To test or not to test for inherited thrombophilias

Start by looking at whether a DVT was provoked or unprovoked, as well as at the type of provoking factors.


Just because you can test for inherited thrombophilias doesn't always mean you should, according to Martha P. Mims, MD, PhD. At a Friday session, “Who Really Needs a Work-up for Hereditary Thrombophilia?”, she outlined appropriate therapy for venous thromboembolism (VTE), as well as highlighting some instances where testing might change management.

“One question that I get a lot is a primary care doctor will send a patient to me and ask ‘How long do I have to anticoagulate this patient?’ There's not really a hard and fast rule, so it requires a little bit of thinking,” said Dr. Mims, who is professor and chief of hematology and oncology in the department of medicine at Baylor College of Medicine in Houston. “There's a lot of anxiety related to having a clot and knowing what to do.”

Start by looking at whether a deep venous thrombosis (DVT) was provoked or unprovoked, as well as at the type of provoking factors, Dr. Mims advised. Transient major provoking factors include major surgery, fractures or major trauma, joint replacement, immobilization for more than three days, and pregnancy or oral contraceptives, while transient minor provoking factors include minor surgery, immobilization for less than three days, and minor leg injuries.

Persistent major provoking factors include malignancy, high-risk thrombophilia like antithrombin deficiency, and a history of DVT. “Once you're had a DVT, the risk of having another one is there, and you have to talk to people and think about that,” said Dr. Mims. Age is considered a minor persistent provoking factor.

Unprovoked DVTs in patients without risk factors are particularly problematic, Dr. Mims said. “When somebody has a DVT out of the blue—they haven't been on a long plane trip, they're not obese, they haven't had an injury, or you can't really put a risk factor there—that actually puts people at a higher risk of having a recurrence.”

With provoked DVTs, Dr. Mims said she considers the risk factors and whether they are modifiable, like oral contraceptives, or if they're persistent, like an underlying malignancy. “And interestingly, I'm not sure how many people know about this, being a man puts you at higher risk of recurrence,” she said. “I don't know why that is, we're not sure why that is, but it's certainly true.”

At the initial diagnosis of VTE, everyone should get anticoagulation unless there is a strong contraindication, she said. “The exceptions to this might be every once in a while you'll get a CT chest for somebody, and you'll see there's a distal thromboembolism there that's tiny, in a subsegmental vein. There is a lot of discussion going on now whether those asymptomatic subsegmental [pulmonary embolisms] need to be anticoagulated,” Dr. Mims said. “But if you've got somebody with a proximal blood clot in an arm or a leg, that needs to be treated.”

In the acute period of a clot, there's probably no point in testing for thrombophilias, Dr. Mims said. “It's not going to affect what you do for the next three months, you're going to get inaccurate results, your patient's going to have to pay for it, and it's not going to be helpful to them,” she said.

Dr. Mims said she is often asked about use of thrombophilia testing to help determine length of therapy. For a provoked DVT with major or transient risk factors, anticoagulation can probably be stopped at three months. However, with unprovoked DVT, it's probably best to lean toward long-term anticoagulation, “but that can be tricky,” Dr. Mims said. “Patients don't want to take it, they want some proof, they want you to show them hard evidence. And it's really those unprovoked DVTs where you might want to give some thought to thrombophilia testing if it's going to push you one way or the other.”

These cases require evaluation of clotting risk as well as bleeding risk, Dr. Mims said. “Sometimes we don't think about that. We just really focus on ‘They've had a blood clot, we're worried they're going to have another blood clot,’ but you have to think about bleeding risk as well,” particularly in older patients. Patient preference should also be considered, she said. If a patient says she has no problem taking her apixaban, for example, “I'm more likely just to leave them on there or maybe put them on a lower dose of apixaban than to take them off.”

Dr. Mims provided a rundown of the recurrence risk for each type of inherited thrombophilia and how that affects decisions about thrombophilia testing in patients with unprovoked DVT. Factor V Leiden mutation and prothrombin gene mutation have about the same recurrence risk as the general population, “So I don't really think too much about it,” she said. “I might find it, but it doesn't really tell me too much about recurrence risk.”

For patients with deficiencies in proteins S or C, recurrence risk is not that high unless there's family history, she said. “[If] somebody comes to you with a family history, you might consider protein C or S testing.” Antithrombin probably carries the highest recurrence risk, especially if family history is present, she noted. “If I'm going to pick things to test, antithrombin would be way up there on my list.”

In summary, testing for inherited thrombophilias is generally probably only useful if a DVT is unprovoked, if the patient has a strong family history, and if withdrawal of anticoagulation is being considered, Dr. Mims said. “The data really favor only testing for antithrombin, protein S, and protein C, because that's really where the high risks are in terms of unprovoked DVTs.”