Chapter 53: Anticoagulation

Question 1

Where are DVTs most commonly found?

Answer 1

deep veins of legs, thighs, and pelvis, but they can occur anywhere in the body

Question 2

Name (3) factors that lead to activation of the coagulation process

Answer 2

1. blood vessel injury
2. prothrombotic conditions
3. blood stasis

Question 3

Explain the MOA of UFH, LMWH, and Arixtra® in your own words.

Answer 3

UFH, LMWH, and fondiparinux (Arixtra®) work by binding to antithrombin (AT), a naturally occurring anticoagulant in the body, which causes a confirmational change in AT, making AT work MUCH better (roughly 1,000-fold more activity). Upon UFH and LMWH binding, AT goes on to inactivate clotting factors, including thrombin (IIa) and factor Xa.

UFH inhibits clotting factors Xa:IIa in a 1:1 ratio while LMWH inhibits the same clotting factors in a 3:1 ratio (more Xa inhibition)

Fondiparinux (Arixtra®) inhibits clotting factors Xa:IIa in a 100:1 ratio (much more Xa activity than either UFH or LMWH).

Question 4

Does LMWH inhibit factor Xa or IIa more?

Answer 4

Xa. LMWH has a much shorter chain, and when binding AT, the chain is too short to adequately bind and inhibit thrombin (IIa). LMWH inhibits Xa:IIa in a 2-4:1 ratio compared to UFH 1:1 ratio and fondiparinux (Arixtra®) 100:1 ratio

Question 5

What injectable direct thrombin inhibitor is the drug of choice for patients that develops HIT in the hospital setting?

Answer 5

Argatroban

Argatroban is a direct thrombin (factor IIa) inhibitor indicated for the treatment of HIT. Initial dose of argatroban for HIT is 2mcg/kg/min IV. Maintenance dose should be adjusted to a target aPTT of 1.5 to 3x baseline (not to exceed 100 seconds OR 10mcg/kg/min)

Other direct thrombin inhibitors are dabigatran (Pradaxa®) oral, bivalirudin (Angiomax®) IV, and desirudin (Iprivask®) SC injection.

Argatroban is the only direct thrombin inhibitor FDA approved for treatment of HIT. Bivalirudin is used off label for HIT.

Question 6

Give a quick run down of clot formation starting with clotting factor Xa.

Answer 6

Factor Xa activates factor II (prothrombin) to factor IIa (thrombin).

Thrombin activates fibrinogen to fibrin which can then go on to form a stable clot.

Question 7

Name (4) available factor Xa inhibitors. Include brand and generic, route of administration, and label each one whether they are direct or indirect factor Xa inhibitors

Answer 7

Fondiparinux (Arixtra®) SC, indirect Xa inhibitor
Rivaroxaban (Xarelto®) oral direct Xa inhibitor
Apixaban (Eliquis®) oral direct Xa inhibitor
Edoxaban (Savaysa®) oral direct Xa inhibitor

Fondiparinux (Arixtra®) is an indirect factor Xa inhibitor because it’s MOA involves it binding to antithrombin, causing a confirmational change, thereby increasing AT’s activity to inhibit factor Xa, thus indirect factor Xa inhibitor.

Question 8

Warfarin is a vitamin K antagonist. Which clotting factors does warfarin inhibit?

Answer 8

Factors II, VII, IX, and X

Interestingly, without adequate vitamin K, the liver still produces these clotting factors (II, VII, IX, and X), but they have reduced anticoagulant activity.

Question 9

Patients with what PMH would NOT be eligible to receive any of the NOACs?

Answer 9

Patients with a prosthetic heart valve should not receive dabigatran (Pradaxa®), Rivaroxaban (Xarelto®), Apixaban (Eliquis®), or Edoxaban (Savaysa®).

Question 10

Can factor Xa inhibitors and direct thrombin inhibitors be used for VTE prophylaxis?

Answer 10

Yes, but they are indicated for specific conditions such as s/p knee/hip surgery or hip replacement surgery, etc.

Question 11

What is the VTE prophylaxis dose of Lovenox®?

Answer 11

Enoxaparin (Lovenox®)

40mg SC daily or…
30mg SC BID or…

If severe renal impairment (CrCl

Question 12

A patient is going on a long-distance flight and asks whether they should take an aspirin to prevent clots from forming in their legs. What is your response?

Answer 12

Aspirin and other anticoagulants should NOT be used for this purpose without a compelling indication. Recommend the patient gets up and moves around on the plane, do calf exercises, and wear compression stockings during travel.

Question 13

Which of the following is/are not considered risk factors for developing VTE? (Select all that apply)

A.  Previous VTE
B. Cancer
C. Pregnancy
D. Chronic angina
E. Use of Evista®

Answer 13

D, chronic angina, is the only answer listed that is not a risk factor for developing VTE.

E. Raloxifene (Evista®) is an oral selective estrogen receptor modulator used for the prevention of osteoporosis in post-menopausal women and to reduce the risk of invasive breast cancer in post-menopausal women with osteoporosis and in post-menopausal women at high risk for invasive breast cancer

Question 14

How long should a provoked DVT/PE be treated with anticoagulation?

Answer 14

3 months

Any VTE that is provoked (caused) either by surgery or a transient (reversible) risk factor should be treated for 3 months.

Question 15

If a patient on warfarin is diagnosed with HIT, why should warfarin be discontinued AND the patient given vitamin K?

Answer 15

Warfarin use with a low platelet count has a high correlation with warfarin-induced limb gangrene and necrosis.

This seems counterintuitive to stop an anticoagulant in a patient that is at high risk of thrombosis. Instead of warfarin, argatroban is the anticoagulant of choice to treat HIT.

Remember, argatroban is a direct thrombin inhibitor given IV that has no cross-reaction with HIT, nor does it have an antidote. Argatroban does not need to be renally dose adjusted.

Question 16

What is the anticoagulant of choice in a patient with a history of HIT that requires PCI or urgent cardiac surgery?

Answer 16

Bivalirudin (Angiomax®)

Question 17

Heparin is available in which of the following dosage forms? (Select all that apply)

A. IV
B. Oral
C. SC
D. IM
E. SL

Answer 17

A and C are correct.

Heparin solution is available to be given as an IV bolus/infusion or SC injection.

B, D, and E are incorrect.
Heparin CANNOT be given IM due to hematoma risk.

Question 18

What is a typical VTE prophylaxis dose for heparin?

Answer 18

5,000 units SC Q8h

Question 19

What is the inpatient VTE heparin treatment dose(s)?

Answer 19

80 units/kg IV bolus followed by 18 units/kg/hr infusion

Question 20

What body weight is heparin dosing based on?

Answer 20

Actual body weight

Question 21

What is the inpatient ACS/STEMI heparin treatment dose(s)?

Answer 21

60 units/kg IV bolus (max 4,000 units), followed by 12 units/kg/hr (max 1,000 units/hr) infusion

Question 22

T/F:

It is safe to give Lovenox® to a patient with a history of HIT?

Answer 22

False

HIT antibodies have cross sensitivity for LMWHs. LMWHs are contraindicated in patients with a history of HIT.

Question 23

Which of the following are SE of heparin?

A. Thrombocytopenia
B. Hypokalemia
C. Hyperkalemia
D. Nephrotoxicity
E. Osteoporosis

Answer 23

A, C, and E are correct
Long-term use of heparin is associate with osteoporosis and hyperkalemia.

B and D are incorrect
Heparin causes hyperkalemia, not hypokalemia. Heparin is not nephrotoxic, it is hepatically metabolized and does not need any dose adjustments for renal impairment (nor hepatic dose adjustments despite hepatic metabolism). Dose should be adjusted based on aPTT.

Question 24

What is the antidote to heparin? How much of the antidote would be needed to reverse 10,000 units?

Answer 24

Protamine

Roughly 1mg of protamine reverses 100 units of heparin. So, to reverse 10,000 units you would need 100mg of protamine. HOWEVER, the maximum dose of protamine is 50mg. Also, this is kind of a trick question. You really need more information about the infusion rate heparin was being given. Only heparin given in the preceding 2 to 2.5 hours needs to be reversed. The half-life of heparin is 1.5 hours.

Example: Suppose the heparin was being infused at a rate consistent with treatment of VTE (18 units/kg/hr) and the patient was 74 kg. 18 x 74 = 1,332 units/hr x 2.5 hours = 3,330. The patient would need 33.3mg of protamine to reverse this.

Question 25

The aPTT is used to monitor patients receiving heparin. What is the aPTT therapeutic range for heparin?

Answer 25

Therapeutic range for heparin aPTT is 1.5 - 2.5 x patient’s baseline aPTT. A normal aPTT in a healthy patient is typically 30-40 seconds. So 1.5 - 2.5 these values would be about 45-60 to 75-100

Question 26

What is the treatment dosing of enoxaparin for VTE?

Answer 26

1mg/kg SC Q12h or…

1.5mg/kg SC daily (inpatient only) or…

If severe renal impairment (CrCl

Question 27

What lab value should be monitored for efficacy in patients taking enoxaparin? Monitoring is only recommended in certain patient populations. What are they?

Answer 27

Anti-Xa levels should be monitored in pregnant patients with a mechanical heart valve, obesity, low body weight, pediatrics, elderly, and renal impairment.

Anti-Xa levels (peak) should be obtained 4 hours post dose.

Note: unlike heparin, aPTT is NOT used to monitor LMWHs like enoxaparin.

Question 28

What boxed warning do LMWHs have?

Answer 28

Patients receiving spinal or epidural anesthesia or spinal puncture are at risk of hematoma and subsequent paralysis

Question 29

What dosing of enoxaparin should a 69 y/o patient with STEMI receive?

Answer 29

Dosing of enoxaparin for the treatment of STEMI has a cutoff at 75 years old. Patients less than 75 y/o should receive a 30mg IV bolus dose + 1 mg/kg SC dose, followed by 1 mg/kg SC Q12h (max 100mg for the first two doses only).

If this patient had a CrCl less than 30 ml/min, the only change to the dosing schedule would be giving 1 mg/kg SC daily instead of Q12h

Question 30

In patients being managed with PCI, when is it safe to give enoxaparin and how much should be given?

Answer 30

If the last dose of SC enoxaparin was given 8-12 hours before balloon inflation (PCI), give 0.3 mg/kg IV bolus now

Question 31

Which of the following statements regarding fondiparinux is correct (Select all that apply)

A. Fondaparinux brand name is Argatroban
B. For VTE prophylaxis, it should be given SC daily in patients with severe renal impairment (CrCl less than 30 ml/min)
C. Side effects include bleeding, hypokalemia, and hypotension
D. Side effects include bleeding, hyperkalemia, and hypertension
E. MOA is an indirect factor Xa inhibitor

Answer 31

C and E are correct
Fondaparinux binds to anti-thrombin, thereby indirectly inhibiting factor Xa.

A, B, and D are incorrect
Fondiparinux brand name is Arixtra®. Argatroban is a direct thrombin inhibitor used in the treatment of HIT. Fondiparinux is contraindicated in patients with severe renal impairment (CrCl less than 30 ml/min) and therefore must be avoided. It’s also contraindicated in patients with active major bleed, thrombocytopenia, bacterial endocarditis, and patients less than 50kg (only if using if as prophylaxis).

Side effects include bleeding, HYPOkalemia, and HYPOtension

Question 32

Which patient should NOT receive warfarin?

A. A patient that enjoys eating spinach salads
B. A patient with a platelet count of 80
C. A patient that is breastfeeding
D. A patient with HF
E. Warfarin is safe to use in all the above patients

Answer 32

B. Warfarin cannot be used in patients with a low platelet count (normal platelet count is 150-450) due to high correlation with warfarin-induced limb gangrene and necrosis

So, if a patient is on warfarin and diagnosed with HIT, the warfarin should be discontinued and vitamin K should be administered, even though the patient is at high risk of thrombosis. Remember, the direct thrombin inhibitor argatroban is the DOC for patients who develop HIT and require anticoagulation

Warfarin may be restarted once platelet count has recovered to at least 150,000/mm^3

Warfarin is safe in breastfeeding and is not thought to pass into breast milk.