Hemostasis 1 (Thomas) Flashcards

(91 cards)

1
Q

What are the microscopic features of healthy platelets?

A

Round, ovoid, or elongated; contain fine pink to purple granules

If larger than normal RBCs, they are likely stress platelets, mega platelets, or giant platelets.

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2
Q

What indicates the presence of platelet clumps in a blood smear?

A

Finding clusters of platelets on the smear (especially at the edges) indicates clumping and helps explain spurious thrombocytopenia.

This may lead to a mistakenly decreased automated platelet concentration.

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3
Q

Why may platelets lack granules in blood smears?

A

Platelets may become activated during collection, releasing granules as part of the activation process

Granules may also become centralized in activated platelets.

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4
Q

Why may platelets have pseudopods on blood smears?

A

Platelets may have pseudopodia if activated during collection

Pseudopodia are temporary, arm-like projections from an activated platelet that are critical for its function in hemostasis, or the process of stopping bleeding.

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5
Q

What is the lifespan of platelets in health?

A

Approximately 5-10 days, varies by species

Life span comparison: RBCs > platelets > neutrophils.

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6
Q

What is the major mediator of thrombopoiesis and where is it produced?

A

Thrombopoietin (TPO), produced in the liver.

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7
Q

Function of platelets?

A
  • Primary hemostasis to patch lesions in vessel wall
  • Provide a surface to support secondary hemostasis (=coagulation)
  • Promotes vascular repair and revascularization

With activation (in vivo/in vitro), may:
* Form pseudopods
* Centralize and release granules
* Aggregate

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8
Q

Cell source of platelets in mammals?

A

Bone marrow, specifically megakaryocytes.

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9
Q

What happens to phosphatidylserine during platelet activation?

A

Phosphatidylserine flips from the inner platelet membrane to the outer membrane.

Provides a surface for coagulation factors to bind, supporting secondary hemostasis.

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10
Q

Describe the process of primary hemostasis.

A
  1. Endothelial damage exposes collagen
  2. vWF binds collagen → platelets tether
  3. Platelets activate & release ADP + TxA2
  4. Platelets change shape, expose fibrinogen binding sites
  5. Platelets aggregate to form platelet plug
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11
Q

List the major cells and molecules involved in primary hemostasis.

A
  • Platelets
  • vWF
  • Collagen
  • Fibrinogen
  • Vessel wall (endothelium, sub-endothelium)
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12
Q

Explain process of platelet adhesion, including the role of VWF and collagen.

A

When endothelium is damaged, sub-endothelium collagen is exposed.

  • vWF binds to this collagen and undergoes a conformational change that exposes binding sites for platelet receptors.

Freely flowing platelets will tether to vWF and make contact with collagen.

  • This will trigger degranulation of TxA2 and ADP, shape change, and exposure of membrane flipping.
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13
Q

Why is vWF more important in vessels with high shear as compared to vessels
with slow blood flow and low shear?

A

In fast flowing vessels, high shear gives platelets very little time to attach due to strong force that disrupts weak bonds.
* VWF is essential for rapid, strong capture of platelets more efficiently.

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14
Q

Role of granules in the formation of the primary hemostatic plug?

A

Granules provide the chemical signals (ADP, plus TxA2 synthesis) that propagate and amplify platelet activation and recruitment, ensuring enough platelets are linked together by fibrinogen to form the primary hemostatic plug.

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15
Q

Role of fibrinogen in the formation of the primary hemostatic plug?

A

Fibrinogen acts as a bridging molecule, binding to exposed fibrinogen receptors on adjacent platelets.

This results in platelet aggregation, linking platelets together to form the primary hemostatic plug.

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16
Q

After platelets are activated, they release ___ (dense granules) and ________________, which drive further activation and recruitment.

A

After platelets are activated, they release ADP (dense granules) and thromboxane A2 (TxA2), which drive further activation and recruitment.

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17
Q

When platelets are activated…

they undergo a ___________ (pseudopod formation and spreading).

This activation/shape change process is what enables the __________________ on platelet ________________ (primarily GPIIb/IIIa) to be expressed and functional.

A

they undergo a shape change (pseudopod formation and spreading).

This activation/shape change process is what enables the fibrinogen binding site on platelet surface receptors (primarily GPIIb/IIIa) to be expressed and functional.

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18
Q

Phosphatidylserine (PS) flips from
_______ membrane to ______ member for provide surface for ____________(secondary hemostasis).

A

Phosphatidylserine (PS) flips from inner membrane to outer membrane to provide surface for coagulation (secondary hemostasis).

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19
Q

Source of thromboxane A2?

A

Thromboxane A2 (TxA2) is produced from platelet membrane lipids after platelets are activated.

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20
Q

______________ hemostasis (coagulation) is an enzymatic cascade that’s stimulated at the same time as __________ hemostasis.

A

Secondary hemostasis (coagulation) is an enzymatic cascade that’s stimulated at the same time as primary hemostasis.

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21
Q

Secondary hemostasis…

Leads to __________ generation from ____________.

A

Leads to thrombin (F2a) generation from prothrombin (F2).

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22
Q

Roles that thrombin plays in hemostasis?

A
  • Cleaves fibrinogen –> fibrin to stabilize primary hemostatic plug
  • Activates platelets & factors V, VIII, and XI
  • Feedbacks on coagulation cascade
  • Activates FXIIIa which crosslinks fibrin at D regions to stabilize clot
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23
Q

Role of fibrinogen in hemostasis?

A

Fibrinogen, when turned into fibrin, assists with secondary homeostasis to form a thrombus (clot) during coagulation.

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24
Q

Role of fibrinogen in the coagulation cascade?

A
  • Fibrinogen (F1) is cleaved into fibrin by thrombin (IIa)
  • Fibrin monomers form protofibrils, which is usually unstable.
  • Protofibrils cross link at a “D region” to stabilize clot – done by Factor XIIIa (activated by thrombin). This is a stable form.
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25
Organ responsible for producing most of the coagulation factors.
Coagulation factors (in coagulation cascade) include enzymes & non-enzymatic co-factors. These are usually produced in the **liver.**
26
Role of Ca cations in coagulation, how anticoagulants used for blood collection prevent clotting, and why hypocalcemia causes clinical problems with hemostasis.
Ca+ cation is a cofactor and bridge for clotting factor and membrane interaction. Anticoagulants used in collection binds to Ca cation to prevent binding to the clotting factor and membrane. If animal has low Ca (hypocalcemia), this will impair the clotting process & cause bleeding disorders, however, usually the animal will be dead due to muscular complication rather than disrupted hemostasis.
27
# Secondary hemostasis... Thrombin cleaves __________ (F1) into ______ (F1a) to stabilize primary hemostatic plug (= platelet plug).
Thrombin cleaves **fibrinogen (F1)** into **fibrin (F1a)** to stabilize primary hemostatic plug (= platelet plug). ## Footnote Also activates platelets = recruit extra platelets to form secondary plug
28
Where is phosphatidylserine found in resting platelets?
Phosphatidylserine (PS) is a located in the inner membrane in resting platelets.
29
What happens to phosphatidylserine with platelet activation, and what role does it play in coagulation?
During platelet activation, PS is flipped out to the outer membrane and provides a surface for coagulation factors bind to PS (supports secondary hemostasis).
30
What initiates activation of the intrinsic coagulation pathway?
Contact with negatively charged surfaces, primarily collagen in the vessel wall.
31
What initiates activation of the extrinsic coagulation pathway?
Exposure of tissue factor (TF = Factor III) binding to Factor VII in the presence of calcium ## Footnote Tissue factor is normally not in blood but expressed by activated endothelium and WBCs.
32
List the factors in the common coagulation pathway.
X → V → II → I | Enzymes: Xa, IIa ## Footnote Starts with X (10): X marks the spot; X is the crossroads Order: 10, 5, 2, 1 (10 / 5 = 2(1))
33
What role does thrombin play in hemostasis?
Cleaves fibrinogen to fibrin, activates platelets & factors V, VIII, and XI, and crosslinks fibrin to stabilize the clot.
34
What is the role of fibrinogen in hemostasis?
Fibrinogen is cleaved into fibrin by thrombin, forming a stable clot through crosslinking.
35
What is the appropriate blood tube for coagulation tests?
Blue top (trisodium citrate).
36
What does the Prothrombin Time (PT) test measure?
The time it takes plasma to clot after addition of tissue factor and calcium, assessing the extrinsic pathway.
37
What is the significance of finding pseudopodia on platelets?
Indicates activation during the collection process.
38
What is the primary function of platelets?
Primary hemostasis to patch lesions in the vessel wall.
39
Describe the role of thromboxane A2 in hemostasis.
Acts with ADP to further activate platelets and recruit additional platelets to the injury site. ## Footnote This amplifies aggregation, ensuring enough platelets express fibrinogen-binding receptors so that fibrinogen can link adjacent platelets and form the primary hemostatic plug.
40
What are the three major pathways of secondary hemostasis?
* Intrinsic pathway * Extrinsic pathway * Common pathway
41
What happens to platelets when they are activated?
They release ADP and thromboxane A2, undergo shape change, and express fibrinogen binding sites.
42
What is the source of most coagulation factors?
Produced in the liver.
43
What is the role of calcium cations in coagulation?
Serves as a cofactor for clotting factor and membrane interaction.
44
What is the difference between primary and secondary hemostatic plugs?
Primary is fragile and unstable, while secondary is stable and forms a thrombus.
45
What stabilizes the primary hemostatic plug?
Fibrinogen links adjacent platelets via fibrinogen receptors.
46
How does hypocalcemia affect hemostasis?
It impairs the clotting process, potentially causing bleeding disorders.
47
List the factors in the intrinsic coagulation pathway in order.
* XII (12) * XI (11) * IX (9) * VIII (8) * X (10)
48
What is the role of phosphatidylserine in coagulation?
Provides a surface for coagulation factors to bind during secondary hemostasis.
49
True or False: The extrinsic pathway is initiated by tissue factor found in blood.
False ## Footnote Tissue factor is normally not in blood.
50
What activates fibrinogen (I) to fibrin (Ia)?
IIa | Thrombin
51
What stabilizes the initial clot plug?
Fibrin cross-linked by XIIIa | XIIIa = 13a
52
What is the appropriate blood tube for coagulation tests?
Blue top (trisodium citrate)
53
What does Prothrombin Time (PT) measure?
The time it takes plasma to clot after addition of tissue factor and calcium
54
Which pathways are assessed by PT?
* Extrinsic pathway (Factor VII) * Common pathway (Factors X, V, II [prothrombin], and fibrinogen [F1])
55
What clinical conditions can PT help detect?
* Vitamin K deficiency * Liver disease * Warfarin therapy * Deficiencies of factors VII, X, V, II, or fibrinogen
56
What does Partial Thromboplastin Time (PTT or aPTT) measure?
The time it takes plasma to clot after addition of a contact activator, phospholipid, and calcium
57
Which pathways are assessed by PTT?
* Intrinsic pathway (Factors XII, XI, IX, VIII) * Common pathway (Factors X, V, II, fibrinogen)
58
What clinical conditions can PTT help detect?
* Hemophilia A or B * Heparin therapy * Lupus anticoagulant * Severe liver disease * Deficiencies of intrinsic pathway factors
59
What is the key distinction between PT and PTT?
* PT = extrinsic + common pathway * PTT = intrinsic + common pathway
60
What are the clinical consequences of coagulation defects?
* Deep tissue hemorrhage (hematomas, hemarthroses, intramuscular bleeds) * Delayed bleeding after trauma or surgery
61
What are examples of coagulation defects?
* Hemophilia A (factor VIII deficiency) * Hemophilia B (factor IX deficiency) * Vitamin K deficiency * Liver disease * Anticoagulant therapy
62
Describe the major coagulation pathway in vivo and where the coagulation occurs.
**Intrinsic pathway** Initiated by TF/VIIa → small thrombin Amplification: thrombin feedback → lots of thrombin Requires TF-bearing cell + PS platelet Coagulation occurs at the site of a blood vessel injury, where the endothelium is damaged, and subendothelial tissue becomes exposed to the blood.
63
Which coagulation pathways involve vitamin K-dependent factors?
All three (extrinsic, intrinsic, and common) involve vitamin K-dependent factors. Vitamin K dependent factors: II, VII, IX, X (2, 7, 9, 10)
64
What are the laboratory consequences of intrinsic pathway defects?
* ↑ aPTT (PTT prolonged) * Normal PT
65
What are the laboratory consequences of extrinsic pathway defects?
* ↑ PT (prolonged) * Normal aPTT
66
What are the laboratory consequences of Common pathway defects?
* ↑ PT and ↑ aPTT * May also see low fibrinogen or evidence of consumption (↑ D-dimers in DIC)
67
What initiates the formation of the primary hemostatic plug?
Endothelial damage → collagen is exposed → von Willebrand factor (vWF) rapidly binds to collagen.
68
What conformational change occurs in vWF, and why is it important?
vWF undergoes a conformational change → exposes binding sites for platelet receptors → platelets tether to the injured site and become activated.
69
What do activated platelets secrete and from where?
ADP from dense granules; Thromboxane A2 (TxA2) produced from membrane lipids.
70
What is the function of ADP and Thromboxane A2 in primary hemostasis?
They recruit and activate additional platelets to the site of injury.
71
How do platelets change shape during activation?
Platelets transform from smooth, round cells into irregular cells with pseudopods, increasing their surface area for binding.
72
What changes occur on platelet membranes during activation?
Platelets expose fibrinogen binding sites on their receptors; Phosphatidylserine flips to the outer membrane, providing a surface for coagulation factor assembly.
73
How do platelets bind to each other in the primary plug?
Platelets are cross-linked via fibrinogen, which binds to fibrinogen receptors on adjacent platelets.
74
What are the characteristics of the primary hemostatic plug?
Fragile and unstable; Provides rapid bleeding control in small vessels.
75
What triggers the intrinsic pathway of secondary hemostasis?
Contact with negatively charged surfaces (e.g., collagen).
76
Why is it called the 'intrinsic' pathway?
Because all the required factors are normally present within the blood vessels.
77
How can we demonstrate intrinsic factors in collected blood?
They will be present in blood collected in a tube without anticoagulants.
78
Describe the intrinsic pathway activation sequence.
XII → XIIa upon contact with negatively charged collagen; XIIa activates XI → XIa (with calcium); XIa activates IX → IXa; IXa, with cofactor VIIIa, calcium, and a phospholipid surface, continues the cascade.
79
What triggers the extrinsic pathway of secondary hemostasis?
Expression of tissue factor (TF, Factor III) by extravascular cells or monocytes.
80
Why is it called the 'extrinsic' pathway?
Because tissue factor is **not** normally present in circulating blood.
81
Describe the extrinsic pathway activation sequence.
* TF binds to Factor VII in the presence of calcium * On a phospholipid surface, TF–VII complex activates X → Xa * TF–VII complex also activates IX → IXa (this activation occurs only in vivo).
82
What initiates the common pathway?
Factor X activation → Xa.
83
How can Factor X be activated?
By the TF–VIIa complex (extrinsic pathway); By the IXa–Ca–phospholipid–VIIIa complex (intrinsic pathway).
84
Describe the key steps of the common pathway.
Xa with calcium, phospholipid, and cofactor Va converts Prothrombin (II) → Thrombin (IIa); Thrombin converts Fibrinogen (I) → Fibrin (Ia); Factor XIIIa cross-links fibrin, stabilizing the clot.
85
What is the difference in stability between primary and secondary plugs?
**Primary plug** = fragile, temporary, stops bleeding quickly but not durable **Secondary plug** = stabilized by fibrin cross-linking, strong enough to maintain hemostasis long-term.
86
What is TxA2?
**Thromboxane A2** Potent lipid mediator produced primarily by platelets that promotes platelet aggregation, vasoconstriction, and smooth muscle contraction.
87
What is ADP?
**Adenosine diphosphate** Crucial signaling molecule released by platelets at the site of vascular injury that triggers a cascade of events leading to the formation of a temporary platelet plug.
88
Where is vWF produced?
Endothelial cells
89
What is factor III?
Tissue factor
90
What factors are involved in the extrinsic pathway?
* Tissue factor (III) * Factor VII (7)
91
What factors are involved in intrinsic pathway?
* VII (12) * XI (11) * IX (9) * VIII (8)