ASPIRIN ↓ Cox inhibition ↓ (PROSTACYCLIN) PGI 2 & TXA 2 (THROMBOXANE) LOW DOSE ASPIRIN

1)PREVENT ARTERIAL THROMBOSIS IHD, STROKE 2) UNSTABLE ANGINA 3) RECENT MI 4) TIA 5) ARIFICIAL VALVES

6) PTCA 7) PERIPHERAL ARTERIAL OCCLUSIVE DISEASE 8) CHRONIC LIMB ISCHEMIA

Aspirin ADR

DIPYRIDAMOLE - VASODILATOR - THALLIUM IMAGING - INHIBIT PLATELET ADHESION TO VESSEL WALL ↑ cAMP ↓ PLATELET CALCIUM INHIBIT AGGREGATION + ASPIRIN – STROKE, TIA ? SUPERIOR

CLOPIDOGREL & TICLOPIDINE INHIBIT ADP – INDUCED EXPRESSION OF PLATELET GP RECEPTORS ↓ DECREASE FIBRINOGEN BINDING ↓ DECREASE PLATELET AGGREGATION

CLOPIDOGREL → PRODRUG, TICLOPIDINE → NEUTROPENIA ↓ CBC – 2 WEEKS UPTO 3 MONTHS

THROMBOTIC STROKE SICKLE CELL ANEMIA ACS INTERMITTENT CLAUDICATION PCI CHRONIC ARTERIAL OCCLUSION OPEN HEART SURGERY AV SHUNT

ABCIXIMAB - PCI + Aspirin & Heparin - in MI - Bleeding, thrombocytopenia, hypotension, Brady cardia

TIROFIBAN & EPTIFIBATIDE - Competitive, reversible inhibitors of fibrinogen binding to GPII b / III a - ACS – unstable angina, NSTEMI - Angioplasty & stenting - Bleeding

FIBRINOLYTICS: Streptokinase Alteplase Urokinase Reteplase Anistreplase Tenecteplase

Streptokinase 1.5 million units over 60 min Alteplase 15mg bolus 0.75mg/1kg – 30 min 0.5mg/kg- 60 min

Reteplase – 10mg bolus 10mg after 30min Tenecteplase – IV bolus 0.5 mg /kg

Coagulation factor concentrates Desmopressin

HEMOSTATIC AGENTS: ε - Aminocaproic acid Aprotinin TOPICAL ABSORBABLE: Thrombin Microfibrillar collagen hemostat Absorbable gelatin Oxidized cellulose

THROMBOLYTIC THERAPY ADV- Availability, rapid administration DISADV – Intracranial hemorrhage - Uncertainty of whether normal coronary flow has been restored - Reocclusion

-Most effective within 12 hour (relative mortality decreased by 18%) - Little benefit beyond 12 hour Not for resolved chest pain, ST segment depression

Fibrin selective agents should be used with anticoagulants – UFH, LMWH, fondraparinux & bivalirudin Monitoring of thrombolytic therapy!

Patency is 30% PCI patency 95% (TIMI 3)

Persistent angina Persistent ischemic changes on ECG <50% Reduction in ST elevation min after initiation of thrombolysis ---rescue PCI.

Routine coronary angiography & PCI within 24h of thrombolysis

Complications: Intracranial bleeding 0.7 – 0.9% Major bleeding requiring treatment 10% Venipuncture & arterial puncture.

Diagnosis of coagulation defects Prolonged APTTDefective Intrinsic Pathway No change in PT No change in APTTDefective Extrinsic Pathway Prolonged PT Prolonged APTTDefective in Common pathway Prolonged PT

Absolute C/I: 1) H/o intracranial hemorrhagic / hemorrhagic stroke 2) Ischemic stroke within 3mo 3) AVMs, aneurysms, tumor 4) Closed head injury within 3 mo 5) Aortic dissection 6) severe uncontrolled HT – SBP > 180, DBP > 110 7) Active bleeding / bleeding diathesis 8) Acute pericarditis.

Blood Vessel Injury IX IXa XI XIa X Xa XII XIIa Tissue Injury Tissue Factor Thromboplastin VIIa VII X Prothrombin Thrombin Fibrinogen Fribrin monomer Fibrin polymer XIII Intrinsic PathwayExtrinsic Pathway Factors affected By Heparin Vit. K dependent Factors Affected by Oral Anticoagulants

Thrombosis  Arterial Thrombosis : Adherence of platelets to arterial walls - White in color - Often associated with MI, stroke and ischemia  Venous Thrombosis : Develops in areas of stagnated blood flow (deep vein thrombosis), Red in color- Associated with Congestive Heart Failure, Cancer, Surgery.