MLAB 1227 Coagulation Keri BrophyMartinez

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MLAB 1227- CoagulationKeri Brophy-Martinez

• Thrombosis

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Thrombosis

• Imbalances between clotting activity and
  fibrinolytic processes
• Causes increased tendency to form thrombi
• Involves the naturally occurring inhibitors of
  coagulation (those that control the amount of
  clotting) where the clots can form, but
  uncontrollably
• More than one hemostatic defect or abnormality
  increases risk

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Terms

• Hypercoagulation more clotting activity than
  normal
• Thrombosis formation of platelet and/or fibrin
  mass in a vessel
• Thrombus fibrin mass consisting of fibrin,
  platelets and trapped cells
• Embolus piece of thrombotic material
• Embolism obstruction in circulatory system
  caused by embolus

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Terms cont

• Plaque consists of lipids, fibrous connective
  tissue, macrophages and smooth muscle cells
• Thrombophlebitis thrombus of superficial veins
  of legs self-limiting and benign
• Deep vein thrombosis involvement of deep veins
  of legs
• Thrombophilia any disorder associated with an
  increased tendency to cause venous thromboembolism

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Thrombus Formation

• Two types
• Arterial
• Venous

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Arterial Thrombus Formation

• Occurs when activation of blood coagulation
  exceeds ability of the anticoagulant/inhibitors
  and fibrinolytic system to prevent the formation
  of fibrin.
• White thrombi composed of platelets, fibrin and a
  few WBCs and RBCs
• Form at areas where the flow has been disturbed
  via damage to endothelium, especially
  atherosclerotic plaques

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Arterial Thrombus Formation

• Thrombosis initiated by rupture of the plaque,
  exposing material to subendothelium in the blood
• Causes platelet plasma coagulation factor
  activation which results in fibrin formation.
  The end result is a thrombus that can obstruct
  the artery or an embolus breaks off and lodges in
  the heart or brain, causing tissue death

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Arterial Thrombus Formation

• Risk factors associated with plaque formation
• Hypercholesterolemia
• Hypertension
• Smoking
• Physical inactivity
• Obesity
• Diabetes

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Venous Thrombi

• Occurs when activation of blood coagulation
  exceeds ability of the anticoagulant/inhibitors
  and fibrinolytic system to prevent the formation
  of fibrin.
• Most occur in veins in lower limbs

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Venous Thrombi

• Red thrombi
• Form in veins
• Composed of rbcs trapped in fibrin mesh with few
  platelets and WBCs
• Form in areas of slow or disturbed blood flow,
  where venous segments have been exposed to direct
  trauma

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Venous Thrombi

• Risk factors associated with venous thrombosis
• Venous stasis
• Vessel wall damage
• Factor V leiden and protein C resistance
• Deficiency of AT3, Protein C, Protein S, heparin
  cofactor II
• Increased PT levels
• Antiphospholipid antibodies
• Hyperhomocysteinemia
• Decreased fibrinolytic activity
• Malingnancy
• Misc( those associated with plaque formation,
  pregnancy and oral contraceptive use)

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Thrombophilia

• 2nd most common cause of death
• Inherited or acquired

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Inherited

• Predisposing genetic defect that results in a
  tendency to thrombose
• Changes involve an increase in procoagulant
  potential, a defect of decrease in natural
  inhibitors and/ or abnormalities of fibrinolysis
  or platelet activation

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Inherited Clinical Presentation

• Venous thromboembolis prior to age 45
• Recurrent VTE
• Family history of VTE
• Thrombosis in an unusual site (cervical/ visceral
  veins)

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Inherited States Associated with Thrombosis

• Antithrombin III deficiency
• ATIII binds thrombin to inhibit coagulation.
  When deficient thrombin may uncontrollably
  convert fibrinogen to fibrin clots.
• Deficiency of Protein C or S
• Protein C and S work together to inactivate
  factors V and VIIIC to control the amount of
  coagulation occurring. A deficiency of either
  will result in increased chance of thrombi or
  emboli.

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Inherited States Associated with Thrombosis

• Factor V Leiden
• Genetic mutation of factor V which causes
  resistance to the action of Protein C
• Factor II 20210 mutation
• Problem with Protein C or S
• Dysfibrinogenemia
• Structurally altered fibrinogen molecule

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Acquired States

• Antiphospholipid Antibody Syndrome
• Includes the lupus anticoagulant, anticardiolipin
  antibodies and others are antibodies that prolong
  phospholipid dependent clotting assays in vitro
• Patients show no bleeding disorder
• Malignancy
• Pregnancy Oral Contraceptives
• Postoperative States
• Hematologic Disorders

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Antithrombotic Therapy

• Goal is to treat or prevent thrombosis

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Antithrombotic Therapy 3 Categories

• Antiplatelet Drugs
• Aspirin
• Inhibits the formation of thromboxane A2
• Anticoagulant Drugs
• Heparin
• binds to AT3 to produce an anticoagulant effect
• Oral Anticoagulant
• Coumadin drugs interfer with vitamin K action of
  the liver
• Thrombolytic Drugs
• Plasminogen activators are used to lyse thrombi
  in vivo