Pathology - Circulatory Disturbances: Hemostasis And Disturbances

Front 1

List 4 components of normal hemostasis.

Back 1

1. primary hemostasis (platelets)

2. secondary hemostasis (coagulation cascade)

3. fibrinolysis

4. regulation of hemostasis

Front 2

List 3 general types of abnormal hemostasis.

Back 2

1. hemorrhage

2. thrombosis

3. DIC

Front 3

What does hemostasis accomplish, what are the 3 major components of hemostasis, and how are these components activated?

Back 3

Prevents blood loss, while maintaining blood in fluid state.

Platelets

Endothelial cells

Blood clotting proteins in plasma

Activation, and subsequent coagulation, triggered by injury to the vessel (endothelium)

Front 4

What are the 5 steps of hemostasis? Which steps are involved in primary hemostasis and which steps are involved in secondary?

Back 4

1. vasoconstriction

2. platelet plug formation

3. coagulation to form fibrin mesh

4. fibrinolysis

5. repair at damaged site

Steps 1 and 2 = primary hemostasis

Step 3 = secondary hemostasis

Front 5

What occurs during primary hemostasis?

Back 5

-immediate vasoconstriction: reflex- and endothelin-induced

-vessel injury exposes subendothelium (BM)

-platelets activated when exposed to ECM: collagen, proteoglycans, fibronectin, glycoproteins

-platelets adhere: directly (collagen) or via von Willebrand's factor

-platelet shape change consolidates platelet plug

-platelet degranulation: alpha and dense granules, thromboxane, ADP, Ca++

-platelet aggregation forms loose plug --> primary hemostatic plug

Front 6

What does thromboxane do during primary hemostasis?

Back 6

Induces vasoconstriction. Necessary for platelet aggregation.

Front 7

What occurs during secondary hemostasis?

Back 7

Tissue factor produced by endothelial cells.

Phospholipid complex (on platelet surface).

Plasma clotting factors become activated.

Fibrin formation

Fibrin cements the platelet aggregate --> secondary hemostatic plug

Front 8

What is the end product of secondary hemostasis?

Back 8

Fibrin, which comprises the secondary hemostatic plug.

Front 9

What are the components of the coagulation cascade in secondary hemostasis?

Back 9

Enzymatic coagulation factors.

Non-enzymatic coagulation factors.

Ca++

Phospholipid membs

Front 10

Intrinsic, extrinsic, and common pathways work together to produce _____, AKA factor ____, with a final product of _____, AKA factor ____>

Back 10

thrombin

II

fibrin

I

Front 11

What occurs/what is involved in the intrinsic pathway of secondary hemostasis?

Back 11

-contact factors

-vascular injury: pre-kallikrein-HMWK and factor XII bind to phospholipids of injured endothelial cells

-catalytic cascade

-IXa, VIIIa, phospholipid and Ca++ from TENASE

-tenase activates factor X and initiates common pathway

Front 12

What occurs/what is involved in the extrinsic pathway of secondary hemostasis?

Back 12

Tissue factor: sub-endothelium, activated endothelium

-endotoxin, TNF, IL-1, thrombin all stimulate TF production: sepsis

-TF-VIIa activates X

Front 13

What occurs/what is involved in the common pathway of secondary hemostasis?

Back 13

-activated Xa: bound to endothelial or platelet memb, converts prothrombin (II) to thrombin (IIa)

-thrombin has multiple functions

FIBRIN FORMATION

Front 14

Fibrin is formed from _____ by _____.

Back 14

fibrinogen

thrombi

Front 15

True or false?

Fibrin self-polymerizes.

Back 15

True

Front 16

Fibrin self-plymerizes and is cross-linked by factor _____.

Back 16

XIIIa

Front 17

What is formed by cross-linking of fibrin, and platelet contraction?

Back 17

a strong, fibrin-platelet thrombus

Front 18

How is a thrombus retracted?

Back 18

By platelet retraction: allows blood flow around, and pulls damaged vessel edges closer together.

Front 19

True or false?

Intrinsic and extrinsic cascades reflect in-vivo events.

Back 19

False

Front 20

What happens when tissue factor is exposed to plasma major activator?

Back 20

IX activation --> by-pass intrinsic pathway

(Thrombin on its own cannot convert enough fibrinogen to fibrin.)

Front 21

Thrombin activates _____ and factor ____, ___ , ____, and ____. What is accomplished by activation of these factors?

Back 21

platelets

V

VIII

XI

XII

Activation of large quantities of thrombin.

Front 22

True or false?

The fibrin-platelet plug is normally permanent.

Back 22

False. Temporar

Front 23

What controls thrombus size?

Back 23

Fibrinolysis, which is dissolution of the fibrin-platelet plug.

Front 24

What does thrombomodulin do?

Back 24

Blocks coagulation cascade

Front 25

What is the key enzyme in fibrinolysis?

Back 25

Plasmin

Front 26

Plasminogen is activated into ____ by _____ and _____.

Back 26

plasmin

coagulation factors

plasminogen activators in endothelium and tissue

Front 27

Fibrin is degraded to ______, which are an important clinical measurement of ____.

Back 27

fibrin degradation products (FDP)

uncontrolled coagulation

Front 28

What does the regulation of hemostasis achieve?

Back 28

Restriction of clot to site of vessel injury

Front 29

What is antithrombin III (ATIII) and what does it do?

Back 29

The most potent anticoagulant.

Binds to heparan sulfate on endothelium and degrades all activated coagulation factors, except VIIa.

Front 30

What 3 compounds inhibit thrombosis?

Back 30

ATIII

Protein C

TFPI (tissue factor pathway inhibitor)

Front 31

What are the 2 types of fibrinolytic inhibitors?

Back 31

Plasminogen activator inhibitor-1 (PAI-1): inhibits tiss plasminogen activator, and therefore plasmin formation; inactivates protein C, plasmin, and thrombin

Antiplasmins: co-operatively prevent excess plasmin activity (slows thrombus dissolution

Front 32

What are the 2 broad categories of hemostatic disorders?

Back 32

Too little coagulation --> hemorrhage

Too much coagulation --> thrombosis

Front 33

List 4 things that can cause hemorrhage.

Back 33

Abnormal func/integrity of major factors that influence hemostasis:

1. blood vessel

2. endothelium

3. platelets

4. coagulation factors

Front 34

What can compromise a blood vessel that might cause hemorrhage?

Back 34

Trauma (rhexis)

Vascular erosion: inflammatory, invasive tumors, fungi (eg Aspergillus)

Diapedesis (small defects in otherwise intact vessels allow some RBC to escape)

Blood vessel wall malformation: Ehlers-Danlos syndrome, vit C deficiency

Front 35

What can cause endothelial injury that leads to hemorrhage?

Back 35

Endotoxemia

Vasculitis: virus (eg canine adenovirus-1), tick-bourne diseases

Uremic toxins

Immune complexes (Type III hypersensitivity rxn)

Front 36

What can cause platelet dysfunction/depletion that leads to hemorrhage?

Back 36

Thrombocytopenia (decreased platelet #): decreased production in bone marrow, increased destruction (immune-mediated, some viruses), increased use (DIC)

Abnormal platelet function: inherited, drug-induced (Aspirin), uremia (renal failure)

Secondary platelet dysfunction: von Willebrand's disease (esp in Doberman's)

Front 37

What can go wrong with coagulation factors, which may lead to hemorrhage?

Back 37

Congenital defects (hemophilia): decreased conc, functional deficiency

Acquired defects: decreased production - liver disease (most factors), vit K deficiency (affects II, VII, IX, X), eg that caused by Warfarin; increased consumption - DIC

Front 38

True or false?

Cardiac tamponade can be expected in dogs with Warfarin toxicity.

Back 38

True

Front 39

List 6 types of hemorrhage.

Back 39

Petechiae

Purpura

Ecchymosis

Suffusive

Hematoma

Hemorrhage within body cavity

Front 40

What are petechiae?

Back 40

Very small (1-2mm) areas of hemorrhage on serosal surfaces, caused by diapedesis, indicating minor vascular damage

Front 41

What is purpura?

Back 41

Small (3mm-2cm) areas of hemorrhage.

Front 42

What is ecchymosis?

Back 42

Larger (2-cm) areas of hemorrhage that indicate more extensive vascular damage. Includes subcutaneous hematomas (bruises).

Front 43

Explain the colouration of a bruise.

Back 43

Macs degrade and phagocytose RBCs --> release of red-blue Hb, blue-green bilirubin, and gold-brown hemosiderin

Front 44

What is suffusive hemorrhage? What can cause it?

Back 44

Hemorrhage that affects a large contiguous area. eg. caused by vit C deficiency in GPs

Front 45

What is hematoma?

Back 45

Hemorrhage within a confined space. eg aural hematoma

Front 46

List 3 types of hemorrhage within a body cavity.

Back 46

hemoabdomen

hemothorax

hemopericardium

Front 47

True or false?

Rapid loss of up to 20% of blood V can be tolerated by the body.

Back 47

Tru

Front 48

True or false?

Slow rate of blood loss can be tolerated.

Back 48

Tru

Front 49

Rapid loss of >20% blood V usu results in _____.

Back 49

hypovolemic shoc

Front 50

What are the possible clinical consequences of hemorrhage?

Back 50

hypovolemic shock

cardiac tamponade

loss of iron and subsequent iron deficiency anemia: predominantly external hemorrhage (from GIT); internal hemorrhage - iron is preserved and recycled

Front 51

What are 3 possible resolutions of hemorrhage?

Back 51

1. resorption: small amount

2. organization: larger amounts, phagocytosis and digestion of Hb

3. organizing hematom

Front 52

Define thrombosis.

Back 52

Formation of inappropriate (excessive) thrombus in the wall of a blood or lymphatic vessel, or heart, or free in lumen (thromboembolism)

Front 53

Draw Virchow's triad.

Back 53

Front 54

What can cause endothelial injury, leading to thrombosis?

Back 54

vasculitis (viral, bacterial, fungal)

immune-mediated

toxic

DIC

Front 55

Endothelial injury exposes ____, _____, and _____. Why do exposure of these things cause thrombosis?

Back 55

TF (affecting extrinsic coagulation)

collagen

fibronectin

All are potent stimuli for platelet adhesion, and trigger the coagulation cascade.

Front 56

What usually prevents thrombus formation in the heart or arterial circulation?

Back 56

High rate of flo

Front 57

List 2 ways that blood flow can be altered, and how these can lead to thrombosis.

Back 57

Reduced blood flow: systemic heart failure, local congestion

Turbulent blood flow: aneurysm, narrowing vessels

Alteration in flow can lead to increased contact of platelets and endothelial cells, and the accumulation of activated coagulation factors.

Front 58

What can cause hypercoagulability, leading to thrombosis?

Back 58

1. Increased conc of activated clotting factors: increased activation (inflammation, stress, pregnancy, surgery, renal disease), or decreased degradation (liver disease).

2. Decreased conc of anti-coagulation factors: decreased ATIII w renal disease in dogs

Front 59

Cardiac and arterial thrombi are usually due to ____.

Back 59

endothelial damage

Front 60

Cardiac and arterial thrombi are made up of predominantly ____ and _____ and are therefore ____ in colour.

Back 60

platelets

fibrin

pale

Front 61

Venous thrombi are usu due to ____.

Back 61

blood stasi

Front 62

Which cells are commonly incorporated into venous thrombi, and how does this affect the colour of the thrombi?

Back 62

RBCs

red

Front 63

When performing a PM, it important to distinguish cardiac/arterial thrombi and venous thrombi from _______ coagulation.

Back 63

post-mortem

Front 64

What prevents the incorporation of RBCs in cardiac and arterial thrombi?

Back 64

fast flow of bloo

Front 65

What are 4 possible fates of the thrombus?

Back 65

Propagation: accumulate more platelets and fibrin, eventully leading to vessel obstruction.

Dissolution: removal by fibrinolytic activity.

Organization and recanalization: fibrosis.

Embolism: dislodge and travel to other sites.

Front 66

What are thromboemboli?

Back 66

Dislodged fragments of thrombus.

Front 67

What 3 things may occur if a thromboembolism lodges in a smaller vessel?

Back 67

1. venous thromboembolism: typically lodge in pulmonary cir

2. arterial thromboembolism: lodge downstream, typically at a vascular bifurcation

3. cardiac thromboembolism: often lodge at iliac bifurcation

Front 68

What kind of thromboembolism is a saddle thrombus?

Back 68

cardiac thromboembolism bc lodging at iliac bifurcation

Front 69

Besides thromboemboli, what other types of emboli are there?

Back 69

bacterial emboli: abscesses or valvular endocarditis

fat emboli: fracture (releasing bone marrow), usu lodge in pulmonary circ

fibrocartilaginous emboli: ruptured intervertebral disc, localized spinal cord infarction

intravascular parasites: heartworm

malignant neoplasms

Front 70

What does DIC stand for?

Back 70

Disseminated intravascular coagulation.

Front 71

What is DIC?

Back 71

Sever malfunction of hemostasis, often resulting in death, that is characterized by excessive (systemic) generation of thrombin/TF.

Front 72

What causes DIC?

Back 72

-diffuse vascular damage (trauma, vasculitis, burns): exposure of endothelial TF

-bacteremia and systemic infections: intravascular generation of TF by endothelial cells and monocytes.

Front 73

Explain the pathogenesis of DIC.

Back 73

Excessive generation of TF --> TF-induced activation of extrinsic cascade --> Thrombin production, platelet aggregation, and fibrin formation --> widespread intravascular clots, widespread consumption of clotting factors and platelets, and thrombin-stimulated fibrinolysis.

Widespread intravascular clots lead to thrombosis.