ability to maintain blood in a fluid state and prevent loss from sites of vascular damage.
list 3 major components to the hemostatic system
- 1. vascular wall
- 2. platelets
- 3. coagulation proteins
define primary hemostatic plug
vascular injury exposes subendothelial collagen, resulting in platelet activation. this is followed by activation of coagulation proteins to create a more stable meshwork to seal off the damaged site.
define primary hemostasis
platelet response to vascular injury
list 3 parts of primary hemostasis
- 1. adhesion
- 2. activation
- 3. aggregation
define primary hemostasis adhesion
adhesion of platelets to the damaged endothelial site by activation of surface membrane receptor (glycoprotein Ib/IX) and adhesive protein (vW factor).
define primary hemostasis activation
platelets are activated by binding to vWF causing release of 2nd messenger within platelets, to change shape from discoid to spherical, that causes secretion of cytoplasmic ADP in turn activating glycoprotein IIb/IIIa receptor and contraction of the platelet mediated through actin fibers.
define primary hemostasis aggregation
release of cytoplasmic ADP causes activation of adjacent platelets and platelet-platelet binding mediated by fibrinogen and gpIIb/IIIa receptor.
define secondary hemostasis
- fibrin clot formation.
- coagulation proteins generate thrombin which converts fibrinogen to fibrin which adds stability to the clot after fibrin monomers are cross-linked by Factor XIII
define the secondary hemostasis intrinsic pathway
- 1. kallikrein activates F-XII
- 2. F-XIIa activates F-XI
- 3. F-XIa activates F-IX
define the secondary hemostasis extrinsic pathway
sequence of activation of F-VII by tissue factor
define the secondary hemostasis common pathway
- 1. activation of X to Xa
- 2. conversion of prothrombin II to thrombin
- 3. conversion of fibrinogen to fibrin monomers
how is a fibrin clot formed?
fibrin monomers polymerize and are made more stable by cross-linking by F-XIII
what does primary hemostasis regulate?
regulation of platelets
what three regulator systems exist for secondary hemostasis
- 1. serine protease inhibitors
- 2. protein C system
- 3. fibrinolysis
describe serine protease inhibitors
best know SERPIN: antithrombin, which is activated by heparin to bind with thrombin which inhibits thrombin from participating in the generation of fibrin monomers. antithrombin can also inactivate Factor X.
define the protein C system
- regulates major cofactors of the coagulation cascade: F-Va, VIIIa.
- activated protein C (APC) is the major effector enzyme, protein S is a major cofactor.
- - limits generation of a fibrin clot.
- - in the presence of fibrin, tissue plasminogen activator (TPA) can activate plasminogen to plasmin. plasmin breaks down cross-linked fibrin monomers.
- - TPA is therapeutic in recent myocardial infarcts.
- - uncontrolled activation of plasmin can lead to bleeding complications.
explain how shifts in different directions of coagulation or regulation can result in different events
- balance in favor of procoagulation: thrombosis
- favor of regulation: bleeding disorders
list 4 common screening tests used to evaluate hemostasis
- 1. prothrombin time (PT)
- 2. partial thromboplastin time (PTT)
- 3. platelet count
- 4. bleeding time
define prothrombin time
- - measurement of time needed for plasma to form a clot in the presence of added tissue thromboplastin (to initiate the extrinsic coag. cascade) and calcium ions.
- - prolonged PT: decreases or abnormalities in F-VII, X, V, II and/or fibrinogen.
- - measures degree of anticoagulation in patients receiving oral anticoagulants
define partial thromboplastin time (PTT)
- - measurement of the time needed for plasma to form a clot in presence of added kaolin (to activate contact-dependent F-XII), cephalin and calcium.
- - accesses the intrinsic coag. cascade.
- - Prolonged PTT: decrease/abnormality of F-XII, XI, IX, VIII, V, X, II and fibrinogen.
- - measure degree of anticoagulation in patients receiving heparin
describe the platelet count test
- normal range: 150-400k/uL.
- decrease in number: thrombocytopenia
- increase in platelets: thrombocytosis and thrombocythemia
what are the diagnostic clues for different types of bleeding disorders (platelet problem vs. coagulation problem vs. regulatory system)
- platelet problem: mucosal bleeding
- coagulation problem: deep tissue hematomas
- regulatory problem: screening tests are normal
what are several clinical manifestations of Primary Hemostasis disorders?
mucocutaneous bleeding, prolonged bleeding time, thrombocytopenia
what are several clinical manifestations of Secondary Hemostasis disorders?
soft tissue bleeding, prolonged PT and/or PTT and/or thrombin time
what are several clinical manifestations of regulatory system disorders?
soft tissue bleeding, normal screening tests
list 3 congenital bleeding disorders
- 1. von Willebrand's syndrome
- 2. hemophilia a
- 3. hemophilia b
define vW syndrome and describe its different types as well as lab test results
- - autosomal dominant with decreased or abnormal vWF.
- - Type I: decreased amounts of vWF
- - Type II: abnormal vWF
- - Type III: absence of vWF
- - Lab tests: prolonged bleeding time, prolonged PTT, decreased vWF/F-VII
what treatment options are available for vWS?
- - desmopressin: releases vWF from endothelial cells
- - antifibrinlytic agents
- - F-VIII concentrates containing vWF
- - cryoprecipitate for severe cases
describe the Factor VIII complex
- - this complex is involved in both hemophilia A and vWs.
- - it is composed of vWF and factor VIII procoagulant. both are produced by different genes on different chromosomes.
- - vWF functions both as a carrier molecule for F-VIII and as a glue between damaged endothelials and platelets (1 hemostasis)
- - Factor VIII procoagulant is released from vWF after clot formation and participates in generation of F-X (2 hemostasis)
- - synthesized in the liver
define hemophilia A, its important clinical aspects, and lab screening results
- - sex-linked recessive disorder due to decreased production of F-VIII
- - clinical hallmark: soft-tissue bleeding
- - lab: normal bleeding time, prolonged PTT, decreased VIII, normal vWF, normal IX
what therapy options exist for hemophilia a
F-VIII concentrates, desmopressin, fibrinolytic inhibitors
describe hemophilia b
- sex-linked recessive disorder due to decreased production of F-IX
- lab results include normal bleeding time, prolonged PTT, normal VIII/vWF and decreased IX
prolonged PTT with no increased risk of bleeding is due to what?
F-XII deficiency and contact factor deficiencies
risk of bleeding with normal PT and PTT tests is due to what?
platelet disorder and F-XIII deficiency (able to form a fibrin plug but it is unstable to due lack of cross-linking from F-XIII)
list 4 types of platelet disorders
- 1. thrombocytopenia
- 2. idiopathic thromocytopenia purpura (ITP)
- 3. thrombotic thrombocytopenic purpura (TTP)
- 4. disseminated intravascular coagulation (DIC)
- - decrease in platelet count (<100k/uL)
- - <20k results in spontaneous bleeding
define idiopathic thrombocytopenic purpura
immune mediated destruction of platelets
define thombotic thrombocytopenic purpura
acute disorder with unknown cause causing intravascular platelet activation with formation of platelet-rich microthrombi.
define disseminated intravascular coagulation (DIC)
uncontrolled activation of the hemostatic system. there is both systemic thrombin formation and systemic plasmin formation. coagulation factors are activated and consumed faster than they can be produced resulting in bleeding and microvascular thrombi.