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Pathology > Thromboembolic Diseases > Flashcards

Thromboembolic Diseases Flashcards

1
Q

What is Hemostasis?

A

Process by which blood clots form at sites of vascular injury

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2
Q

What are the two groups of hemostasis disorders?

A
  1. Hemorrhagic disorder

2. Thrombotic disorder

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3
Q

What is a hemorrhagic disorder?

A

excessive bleeding due to either blunted or insufficient hemostasis mechanisms

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4
Q

What are thrombotic disorders?

A

Blood clots form within intact blood vessels or within chambers of the heart

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5
Q

What is Disseminated Intravascular Coagulation?

A

Generalized activation of clotting paradoxically produces bleeding due to consumption of coagulation factors

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6
Q

What is the first step of Hemostasis?

A

Arteriolar vasoconstriction

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7
Q

What is the role of Arteriolar Vasoconstriction in Hemostasis?

A

It immediately reduces blood flow to the injured area

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8
Q

What mediates arteriolar vasoconstriction in hemostasis?

A
  1. Reflex neurogenic mechanisms

2. Augmented by local secretion of factors such as endothelin

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9
Q

What are the steps of Hemostasis?

A
  1. Arteriolar Vasoconstriction
  2. Primary hemostasis
  3. Secondary hemostasis
  4. Clot Stabilization and Resorption
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10
Q

What happens in Primary Hemostasis?

A

There is formation of Platelet Plug

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11
Q

What are the steps in forming the Platelet Plug?

A
  1. Platelet adherence
  2. Platelet activation
  3. Release of secretory granules
  4. Recruitment of additional platelets
  5. Platelet Aggregation
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12
Q

How does the platelet adhere and activate in the first step of platelet plug formation?

A

It adheres due to the disruption of the endothelium exposing subendothelial von Willebrand factor (vWF) and collagen. These promote adherence and activation

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13
Q

What happens when the platelets are activated?

A
  1. Shape change from small rounded disc to flat plates with spiky protrusions increasing surface area
  2. Release of secretory granules
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14
Q

What happens when the platelets release secretory granules?

A

There is recruitment of additional platelets, which undergo aggregation to form primary hemostatic plug

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15
Q

What happens in secondary hemostasis?

A

There is deposition of fibrin

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16
Q

What are the steps in secondary hemostasis?

A
  1. Exposing of tissue factor due to injury
  2. Tissue factor binds and activates factor VII
  3. Coagulation Cascade
  4. Thrombin generation
  5. Thrombin cleaving fibrinogen to fibrin
  6. Formation of fibrin mesh
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17
Q

What is a tissue factor?

A

A membrane-bound procoagulant glycoprotein that is normally expressed by subendothelial cells in the vessel wall such as smooth muscle cells and fibroblasts

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18
Q

What initiates the coagulation cascade?

A

Tissue factor binding and activating factor VII

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19
Q

What is the role of the fibrin mesh?

A

It consolidates the initial platelet plug

20
Q

What happens in Clot Stabilization?

A

Polymerized Fibrin and platelet aggregates undergo contraction to form a solid, permanent plug.

21
Q

What happens in Clot resorption?

A

Counterregulatory mechanisms are set into motion that limit clotting to the site of injury, eventually leading to clot resorption and tissue repair

22
Q

What are the counterregulatory mechanisms leading to clot resorption?

A

Tissue Plasminogen activator (t-PA), Thrombomodulin

23
Q

What are the secretory granules released by platelets?

A

ADP and thromboxane (TXA2)

24
Q

What is the function of t-PA?

A

Fibrinolysis

25
Q

What is the function of thrombomodulin?

A

Blocks coagulation cascade

26
Q

Where do platelets come from?

A

They are shed by megakaryotes in the bone marrow into the blood stream

27
Q

What are the two types of cytoplasmic granules found in platelets?

A

alpha granules

delta granules

28
Q

What do alpha granules contain?

A

they have the adhesion molecule P-selectin on their membranes and Proteins involved in coagulation and Proteins involved in Wound healing

29
Q

What are the proteins involved in coagulation that are found in P-selectin?

A

Fibrinogen, Coagulation factor V, vWF

30
Q

What are the proteins involved in Wound healing that are found in P-selectin?

A

Fibronectin, Platelet factor 4, Platelet-derived growth factor, Transforming growth factor beta

31
Q

Other than wound healing, what is the platelet factor 4 involved in?

A

It is a chemokine that binds to heparin

32
Q

What do the delta granules contain?

A

ADP, ATP, ionized calcium, serotonin, epinephrine

33
Q

What is the role of the von Willebrand factor?

A

It acts as a bridge between Platelet surface receptor glycoprotein Ib (GpIb) and exposed collagen

34
Q

What is the disease in where there is a deficiency in GpIb?

A

Bernard-Soulier Syndrome

35
Q

What accompanies the shape change of platelets?

A
  1. Alterations in glycoprotein IIb/IIIa

2. Translocation of negatively charged phospholipids (phosphotidylserine) to platelet surface

36
Q

What is the role of alteration of glycoprotein IIb/IIIa in coagulation?

A

It increases the affinity of platelets for fibrinogen

37
Q

What is the role of phosphatidylserine translocation in coagulation?

A

The phospholipids bind calcium and serve as nucleation sites for the assembly of coagulation factor complexes

38
Q

What is the receptor for thrombin found in platelets?

A

Protease-Activated Receptor (a G-protein-coupled receptor)

39
Q

What is the mechanism of action of aspirin as an anticoagulant?

A

It inhibits cyclooxygenase, an enzyme that is required for thromboxane synthesis

40
Q

What is the disease that is characterized by decreased GpIIb-IIIa?

A

Glanzmann thromboasthenia (inherited)

41
Q

What is the coagulation cascade?

A

It is a series of amplifying enzymatic reactions that leads to deposition of an insoluble fibrin clot.

42
Q

What would activate the intrinsic pathwaw?

A

Negatively charged substance such as glass beads

43
Q

What would activate the extrinsic pathway?

A

Exposure of tissue factor

44
Q

What are the Factors that require binding of Calcium?

A

Factors X, IX, VII, II

45
Q

Where does Calcium bind in Factors X, IX, VII and II?

A

They bind in the Gamma- carboxylated glutamic acid residues

Pathology (5 decks)

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