Overview of Hemostasis and Coagulation

Question 1

What is hemostasis?

Answer 1

-ability to maintain blood in a fluid state and prevent loss from sites of vascular damage

Question 2

What are the 3 major components of the hemostatic system?

Answer 2

-vascular wall, platelets and coagulation proteins

Question 3

What are the three A’s of platelet response?

Answer 3

• adhesion
• activation
• aggregation

Question 4

What happens during the adhesion stage of platelet response to vascular injury?

Answer 4

• platelets adhere to to damaged endothelial site

- this involves the activation of a surface membrane receptor, an adhesive protein and an appropriate surface

Question 5

What does von Willebrand factor do?

Answer 5

• mediates adherence of platelets to the subendothelial collagen
• glycoprotein Ib binds to vWF

Question 6

What happens during the activation stage of platelet response to vascular injury?

Answer 6

• additional platelets are recruited
• second messenger molecules released after binding to vWF that lead to shape change from disc to sphere, secretion of ADP, activation of glycoprotein IIB and IIIa receptor
• contraction of platelet mediated though actin fibers

Question 7

What happens during the aggregation stage of platelet response to vascular injury?

Answer 7

• Platelets interacting with other platelet
• release of cytoplasmic ADP into local milieu causes activation of adjacent platelets
• platelet-platelet binding mediated through fibrinogen and gp IIb/IIIa receptor

Question 8

What conversion adds stability to the clot after fibrin cross-linking by Factor XIII?

Answer 8

-Thrombin converts fibrinogen to fibrin

Question 9

What is the intrinsic pathway of clot formation?

Answer 9

• activation of Factor XII by kallikrein
• activation of Factor XI by Factor XIIa
• Factor XIa activates Factor IX

Question 10

What is the extrinsic pathway of clot formation?

Answer 10

-activation of Factor VII by tissue factor

Question 11

What is the common pathway of clot formation?

Answer 11

• activation of X to Xa
• conversion of prothrombin II to thrombin
• conversion of fibrinogen I to fibrin monomers

Question 12

A fibrin clot is formed by fibrin monomers generated by what polymerize and what stabilizes these strands?

Answer 12

• thrombin generates fibrin monomers for polymerization

- monomers are made more stable by covalent cross-linking by factor XIII

Question 13

Secondary hemostasis is defined by regulation of coagulation. What are antithrombins?

Answer 13

-inhibition of thrombin and Factors IXa-XIIa of coagulation cascade through formation of inactive enzyme-inhibitor complex

Question 14

What is the best known antithrombin?

Answer 14

• antithrombin III
• in presence of heparin, becomes activated so that it can form a complex with thrombin
• destroys ability of thrombin to participate in generation of fibrin monomers

Question 15

What is the function of the protein C system?

Answer 15

• regulation of major cofactors of the coagulation cascade Factors Va and VIIIa
• Activated protein C is major effector enzyme; protein S is major cofactor

Question 16

Protein C or Protein S deficiencies result in what issues?

Answer 16

-hypercoagulable states

Question 17

How does Factor V Leiden mutation promote coagulation?

Answer 17

-resistance to enzyme inactivation by the Protein C/S complex

Question 18

What is fibrinolysis?

Answer 18

• limits generation of fibrin clot
• in presence of fibrin, tissue plasminogen activator can bind to plasminogen and convert to plasmin
• plasmin breaks down previously cross-linked fibrin monomers into fibrin degredation products

Question 19

Uncontrolled activation of plasmin can result in what complications?

Answer 19

• bleeding complications due to fibrinolysis

- and fibrinogenolysis

Question 20

What is prothrombin time?

Answer 20

• measurement of time needed for plasma to form a clot in the presence of added tissue thromboplastin and calcium ions
• Prolonged PT can result from decreases or abnormalities in in Factors II, V, VII, X and fibrinogen
• routinely used to measure degree of anticoagulation in patients receiving oral anticoagulants

Question 21

What is the international normalized ratio?

Answer 21

• ratio of patient PT time/control PT time

- allows to compare between lab and anticoagulant patients

Question 22

What is partial thromboplastin time?

Answer 22

• PTT
• measurement of time needed for plasma to form a clot in the presence of added ground glass or kaolin, cephalin and calcium ions
• used to measure degree of anticoagulation in patients receiving heparin

Question 23

What is thrombocytopenia?

Answer 23

-decrease in platelet number

Question 24

What is thrombocytosis?

Answer 24

-increase in platelet number

Question 25

What is the normal range for bleeding time?

Answer 25

- 2-8 min | - prolonged when there are abnormalities of platelet number or function

Question 26

What is the significance of mixing study results?

Answer 26

- If clotting time is corrected then there is a deficiency of some factor - if clotting time is not corrected, then a factor-specific or lupus anticoagulant type of inhibitor might be present

Question 27

What are the characteristics of disorders of primary hemostasis?

Answer 27

- mucocutaneous bleeding/bleeding associated with trauma | - lab manifestations include a prolonged bleeding time and/or thrombopenia

Question 28

What are the characteristics of disorders of secondary hemostasis?

Answer 28

- soft tissue bleeding - bleeding associated with trauma - lab manifestations: prolonged PT/PTT and/or thrombin time

Question 29

What are the characteristics of disorders of the regulatory system?

Answer 29

- soft tissue bleeding/bleeding on trauma | - lab manifestations: normal

Question 30

What is Factor VIII Complex?

Answer 30

- set up for vWF disease and hemophilia - this is composed of vWF and factor VIII procoagulant - Factor VIII is released from vWF when clot is formed - Factor VIII participates in the generation of Factor X

Question 31

What are the characteristics of von Willebrand disease?

Answer 31

- AD disorder - decreased production of vWF - Most common inherited, 1% of pop affected - clinical signs: mucocutaneous bleeding - leads to decreased production of Factor VIII - lab findings: prolonged bleeding, prolonged PTT and decreased vWF & VIII - desmopressin for mild cases

Question 32

What are the characteristics of Hemophilia A?

Answer 32

- X recessive - decreased production of VIII - most common hereditary cause for serious bleeding- hemarthrosis, intramuscular hematomas, intracranial hemorrhage - symptoms start early in life and high rate of spontaneous gene mutations responsible (30%) - lab: normal bleeding time, prolonged PTT, decreased VIII <1% severe cases - replacement VIII - complications: joint disease, pseudotumors, fatal hemorrhage - therapy complications- transfusion-transmitted diseases, formation of antibodies to transfused VIII, allergic rxn

Question 33

What are the characteristics of Hemophilia B?

Answer 33

- X recessive - decreased production of IX - similar to VIII deficiency, mild cases hard to diagnose - lab: low levels of IX - complications: similar to VIII

Question 34

What are the characteristics of thrombocytopenia?

Answer 34

- clinical: petechial hemorrhages in skin and mucous membranes - conditions arising from this: sepsis, DIC, TTP, vasculitis, burns, fat emboli, hemorrhage

Question 35

What are the characteristics of Immune Thrombocytopenic Purpura?

Answer 35

- also ITP - immune-mediate destruction of platelets, directed at the platelet membrane antigens - Acute- in childhood resulting in severe thrombocytopenia- self limiting - Chronic- in adults onset gradual, no antecedent infection, females with autoimmune disorders predominate - increased risk of bleeding, petechial hemorrhage, bruising - therapy: corticosteroids, intravenous antibodies, splenectomy

Question 36

What are the characteristics of Thrombotic Thrombocytopenic Purpura?

Answer 36

- intravascular platelet activation with formation of platelet-rich microthrombi throughout circulation - deficient in MMP that normally degrades very high molecular weight multimmers of vWF - results in accumulation of abnormally large vWF in plasma - high mortality - fever, thrombocytopenia, renal failure, microangiopathic hemolytic anemia - lab: thrombocytopenia, schistocytes in peripheral blood smear, reticulocytosis; normal coag parameters, increased bilirubin and LD

Question 37

What are the characteristics of DIC?

Answer 37

- uncontrolled activation of hemostatic system, systemic thrombin formation and systemic plasmin formation - coag factors consumed resulting in bleeding and microvascular thrombi - Clinically things that can cause DIC- bleeding from multiple sites, hypotension, shock, disfunction of things that need blood, gram negative sepsis - therapy- remove initiating stimulus, support coag factor reserve

Question 38

Vascular injury exposes

Answer 38

subendothelial collagen, which results in platelet activation (primary hemostatic plug), followed by activation of coagulation proteins to produce a more stable meshwork associated with the platelet plug to seal off the damaged site and prevent further blood loss