Pathology - Coagulation and Thrombosis Flashcards

1
Q

Define hemostasis

A

Arrest of bleeding following vascular injury (i.e. blood vessel injury)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the three main steps of hemostasis?

A
  1. Vasoconstriction:
    surrounding endothelium and smooth muscle constricts to slow the blood flow and decrease blood loss
  2. Platelet plug formation:
    platelets adhere to the site of injury and form a temporary plug that stops blood loss
  3. Blood clot formation:
    more robust, long-lasting structure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the key events of primary hemostasis? What are the key events of secondary hemostasis?

A

Primary hemostasis:
* Vasoconstriction
* Platelet plug formation
(begins within seconds of injury, last only a few minutes)

Secondary hemostasis:
* Blood clot formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe vasoconstriction (first step following vascular injury)

A
  • Smooth muscle cells contract
  • Opposed endothelial cells stick together
  • Secretion of endothelin by damaged endothelium promotes vasoconstriction

It is a temporary, initial, limited response.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What forms the platelet plug?

A

Anucleate fragments of megakaryocytes (i.e. platelets), which start to adhere to the site of injury.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Name compounds produced by healthy endothelial cells under normal conditions that help prevent blood clot formation.

A

Healthy, normal endothelial cells secrete vasodilators:
* prostacyclin (prostaglandin)
* nitric oxide
These vasodilators keep the blood vessels open and prevent blood cells from sticking to blood vessel walls.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the process by which platelets stick to damaged endothelial cells.

A
  1. Damaged endothelial cells have surfaces of exposed collagen and platelet-adhesion glycoprotein von Willebrand Factor
  2. Collagen attracts platelets, that aggregate and stick to it (and to vWF)
  3. These platelets become activated and “sticky”, attracting more platelets
  4. Platelets and endothelial cells secrete pro-coagulants which further attracts platelets and consolidates plug formation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Name 4 pro-coagulants released by platelets that promote vasoconstriction and platelet aggregation/consolidation

A

Tissue factor (factor III)
Thromboxane A2
ADP
Serotonin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the 4 steps of platelet plug formation during primary hemostasis

A
  1. Platelet Adhesion
  2. Activation and release of cytokines
  3. Platelet Aggregation
  4. Platelet Consolidation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the most common drug for preventing coagulation?

A

Acetylsalicylic acid - ASA (aspirin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How is ASA use to prevent blood clotting and coagulation?

A

It inhibits the production and secretion of thromboxane A2 by platelets, thus preventing clotting.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What compound initiates the coagulation cascade?

A

Tissue factor (factor III)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the main component of a blood clot that differentiates it from a platelet plug?

A

Deposition of FIBRIN on platelet plug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the end result of the coagulation cascade?

A

Activation of thrombin (factor IIA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the key steps in clot formation (at the end of the coagulation cascade)

A
  • Prothrombinase (enzyme), in the presence of calcium, will convert pro-thrombin to thrombin
  • Activated thrombin will cleave fibrinogen, converting it to fibrin.
  • Factor XIII will carry out the cross-linking of the fibrin network, forming the blood clot
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the role of thrombin (factor IIA)?

A

Cleaves fibrinogen into fibrin, which forms the blood clot.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Production of small amounts of thrombin will very quickly trigger a…

A

positive feedback loop, which will lead to the production of large amounts of thrombin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Name 3 important coagulation factors in the coagulation cascade

A
  1. Calcium
  2. Phospholipids
  3. Plasma protein factors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the role of calcium in the coagulation cascade?

A

It is essential for many of the proteolytic steps of the coagulation cascade. It activates factors II, VII, IX, X.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Calcium activation of factors II, VII, IX, X requires … as a cofactor

A

Vitamin K

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is coumadin

A

Common anti-coagulant, blocks activation of factors II, VII, IX and X by calcium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Why do we need to do lab tests to screen activity of the coagulation cascade? PT/INR or PTT tests

A

These tests measure how long it takes for blood to clot and are used to monitor anticoagulation therapy.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How is coagulation restricted to the site of injury?

A
  • By blood flow: blood flow will wash away coagulation factors and platelets to limit the size of the platelet plug
  • Natural anticoagulants bind to receptors on normal endothelial cells, preventing coagulation to occur on healthy areas
  • Inhibitors of platelet adhesion
24
Q

Define fibrinolysis

A

Process by which the body breaks down and removes blood clots.

25
Q

What is the role of plasmin?
How is plasmin activated?

A

Plasminogen is converted to plasmin by plasminogen activators.
Plasmin breaks down fibrin and contributes to clot lysis.

26
Q

What is streptokinase?

A

Streptokinase is a bacterial product used clinically to lyse clots (it can activate plasminogen).

27
Q

Fibrinolysis leads to production of..

A

fibrin split products (FSPs)

28
Q

What do elevated levels of FSPs indicate?

A

Abnormal thrombotic states (excessive clot formation and breakdown)

29
Q

What is thrombosis

A

It is the pathologic counterpart of normal hemostasis. Abnormal blood clot formation leading to blood flow obstruction.

30
Q

Decribe Virchow’s triad

A

Virchow’s triad describes the 3 primary factors contributing to thrombosis.
* Endothelial injury/dysfunction
* Hyper-coagulability
* Abnormal blood flow

31
Q

Where does endothelial injury/dysfunction usually occur? How does dysfunctional endothelium contribute to thrombosis?

A

It often occurs in the heart and arteries (areas of high flow).

Dysfunctional endothelium will increase its secretion of pro-coagulant factors and decrease fibrinolysis.

32
Q

What are some causes of endothelial injury/dysfunction (6)

A
  • infection
  • abnormal blood flow
  • cytokines and other mediators
  • exposure to toxins (eg. cigarette smoke)
  • metabolic abnormalities (hypercholesterolemia)
  • physical injury
33
Q

Normally, blood flow is…

A

laminar

34
Q

Name two types of abnormal blood flow

A
  1. Stasis
  2. Turbulence
35
Q

Abnormal blood flow leads to…

A

endothelial cell injury/dysfunction (through flow-induced changes in gene expression) which promotes activation of coagulation.

36
Q

How can blood stasis lead to thrombosis (abnormal blood flow)?
What type of vessel does it usually occur in?

A
  • Blood flow is not sufficient to wash away clotting factors and platelets
  • Gives more time for platelets to come in contact

Usually occurs in veins (risk factor for venous blood clots).

37
Q

How can turbulent flow lead to thrombosis (abnormal blood flow)? What type of vessel does it usually occur in?

A
  • Leads to endothelial cell injury/dysfunction
  • Creates countercurrents and local pockets of stasis

Usually occurs in the heart and arteries (risk factor for cardiac and arterial thrombi).

38
Q

Define hypercoagulability

A

Condition in which blood has an increased tendency to form blood clots.

39
Q

What is the primary cause of hypercoagulability? What are some secondary risk factors (3)

A

Primary cause: genetically inherited mutations in coagulation factors

Secondary risk factors of hypercoagulability states:
- Immobilization (eg. after injury)
- Oral contraceptives and pregnancy
- Mucin from some carcinomas

40
Q

What is an emboli?

A

Solid, liquid or gas carried by blood to a distant site.

41
Q

What is a thromboembolus?

A

A blood clot that has broken loose from its site of origin and started propagating through the bloodstream.

42
Q

What are systemic emboli?

A

Emboli primarily derived from the heart or large arteries

43
Q

What are the two types of thrombi?

A

Arterial thrombi (white thrombi)
Venous thrombi (phlebothrombosis) (red thrombi)

44
Q

What are the key characteristics of arterial thrombi and venous thrombi? (4 features each)

A

Arterial thrombi
* White thrombi (rich in platelets)
* Occurs in zones of turbulence and endothelial injury/dysfunction
* Tissue infarction
* Embolism is rare

Venous thrombi
* Red thrombi (rich in RBCs trapped in the clot)
* Occurs in zones of blood stasis
* Congestion and edema in vascular beds
* Embolism is common

45
Q

What is a mural thrombus?

A

Thrombi occurring in heart chambers or aortic lumen

46
Q

What are vegetations?

A

Thrombotic masses forming on heart valves

47
Q

What is a key feature of thrombi under the microscope?

A

Lines of Zahn

48
Q

What are the possible fates of the thrombus (4)

A
  1. propagation (thrombus grows in size)
  2. embolization (thrombus detaches and travels through bloodstream)
  3. dissolution (breakdown of thrombus through fibrinolysis)
  4. organization and recanalization (thrombus becomes integrated into the blood vessel wall and new blood vessels form through it)
49
Q

What can happen if a venous thrombus forms above the knee joint?

A

Pulmonary embolism

50
Q

What is migratory thrombophlebitis?

A

Special subtype of thrombosis
* also called Thrombeau syndrome
* recurrent inflammation due to thrombosis
* usually associated with adenocarcinomas (pancreatic or lung cancer)

51
Q

What is disseminated intravascular coagulation (DIC)?

A

Widespread coagulation and thrombosis, leading to excessive clotting and excessive bleeding at the same time

52
Q

What is an infarction

A

Ischemic necrosis caused by occlusion of the vascular supply to the downstream affected tissue

53
Q

What are the effects of vascular occlusion

A

Can range from inconsequential effects to tissue necrosis leading to organ dysfunction and sometimes death

54
Q

What factors influence infarct development (4)

A
  1. Collateral blood supplies
    * These are alternative vessels supplying the tissue - more collateral blood supply will decrease the severity of the infarct
  2. Rate of occlusion
    * How quickly a vessel becomes blocked or obstructed
    * Sow occlusion gives time for compensatory mechanism to develop, rapid occlusion does not
  3. Intrinsic susceptibility of the tissue to ischemic injury
  4. Blood oxygenation
    * Low blood O2 increases the risk and severity of infarcts
55
Q

Describe the difference between red hemorrhagic infarcts and white hemorrhagic infarcts

A

Red (hemorrhagic) infarcts:
* Affected area appears red due to the presence of blood
* Occur in tissues with collateral blood supply (lungs, intestines)
* Associated with venous occlusions

White (hemorrhagic) infarcts:
* Affected tissue appears white or pale due to lack of blood flow
* Occur in solid organs with single blood supply (heart, kidney, spleen)
* Associated with arterial occlusions

56
Q

Infarcts tend to be shaped like…

A

a triangle i.e. wedge-shaped (and the wedge of the triangle points to where the blockage is)