You are working at a family medicine clinic with Dr. Hill. She tells you, “The next patient, Mr. Smith, is a 53-year-old male with a chief concern of swelling and pain in his left lower extremity.”

Before you go to see Mr. Smith, a quick review of the chart reveals that he has type 2 diabetes, obesity, hypertension, and hyperlipidemia. You note that he has not been to the office in the past six months, and it appears that he should be out of all of his medications.

When you enter the examination room, Mr. Smith, a middle-aged male, greets you from where he is sitting. You introduce yourself and ask him what brings him to the office today.

He replies, “It’s my left leg. The past four days it has been red, swollen, and painful—and it seems to be getting worse.”

You ask him to tell you more about this problem.

He says, “It began several days ago, and the swelling seems to be getting worse. It hurts all the time; it doesn’t even get better when I rest it. It seems to get a little worse when I move around. It hurts to walk as soon as I try to stand on it.”

Now that you have a general sense of Mr. Smith’s issue, you ask more focused questions.

“Did you do anything to injure your foot?”

He replies, “I do not remember any injury, but there has been this sore on the bottom of my foot for several months. There’s nothing draining out of the sore and it doesn’t hurt, although my foot doesn’t have much feeling in it.”

“Before this happened, were you sitting down for a long time without getting up and using your legs, such as taking a long airplane trip; or have you been on bed rest?”

“I wish I could go somewhere on an airplane and get a good vacation, but I can’t afford anything like that. I haven’t been on bed rest. I’ve been pretty busy lately.”

“When was the last time you were in the office?”

“It has been a long time now because my daughter and new baby recently moved in with me and I have been trying to take care of the baby as well as keep my job as a bus driver,” he explains.

“Have you been taking your medication?”

He replies, “I have been out of my medication for several weeks now.”

After talking with Mr. Smith more, you discover:

Social History: Does not drink alcohol, but does smoke 1.5 packs of cigarettes daily, he is unmarried, and lives in public housing with his three children and one grandchild.

Review of Systems: No fever or chills, no chest pain, no shortness of breath, and no swelling of the right leg.

You examine Mr. Smith and find:

Vital Signs: T 36.5 °C (97.8 °F), BP 140/90, HR 85, RR 12, O2 98%

Cardiovascular and lung exam: Unremarkable

Lower extremity exam:
Prothrombopenic drugs like warfarin are not suitable for initial therapy in thromboembolism because their onset of action is too slow.
Mr. Smith’s entire left leg is swollen, warm and erythematous. The measurement of the circumference of the largest left calf section is 3.5 cm larger than his right calf at the same location.

There is pitting edema. The leg is tender to the touch, especially along the distribution of the deep venous system.

Dorsalis pedis and posterior tibialis pulses are palpable on both feet. Digital capillary refill time is two seconds. Deep tendon reflexes are present (2+).

He has decreased sensation and is unable to determine the location of a monofilament test on either foot up to the ankle in a stocking distribution.

You note a 2 cm ulceration on the plantar surface of Mr. Smith’s left foot.

At this point, you excuse yourself to discuss your findings with Dr. Hill, assuring Mr. Smith you will return in a few moments.

Mr. Smith’s concern of swelling that is unilateral is an important finding to support the diagnosis of cellulitis, lymphedema, or deep vein thrombosis (DVT). In contrast, for venous insufficiency one would expect bilateral leg swelling. Peripheral artery disease (PAD) is not particularly associated with edema.

Cellulitis and DVT are acute processes. Lymphedema, PAD, and venous insufficiency are less likely, given the acute nature of Mr. Smith’s symptoms.

Since PAD, venous insufficiency, and lymphedema are not infectious processes, the lack of fever in Mr. Smith’s case keeps these diagnoses on the differential.

· In Mr. Smith’s case, the acute unilateral swelling, erythema, and warmth in a diabetic patient, make cellulitis (A) likely. The presence of a fever would support the diagnosis of an infectious process like cellulitis. But the fact that Mr. Smith does not have a fever doesn’t rule out a diagnosis of cellulitis as it is certainly possible to have localized cellulitis without fever.

· In Mr. Smith’s case, you feel that the acute nature of his symptoms—the unilateral swelling, and the presence of risk factors such as obesity, smoking, and diabetes—make DVT (B) a very likely diagnosis. Mr. Smith does not have a fever, but the inflammatory process due to a thrombus in his vein could explain his unilateral lower extremity edema.

· Lymphedema (C) can be present unilaterally, however this is usually a more chronically developing problem, making this diagnosis less likely.

· While venous insufficiency (G) could contribute to the development of a DVT, the acute and unilateral nature of Mr. Smith’s symptoms make you think a diagnosis of venous insufficiency alone is less likely.

· In Mr. Smith’s case, a diagnosis of PAD (E) seems unlikely given the lack of claudication and normal pulses on examination. Although PAD may not be the primary cause of Mr. Smith’s leg swelling and pain, it could potentially be contributing to it by increasing his risk for a foot ulcer. Mr. Smith’s history of smoking and diabetes increases the likelihood that he has PAD.

Less Likely Diagnoses

Muscle strain (D)—Although this can be a cause of swelling and pain, in a patient with intact mental status, a history of trauma should be present to consider this.

Popliteal cyst (F)—This should be palpable behind the knee and rarely would cause the extensive swelling and pain seen in Mr. Smith.
Prothrombopenic drugs like warfarin are not suitable for initial therapy in thromboembolism because their onset of action is too slow.
TEACHING POINT

Differential of Unilateral Lower Extremity Edema
Most Likely Diagnoses

Lymphedema

· Lymphedema is generally painless, but patients may experience a chronic dull, heavy sensation in the leg. In the early stages of lymphedema, the edema is soft and pits easily with pressure. In the chronic stages, the limb has a woody texture and the tissues become indurated and fibrotic.

· Lymphedema initially involves the foot and gradually progresses up the leg so that the entire limb becomes edematous.

Cellulitis

· Cellulitis is an acute inflammatory condition of the skin characterized by localized pain, erythema, swelling, and heat.

· Small breaks of skin are associated with streptococcal infection, whereas staphylococcal cellulitis is commonly associated with larger wounds, ulcers, or abscesses.

· Patients with diabetes are more susceptible to infections like cellulitis. Diabetic neuropathy causes an unawareness of abnormal pressure distribution. Ill-fitting shoes, cuts, or punctures can then lead to the development of ulcers.

· Vascular disease with diminished blood supply contributes to the development of the lesion, and infection is common.

DVT

· Classic symptoms of DVT include swelling, pain, and discoloration in the affected extremity.

· Physical examination may reveal the palpable cord of a thrombosed vein, unilateral edema, warmth, and superficial venous dilation.

· Classic signs of DVT include Homan’s sign (pain on passive dorsiflexion of the foot), edema, tenderness, and warmth. While difficult to ignore, they are of low predictive value and can occur in other conditions such as musculoskeletal injury, cellulitis, and venous insufficiency.

· Chronic venous insufficiency may result from DVT and/or valvular incompetence. Following DVT, the valve leaflets become thickened and contracted so that they are incapable of preventing retrograde flow of blood; the vein becomes rigid and thick-walled. Although most veins recanalize after an episode of thrombosis, some may remain occluded. Secondary incompetence develops in distal valves because high pressures distend the vein and separate the leaflets.

· Primary deep venous thrombosis can also occur without previous thrombosis. Patients with venous thrombosis often complain of a dull ache in the leg that worsens with prolonged standing and resolves with leg elevation. Examination reveals increased leg circumference, edema, and superficial varicose veins.

· The presence of a thrombus in a vein may be accompanied by an inflammatory response in the vessel which may be minimal or may be characterized by granulocyte infiltration, loss of endothelium, and edema. This inflammatory process may also result in a low-grade fever.

· Smoking and obesity are the most robust risk factors in the development of DVT. Diabetes, sedentary lifestyle, hypertension, hyperlipidemia, increasing age, prolonged immobility, surgery, trauma, malignancy, pregnancy, estrogenic medications (e.g., oral contraceptive pills, hormone therapy, tamoxifen (Nolvadex)), congestive heart failure, hyperhomocysteinemia, diseases that alter blood viscosity (e.g., polycythemia, sickle cell disease, multiple myeloma), and inherited thrombophilias are other potential risk factors in the development of DVT.

Venous insufficiency

· The edema of venous insufficiency can be differentiated from chronic lymphedema as venous insufficiency edema is softer, and there is often erythema, dermatitis, and hyperpigmentation along the distal aspect of the leg. Skin ulceration may occur near the medial and lateral malleoli.

· Obesity is commonly associated with venous insufficiency.

Peripheral artery disease

· Peripheral artery disease (PAD) is the presence of systemic atherosclerosis in arteries distal to the arch of the aorta. As a result of the atherosclerotic process, patients with PAD develop narrowing of these arteries.

· Patients with PAD have a history of claudication, which manifests as cramp-like muscle pain occurring with exercise and subsiding rapidly with rest. In addition, later in the course of the disease, patients may present with night pain, nonhealing ulcers, and skin color changes.

· An ankle-brachial index (ABI) can be done to determine the presence of PVD. An ABI of < 0.9 is consistent with the disease. · Classic risk factors for PAD are smoking, diabetes mellitus, hypertension, and hyperlipidemia. Obesity (body mass index (BMI) > 30) increases risk for PAD as well.

· Recent trials have added chronic renal insufficiency, elevated C-reactive protein levels, and hyperhomocysteinemia to the list of risk factors.

· The greatest modifiable risk factor for the development and progression of PAD is cigarette smoking. Cigarette smoking increases the odds for PAD by 1.4 for every ten cigarettes smoked per day.

· Arterial insufficiency is four times more prevalent in patients with diabetes than in those without diabetes. Nearly half of patients who’ve had diabetes for 20 years or more have PAD, usually below the knees.

Dr. Hill praises you, “Very nice clinical reasoning. It looks as though you have correctly narrowed your differential down to two primary diagnoses: cellulitis and deep venous thrombosis (DVT). It is important to make sure when crafting a differential for unilateral lower extremity swelling that DVT is always on that list as it’s a condition that can lead to death if missed. Let’s consider what type of information would be most helpful to obtain next.”
Prothrombopenic drugs like warfarin are not suitable for initial therapy in thromboembolism because their onset of action is too slow.
Dr. Hill asks:

“What test do you think we should order?”
You tell Dr. Hill, “I guess we should have a Doppler ultrasound done because it has the best predictive value for a DVT.”

“Suppose I told you that this test was relatively expensive and often overused,” Dr. Hill proposes, “Would that change your thinking?”

You respond, “Well you mentioned that the D-dimer test is highly sensitive. Perhaps we could rule out DVT by doing that one.”

“Very good thinking. That is precisely the appropriate role of that study. But, remember that the D-dimer test is best used to rule out a DVT if the pretest probability of having a DVT is relatively low.”

“Is there some way to estimate Mr. Smith’s pretest probability of having DVT?”
“I have read that no singular clinical finding is helpful in that,” you tell her.

“That is true,” Dr. Hill concurs. “But if we use several clinical findings, we may be able to do a better job of predicting pretest probability. I am speaking here of the Wells criteria.”

TEACHING POINT

Wells Criteria for the Diagnosis of DVT
Active cancer (treatment ongoing or within previous six months or palliative)

1

Paralysis, paresis, or recent plaster immobilization of the legs

1

Recently bedridden for more than three days or major surgery within four weeks

1

Localized tenderness along the distribution of the deep venous system

1

Entire leg swollen

1

Calf swelling by more than 3 cm compared with the asymptomatic leg (measured 10 cm below the tibial tuberosity)

1

Pitting edema (greater in the symptomatic leg)

1

Collateral superficial veins (non-varicose)

1

Alternative diagnosis as likely or more likely than that of deep vein thrombosis

-2

Low probability 0 or less, moderate probability 1–2, high probability 3 or more.

You conclude, “Given Mr. Smith’s high pretest probability of DVT, I don’t think I would trust a negative D-dimer result even with its high sensitivity. I think we have to get Mr. Smith a Doppler ultrasound instead.”

Dr. Hill agrees. “Ultrasonography is recommended as the initial test in a patient with high pretest probability.” And adds, “are there other diagnostic studies that you would order now?”

A CBC (C ) with leukocytosis might make you consider an infectious process. Given you are in clinic and he has not been seen in almost 6 months electrolytes, glucose, BUN & creatinine (E) as well as a Hemoglobin A1c (F) would be important to evaluate diabetic control and renal function.

You and Dr. Hill return to Mr. Smith’s room together. After greeting him, Dr. Hill explains, “Mr. Smith, we have a good idea of what may be causing the issues with your leg. We would like to gather some more information by taking a blood sample and sending you over to radiology for a Doppler ultrasound so that we can determine the best course of treatment for you.”

After Mr. Smith assents to the plan, Dr. Hill washes her hands and asks to take a look at his leg. She agrees with your assessment.

She walks you through a diabetic foot examination:

On Mr. Smith’s exam, Dr. Hill finds 3 out of 10 sites imperceptible using the 10-gram monofilament test, indicating some loss of protective sensation.

She finds Mr. Smith’s dorsalis pedis and posterior tibialis pulses intact bilaterally.

She notes a 2 cm ulcer on the plantar surface of his foot , with some surrounding erythema, and callous formation. The ulcer is deep, including full skin thickness, down to muscles and ligaments, but no exposed tendons, or bony involvement, and there appears to be no abscess formation.

She finds that the skin on Mr. Smith’s feet is dry and his toenails are dystrophic and incurvated, demonstrating inappropriate self-care.

At the end of the diabetic foot exam, Dr. Hill turns to you and asks, “What do you think we should do about his foot ulcer?”

You admit, “I’m not sure about that. Would antibiotics help?”

“They would if his wound is infected, but first we should evaluate the grade of the ulcer,” Dr. Hill explains.

You and Dr. Hill determine that Mr. Smith’s foot ulcer does not require antibiotics at this time, but does require debridement, which you will address after he’s had his tests done. Mr. Smith has his blood drawn and a Doppler ultrasound performed.

A few hours later, you see that the results of the labs have returned:

Complete Blood Count:

Lab Value

Conventional

SI

WBC

7.5 x103/μL

7.5 x109/L

Hgb

13.7 g/dL

137 g/L

Hemoglobin A1C

10.2 %

.102

Chemistry:

Lab Value

Conventional

SI

Na

137 mEq/L

137 mmol/L

K

4.0 mEq/L

4.0 mmol/L

Cl

98 mEq/L

98 mmol/L

C02

25 mEq/L

25 mmol/L

BUN

18 mg/dL

6.3 mmol/L

Creatinine

1.0 mg/dL

88 mmol/L

Glucose

232 mg/dL

12.7 mmol/L

WBC is normal (A, D), which does not support an infectious process. Between the lack of leukocytosis, the lack of fever, and the clinical findings of a grade 2 ulcer, cellulitis is now a very unlikely diagnosis for Mr. Smith.

While there is evidence for uncontrolled diabetes, renal function (BUN & creatinine) appears normal (E) and he is not anemic because he has a normal hemoglobin (C).

Dr. Hill informs you, “I just received a call from the radiologist. It looks as if our suspicions were correct. Doppler ultrasound shows that Mr. Smith has a DVT in the femoral vein. So now the question is: What do we do about it?”

You respond, “Well he needs anticoagulation to prevent a pulmonary embolus (PE), right?”

“Right. His short-term risk of a PE is high, so we need to anticoagulate him right away.”

TEACHING POINT

Prevention of Embolism

More than 95% of pulmonary emboli arise from thrombi in the deep venous system of the lower extremities. Ninety percent of deaths due to pulmonary embolism result within an hour or two—before diagnostic and therapeutic plans can be implemented. Therefore, prevention and prompt treatment of DVT is the most effective approach to prevent embolism and death due to PE.

TEACHING POINT

Goals of DVT Therapy

1. Immediate inhibition of the growth of thromboemboli and prevention of pulmonary embolism

2. Promotion of thromboembolic resolution

3. Prevention of recurrence

The day-to-day risk of the development of a pulmonary embolism (PE) is high in patients with acute DVT, so immediate anticoagulation is necessary. It is important to choose an anticoagulant that will act immediately to prevent any further clot formation.

A picture containing box and whisker chart Description automatically generated

* Image Credit to ASH 2020 Guidelines

Which of the following can be an appropriate treatment option for the initial management of an acute DVT?

Rivaroxaban (C) can be initiated on its own for the treatment of acute DVT. Unfractionated heparin or LMWH overlapping with the initiation of warfarin is also appropriate (B, D). Both Warfarin (E) and Dabigatran (A) cannot be initiated as monotherapy. Warfarin requires overlap (also known as bridging) with unfractionated heparin or LMWH. Dabigatran requires lead-in or pretreatment of a parenteral anticoagulant (such as heparin or LMWH) for 5 to 10 days prior to initiating.

Dr. Hill calls Mr. Smith’s pharmacy and finds that his insurance will only cover dabigatran and does not cover any other DOAC. Unfortunately, insurance does not cover the necessary pre-treament parenteral agent enoxaparin (injectable low molecular weight heparin) without prior approval, which may take a few days to achieve. (It is late in the day when you are seeing him.) Dr. Hill asks you if you think he would be better managed in the hospital or as an outpatient.

After thinking about it for a minute you respond, “I don’t think it is acceptable to send him home if we can’t ensure that he will be able to get enoxaparin or one of the DOACs that can be used for monotherapy tonight. His day-to-day risk of a pulmonary embolus is too high. Also, I am worried about his ability to adhere to new complicated instructions, given that he has a busy home and work life and has not been able to prioritize his own care. He needs to have a plan for managing his medications and he has this foot ulcer that needs care. I think it would be best to stabilize him in the hospital and work on having a more supportive home environment.”

Dr. Hill replies, “Excellent. I agree that Mr. Smith will be best treated in the hospital. Let’s look into how we will do that.”

TEACHING POINT

Requirements for Treating DVT on Outpatient Basis

In order to treat DVT on an outpatient basis:

The patient must be:

· Hemodynamically stable

· With good kidney function

· At low risk for bleeding

· Able to afford medications

· Adherent to medications

The home environment must be:

· Stable and supportive

· Capable of providing the patient with daily access to INR monitoring (if using warfarin as the anticoagulant)

For many years, the standard of care for DVT management was admission to the hospital and administration of unfractionated heparin overlapping with the initiation of warfarin. Now, most patients with DVT may be managed in the outpatient setting, though there are a few important exceptions. Inpatient management remains the best option for patients who are hemodynamically unstable, who are at serious risk of acute bleeding with the initiation of anticoagulation (e.g. those with prior admission for gastrointestinal bleeding), or who have obstacles to outpatient management. Examples of this include the inability to afford DOACs and LMWH, those who do not have adequate support at home, or who have a history of issues with adherence to medications and treatment plans.

While it may not appear to be the most cost-effective decision to have to be hospitalized, in this case, it is the right decision in light of the inability to get the patient appropriate treatment in a timely fashion that could be fatal if left untreated or undertreated.

TEACHING POINT

Parenteral Agents

There are three parenteral therapies used to either bridge with warfarin or pretreat prior to initiation of dabigatran: unfractionated heparin, low-molecular weight heparin (LMWH), and fondaparinux.

You and Dr. Hill decide to have Mr. Smith anticoagulated on LMWH because it doesn’t require laboratory testing and dosage titration and Mr. Smith may be more comfortable if he’s not hooked up to an IV.

Dr. Hill adds, “We only want to use low molecular weight heparin for a short term. After five days we will start dabigatran since he will need a longer course of anticoagulant therapy to reduce his risk of PE. In his case, his risk factors are not readily reversible, which will factor into our thinking about the duration of his treatment. If, for example, he had developed his DVT as a complication of surgery (a common and transient risk factor), we would have less cause for concern about his risk for recurrence of his DVT.”

TEACHING POINT

DVT Treatment After Initial Stabilization
After initial stabilization with a therapeutic anticoagulant to prevent thrombus progression, a decision must be made on the primary treatment to promote resolution of the thrombus and for how long. DOACs and warfarin remain the mainstays of this treatment phase.

Direct Oral Anticoagulants

DOACs are direct-acting agents that are selective for one specific coagulation factor, either thrombin (e.g., dabigatran) or factor Xa (e.g., rivaroxaban, apixaban, and edoxaban, all with an “X” in their names)

Direct thrombin inhibitors

Dabigatran is a direct thrombin inhibitor that may be taken orally. Dabigatran also has been demonstrated in meta-analyses to lead to fewer bleeding complications compared to warfarin. The reversal agent (idarucizumab) was approved by the FDA, which may be useful in the case of serious bleeding.

Factor Xa inhibitors

Fondaparinux is a parental form of this class of drugs and could be used instead of LMWH in the initiation stage. Rivaroxaban and apixaban are oral factor Xa inhibitors which may be used immediately as monotherapy for VTE. Although these drugs have been found to be as effective as, and generally safer (i.e. fewer bleeding complications) than warfarin and LMWH, the negatives of this class of medications include high cost. Andexanet alfa was recently approved as a reversal agent, though its availability may be limited depending on hospital setting.

One big advantage of DOACs is they don’t require frequent laboratory monitoring and dose adjustments. An important contraindication is that neither direct thrombin inhibitors nor factor Xa inhibitors may be used in pregnant patients (unlike heparin, they cross the blood-placenta barrier) or in patients with significant renal disease.

Warfarin

Prothrombopenic drugs like warfarin are not suitable for initial therapy in thromboembolism because their onset of action is too slow. Their only role is in maintaining anticoagulant protection for prolonged periods. Before the development of the direct oral anticoagulants (DOACs), warfarin was the mainstay of the management of DVT and still an acceptable option for many patients. Warfarin is a better option for patients who can’t afford the cost of the DOACs, have difficulty taking medication more than once a day, or have a CrCl < 30 mL/min. Its disadvantages include its highly variable dosing range, its requirement of frequent laboratory monitoring, and its high rate of interactions with other medications. Warfarin requires monitoring. An INR is checked and the warfarin dose is titrated every three to seven days to achieve a goal INR of 2.0–3.0. Dr. Hill says, "Since we are planning on treating Mr. Smith in the hospital, one of the advantages of inpatient treatment is that we can get the wound team nurse to evaluate his ulcer and make some recommendations. While we have Mr. Smith in the hospital, are there other specialists or team members that we can involve to improve his health?" You suggest, "What about an endocrinologist to help with diabetes management?" "Now there's an interesting thought. What do you think is complicating Mr. Smith's glucose control?" You contemplate this, "In thinking about his history, it seems that he has been nonadherent with his medication regimen, diet, exercise program, and his follow-up appointments for some time. He describes a stressful social situation at home with family and financial problems, as well as work-related stress." "How do you think an endocrinology consult will help with that?" Dr. Hill wants to know. "I see your point," you admit. "His problems in managing his chronic illness seem to be more social than medical." "That's right." Dr. Hill adds, "It's possible that an endocrinology consult might be useful down the road, especially if he is brittle or otherwise difficult to control on routine medication, but we really have not had the opportunity to see if standard care will be successful because of his social factors." "So, I guess it might be better if we get some recommendations from a diabetes educator, a social worker and maybe even the Pharm D," you suggest. "Excellent! Ideally, we could all meet in a room and map out a plan for his care, but this isn't practical in reality. Instead, our role, as the family clinician, is to assume responsibility for coordinating and directing his care and ensuring that everyone on the team is working toward the same goal." Dr. Hill explains. Dr. Hill explains to you the importance of testing for inherited thrombophilia, "Patients with DVT secondary to an inherited thrombophilia are treated differently than others." Which of the following criteria are potential reasons to screen for inherited thrombophilia? i nitial unprovoked thrombosis occurring before age 40, family history of venous thromboembolism, recurrent venous thrombosis, and thrombosis occurring in unusual vascular beds are all potential reasons to screen for inherited thrombophilias. There is no indication to screen all patients who present with a DVT. You and Dr. Hill return to Mr. Smith's exam room to discuss your findings and recommendations with him. Dr. Hill begins, "Mr. Smith, the reason your leg is so swollen and painful is that you have a blood clot in one of your veins. The good news is that we can treat this condition quite easily and quickly. We would like to admit you to the hospital to treat the blood clot that you have and start you on some medication which will keep you from getting another clot." "Hospitalization? I don't have time to go into the hospital. I have a job and a family to take care of." "I understand that," Dr. Hill assures him. "I hear you saying that it is very difficult to take care of yourself and your family, especially in this day and time, and I agree. But, if we don't treat the blood clot in your leg, there's a real risk that it will travel to your lungs and could kill you. You will only need to be in the hospital for a few days, and we would like to use this time to get your other health issues, like high blood pressure and diabetes under control. We also need to take care of that ulcer on your foot." "It sounds like I don't have much of a choice. I guess I'll have to go to the hospital. Why do I have a blood clot, anyway?" Mr. Smith wants to know. You tell him, "Well, as we've discussed before, your smoking puts you at significant risk for a blood clot. Although you may not be aware, the fact that your body weight is higher than recommended also puts you at some risk of a blood clot. After we've addressed this immediate problem with your blood clot, we'd like to see you here at the clinic to revisit your smoking and your weight to see if we can work together to reduce your risk of another blood clot, as well as improve your health overall." Mr. Smith seems satisfied, and preparations are made for the hospital admission. Several days have gone by and you and Dr. Hill are now rounding on your patients in the hospital. When you get to Mr. Smith, you tell Dr. Hill: "This is Mr. Smith's third day in the hospital. He says he is feeling better, the pain and swelling in his leg is improving. His temperature is 36.2 °C (97.2 °F), his pulse is 80 beats per minute, his respiratory rate is 16 breaths per minute, his blood pressure is 128/78 mmHg. On exam, his foot ulcer has some fresh granulation tissue on the wound edges. Labs include his fasting glucose this morning was 128 mg/dL (7.0 mmol/L). His CBC was normal and his platelets are stable from admission." Dr. Hill responds, "Good. I just got word from his pharmacy that the enoxaparin has now been approved by his insurance, so if he can inject himself for two more days, he can go home. We will need to arrange a close follow-up with visiting nurses and at our office, so he can continue his treatment for his diabetic foot ulcer." You comment, "This all seems so much easier than it would have been if he were taking warfarin. How long would it take to get his INR to the therapeutic range if he were using warfarin?" Dr. Hill tells you, "It varies a lot from person to person, but it commonly takes at least five days for a patient's INR to get above 2.0. When starting it, you have to balance speed with the risk of overshooting his INR goal and ending up increasing his risk of bleeding by making him supratherapeutic. It is good to consider warfarin dosing since it is still commonly used. It is a very effective medication, but it can be dangerous as well." "What do you think we should do next?" Dr. Hill wants to know. After contemplating this for a moment, you conclude, "Since his insurance has now approved the prior authorization for 2 days of enoxaparin he can finish the pretreatment phase at home. He has been on enoxaparin for three days now. My understanding is that he needs to be on enoxaparin for 5 days and then he can begin the dabigatran. He will need to be able to give himself the enoxaparin at home for 2 days and then be able to start the oral dabigatran about 12 hours after his last dose of enoxaparin. His floor nurse has been showing him how to give the injections, so I think he will be able to do it. He said he doesn't like it very much, but he would do it if he has to." You continue, "He's back on his regular medications which have improved his blood pressure and glucose. The foot ulcer has been debrided and is getting better. There doesn't seem to be much more for us to do in the hospital, so I think he might be ready to go home later today." "I agree," Dr. Hill replies. "What type of arrangements will he need at home?" "Home health should be able to manage his wound. I would think with that and close follow-up in the office, he should do well," you predict. “We also need to make sure he understands the timing of the enoxaparin and transition over to the dabigatran, and that he knows where to pick up both his medications. You also remind Dr. Hill that Mr. Smith's obesity and smoking still pose tremendous risks to his health and that in future visits to the clinic, he should be counseled regarding weight loss and smoking cessation as well as managed for hypertension, hyperlipidemia, and diabetes.