How Long to Anticoagulate

Your patient suffered a venous thromboembolic event. It might have been a pulmonary embolism or a deep vein thrombosis. Now you need to decide how long to anticoagulate them for. There are many considerations that go into this decision. I will try to outline a practical way of thinking about this common scenario.

The Most Important Factor in Deciding How Long to Anticoagulate

The most important factor in your decision is recurrence risk. And the most important determinant of recurrence risk is whether the clot was provoked or unprovoked. The reason is that the clot circumstances are the most important determinant of recurrence risk. And the higher the recurrence risk, the more we will agree to extend anticoagulation.

Provoked and Unprovoked Clots

A purely provoked clot is a clot that happened after a specific event. For instance, blood clots after surgery or after an injury. On the other end of the spectrum are unprovoked clots. A purely unprovoked clot is a clot that happened without any backstory. A person was living their usual, and normal, lives when it happened.

The recurrence risk after a purely provoked clot is low. Perhaps 3% over 5 years. On the other hand, the recurrence risk after a purely unprovoked clot is higher. Perhaps, 20-30% over 5 years. So, we will tend to treat the provoked clots for a shorter period of time (perhaps 3 months) and the unprovoked clots for a longer period of time.

In real life, however, it is often hard to determine if a clot is provoked or unprovoked. Many situations fall in the grey zone in between these categories. For instance, a patient might not have a specific cause, but they may have some varicose veins or some degree of iliac vein compression. Are these enough to explain the clot? Will fixing these take away the risk and allow short-term anticoagulation?

Assess Recurrence Risk

All this sounds simple enough. But in real life the circumstances of the clot are often not as simple as this. For example, a person might develop a blood clot after flight. On the one hand, we know that flying is a risk factor for venous thrombosis. But on the other hand, it is a weak risk factor. So many people fly all the time and never have a clot, right? Deciding what to do in these common “grey” situations requires clinical judgement and to take into account other factors that I will discuss below.

For this reason some recommendation documents have been steering us away from the terms “provoked” and “unprovoked”. Instead, the “modern” way is to describe perceived recurrence risk. We can often categorize patients into categories of low, intermediate and high recurrence risk. Then, we should try to tailor how long to anticoagulate depending on our assessment.

Cancer Associated Thrombosis

A clot that happened in the setting of cancer or cancer treatment will recur at a high rate if we do not anticoagulate. So we offer patients with cancer associated thrombosis long-term anticoagulation. Typically, we treat for as long as the cancer is present or for at least a few months after cure. The reason we usually extend therapy beyond cure is to allow for some surveillance to make sure the cancer is indeed gone.

Considerations in How Long to Anticoagulate in Cancer Associated Thrombosis

While these rules for treatment make sense, there are often more complicated decisions to make. Here are a few considerations:

• Bleeding risk – Unfortunately, the risk for bleeding in cancer patients is high. So, balancing bleeding and clotting risk is often hard to do. Also, we need to take into account what might be more dangerous for any particular patient. This is often a matter of clinical judgement. There are no hard and fast rules that I know of to do this. We often discuss each case as a team to try to come to a sound decision.
• Cancer type – Not all cancers cause clotting to the same degree. And also some cancers are known to bleed more than others. While it is hard to know the risk for any particular cancer, we try to take these factors into consideration.
• Location of the primary tumor and presence of metastases – There are certain cancer locations that make us worry about bleeding more than others. For instance intracranial tumors. An intracranial hemorrhage has the potential to be more devastating than a muscle bleed, though both are unwanted outcomes. Also, widespread cancer is a cause for concern, both for clotting but also for bleeding.
• Clot location – If a patient suffered a significant deep vein thrombosis or pulmonary embolism, it is clear we need to treat them. But what if the clot was a calf DVT or a subsegmental PE? Then the decision can be much more difficult. There are few high quality data to guide us.
• Impact of another clot – When we try to balance clotting and bleeding risk, one thing to think about is the potential harm another clot will cause. For some reason recurrence in a person who had a deep vein thrombosis tends to be of another DVT. And recurrence of a pulmonary embolism tends to be PE. We also take into consideration a person’s reserves. For instance, can their heart and lungs withstand another clot if that happened?
• Need for procedures – Many cancer patients need procedures. For instance, surgery to remove the tumor, or procedures to insert catheters. Each such procedure means stopping anticoagulation for a period of time. Frequent procedures may impact our decisions about how long to anticoagulate and about the type of anticoagulation.
• Goals of care – Finally, but importantly, we need to consider a patient’s goals. How difficult is it for them to take another medicine? What are their wishes?

Where is the Clot?

In clot, like in real estate, location matters. First, is the clot in the deep or superficial veins? We tend to treat superficial thrombophlebitis for a limited amount of time, if we treat them at all. Studies direct us toward 45 days of treatment with either fondaparinux or rivaroxaban. But we always treat a deep vein thrombosis.

Second, is a DVT proximal or distal. A distal DVT means that it is in the calf veins. Guidelines allow us to observe these clots. Sometimes, we will only treat a calf DVT if it is close to the popliteal vein, if it grows or if it causes much discomfort. If we do treat, we often treat for 6 weeks to 3 months. But we might extend therapy if the cause for the clot is an ongoing risk-factor such as cancer.

A similar situation exists for pulmonary embolism. We will always treat a significant PE. But a we might decide to observe a distal, subsegmental PE, especially if there are no symptoms.

Upper Extremity Deep Vein Thrombosis

Upper extremity DVT are a bit different, so we should mention them separately. First, we do not have as much data about these clots compared to lower extremity DVT. So we tend to extrapolate. Treatment duration is often a derivative of what we would do for a similar clot in a leg vein. Second, the consequences of upper extremity deep vein thrombi are usually not as severe as clots in the legs. The clot volume is lower and the chances of embolization are also lower. This is not to say that fatal pulmonary emboli are impossible. But they are less common than for lower extremity DVT. That also pushes clinical practice toward a more lenient approach.

Catheter Associated DVT

But we still need to mention one type of upper extremity DVT separately. These are catheter associated DVT. The question of how long to anticoagulate when a clot forms around an intravenous catheter comes up often. The most typical recommendation here is first, that the catheter does not necessarily need to come out. In fact, sometimes a catheter will remain in place, and a patient will continue to take anticoagulation for a long time. Second, if the catheter does come out, we tend to treat for 3 months after that. The idea is that if the catheter provoked the clot, we should treat as if the event was provoked.

By the way, the question of how long to anticoagulate before removing a catheter is a different question. And there are no real data to guide us here. Some advocate treating for a few days before pulling a catheter to prevent embolization. Others just remove the catheter when they find the clot.

Bleeding Risk Dictates How Long to Anticoagulate

Many of us think about clotting risk and forget about bleeding risk. That is only natural, because a clot is what has already happened to the patient. But bleeding can be just as devastating if not more devastating the clotting. So, as you can imagine, if a patient has a high bleeding risk, long-term anticoagulation is not going to be favorable.

We know of some factors that seem to be associated with bleeding. For instance older age, poor liver function, low platelet count and a prior bleed. Anticoagulation in renal failure is associated with higher bleeding risk than for normal renal function. Also, we know that combining some medications adds risk. For instance, combining NSAIDs and anticoagulation can result in bleeding. But in real life it can still be hard to predict bleeding for a particular patient.

Testing to Determine How Long to Anticoagulate

The bottom line is that testing does not really help us determine how long to anticoagulation. And still, it is hard to shake the feeling that thrombophilia testing is not helpful. Face value, it should help, right? The presence of a thrombophilia means that there is a higher chance of clotting, right? But in practice, other factors are usually more powerful. So whether a thrombophilia exists or not usually does not alter our decisions about anticoagulation duration.

Another common test is d-dimer. We know that persistently elevated d-dimer is associated with elevated risk for recurrent clots. And this is actually true for both provoked and unprovoked venous thrombosis. But again, it has only marginal usefulness. This is because once we know an event was provoked or unprovoked, that drives most of the recurrence risk. For instance, a low d-dimer in a man who had an unprovoked event does not mean they have a low chance of another clot if they don’t take anticoagulation. It just means their risk is lower than if the d-dimer was high.

What does the Patient Want to Do?

A patient should always have a say in decisions about their health. So while we can present these data to patients and make recommendations about how long to anticoagulate, they will need to decide for themselves. For instance, if you look back at the CHEST guidelines from 2008, you will see that we used to treat an unprovoked first clot for only 3-6 months. So why are we advising longer treatment now? Have the data about recurrence risk changed significantly? I don’t think so. I think the main change was how we thought about balancing the risk of bleeding and clotting. But a patient might have another opinion. When that is the case, we should do our best to come to a reasonable path through joint decision making.

Patients impact decisions in other ways as well. For instance, they might have issues with complying with one anticoagulant, but not with another. Maybe they read something about one blood thinner or another. Or maybe it is a matter of cost. So they may agree for a longer treatment period if we can prescribe a different anticoagulant. Again, if a patient has a different opinion about anticoagulation duration than ours, we should understand where they are coming from and see if we can’t find ways to offer practical sound advice.