ANTICOAGULANT AND TREATMENT FOR BLEEDING

PHARMACOLOGY 2
PCH502|UNIVERSITY OF THE IMMACULATE CONCEPTION| JR UMBANA MIDTERM
DRUGS USED IN COAGULATION DISORDERS S
o DEEP VENOUS THROMBI  severe swelling & pain of
INTRODUCTION affected extremity
HEMOSTASIS o PULMONARY EMBOLISM  clot travels as an embolus
refers to the finely regulated dynamic process of maintaining through right side of heart & into pulmonary arterial
fluidity of the blood, repairing vascular injury, and limiting circulation
blood loss while avoiding vessel occlusion (thrombosis) and SUMMARIZED PLATELET RESPONSE TO VASCULAR INJURY
inadequate perfusion of vital organs. (LIPPINCOTT)
A. RESTING PLATELETS
THROMBOSIS  Platelets acts as vascular sentries  circulate freely
formation of an unwanted clot within a blood vessel  Prostacyclin (Prostaglandin I2)
most common abnormality of hemostasis o Synthesized by endothelial cells
o Inhibitor of platelet aggregation
Bleeding disorders related to the failure of hemostasis are less o Binds to platelet membrane receptor  ↑ cAMP = ↓
common than thromboembolic disorders Ca2+ = platelet aggregation prevention
o DAMAGED ENDOTHELIAL CELLS  ↓ Prostacyclin 
THROMBOTIC DISORDERS platelet aggregation
 Acute Myocardial Infarction  THROMBIN, THROMBOXANES, COLLAGEN  can bind to
 Deep Vein Thrombosis platelet membrane receptors  stimulation of platelet
 Pulmonary Embolism aggregation
 Acute Ischemic Stroke B. PLATELET ADHESION

BLEEDING DISORDER & TREATMENTS
 Hemophilia A  RECOMBINANT FACTOR VIII
 Vit K deficiency  Vit K
Bleed from surface sites
Primary Hemostasis Defects
Gingiva, skin, heavy menses
Platelet Function Defects
Von Willebrand Disease
 Endothelium injured  platelets adhere to cover exposed
Bleed into deep tissues
Secondary Hemostasis Defects
Joints, muscle, retroperitoneum collagen & von Willebrand factor  platelet activation
Hemophilia A Deficiency of Factor VIII C. PLATELET ACTIVATION
Hemophilia B Deficiency of Factor IX  Platelet release after adhesion in collagen:
o Thromboxane A2 (TXA2) vasoconstrictor
o Adenosine Diphosphate (ADP)
COAGULATION o Serotonin  vasoconstrictor
 AKA “clotting” o Platelet Activation factor
 process by which blood changes from a liquid to a gel, o Thrombin
forming a blood clot  These signaling molecules bind to receptors in the outer
 blood coagulates due to transformation of soluble membrane of resting platelets circulating nearby
fibrinogen into insoluble fibrin by the enzyme Thrombin. D. PLATELET AGGREGATION
 THROMBUS  clot that adheres to a vessel wall  release of platelet
 EMBOLUS  intravascular clot that floats in the blood granules containing
 ARTERIAL THROMBOSIS  rendered by thrombogenic mediators, such as ADP
atherosclerosis; High shear force environment of arteries and serotonin that
o Aka PLATELET-RICH CLOT or WHITE THROMBI activate other platelets
o OCCLUSIVE ARTERIAL THROMBI  can produce  activation of
ischemia of extremities or vital organs thromboxane A2
 VENOUS THROMBOSIS  triggered by blood stasis or synthesis
inappropriate activation of the coagulation cascade;  activation/conformation
o Aka FIBRIN-RICH or RED THROMBI change of glycoprotein {GP) αIIb βIII integrin (IIb/IIIa)



ALLEN GABE LOQUIAS | BS PHARMACY 2B

, PHARMACOLOGY 2
PCH502|UNIVERSITY OF THE IMMACULATE CONCEPTION| JR UMBANA MIDTERM
receptors  enabling it to bind FIBRINOGEN – cross links S
adjacent platelets  platelet aggregation
 each activated platelet can recruit other platelets




BLOOD COAGULATION CASCADE
THE TISSUE FACTOR VIIa COMPLEX PATHWAY
 Main initiator of blood coagulation in vivo by the EXTRINSIC
PATHWAY
E. CLOT FORMATION  EXTRINSIC PATHWAY (PT) begins when there is injury to
 activation of coagulation system cascade  THROMBIN the endothelial tissue (i.e., skin tissue), exposing tissue
generation and FIBRIN CLOT factor (factor III) to the blood.
 THROMBIN - serine protease, catalyzes the hydrolysis of  Tissue factor then becomes bound with calcium and factor
fibrinogen to fibrin & activate Factor XIII VIIa to activate factor X.
o Also exerts anticoagulant effects by activating the  Factor VII is present in the blood and requires vitamin K to
protein C pathway be activated.
 FACTOR XIII – a transaminase that cross-links fibrin polymer STEPS:
and stabilizes clot 1. Exposure of TF on damaged endothelium or blood that
F. FIBRINOLYSIS has extravasated into tissue
 Process of fibrin digestion (proteolytic) 2. TF binds to factor VIIa to form a complex
 PLASMIN  a serine protease responsible for degrading 3. TF-VIIa Complex activate factor X & IX
fibrin clots 4. Xa + Va + Ca2+ forms Prothrombinase complex -
 PLASMINOGEN  inactive form catalyze conversion of Prothrombin (factor II) to
 PLASMINOGEN ACTIVATOR (t-PA)  converts plasminogen Thrombin (factor IIa)
to plasmin 5. Thrombin amplifies clot by activating factors V, VIII, XI
 ACTIVATORS: (INTRINSIC FACTORS)
o Tissue plasminogen activator
o Urokinase
o streptokinase
 NEGATIVE REGULATORS:
o Plasminogen activator inhibitor
o α2 antiplasmin
 DISSEMINATED INTRAVASCULAR COAGULATION (DIC)
o excessive generation of thrombin and fibrin in the
circulating blood
o Tx = control underlying disease INTRINSIC PATHWAY
 AMINOCAPROIC ACID  FIBRINOLYSIS INHIBITOR  Involves factors 12, 11, 9, 8
 begins when factor XII or the Hageman factor is exposed to
collagen, kallikrein, and high molecular weight kininogen
(HMWK) and is subsequently activated

ALLEN GABE LOQUIAS | BS PHARMACY 2B