel that needs to be plugged.
A blood clot can form of in variety of different ways if you have slow blood flow through your legs or if you have developed a blood clot in your leg and a piece breaks off and moves to the lungs called a pulmonary embolus. We know that in many situations that people are aware that they are at risk for blood clots we can prevent blood clots from happening. We as members of World Thrombosis Day, I’m a member of the World Thrombosis State Steering Committee, you know, we see that one in four people worldwide die from conditions caused by thrombosis, and our goal is to bring awareness to both patients, the general public and practitioners, physicians and clinicians of all types and backgrounds about the risk of thrombosis and what thrombosis looks like.
How would a patient with thrombosis typically present?
Jean: So, so, and there are the routine ways. And then there are also some subtle ways that people should be aware of. But most commonly, if someone has a deep vein thrombosis in the leg, they often get a pain, particularly pain in the calf. Some people think they have a charlie horse. They may have stepped off the curb incorrectly or did some sort of sporting activity that that’s causing a calf pain.
But it it’s not like a cramp that goes away. It’s a pain that persists. Other people will have swelling, so one leg will have some swelling around the ankle where the other leg doesn’t, and some patients end up with both swelling and pain. People can have sort of a change in the skin colour in their leg, it may be a little more reddish or purplish blue looking than the other leg, and that’s for pulmonary, that’s for deep vein thrombosis that occurs in the legs.
For patients who have a pulmonary embolus, patients often notice shortness of breath. Sometimes it’s when they’re sitting still, but sometimes it can be a little more subtle, like only when they’re going upstairs so they have more shortness of breath going upstairs or doing physical activity tasks around the house, walking the dog, they may be more short of breath than normal, they can often have a cough or they can have pain. Pain if they take a deep breath. Pain in the side of the chest, in the front or the back that is associated with the pulmonary embolus.
Again, if you develop a blood clot in the leg and we call it a deep vein thrombosis and when there’s a blood clot in the lungs, we call it a pulmonary embolus and could together the DVT as we call it and PE are known as VTE. Venous thromboembolism. And we know, as I stated before, that one in four people worldwide die from conditions and complications caused by thrombosis.
What are the risks of the condition?
Jean: So any factors that decrease the blood flow or increase the hypercoagulability of the blood, the stickiness of the blood and anything that damages the blood vessels can result in a clot and so this can become this can come from prolonged bed rest, from wearing a cast, from having knee surgery and having your leg in an immobiliser. Or particularly abdominal or pelvic surgery.
Pregnancy is a very high-risk state for developing clots because the pregnancy hormones increase the pro clotting factors and decrease the natural anticoagulant factors. So pregnant women are at increased risk of developing clots compared to people who are not pregnant. Oral contraceptive pills with oestrogen and progesterone work in the same way. To change the coagulation status of the blood, or the ease with which it clots, and so they make patients more hypercoagulable or more likely to develop a clot.
Hormone replacement therapy has some risks associated with it. Being overweight is actually on an increased risk for developing clots and people forget that being overweight with a body mass index of greater than 30 or 35 has just a higher risk of developing a blood clot as someone who has an inherited family disorder of blood clots known as the heterozygous prothrombin gene mutation, and so there are many more people that are overweight, then there are those that have inherited family related disorders for clotting. Smoking can result in in venous thromboembolism.
Cancer is also a known cause of thrombosis with something like 20% of patients with cancer developing thrombosis. Heart failure and inflammatory disorder disorders also are a risk for thrombosis. Inflammatory disorders such as inflammatory bowel disease and some rheumatologic disorders like rheumatoid arthritis or lupus, can also cause blood clots when patients are having flares of those disease.
Age is a risk factor for blood clots that that no one can escape and that everyone has. And as people age, we find a strong cutoff around age 60 where once people get over the age of 60, their risk for developing a blood clot starts to increase very rapidly.
Each year there are about 10 million cases of venous thromboembolism worldwide. So this is a problem that those of us who do coagulation are aware of and those of us on the World Thrombosis Day Steering Committee are aware of, but not others in the world. And so we’re trying to bring awareness to this this common problem.
What are the treatment options?
Jean: Well, first you have to be able to diagnose a blood clot or a thrombosis, either a deep vein thrombosis or pulmonary embolus. So if someone develops symptoms, sometimes it can be hard just looking at the leg to tell if there is a blood clot, and certainly the only way you can tell whether or not someone has a pulmonary embolus is to do a specific study that’s dedicated to detecting a pulmonary embolus.
Us so often in emergency rooms, physicians and clinicians there will use a D dimer blood test as what we call pretest probability to determine if someone should get more involved testing if the D dimer level is higher than it should be, an ultrasound can be used of the leg or the arm to look for a deep vein thrombosis, and the best way to look at the lungs for pulmonary embolus is to use what we call pulmonary embolus CT scan imaging, which is a CAT scan that uses intravenous dye that can look at the blood vessels in the lungs to determine if there’s a blood clot.
For many patients in whom we can identify risks for developing blood clots, we can actually use preventative medications that prevents the development of blood clot. These are often medications that are used to treat blood clots, but at a lower dose and what we call a prophylactic dose. So there’s less intensity and less risk for bleeding, but they can be very effective at preventing blood clots.
The specific treatment for a patient who is diagnosed with a new blood clot can differ based on what else is going on with the patient, what their renal statuses or their kidney function and what their platelet count is and their coagulation factor levels. Which are part of the liver assessment in making sure that people livers are functioning appropriately. There are different types of anticoagulants based on how they’re delivered. There are intravenous treatments such as heparin. There are injectable treatments that are injected under the skin such as low molecular weight heparin, the most common one in the United States is enoxaparin. In other parts of the world tinzaparin or Nadroparin and are used as low molecular weight heparin’s.
And in some situations where we feel it’s risky to use what we call pharmacologic or medic medication based anticoagulation, we can sometimes use mechanical compression stockings or pneumatic intermittent compression that our boots that wrap around patients legs that inflate and compress the legs and then deflate intermittently, and these are often used in patients while they’re in the operating room and after they come out of the operating room when using anticoagulation may be risky because we don’t want to cause bleeding in patients who have, you know, just came out of the operating room with incisions and sutures in a risk for bleeding.
Have there been any developments in treatment in the last years or are there any in trials or development now?
Jean: Well, that’s an excellent question. And two, I have been working in the thrombosis field in the anticoagulation field for many years and in the past, even just a decade ago, the only treatments available to manage patients who developed a deep vein thrombosis or pulmonary embolus were the intravenous or subcutaneous heparin’s and low molecular heparin and warfarin, or Coumadin or vitamin K antagonists. All of those words are for the same type of medication that prevents the liver from making blood clotting factors in a way that they’re activated and caught and result in anticoagulation.
But warfarin is very difficult to manage because you take one pill today and you don’t really see the effects for three to four days and so there takes some time to assess the level of anticoagulation. It is a very it’s a drug that has a very narrow tolerance, in other words, if you have too much, you’re at risk for bleeding, and if you have too little, you’re at risk for clotting. And many things affect whether or not people stay in what we call the therapeutic range and this includes dietary factors, particularly foods that contain vitamin K. Or things like alcohol and medications, particularly chemotherapy medications, but other medications as well.
So about a decade ago the drugs called direct oral anticoagulants became available and direct anti oral anticoagulants are drugs that unlike warfarin, where it takes three or four days to see in an effect. You can swallow one of these pills and have full therapeutic intensity anticoagulation in your blood within two to four hours after swallowing a pill. So these have been a huge improvement for patients who require anticoagulation for a deep vein thrombosis or pulmonary embolism and at lower doses to prevent deep vein thrombosis or pulmonary embolism.
So, so these drugs are here now. They are used for a variety of indications and a variety of causes of deep vein thrombosis or pulmonary embolism. There are a few situations such as mechanical heart valves or patients still require warfarin anticoagulation. But most people who have a deep vein thrombosis or pulmonary embolus can take one of these new, easier to use drugs.
Now the risks associated with anticoagulation are bleeding, bleeding and bleeding. And really the drugs themselves do not cause any long term damage, but by being on an anticoagulant day in, day out and in some cases for years, there is an increased risk of bleeding. Although the direct oral anticoagulants can decrease this risk of bleeding and the risk is lower than with warfarin. We still see bleeding, particularly in older patients or particularly in patients who have cancer and other reasons to have bleeding.
And so right now that there are exciting new developments in the area of what we call contact factor inhibition, an inhibition of factor 12 and factor 11, and studies are just getting off the ground in people to look at these drugs in a variety of different types of settings to either prevent deep vein thrombosis or pulmonary embolus, or to treat pulmonary embolus and deep vein thrombosis.
Are there any warning signs a GP or their patient can look out for?
Jean: Well, it depends. So that’s a great question. And so there are known risk factors that anybody has particularly major surgery or major trauma. So patients who have abdominal surgery, knee replacements or hip replacements are probably the most highest risk surgeries for developing blood clots, such that patients get some form of medication after the joint replacement to prevent a deep vein thrombosis in the leg, the signs and symptoms I’ve discussed, if you develop a deep vein thrombosis in the leg, you may develop a pain in the calf, or pain in the thigh, swelling in the leg, or a change in the skin colour of that leg compared to the other leg.
Shortness of breath, problems of do climbing stairs or even walking fast on the flat. A cough, back pain, chest pain, pain with deep breathing. All of these may be signs of a pulmonary embolus and so both GPs and patients should be aware of these signs. If somebody has had a blood clot in the past, we know that their risk for developing a clot in high-risk situations is higher, particularly if they’ve been identified as having an inherited blood clotting disorder or family members who’ve had blood clots at young age. You know, below the age of 50 or even below the age of 40 or 45.
And so these patients who are undergoing high risk surgeries can get prophylactic as we call it anticoagulation to prevent a clot in these situations. Now to identify whether someone is at risk for clot, the patient and their GP can work together to review a VTE risk assessment and determine what a patient risk is for developing blood clots.
We would love to have a very precise calculator for this. Many groups are working on this. We have not yet come up with the ideal one, but as I said, we do know that people who are admitted to the hospital for more than three days or on bed rest for more than three days. Or have major abdominal or pelvic surgery. Or surgery on the hip or the knee are particularly at risk for developing thrombosis.
Some patients, long air travel can also precipitate a blood clot in certain situations and so people should be on the lookout and discuss with their GP whether long distance travel is a specific risk for them. Anybody who has these risk factors and have not yet discussed it with their GP, certainly should, particularly before they undergo any types of elective surgery or other situations where they may be at bed rest or have say a cast on their leg they broke their leg or an immobiliser or things like that. Doctors who are aware of these risk factors can take preventive measures to prevent their patients from developing blood clots.
What is the likelihood of recurrence of the condition?
Jean: So, so patients who’ve had one blood clot, their risk for getting another never goes back to normal, particularly if they are young because in in young people it can take, it takes a lot of trigger force if you will, to trigger a blood clot. So, we know that their particular individual coagulation status may suggest that they are more at risk. We do know that if you did get a blood clot after major surgery, such as having your gallbladder out or appendix out or your leg was in a cast that we can give you a few months of anticoagulation from three to six months.
And the likelihood for having a blood clot come back in that situation is significantly lower and almost is 0, unless you have some complicating factors such as residual vein thrombosis. Patients who develop blood clots in the setting of pregnancy similarly have a low risk of having it come back. But patients who have inflammatory disorders such as inflammatory bowel disease, Crohn’s disease, ulcerative colitis or rheumatologic disorders such as lupus and sickle cell disease for some patients. And others may be at higher risk for developing anticoagulation.
We do see some patients that develop either a deep vein thrombosis or pulmonary embolus who have no obvious precipitating factors. They didn’t have surgery in the last 8 to 12 weeks before presenting with the clot. They did not go on long air travel. They have no inflammatory bowel disease or other provoking factors that put them at risk for forgetting a clot. It sort of, if you will, has come out of the blue and these patients have an increased risk of developing recurrent blood clot if anticoagulation is stopped such that based on data accumulated over the last 20 years, the risk of getting a new clot if anticoagulation is stopped at the first year and someone who has truly had an unprovoked clot is about 10% per year for the first two years and somewhere around 3 to 5% after that.
But it’s cumulative. So when you reach five years, the risk is about 30 to 40% of having a recurrent blood clot if you stop anticoagulation after this unprovoked deep vein thrombosis or pulmonary embolus. The risk significantly starts to trail off after five years and goes down over the course of time, but it’s still higher even 20 years out compared to people who have never had a blood clot.
When should a GP refer?
Jean: Well, so that’s an excellent question and that sort of segways off the last question. I think many GPs feel comfortable starting anticoagulation when a blood clot is newly diagnosed. But then the questions get more nuanced about how long should somebody be on anticoagulation for again, if it’s, clearly strongly provoked clot in the setting of temporary risk factors that resolve. Such as obvious surgical date or leg injury. With surgery, you know people can clearly note the time of that event and know that after three to six months that triggering risk factor is gone.
With the patients who develop clots out of the blue or for patients who have strong inflammatory disorders or even congestive heart failure, those risk factors don’t really change overtime and there may have been something else that triggered the clot. But we can’t really tell if their risk has completely resolved or is continued, and this is coming from someone who’s practised in the anticoagulation and thrombosis world for over a decade, I won’t tell you how many.
So if the GP has any question about how long to anticoagulate a patient, they should refer. Similarly, there can be very complex situations in which patients have poor kidney function, have poor liver function, which makes the clotting factors or have low platelet counts or particularly cancer, where it gets difficult to piece together the risks and benefits and determine how much anticoagulation and for how long and so that’s when GPs, if they do not feel comfortable, should definitely refer patients to a vascular specialist, either a cardiologist, a haematologist, or someone who deals with thrombosis.
What role does the GP play in the treatment of the condition?
Jean: Yeah. So in summary, the GP can be the first clinician or physician that a patient comes in contact with when they have signs or symptoms of a DVT or PE and so GPs should be aware that their patient might have a clot and it should be at the forefront of their minds.
I’ve seen many young women with inherited blood clotting disorders started on combination oral contraceptives and develop leg swelling or leg pain and they will go to an emergency room and because they’re in there, say early 20s, people don’t often think that they might have a blood clot and they come back, you know, a day a week later with a larger deep vein thrombosis or even a pulmonary embolus.
So GP should be aware that patients are at risk. For their patients that have known precipitating risk factors, including obesity they should be assessing their patients for risks, particularly if they’re heading for surgery. Or if they’ve had a blood clot, or there’s a strong family history of blood clots. You know, being aware of the increased risk of thrombosis during pregnancy, hormonal treatments and surgery. And so GPs should be able to counsel their patients. About these risks, and or refer them, if needed to either prevent a clot or again sort of weigh in on the treatment.
Thank you for your time here today in the PodMD studio. To sum up for us, could you please identify the three key take home messages from today’s podcast on thrombosis?
Jean: Well, again, thank you for inviting me to speak about thrombosis on behalf of world thrombosis day. Thrombosis, as I discussed, is extremely common with one in four people actually dying from complications of deep vein thrombosis or pulmonary embolus, and it’s listed in the top three cardiovascular causes of death worldwide. So being aware of the signs and symptoms of VTE is something that anybody can do to help recognise a deep vein thrombosis or pulmonary embolus when they may be having it or a family member may have one, and to alert their GPs to their possible risks as well.
We know that anytime someone has prolonged immobility with hospitalisation or sitting for long periods of time, either air travel or working and not getting up from their desk can increase the risk for developing clot as well.
We suggest people stay hydrated and get up and move around and stretch to ensure that the blood is flowing through the legs. The World Thrombosis Day campaign has a number of very important resources and information to help the general public as well as medical experts understand the condition, so we really encourage you to visit the worldthrombosisday.org website.
To learn more and to join us in recognising World Thrombosis Day on October 13th of every year, but especially this year.
Thanks for your time and the insights you’ve provided.
Jean: This has been great and thank you so much for having me. I hope this has been useful and if there are any questions please don’t hesitate to get in touch with me. And you can just Google my name and my e-mail address would be over there. So please get in touch with me.