Thrombolytics vs Anticoagulants vs Antiplatelets (Blood Clotting)
Table of Contents
Blood Clotting (Coagulation)
Blood clotting (hemostasis) prevents excessive bleeding when a blood vessel is injured. It involves platelets, clotting factors, and vitamin K-dependent proteins.Three Stages of Blood Clotting
1. Vascular Spasm (Vasoconstriction)
- Immediate response after vessel injury
- Blood vessels constrict to reduce blood flow
- Triggered by:
- Injury to smooth muscle
- Pain reflexes
- Release of endothelin from damaged endothelial cells
2. Platelet Plug Formation (Primary Hemostasis)
- Platelet Adhesion – Platelets stick to exposed collagen (via von Willebrand Factor, vWF).
- Platelet Activation – Platelets release ADP, thromboxane A2, serotonin.
- Platelet Aggregation – More platelets clump together, forming a temporary plug.
3. Coagulation Cascade (Secondary Hemostasis)
Purpose: Stabilize the platelet plug with fibrin mesh. This involves a cascade of clotting factors, many of which are vitamin K-dependent (e.g., II, VII, IX, X).Two Pathways Converge into a Common Pathway:
- Intrinsic Pathway
- Extrinsic Pathway
- Common Pathway
Intrinsic Pathway (Slower, triggered by blood contact with collagen)
- Factors involved: XII → XI → IX → VIII → X
- Activated by: Trauma inside blood vessels
Extrinsic Pathway (Faster, triggered by tissue damage)
- Factor III (Tissue Factor, TF) + Factor VII → Activates X
- Activated by: External injury
Common Pathway
- Factor X (with Factor V) converts prothrombin (II) → thrombin (IIa).
- Thrombin converts fibrinogen (I) → fibrin (Ia).
- Fibrin forms a mesh, stabilizing the clot with Factor XIII.
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🩸 Coagulation Cascade Flow Chart
Intrinsic Pathway
Factor XII → XIIa
↓
Factor XI → XIa
↓
Factor IX → IXa
↓ + Factor VIIIa
Activates Factor X
Extrinsic Pathway
Tissue Injury
↓
Tissue Factor (TF)
↓
Factor VII → VIIa
↓
Activates Factor X
Common Pathway
Factor X → Xa
↓ + Factor Va
Prothrombin (II) → Thrombin (IIa)
↓
Fibrinogen (I) → Fibrin (Ia)
↓ + Factor XIIIa
Stable Fibrin Clot
🧬 Final Result: Fibrin mesh stabilizes the clot!
Clotting Factors & Their Dependence on Vitamin K | |||
| Factor | Name | Role | Vitamin K-Dependent? |
| I | Fibrinogen | Forms fibrin mesh |  No |
| II | Prothrombin | Converts to thrombin |  Yes |
| III | Tissue Factor (TF) | Triggers extrinsic pathway | No |
| IV | Calcium (Ca²⁺) | Required for clotting reactions | No |
| V | Labile Factor | Co-factor for X → II activation | No |
| VII | Stable Factor | Extrinsic pathway activator | Yes |
| VIII | Antihemophilic Factor | Co-factor for IX → X activation | No |
| IX | Christmas Factor | Intrinsic pathway activator | Yes |
| X | Stuart-Prower Factor | Converges both pathways | Yes |
| XI | Plasma Thromboplastin | Intrinsic pathway | No |
| XII | Hageman Factor | Starts intrinsic pathway | No |
| XIII | Fibrin Stabilizing | Strengthens fibrin clot | No |
Vitamin K-dependent factors: II, VII, IX, X (2,7,9,10)
Role of Vitamin K in Clotting
- Source: Green leafy veggies (K1), gut bacteria (K2).
- Function: Helps liver produce functional clotting factors.
- Deficiency: Leads to bleeding disorders (e.g., newborns given vitamin K shots).
Antagonists (Blood Thinners):
- Warfarin (Coumadin) – Blocks vitamin K recycling.
- Heparin – Directly inhibits thrombin & Xa.
Blood Clotting common Terminology
Primary Hemostasis
- Definition: Formation of a platelet plug at the site of vessel injury.
- Vasoconstriction (narrows the vessel).
- Platelet adhesion (via vWF binding to collagen).
- Platelet activation (release of ADP, serotonin, thromboxane A₂).
- Platelet aggregation (plug formation).
Secondary Hemostasis
- Definition: Formation of a stable fibrin clot via the coagulation cascade.
- Extrinsic pathway (fast, triggered by tissue factor/TF).
- Intrinsic pathway (slower, triggered by collagen/exposed blood vessel surfaces).
- Both converge at Factor X → thrombin → fibrin.
Fibrinogen (Factor I)
- Role: Soluble plasma protein synthesized in the liver.
- Function: Converted by thrombin into fibrin during clotting.
Fibrin
- Role: Insoluble protein threads that form the clot mesh.
- Function: Stabilizes the platelet plug (with Factor XIII cross-linking).
Prothrombin (Factor II)
- Role: Zymogen (inactive precursor) of thrombin.
- Activation: Converted by Prothrombinase (Xa + Va + Ca²⁺ + PL).
Thrombolytics (Fibrinolytics)
Thrombolytics are medications that actively break down blood clots (thrombi) by dissolving the fibrin mesh that holds them together.
They are often called fibrinolytics, since they enhance the natural process of fibrinolysis.
Thrombolytics Mechanism of Action
- Thrombolytics activate plasminogen (a precursor protein) into plasmin.
- Plasmin is an enzyme that breaks down fibrin, the structural framework of clots.
- This leads to dissolution of existing clots, restoring blood flow to blocked areas.
Thrombolytics do not prevent new clots.
- Target: Fibrin (in thrombi)
- Remember: “Thrombo” = clot, “lytic” = dissolve → Clot-dissolving agents
Thrombolytic Drug (e.g. alteplase, streptokinase)
↓
Activates plasminogen
↓
Converts it into plasmin (active enzyme)
↓
Plasmin degrades fibrin into fibrin degradation products
↓
Clot dissolves and blood flow is restored
Thrombolytics List – Brand Generic Drugs
| Generic Name | Brand Name(s) | Notes |
| Alteplase |
| Most commonly used thrombolytic; recombinant tPA (tissue plasminogen activator) |
| Reteplase | Retavase | Faster onset, slightly different structure than alteplase |
| Tenecteplase | TNKase | Longer half-life, bolus dose only |
Thrombolytics Clinical Uses
- ST-Elevation Myocardial Infarction (STEMI) – if PCI isn’t available
- Pulmonary Embolism (PE) – in hemodynamically unstable patients
- Ischemic Stroke – within 3–4.5 hours of symptom onset
- Deep Vein Thrombosis (DVT) – in select severe cases
Thrombolytics Contraindications
Avoid in patients with:
- Recent surgery or trauma
- Active bleeding
- Severe hypertension
- History of hemorrhagic stroke
- Bleeding disorders
Anticoagulants
Anticoagulants are medications that help prevent blood clots from forming or getting bigger. They’re commonly referred to as “blood thinners,” although they don’t actually thin the blood. Instead, they interfere with the blood clotting process to reduce the chance of dangerous clots that can lead to conditions like heart attacks, strokes, or deep vein thrombosis (DVT).
Think of it like making sure a traffic light stays red so that no cars (platelets and clotting factors) can rush into an intersection and cause a crash. In this case, you’re keeping blood from clotting when it shouldn’t.
Think of it like making sure a traffic light stays red so that no cars (platelets and clotting factors) can rush into an intersection and cause a crash. In this case, you’re keeping blood from clotting when it shouldn’t.
How Do Anticoagulants Work?
The body has a natural process called coagulation (or blood clotting) that helps stop bleeding when we get injured. But sometimes, this process gets out of hand, leading to unwanted clots. That’s where anticoagulants come in, they slow down or block parts of this process. Here’s how they work:1. Inhibiting Clotting Factors:
Blood clotting relies on clotting factors (like Factor Xa, Factor IIa), which are proteins in the blood that react in a chain to form a clot. Anticoagulants block these factors at different points in the chain, making it harder for the clot to form.2. Interfering with Platelet Function:
Some anticoagulants help prevent platelets (the tiny blood cells responsible for sticking together and forming clots) from sticking to each other.Types of Anticoagulants and Their Mechanism of Action
1. Heparin
- How it works: Heparin increases the activity of a natural anticoagulant in the blood called antithrombin, which in turn inactivates clotting factors, particularly Factor Xa and Factor IIa (thrombin).
- Uses: It’s commonly used in the hospital setting for immediate anticoagulation (e.g., during surgery, or for DVT/PE treatment).
2. Warfarin (Coumadin)
- How it works: Warfarin blocks Vitamin K, which is essential for making certain clotting factors in the liver. Without these clotting factors, blood clotting is slowed down.
- Uses: It’s often used for people with atrial fibrillation, heart valve replacements, or deep vein thrombosis (DVT).
3. Direct Oral Anticoagulants (DOACs):
Examples: Apixaban (Eliquis), Rivaroxaban (Xarelto)
- How they work: These drugs directly inhibit Factor Xa, which is crucial for clotting. By doing so, they prevent the conversion of prothrombin into thrombin, which is necessary for clot formation.
- Uses: They’re often prescribed for stroke prevention in atrial fibrillation or the treatment of DVT/PE (pulmonary embolism).
Anticoagulants Mechanism of Action
Heparin
Heparin activates Antithrombin III, which inactivates clotting factors, especially Factor IIa (thrombin) and Xa.
↓
Inhibits Thrombin (IIa) & Factor Xa → Prevents Fibrin Formation
Warfarin
Warfarin inhibits Vitamin K epoxide reductase, reducing synthesis of Vitamin K-dependent clotting factors.
↓
↓ Factors II, VII, IX, X → ↓ Clot Formation
DOACs (e.g., Apixaban, Rivaroxaban, Dabigatran)
DOACs directly inhibit specific clotting factors: Factor Xa (apixaban, rivaroxaban) or Thrombin (dabigatran).
↓
↓ Thrombin or Xa Activity → ↓ Fibrin Clot Formation
Anticoagulants List – Brand Generic Drugs
| Generic Name | Brand Name | MOA – Class Type |
| Warfarin | Coumadin, Jantoven | Vitamin K Antagonist |
| Heparin (UFH) | — | Unfractionated Heparin |
| Enoxaparin | Lovenox | Low Molecular Weight Heparin (LMWH) |
| Dalteparin | Fragmin | Low Molecular Weight Heparin (LMWH) |
| Rivaroxaban | Xarelto | Direct Factor Xa Inhibitor (DOAC) |
| Apixaban | Eliquis | Direct Factor Xa Inhibitor (DOAC) |
| Edoxaban | Savaysa | Direct Factor Xa Inhibitor (DOAC) |
| Betrixaban | Bevyxxa | Direct Factor Xa Inhibitor (DOAC) |
| Dabigatran | Pradaxa | Direct Thrombin Inhibitor (DOAC) |
| Argatroban | — | Parenteral Direct Thrombin Inhibitor |
| Bivalirudin | Angiomax | Parenteral Direct Thrombin Inhibitor |
| Desirudin | Iprivask | Parenteral Direct Thrombin Inhibitor |
- Unfractionated Heparin (UFH): Used for immediate anticoagulation in conditions like DVT, PE, and during surgeries or dialysis.
- Low Molecular Weight Heparin (LMWH): Commonly used for prevention and treatment of venous thromboembolism and in acute coronary syndromes.
- Direct Factor Xa Inhibitors: Used to prevent stroke in atrial fibrillation and treat or prevent DVT and PE.
- Direct Thrombin Inhibitor: Used for stroke prevention in non-valvular atrial fibrillation and treatment of HIT or VTE.
Anticoagulants Clinical Uses
- Deep Vein Thrombosis (DVT) prevention and treatment
- Pulmonary Embolism (PE)
- Stroke prevention in atrial fibrillation
- Post-surgical thromboprophylaxis (after hip or knee replacement)
- Acute Coronary Syndromes (ACS)
- Mechanical heart valves (especially Warfarin)
- Treatment of heparin-induced thrombocytopenia (HIT)
- Venous thromboembolism (VTE)
Anticoagulants Contraindications
- Active bleeding or high risk of bleeding
- Severe uncontrolled hypertension
- Recent hemorrhagic stroke
- Severe liver disease (affecting clotting factor production)
- Thrombocytopenia (especially with heparin)
- Hypersensitivity to the drug
- Pregnancy (some agents like Warfarin are contraindicated)
- Recent major surgery or trauma
Antiplatelets
Antiplatelet medications prevent blood clot formation by inhibiting platelet aggregation. Platelets are crucial in the early stages of clotting, so preventing them from clumping together helps reduce the risk of heart attacks, strokes, and other thrombotic events, especially in individuals with cardiovascular disease.
Types of Antiplatelets and Their Mechanism of Action
1. COX Inhibitors (e.g., Aspirin)
Mechanism:
- Aspirin irreversibly inhibits cyclooxygenase-1 (COX-1) enzyme in platelets.
- This blocks the synthesis of thromboxane A2 (TXA2), a molecule that promotes platelet aggregation and vasoconstriction.
P2Y12 Inhibitors (e.g., Clopidogrel, Prasugrel, Ticagrelor)
Mechanism:
- Block the P2Y12 receptor on platelets, preventing the activation of GP IIb/IIIa and inhibiting platelet aggregation.
- Ticagrelor reversibly inhibits P2Y12, while others like Clopidogrel are irreversible.
GP IIb/IIIa Inhibitors (e.g., Abciximab, Eptifibatide)
Mechanism:
- Block the GP IIb/IIIa receptor on activated platelets, preventing fibrinogen from binding, which is essential for platelet aggregation.
Phosphodiesterase (PDE) Inhibitors (e.g., Dipyridamole, Cilostazol)
Mechanism:
- Inhibit phosphodiesterase enzymes, leading to increased intracellular cAMP levels, which reduces platelet aggregation and promotes vasodilation.
Antiplatelet Mechanisms of Action
Flow Chart
1. COX Inhibitors
Mechanism: Inhibit cyclooxygenase-1 (COX-1) → ↓ Thromboxane A₂ (TXA₂) production
- Aspirin (Irreversible COX-1 inhibition)
Key Points:
- Irreversible platelet inhibition lasts 7-10 days (platelet lifespan)
- Low-dose (81mg) preferred for cardiovascular prevention
- Contraindicated in children with viral infections (Reye's syndrome risk)
↓
2. P2Y12 Inhibitors
Mechanism: Block ADP receptors on platelets → ↓ Activation & aggregation
- Clopidogrel (Prodrug, irreversible)
- Prasugrel (More potent irreversible)
- Ticagrelor (Reversible, direct-acting)
- Cangrelor (IV, rapid-onset)
Key Points:
- Often used with aspirin for dual antiplatelet therapy (DAPT)
- Clopidogrel requires CYP450 activation (check for poor metabolizers)
- Ticagrelor requires twice-daily dosing (but faster onset)
↓
3. GP IIb/IIIa Inhibitors
Mechanism: Block fibrinogen binding to GP IIb/IIIa receptors → ↓ Platelet cross-linking
- Abciximab (Monoclonal antibody, IV)
- Eptifibatide (Peptide inhibitor, IV)
- Tirofiban (Small molecule, IV)
Key Points:
- Used in acute coronary syndromes and PCI
- High bleeding risk - monitor aPTT and platelets
- Abciximab has longest half-life (12-24h platelet recovery)
↓
4. Phosphodiesterase (PDE) Inhibitors
Mechanism: ↑ cAMP → ↓ Calcium mobilization → ↓ Platelet activation
- Cilostazol (PDE3 inhibitor, vasodilator)
- Dipyridamole (PDE5 inhibitor + adenosine uptake blocker)
Key Points:
- Cilostazol used for claudication (improves walking distance)
- Dipyridamole often combined with aspirin for stroke prevention
- Both can cause headache (vasodilation side effect)
↓
Final Antiplatelet Effect
↓ Platelet adhesion/activation/aggregation → ↓ Thrombus formation
Clinical Considerations:
- Balance bleeding vs. thrombosis risk
- DAPT duration varies by indication (e.g., 1-12 months post-PCI)
- Always assess for drug interactions (especially with warfarin/NSAIDs)
Antiplatelets List – Brand Generic Drugs
| Class | Generic Name | Brand Name |
| COX Inhibitor | Aspirin |
|
P2Y12 Inhibitor | Clopidogrel | Plavix |
| Prasugrel | Effient | |
| Ticagrelor | Brilinta | |
| Cangrelor | Kengreal | |
GP IIb/IIIa Inhibitor | Abciximab | ReoPro |
| Eptifibatide | Integrilin | |
| Tirofiban | Aggrastat | |
Phosphodiesterase Inhibitor (PDE) | Dipyridamole | Persantine |
| Dipyridamole + Aspirin | Aggrenox | |
| Cilostazol | Pletal |
Antiplatelets Clinical Uses
| Mnemonics | Clinical Use | Purpose | Examples of Drugs Used |
| P | Prevention of Myocardial Infarction (MI) | Prevent new or recurrent heart attacks in high-risk patients | Aspirin, Clopidogrel, Prasugrel, Ticagrelor |
| A | Acute Coronary Syndrome (ACS) | Reduce risk of clot formation during/after ACS events | Aspirin + P2Y12 Inhibitor (e.g., Clopidogrel, Ticagrelor) |
| P | Post-Percutaneous Coronary Intervention (PCI) | Prevent stent thrombosis | Dual antiplatelet therapy (DAPT): Aspirin + Clopidogrel/Prasugrel/Ticagrelor |
| S | Stroke & Transient Ischemic Attack (TIA) Prevention | Reduce risk of ischemic stroke or recurrent TIA | Aspirin, Clopidogrel, Aggrenox (Aspirin + Dipyridamole) |
| M | Mechanical Heart Valves (Adjunct) | May be used with anticoagulants for enhanced clot protection | Aspirin |
| A | Atrial Fibrillation (non-valvular, low-risk patients) | Stroke prevention (if anticoagulants are contraindicated) | Aspirin ± Clopidogrel (less common now due to newer anticoagulants) |
| P | Peripheral Arterial Disease (PAD) | Improve circulation, prevent cardiovascular events | Cilostazol, Aspirin, Clopidogrel |
| S | Secondary Prevention in Cardiovascular Disease | Ongoing therapy after heart attack, stroke, or vascular intervention |
Aspirin or Clopidogrel long-term |
- Dual Antiplatelet Therapy (DAPT): Aspirin + P2Y12 inhibitor (e.g., Clopidogrel)
- Mnemonic : “PAPS MAPS“
Antiplatelets Contraindications
- Active bleeding (e.g., GI, intracranial)
- Bleeding disorders (e.g., hemophilia)
- Severe liver disease (due to clotting factor synthesis issues)
- Hypersensitivity to specific drug or class
- Severe thrombocytopenia (low platelet count in blood)
