Heme/onc pharm – Heparin, anticoagulants, thrombolytics

Heparin first, then spiral CT of the chest (CT angiogram); in other words, don’t do the imaging before the heparin.

If the patient is already on warfarin and has a PE, do a spiral CT of the chest to confirm before inserting an IVC filter. In other words, don’t just jump on IVC filter; remember you need to actually know the patient has a PE before you insert metal into their vena cava.

If pregnant + PE, give heparin first, then do ventilation-perfusion (V/Q) scan, not a spiral CT. If a V/Q scan shows segmental defects (suggestive of PE) and the Q asks for the next best step in diagnosis, the answer is spiral CT of the chest. Student says, “Wait wtf? I thought we don’t do spiral CT in pregnancy.” You’re right, we don’t. But if they ask for the next best step in diagnosis after V/Q scan, it’s still the answer, even if we aren’t going to do it.

• Superficial thrombophlebitis (ST)
  • 45F + history of varicose veins + painful 1-cm palpable cord at the ankle; next best step? –> answer = “subcutaneous enoxaparin”; compression stockings are the wrong answer. The latter are the correct answer for first step in management for venous insufficiency and varicose veins, but if the patient has an active clot (ST or DVT), you need to give heparin.
  • 45F + painful cord tracking from the ankle to the knee; next best step? –> answer = subcutaneous enoxaparin.

Prior to surgery in patients who need anticoagulation

• On 2CK Surg NBME, they will tell you that a patient soon to be undergoing surgery needs anticoagulation. Ultrasound of the legs shows chronic venous occlusion; the answer is “low dose heparin prophylaxis”; the wrong answer is “therapeutic heparin dose.” The latter would be used for an active DVT or ST, but for patients at mere increased risk, use lower dose.

a) Often times, yes. However USMLE will not assess specifics.

b)  USMLE wants you to know that you give aspirin first for MI, followed by adding an ADP2Y12 blocker (i.e., clopidogrel) for double anti-platelet therapy. Therapies such as beta-blocker, nitrates, morphine, oxygen are usually used. Patients also need a statin (HY).

a) Antiphospholipid syndrome (APLS)

a) Heparin-induced thrombocytopenia (HIT)

b) Type II hypersensitivity –> antibodies against heparin-platelet factor 4 (PF4) complex

c) Stop heparin then give direct-thrombin inhibitor (i.e., dabigatran, bivalirudin, lepirudin); warfarin is the wrong answer.

a) Dabigatran, Bivalirudin, Lepirudin

b) Highest yield point is that they are the treatment for HIT. If a patient gets a drop in platelets following heparin administration, the answer is stop the heparin + give a direct-thrombin inhibitor.

a) Factor Xa inhibitors (Fondaparinux, Apixaban, Rivaroxaban)

• Inhibit solely factor Xa, in contrast to heparin, which has effect on both factor IIa and Xa.
• Can be used for anticoagulation as an alternative to heparin and warfarin.

b) Andexanet alfa –> new drug approved in 2018 that reverses the Xa inhibitors.

a) tPA, Streptokinase

b)

Help convert plasminogen to plasmin.

Plasmin breaks down fibrin meshes.

c)

Within 3-4.5 hours of an ischemic stroke.

Rarely in PE when there is hemodynamic instability.

Contraindications to thrombolytics?

• Many. However HY ones for USMLE:
• Hemorrhagic stroke
• History of intracranial bleeds
• Severe hypertension

How to reverse thrombolytics?

• With anti-fibrinolytics:
  • Aminocaproic acid
  • Tranexamic acid

Reversal agent for the factor Xa inhibitors.

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Factor Xa inhibitors (Fondaparinux, Apixaban, Rivaroxaban)

• Inhibit solely factor Xa, in contrast to heparin, which has effect on both factor IIa and Xa.
• Can be used for anticoagulation as an alternative to heparin and warfarin.

How to reverse?

• Andexanet alfa –> new drug approved in 2018 that reverses the Xa inhibitors.

Anti-thrombolytic.

Reverses the effects of tPA or streptokinase.

Direct-thrombin inhibitors (Dabigatran, Bivalirudin, Lepirudin)

• Directly inhibit factor IIa (thrombin).
• USMLE wants you to know these drug names = directly inhibit thrombin.
• Highest yield point (as mentioned above) is that they are the treatment for HIT. If a patient gets a drop in platelets following heparin administration, the answer is stop the heparin + give a direct-thrombin inhibitor.

Factor Xa inhibitors (Fondaparinux, Apixaban, Rivaroxaban)

• Inhibit solely factor Xa, in contrast to heparin, which has effect on both factor IIa and Xa.
• Can be used for anticoagulation as an alternative to heparin and warfarin.

Direct-thrombin inhibitors (Dabigatran, Bivalirudin, Lepirudin)

• Directly inhibit factor IIa (thrombin).
• USMLE wants you to know these drug names = directly inhibit thrombin.
• Highest yield point (as mentioned above) is that they are the treatment for HIT. If a patient gets a drop in platelets following heparin administration, the answer is stop the heparin + give a direct-thrombin inhibitor.

Factor Xa inhibitors (Fondaparinux, Apixaban, Rivaroxaban)

• Inhibit solely factor Xa, in contrast to heparin, which has effect on both factor IIa and Xa.
• Can be used for anticoagulation as an alternative to heparin and warfarin.

LMWH

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Heparin

• Large, anionic, acidic molecule.
• Heparin upregulates antithrombin, which binds to and inhibits factor IIa (thrombin) and factor Xa.
• Unfractionated heparin
  • Greater inhibition of factor IIa relative to factor Xa.
  • Cleared hepatically; used in renal insufficiency.
  • Easily reversible with protamine sulfate.
  • Given IV.
• Low-molecular weight heparin (enoxaparin, dalteparin)
  • Greater inhibition of factor Xa relative to factor IIa.
  • Cleared renally; contraindicated in renal insufficiency.
  • Not easily reversible compared to unfractionated heparin.
  • Can be given subcutaneously.