How hemostasis is tested on Step 1

Follow the steps from injury to stable clot.

VasoconstrictionReflex spasm and endothelin reduce blood flowAdhesionvWF binds exposed collagen and platelet GpIbActivationPlatelets release ADP and TXA2, change shapeAggregationFibrinogen links GpIIb/IIIa on neighboring plateletsCoagulationFactor cascade makes thrombin → fibrin meshStabilizationFactor XIIIa cross-links fibrin
Hemostasis. Fibrinolysis follows: tPA converts plasminogen to plasmin, which breaks fibrin into D-dimers.

The coagulation cascade and lab tests

Each test measures one arm plus the common pathway.

PT / INRExtrinsic + common pathwayFactor VII (shortest half-life)Prolonged by warfarinProlonged by vitamin K deficiency, liverdiseaseFactors VII, X, V, II, fibrinogenPTTIntrinsic + common pathwayFactors XII, XI, IX, VIIIProlonged by unfractionated heparinProlonged in hemophilia A and BLupus anticoagulant prolongs it in vitrovs
PT vs PTT. Factor VII falls first when vitamin K is lacking, so PT rises before PTT.
  • Antithrombin: inhibits thrombin and factors Xa, IXa, XIa; heparin speeds it up.
  • Proteins C and S: vitamin K–dependent; activated protein C inactivates factors Va and VIIIa. Factor V Leiden resists it.
  • Tissue factor pathway inhibitor: limits the extrinsic pathway.

Anticoagulant, thrombolytic, and antiplatelet drugs

Know the target, the monitoring test, and the reversal.

DrugTargetMonitoringReversal
Unfractionated heparinAntithrombin → thrombin and XaPTTProtamine
Low-molecular-weight heparin (enoxaparin)Antithrombin → mainly XaAnti-Xa level (rarely)Protamine (partial)
WarfarinVitamin K epoxide reductasePT/INRVitamin K; prothrombin complex concentrate
Apixaban, rivaroxabanFactor XaNot routineAndexanet alfa
DabigatranThrombinNot routineIdarucizumab
Argatroban, bivalirudinThrombin (IV)PTTNone specific; used in HIT
Alteplase (tPA)Plasminogen → plasmin—Aminocaproic acid, tranexamic acid
AspirinIrreversible COX-1 → ↓ TXA2—Platelet transfusion
Clopidogrel, prasugrelP2Y12 ADP receptor—Platelet transfusion
Eptifibatide, abciximabGpIIb/IIIa—Stop infusion

Warfarin is teratogenic; heparin does not cross the placenta and is used in pregnancy.

Adverse effects to know

Each drug has a signature complication.

  • Heparin-induced thrombocytopenia: antibodies to heparin–platelet factor 4 cause low platelets and clots 5–10 days after starting heparin.
  • Warfarin skin necrosis: protein C falls faster than the clotting factors, creating a brief hypercoagulable state; bridge with heparin.
  • Warfarin interactions: CYP2C9 inhibitors raise INR; inducers lower it.

Worked example

Explain why bridging is needed.

functions Worked example — painful skin after starting warfarin

Three days after starting warfarin alone for a DVT, a patient develops painful purple skin patches on the thighs that turn black. What happened, and how could it have been prevented?

  1. Warfarin lowers all vitamin K–dependent proteins, but at different speeds.
  2. Protein C has a short half-life, so it falls before factors II, IX, and X.
  3. For a few days, anticoagulant protein C is low while clotting factors remain, causing microvascular thrombosis.
  4. Starting heparin together with warfarin (bridging) until the INR is therapeutic prevents this.

Answer. Warfarin-induced skin necrosis from early protein C depletion; bridge with heparin.