HIT Type 2
Heparin-Induced Thrombocytopenia: Antibodies to Platelet Factor 4 (PF4)-heparin complex; > 50% drop in platelets at day 5–10; paradoxically THROMBOGENIC. Stop heparin -> start Argatroban.
Warfarin Skin Necrosis
Protein C has short half-life (6 hrs); initiating Warfarin without Heparin bridge causes transient hypercoagulable state and microvascular thrombosis.
Reversal Agents
Heparin: Protamine sulfate. Warfarin: 4-Factor PCC + IV Vitamin K. Dabigatran: Idarucizumab. Factor Xa inhibitors (Apixaban/Rivaroxaban): Andexanet alfa.
Anticoagulant Drugs Master Comparison
Anticoagulants block specific coagulation cascade factors to prevent thrombus propagation:
| Anticoagulant Class | Specific Drugs | Target Factor & Monitoring | Clinical Role & Reversal Protocol |
|---|---|---|---|
| Unfractionated Heparin (UFH) | Heparin | Activates Antithrombin III → inactivates Thrombin (IIa) and Xa equally; Monitor PTT (goal 1.5–2.5× control) | Immediate anticoagulation for PE, DVT, ACS; preferred in renal failure (hepatic clearance); Reversal: Protamine sulfate |
| Low Molecular Weight Heparin (LMWH) | Enoxaparin, Dalteparin | Activates Antithrombin III → predominantly inhibits Factor Xa; no routine monitoring (anti-Xa in pregnancy/obesity) | Outpatient DVT/PE treatment, prophylaxis; renal clearance (contraindicated in severe CKD); Partial reversal with Protamine |
| Direct Factor Xa Inhibitors (DOACs) | Apixaban (Eliquis), Rivaroxaban (Xarelto), Edoxaban | Directly bind and inhibit Factor Xa; oral route; no monitoring required | First-line for non-valvular AFib and DVT/PE; rapid onset/offset; Reversal: Andexanet alfa |
| Direct Thrombin Inhibitors | Oral: Dabigatran (Pradaxa); IV: Argatroban, Bivalirudin | Directly bind active catalytic site of Thrombin (Factor IIa); Argatroban cleared hepatically | Argatroban is drug of choice for Heparin-Induced Thrombocytopenia (HIT); Dabigatran reversal: Idarucizumab |
| Vitamin K Antagonist | Warfarin (Coumadin) | Inhibits VKORC1 (Vitamin K epoxide reductase) → blocks gamma-carboxylation of factors II, VII, IX, X, Protein C and S; Monitor PT/INR (goal 2.0–3.0) | Mechanical heart valves, antiphospholipid syndrome; teratogenic (bone defects); Emergency reversal: 4-Factor PCC (Kcentra) + IV Vitamin K |
Antiplatelet Agents & Fibrinolytic Clot Busters
Antiplatelets target initial platelet plug formation, while fibrinolytics dissolve existing fibrin meshes:
| Agent Class | Drugs | Mechanism of Action | Key Indications & Clinical Pearls |
|---|---|---|---|
| Cyclooxygenase Inhibitor | Aspirin | Irreversibly acetylates COX-1 → blocks TXA2 synthesis for platelet lifespan (7–10 days) | Secondary stroke/CAD prevention, acute ACS; low-dose 81 mg inhibits TXA2 without significantly reducing endothelial prostacyclin |
| ADP / P2Y12 Receptor Blockers | Clopidogrel, Ticagrelor, Prasugrel | Irreversibly (Clopidogrel, Prasugrel) or reversibly (Ticagrelor) block ADP P2Y12 receptors → ↓ GPIIb/IIIa activation | Dual Antiplatelet Therapy (DAPT) post-stent; Clopidogrel is a prodrug requiring activation by CYP2C19 |
| GPIIb/IIIa Antagonists | Abciximab, Eptifibatide, Tirofiban | Block GPIIb/IIIa receptor, preventing fibrinogen bridging between platelets | Unstable angina, percutaneous coronary intervention; Abciximab is a chimeric monoclonal Fab fragment; risk of acute severe thrombocytopenia |
| Tissue Plasminogen Activators (tPA) | Alteplase, Reteplase, Tenecteplase | Converts plasminogen to plasmin, which cleaves cross-linked fibrin meshes | Acute ischemic stroke (< 4.5 hours), massive pulmonary embolism with shock, acute STEMI if PCI unavailable; Reversal: Aminocaproic acid or Tranexamic acid |
Board Traps & Common Distractors
- In Heparin-Induced Thrombocytopenia (HIT), platelets drop > 50% and paradoxically cause massive arterial and venous thrombosis; NEVER transfuse platelets (fuels the fire) and NEVER give Warfarin until platelets recover (causes gangrene). Switch immediately to Argatroban.
- Warfarin must ALWAYS be co-administered with a fast-acting anticoagulant (Heparin or LMWH) for at least 5 days and until INR is therapeutic for 2 consecutive days to avoid Warfarin-induced skin necrosis.
- Alteplase (tPA) for acute ischemic stroke is strictly contraindicated if BP > 185/110 mmHg, recent surgery/head trauma within 3 months, active bleeding, or INR > 1.7.