Components OF Normal Hemostasis PDF

Preview

Summary

COMPONENTS OF NORMAL HEMOSTASIS Endothelium Platelets Coagulation cascade Fibrinolysis Endothelial cells secretes plasminogen activator inhibitors(PAIS ) which depress fibrinolysis thus promoting thrombosis Platelets When circulating are smooth discs They contain two specific types of granules: alph...

Description

COMPONENTS OF NORMAL HEMOSTASIS    

Endothelium Platelets Coagulation cascade Fibrinolysis



Endothelial cells secretes plasminogen activator inhibitors(PAIS ) which depress fibrinolysis thus promoting thrombosis

Platelets  When circulating are membrane-bound smooth discs  They contain two specific types of granules: alpha granules and dense granules Platelet alpha granules  Contain fibrinogen, fibronectin, factor V and VII, platelet factor 4,plateletderived growth factor B (TGF-B) Platelet activation On contact with ECM, platelets undergo 1. 2. 3.

ENDOTHELIAL ANTI-PLATELET EFFECTS Physical barrier - Prevents platelets contact with ECM  Endothelial production of prostacyclin and nitric oxide inhibits platelet adhesion to normal endothelium  Mediated by membrane-associated, heparin-like molecules and thrombomodulin and anti-thrombin III









ENDOTHELIAL FIBRINOLYTIC EFFECTS Synthesize tissue type plasminogen activation (t-PA) promoting fibrinolytic activity PROTHROMBOTIC PROPERTIES Normal endothelium produces von Willebrand factor (vWF) facilitates adhesion of platelets to ECM (no synthesize in response to injury) Tissue factor secretion by endothelium is induced by cytokines (e.g TNF, IL-1) or bacteria endotoxin - Tissue factor activates the extrinsic clotting pathway

Adhesion and shape change Secretion (release reaction) Aggregation

Platelet adhesion  Adhesion to ECM is mediated largely via interaction with vWF which acts as bridge between patelet surface receptor and exposed collagen Platelet aggregation  Which activation of coagulation cascade, thrombin is generated , causing further aggregation then platelet contraction constituting hemostatic plug  This is an irreversible “fusion” of platelet Prostaglandin balancing act  PGI2 (endothelium) - Vasodilator - Inhibits platelet aggregation  TXA2 (platelets) - Vasoconstriction - Stimulates platelet aggregation Clinical use of ASPIRIN in cardiac patients  Inhibits TXA2 synthesis by platelets  Benefits patients at risk for coronary artery thrombosis Coagulation cascade Insert pic here





Occurs in phospholipid substrate - Such ason he surface of activated platelets - Held together by calcium ions This helps localize thrombosis - To site of platelets aggregation



These changes occur in Arteries and the heart - Artherosclerosis, Aneurysm, myocardial infraction, cardiac valve lesions - Hyperviscosity syndrome, e.g. sickle cell anemia, polycythemia

Abnormal blood flow  Stasis of blood flow  More commonly a problem on the venous side leading to venous thrombosis  Can occur in the heart given atrial fibrillation

Thrombosis Pathogenesis of thrombosis

Virchow’s triad -

Endothelial injury Stasis or turbulent blood flow Blood hyper coagulability

Hypercoagulability  Any alterations of the coagulation pathways that predispose to thrombosis  Primary(genetic) or secondary (acquired) disorder Hypercoagulability mutation of factor V gene  Factor V leiden mutation is the most common inherited cause of hypercoagulability  Mutant factor V is resistant to the anticoagulant effect of activated protein C - Thus there is a functional difficiency protein C Hypercoagulability Inherited lack of other anticoagulants  Lack of protein S, protein C and antithrombin III  Patients will present with venous thrombosis and recurrent thromboembolism in adolescence and early adulthood  Factor V leiden mutation is most common

Endothelial injury  Sources include: - Severe atherosclerosis - Hypertension - Toxin products (cigarettes, homocysteine) ABNORMAL BLOOD FLOW  TURBULENCE OF BLOOD FLOW - Swirls, eddies and increased pressure are injurious

Hypercoagulability Other associations  Smocking, obesity, oral contraceptives (bcp)  Lupus ‘anticoagulant’ with lupus erythematosus (arterial and venous thrombosis) - Called an anticoagulant because it interferes with a coagulation test, artificially prolonging it - But it is not an anticoagulant. It is a procoagulant

Lupus ‘anti-coagulant’ - Not an anti-coagulant but a PROCOAGULANT Hypercoagulability  Mutation of factor V gene – factor V leiden mutation - Lead to functional deficiency of protein C - Patients will have venous thrombosis and recurrent thromboembolism  Smocking, obesity, lupus anticoagulant, etc

(test tube, hematoma) or inside (post mortem) Red Gelatinous Not attached to the vessel wall



INSERT TABLE CONDITIONS ASSOCIATED W/ AN INCREASED RISK OF THROMBOSIS PRIMARY (Genetic) o Mutations in factor V o Antithrombin III deficiency o Protein C or S deficiency o Fibrinolysis defectsgn SECONDARY (Acquired) o High risk for thrombosis 1.) Prolonged bed rest or immobilization 2.) Myocardial infarction 3.) Tissue damage (surgery, fracture, burns) 4.) Cancer 5.) Prosthetic cardiac valves 6.) DIC 7.) Lupus anticoagulant o Low risk of thrombosis 1.) Atrial fibrillation 2.) Cardiomyopathy 3.) Nephrotic syndrome 4.) Hyperestrogenic states 5.) Oral contraceptive use – injures blood vessel wall 6.) Sickle cell anemia 7.) Smoking MORPHOLOGY OF THROMBI  Thrombi develop IN THE CARDIOVASCULAR SYSTEM  Thus, bleeding into the peritoneal area, for examples, forms a blood clot- not a thrombus

Clot Platelets not involved Occurs outside vessel

Thrombus Platelets involved Occur only inside

  

vessel Red (venous), Pale (arterial) Firm Attached to the vessel wall

Lines of Zahn - Alternating pale layers of platelets & fibrin w/ darker layer of RBC’s. - Imply formation in areas of active blood flow such as in the heart, aorta or larger arteries - Venous thrombi form in a more sluggish flow zone and often lack lines of Zahn ARTERIAL THROMBI Arterial thrombi are usually occlusive Usually begin at a site of endothelial injury and grow along flow of blood Typically are firmly adherent to the injured arterial wall (atherosclerotic plaque)

CLINICAL SETTINGS FOR CARDIAC/ARTERIAL THROMBUS FORMATION  Myocardial infarction (MI)  Rheumatic heart disease  Atherosclerosis







VENOUS Venous thrombi are almost always occlusive o 85-90% of venous thrombi form in lower extremities Superficial veins of the lower extremities o Cause pain, swelling – rarely embolize o Associated w/ varicosities - Varicose Veins – abnormally dilated, tortous veins o Increased risk of infections o Increased risk of varicose ulcers Thrombin in deep leg veins (Popliteal, femoral, Iliac Veins) more likely to embolize - Thrombus from deep leg veins will detach  emboli  heart (will not lodge because of high pressure)  lungs  pulmonary embolism  instantaneous death

-

 

Thrombus from heart  emboli  systemic circulation  forming systemic embolism. Most favorite site of systemic embolism: lower extremities; second most common: upper extremities; next: internal organs About 50% are asymptomatic (formation of collaterals) May produce edema, pain and tenderness

CLINICAL SETTINGS FOR VENOUS THROMBUS FORMATION  Cardiac failure (CHF)  Trauma  Surgery  Burns  3rd term pregnancy and postpartum  Cancer o Migratory thrombophlebitis (Trousseau’s syndrome) o Cancer cells migrate to the venous system inducing inflammation, forming a thrombus in the blood vessel wall. Nagmetastasize na, nagform pa ng thrombus  Bed rest  Immobilization  CLINICAL CORRELATION: o Obstruction o Embolization

  

VASCULAR THROMBI Infective endocarditis Non-bacterial thrombotic endocarditis Verrucous endocarditis (Libman-sacks) - Lupus related

   

 

FATE OF THROMBUS Propagation and obstruction Embolization – source: thrombus Dissolution – nothing left Organization and recanalization

DISSOLUTION OF THROMBI Recent thrombi can undergo total lysis After the first 2-3hr, thrombi won’t undergo lysis o Thus the use of TPa (Tissue Plasminogen activator) is only effective in the first 1-3 hours

ORGANIZATION/RECARNALIZATION Granulation tissue followed by capillary channel formation or  May heal so totally as to leave only a small fibrous “lump” as evidence of a previous thrombus 





 

 

EMBOLISM An embolus is a detached intravascular solid, liquid or gaseous mass that is carried by the blood to a site distant from its point of origin Intravascular foreign material carried in the bloodstream to a point distant from its origin 99% are dislodges thrombus Potential consequence: ischemic necrosis (infarction) o Repeat potential. Not always, depends on the organ Rarely: bullets, fat, air, atherosclerotic fragments, tumor fragments, BM Potential consequences: o Ischemic necrosis (infarction) o

o o

Though pulmonary emboli are common and important, secondary pulmonary infarction is not common Lung is protected by a dual blood supply The brain is not so protected and gets infarcts (stroke) LIQUEFACTIVE NECROSIS

PULMONARY THROMBOEMBOLISM Generally originate from the deep leg veins Usually pass through the right heart into pulmonary vasculature  PULMONARY EMBOLUS: o “paradoxical embolism” – an embolus pass through an interarterial or intraventricular defect to gain access to the system circulation - Source: deep leg veins - Paradoxical because it came from the venous site but it will produce a systemic embolism. This will only happen if you  

  





 

 



     

have a defective heart (septal defect: atrial and ventricular septum) o Most pulmonary emboli (60-80%) are clinically silent because of small size >60% pulmonary AA obstruction usually leads to sudden death Right heart failure Embolic obstruction of medium-sized arteries may result o in hemorrhage w/o infarction because of intact bronchial circulation If bronchial circulation is compromised like in left heart failure: o Then an infarct can occur o Remember, infarction depends on the organ Multiple pulmonary emboli over time may cause pulmonary hypertension and right heart failure Initial PE increases the risk for more PE May occlude main pulmonary artery, across the bifurcation (saddle embolus) [sudden death] or pass into the smaller branching arterioles; multiple emboli may occur

SYSTEMIC THROMBOEMBOLISM Emboli traveling w/in the arterial circulation 80% arise from intracardiac mural thrombi

FAT EMBOLISM SYNDROME Microscopic fat globules derived from long bone fractures (fatty marrow), or rarely from soft tissue, trauma and burns 10% of cases are fatal Pulmonary insufficiency Neurologic symptoms Anemia Thrombocytopenia Fat globules microscopically AIR EMBOLISM Gas bubbles w/in the circulation can obstruct vascular flow to cause distal ischemic injury o Chest wall injury

o

       

Sudden atmospheric pressure changes (decompression sickness e.g. Divers)

AMNIOTIC FLUID EMBOLISM Precipitated labor – biglang lumabas yung baby Pressure in vagnal cavity will push the amniotic fluid to the uterine vessels going to the lungs Torn placental membrane – amniotic fluid release Rupture of uterine veins Infusion of amniotic fluid into maternal venous circulation Lungs show squamous cells, lanugo hair, fat from venix caseosa Pulmonary edema, diffuse alveolar damage DIC...