Hemostasis And Thrombosis Overview-Turnball

Front 1

Steps of Normal Hemostasis

Back 1

1. Vasoconstriction
2. Primary Hemostasis
3. Secondary Hemostasis
4. Antithrombotic counter-regulation

Front 2

Key Points to Each Step

Back 2

1. Vasoconstriction via Endothelin from damaged cells
2. Primary: Platelets Adhesion via vWF and Aggregation via ADP and TXA2
3. Secondary: Fibrin Plug via local activation of coagulation cascade by tissue factors and phospholipids
4. counter regulation: limits process to site of injury

Front 3

Intrinsic Coagulation Cascade

Back 3

1a. Factor XII gets activated and then activates Factor XI
2. Factor XI activates IX 2b. Factor VIII gets activated by Thrombin.
3a. VIII and IX Activate X
3b. Factor V gets activated by Thrombin
4. V + X activate Thrombin
5. Thrombin converts Fibrinogen to Fibrin
6. Thrombin also activates Factor XIII which cross-links Fibrin

Front 4

Extrinsic Coagulation Cascade

Back 4

1. Tissue Factor + VII activates X
2. X + V activate Thrombin
3. Thrombin activates Fibrin
4. Thrombin activates XIII which crosslinks Fibrin

Front 5

what role does Calcium play in coagulation?

Back 5

It holds components together on the phospholipid surface so they can interact.

Front 6

2 main kickers of Antithrombotic counter-regulation

Back 6

Anti-Thrombin and Activated Protein C

Front 7

Fxns of Antithrombin

Back 7

1. Inhibits Thrombin
2. Inhibits IX, X, XI, XII

Front 8

How can you enhance Antithrombin's actions

Back 8

Heparin b/c antithrombin binds to heparin like molecules on endothelial cells

Front 9

How is Protein C activated?

Back 9

Binding of Thrombin to Thrombomodulin

Front 10

Fxns of Protein C?

Back 10

Inactivates V, VIII with the help of Protein S

Front 11

Fibrinolytic Cascade

Back 11

1. Plasminogen is converted to Plasmin with the help of t-PA and the Factor XII-dep pathway
2.Plasmin breaks down the fibrin clot and interferes with fibrin polymerization

Front 12

Where does t-PA come from?

Back 12

Endothelial Cells

Front 13

Why does t-PA work so well?

Back 13

It most active when attached to Fibrin, which helps target fibrinolytic activity to the sites of recent clotting

Front 14

Who stops Fibrinolysis? and where do they come from?

Back 14

Plasminogen Activator Inhibitors!
They are released by endothelium.

Front 15

The modes of Bleeding Disorders

Back 15

1. defect in vessel wall
2. platelet deficiency of dysfunction
3. derangement of coagulation factors

Front 16

Where are Coag factors made?

Back 16

THE LIVER! except for VIII which comes from the endothelium (and a bit from the liver)

Front 17

What's up with Vitamin K and coagulation?

Back 17

Factors II, VII, IX, X and Proteins C and S are all Vitamin K Dependent

Front 18

How can you get Vitamin K Deficiency?

Back 18

Liver Disease
Poor Nutrition
Long Term Antibiotic Therapy

Front 19

PT vs APTT?

Back 19

PT = extrinsic pathway
APTT = intrinsic pathway

Front 20

Factor I
Factor II
???

Back 20

Factor I = Fibrinogen
Factor II = Prothrombin

Front 21

PT tests which factors?

Back 21

1, 2, 5, 7, 10
I, II, V, VII, X

Front 22

What factors does aPTT test?

Back 22

I, II, V, VIII, IX, X, XI, XII
8, 9, 11, 12
1, 2, 5, 10

Front 23

What is the INR?

Back 23

International Normalized Ratio:
normalizes PT values

Front 24

what is a 1:1 mix?

Back 24

Patient's Plasma + Control Plasma
Differentiates a Factor deficiency from an inhibitor. A change when mixed = deficiency. No change = inhibition...

Front 25

Why do we test D-Dimers?

Back 25

they're the result of fibrin degradation. They're increased in any coagulopathy

Front 26

Causes of prolonged PT?

Back 26

Liver Disease
Vit K def
Warfarin Therapy
Factor VII Def

Normal APTT

Front 27

Causes for Prolonged APTT

Back 27

Factor Deficiencies of:
12, 11, 9, or 8
Heparin Therapy
Lupus Anticoagulant
Von Willebrand Disease

PT will be normal

Front 28

Causes of Prolonged PT and APTT

Back 28

SEVERE liver disease
Factor Deficiencies:
2, 5, 10
DIC
Severe Vit K def
initially only PT prolonged, then APTT

Front 29

What is DIC?

Back 29

Disseminated Intravascular Coagulation

Front 30

DIC Pathogenesis

Back 30

Activated Coagulation Sequence
-formation of thrombi throughout microcirculation
-comsumes platelets and coag factors
-fibrinolysis gets upped

Front 31

Possible triggers of DIC?

Back 31

1. release of tissue factor or thromboplastic substances into circ
2. widespread injury to endothelial cells
3. Sepsis
4. OB complications
5. Neoplasms = APL

Front 32

Lab test findings in DIC?

Back 32

1. Prolonged PT and aPTT
2. decreased fibrinogen
3. increased D-Dimer
4. Decreased platelets
5. Schistocytes

Front 33

Treatment for DIC

Back 33

1. Replacement of products
2. treat underlying disorder

Front 34

Kickers for Thrombocytopenia

Back 34

Normal PT and APTT
common in AIDS patients

Front 35

What is ITP?

Back 35

Immune or Idiopathic Thrombocytopenic Purpura

Front 36

ITP:
1. Pathogenesis
2. DX

Back 36

1. Autoimmunity against platelets
2. Normal Coag Tests, decreased platelets, ANTI-Platelet Antibodies!

Front 37

What is TTP?

Back 37

Thrombotic Thrombocytopenic Purpura

Front 38

TTP
1. pathogenesis
2. symptoms

Back 38

1. deficiency of vWF cleaving
2. Pentad:
hemolytic anemia
thrombocytopenia
renal dysfunction
fever
mental status changes

Front 39

TTP
1. Lab tests

Back 39

1. normal coag tests
platelets decreased

Front 40

What is HUS?

Back 40

Hemolytic Uremic Syndrome

Front 41

Differentiate from TTP

Back 41

1. Predominantly Kids
2. Absent Neuro symptoms
3. Dominance of Renal Failure
4. MAHA

Front 42

Coagulation Disorders
broadly and examples

Back 42

Acquired Disorders
Vit K Def
Liver Disease
Autoantibody formation
Congenital
usually a single factor def

Front 43

What is the most common SEVERE bleeding disorder?

Back 43

Factor 8 def

Front 44

Inheritance of Factor 8 def?

Back 44

X-linked recessive

Front 45

Lab workup of Factor 8 Def?

Back 45

Normal PT, prolonged APTT, low factor 8 (duh)

Front 46

What is the most common hereditary bleeding disorder?

Back 46

von Willebrand Disease

Front 47

vW diseas
Key presentation?

Back 47

Spontaneous Bleeding from mucous membranes, wounds, menses
hemophilias are post-traumatic bleeding

Front 48

Inheritance of vW disease?

Back 48

auto dom

Front 49

Types of vW disease

Back 49

Type 1: reduced vWF
Type 2: selective loss of high MW multimers of vWF
Type 3: nearly absent vWF

Front 50

What exactly does von Willebrand factor do?

Back 50

Carrier Protein of VIII
Promotes aggregation after blood vessel injury

Front 51

von Willebrand Disease
Lab eval?

Back 51

-Prolonged bleeding time with normal platelet count
-Normal PT, prolonged APTT
- decreased VIII
-decrease ristocetin cofactor, decreased vWF Ag

Front 52

What is Virchow's Triad?

Back 52

For thrombosis:
1. Endothelial injury (important for heart and arterial circ)
2. Stasis (venous) or turbulent flow (art/card)
3. Blood hypercoagulability
3.

Front 53

Two causes of hypercoagulability i need to know

Back 53

Inherited: Factor V Leiden
Acquired: Lupus inhibitor

Front 54

Factor V Leiden
1.mutation?

Back 54

Causes V not to be inactivated by Protein C (i.e. resistance)

Front 55

Factor V Leiden clinical features

Back 55

recurrent DVT!

Front 56

lab value for Factor V Leiden

Back 56

D-Dimer is elevated

Front 57

What is the acquired cause of thrombosis i need to know?

Back 57

Antiphospholipid Antibody Syndrome (lupus anticoagulant)

Front 58

CLinical manifestations of Antiphospholipid Antibody Syndrome

Back 58

1. recurrent thrombosis
2. spontaneous abortions **
3. thrombocytopenia

Front 59

Pathogenesis of Antiphospholipid Antibody Syndrome

Back 59

In vivo: ANTIBODIES --> hypercoag
in vitro: lupus anticoag (not just lupus patients) results in elevated APTT, normal PT, and the 1:1 doesn't correct APTT