1. Direct Xa inhibitors: directly inhibit Xa without acting through antithrombin. Renally cleared!
- Rivaroxaban (xarelto)
- Apixaban (eliquis) - 40% renally eliminated
2. Heparins: work by activating antithrombin III, and can inactivate both Xa and thrombin. To inactivate Xa all it needs is the pentassacharide (i.e. fonda), but to inactivate thrombin you need the long tail, hence only Unfractionaed heparin and lovenox are capable.
- UFH - hepatic and endothelial elimination, OK in CKD
- Lovenox - all renal metabolism! Must reduce dose for CKD (function of GFR... I think its at GFR 30-60 where you reduce the dose from 40 to 30 and maybe less than that you can't use it?)
- Fonda - renal, dose reduce in CKD
3. Direct thrombin inhibitors: exactly what it sounds like... directly inhibits thrombin... These are the drugs typically used to manage HIT
Bivalent (all injectables only- IV, IM, SubQ)
- Lepirudin - renally metabollzed
- Bivalrudin - renally metabolized... concentration linearly related to GFR... must reduce dose
- Hirudin
Monovalent
- Argatroban - HEPATIC metabolism
- Dabigatran - 80% renally eliminated
4. P2Y-12 receptor blockers: 
- Clopidogrel
- Prasugrel
- Ticagrelor
5. GP IIb/IIIa inhibitors
- Abciximab
6. Vitamin K antagonists
- Coumadin - CYP 2C9 (S enantiomer - 3-5x more potent) and CYP3A4 (R enantiomer)
- Metabolism affected by vitamin K epoxide reductase subunit 1 (VKOR1) mutations {Nature 2004}
7. Excellent paper in Circulation about the use of antiplatelets and anticoagulants in ESRD including this lovely figure:

8. Aminocaprioc Acid 

- Treats bleeding post op - esp cardiac surgery

- Also treats bleeding complications after tPA

- I've also seen it prophylactically used in patients with inherited platelet clotting deficiencies who needed neurosurgery 

9. Management of essential thrombocytosis

- Emergent - platelet pharesis

- Long term - hydroxyurea (3-4% risk of developing acute leukemia with long term hydroxyurea use) mechanism of action - inhibits ribonucleotide reductase, inhibits DNA synthesis - causing S-phase arrest. Also inhibits repair of cells damaged by radiation or chemicals!! That's why. CANNOT use in pregnancy/nursing - category D - evidence of harm

- Long term - anegrolide - inhibits maturation of platelets from megakaryocytes. Cannot use during pregnancy/nursing 

- Interferon-a

- Low dose widely used, but some risk of increased bleeding if the platelet count is very high - the cutoff is 1-1.5 million

10. Hydroxyurea for sickle cell disease 

- shown to increase HbF relative to HbS

- this paper lists a number of theorized mechanisms, including cytotoxic preference for more mature cells, leaving more immature cells alive; altering transcription pathways, etc

- Cannot use during pregnancy/nursing - pregnancy category D. This is basically a chemotherapy agent. 

- Has been shown to improve survival, as well as improve symptoms.