STEPTRACKERPHARMACOLOGY + HEMATOLOGY | HEMATOLOGY | HIGH-YIELD REVIEW

Anticoagulants

Every anticoagulant targets thrombin, factor Xa or vitamin K–dependent synthesis — and each has its own lab test, reversal agent and signature complication.

FOCUS ON
Unfractionated heparin: activates antithrombin → inhibits thrombin (IIa) and Xa; IV, rapid onset; monitor aPTT; reverse with protamine; safe in pregnancy and renal failure; HIT (anti-PF4/heparin IgG, platelets ↓ > 50% at 5–10 days, thrombosis) → stop heparin, start argatroban. LMWH (enoxaparin): mainly anti-Xa; SC; renally cleared; partial protamine reversal. Fondaparinux: Xa via antithrombin. Warfarin: inhibits vitamin K epoxide reductase (VKORC1) → ↓ II, VII, IX, X, protein C, S; monitor PT/INR; slow onset (bridge with heparin); skin necrosis (early protein C drop), teratogenic, many CYP interactions; reverse with vitamin K + 4-factor PCC. DOACs: rivaroxaban, apixaban, edoxaban (Xa → andexanet alfa), dabigatran (thrombin → idarucizumab). Direct thrombin IV: argatroban (hepatic), bivalirudin.
DRUG
TARGET
MONITOR · REVERSAL
KEY POINTS
Unfractionated heparin
Antithrombin → IIa and Xa (also IX, XI, XII)
aPTT · protamine sulfate
ACS, PE, DVT, pregnancy, dialysis; HIT, osteoporosis (long term), hyperkalemia
Enoxaparin · dalteparin
Antithrombin → mostly Xa
Anti-Xa level (obese, renal, pregnancy) · protamine partial
SC, predictable; avoid if CrCl < 30; lower HIT risk
Fondaparinux
Antithrombin → Xa only (synthetic pentasaccharide)
None routine · no specific reversal
HIT-safe option for prophylaxis
Warfarin
VKORC1 inhibition → no γ-carboxylation of II, VII, IX, X, C, S
PT/INR (2–3) · vitamin K, 4-factor PCC (or FFP)
Mechanical valves, AF; teratogenic; skin necrosis; CYP2C9 interactions
Rivaroxaban · apixaban · edoxaban
Direct factor Xa inhibitors
Anti-Xa (not routine) · andexanet alfa, PCC
AF, VTE; no INR checks; avoid in mechanical valves, APS
Dabigatran
Direct oral thrombin inhibitor
Thrombin time · idarucizumab
Dyspepsia, GI bleeding; renally cleared
Argatroban
IV direct thrombin inhibitor
aPTT
HIT (hepatic clearance); falsely ↑ INR
Bivalirudin
IV direct thrombin inhibitor (hirudin analog)
aPTT / ACT
PCI, HIT
Heparin-induced thrombocytopenia
IgG to PF4–heparin → platelet activation
Stop all heparin · argatroban, bivalirudin, fondaparinux
Thrombosis despite low platelets; no platelet transfusion
Warfarin skin necrosis
Protein C (short half-life) falls first → transient hypercoagulability
Prevent with heparin bridge
Risk with protein C deficiency
Warfarin interactions
↑ INR: azoles, macrolides, metronidazole, TMP-SMX, amiodarone, acute alcohol · ↓ INR: rifampin, carbamazepine, vitamin K foods
—
Check INR after any new drug
Heparin vs warfarin
Heparin: large, charged, doesn't cross placenta · warfarin: small, lipid-soluble, crosses
—
Pregnancy → LMWH

Picture it — where anticoagulants hit the cascade

intrinsicextrinsicXIIXIIXTF·VIIXIIIIaXafibrinogen → fibrinplasminogen → plasminlysesanti-Xa: -xabans · LMWH ·fondaparinux · heparin (via AT)anti-IIa: dabigatran,argatroban, bivalirudin,heparin (via AT)alteplase activates · tranexamic acid blocksvitamin K–dependent: warfarin blocks synthesis(also proteins C and S)
Coagulation targetsHeparins work through antithrombin on Xa and thrombin (IIa); LMWH and fondaparinux favor Xa. The -xabans block Xa directly; dabigatran, argatroban and bivalirudin block thrombin directly. Warfarin stops the liver making factors II, VII, IX and X (gold). Thrombolytics boost plasmin; tranexamic acid blocks it.

Schematic diagrams, not to scale.

Mechanism — why warfarin is briefly prothrombotic

Warfarin stops new synthesis
→
Protein C (t½ ~8 h) and VII fall first
→
II and X still presentNet clotting tendency
→
Skin necrosis risk → bridge with heparin

Heparin vs LMWH vs warfarin

FEATURE
UFH
LMWH
WARFARIN
Route
IV/SC
SC
Oral
Onset
Immediate
Fast
Days
Lab
aPTT
Anti-Xa
PT/INR
Reversal
Protamine
Protamine (partial)
Vit K, PCC
Renal failure
OK
Avoid
OK

How it's tested

COMMON CONFUSIONThe extrinsic pathway (factor VII, shortest half-life) is hit first by warfarin — so PT rises first; heparin acts on the intrinsic/common pathways (aPTT).
THE TRAPPlatelets fall on day 7 of heparin with a new DVT → HIT: stop heparin (including flushes) and start a direct thrombin inhibitor; don't give warfarin until platelets recover.
YOUR APPROACHIdentify the drug → target factor → lab → reversal → special population (pregnancy, renal, valves).

If you see… think…

Platelets halve 5–10 days after heparin, new thrombosis → HIT
Painful skin necrosis on day 3 of warfarin → protein C deficiency effect
Heparin overdose → protamine
Dabigatran bleed → idarucizumab
Apixaban or rivaroxaban bleed → andexanet alfa
Warfarin with major bleeding → vitamin K + 4-factor PCC
Anticoagulant in pregnancy → LMWH
Mechanical heart valve → warfarin (not DOACs)
HIT in a patient with liver disease → bivalirudin (argatroban is hepatic)
INR jumps after starting TMP-SMX → CYP2C9 inhibition + albumin displacement