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Internal Medicine I > Lec 4: Bleeding & Thrombosis > Flashcards

Lec 4: Bleeding & Thrombosis Flashcards

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1
Q

What do you call the following : platelet adhesion, aggregation and fibrin clot formation.

A

Procoagulant forces

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2
Q

What are the major components of the hemostatic system?

A
  1. ) Platelets and other formed elements (monocytes and rbcs)
  2. ) Plasma Proteins
  3. ) Vessel Walla
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3
Q

On vascular injury, where do platelets adhere?

A

Denuded vascular intimal surface

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4
Q

Platelet adhesion is mediated by?

clue “molecular glue”

A

von Willebrand Factor

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5
Q

After adhesion, what happens next?

A

Platelet activation and aggregation

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6
Q

Platelet activation and aggregation are enhanced and amplified by?

A

Humoral mediators (eg epinephrine, thrombin)
Mediators from activated platelets (eg ADP, Serotonin)
Vessel Wall ECM

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7
Q

What anchors and stabilizes the platelet plug?

A

Developing fibrin mesh

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8
Q

What is the most abundant receptor on the platelet surface?

it is also an effective target for antiplatelet therapy.

A

GpIIb-IIIa

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9
Q

What receptor on the platelet surface binds with vWF?

A

Gp1b

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10
Q

What converts Gp IIb-IIIa into an active receptor?

A

Platelet activation

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11
Q

The coagulation cascade culminates in…

A

formation of Fibrin

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12
Q

What pathway is initiated by Tissue Factor/ Factor III

A

Extrinsic Pathway

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13
Q

What amplifies the tissue factor pathway?

A

Intrinsic Pathway

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14
Q

What is the immediate trigger for coagulation?

A

Vascular damage…exposing blood to Tissue Factor

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15
Q

Where is the tissue factor found?

A

on the surfaces of the subendothelial cellular components of the vessel wall

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16
Q

Tissue Factor is also shed from…

A

monocytes and platelets

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17
Q

What is the function of factor XIa?

A

propagation and amplification

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18
Q

What happens after the TF binds the serine protease factor VIIa?

A

Activation of Factor X to Factor Xa

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19
Q

TF-Factor VII complex can also activate Factor X INDIRECTLY via…

A

converting Factor IX to Factor IXa

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20
Q

What do you call the multifunctional enzyme that converts soluble plasma fibrinogen into insoluble fibrin matrix?

A

Thrombin

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21
Q

Thrombin also activates…

clue: factor that stabilizes fibrin clot

A

Factor XIII (fibrin-stabilizing factor) into Factor XIIIa

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22
Q

What do you call the mechanisms that seek to preserve blood fluidity and to limit blood clotting to specific local sites of vascular injury?

A

Antithrombotic mechanisms

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23
Q

Give examples of substances that inhibit platelet binding, secretion, and aggregation.

A

Prostacyclin, Nitric Oxide, ectoADPase/ CD39

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24
Q

What are example of anticoagulant factors produced by the endothelial cells?

A

Heparan Proteoglycans, Antithrombin, TF Pathway Inhibitors, Thrombomodulin

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25
Give examples of substances that activate fibrolytic mechanisms
Tissue Plasminogen Activator 1, Urokinase, Annexin-2
26
How does Antithrombin neutralize Thrombin?
by forming a complex between the active site of the enzyme and the reactive center of the antithrombin. rate of the formation of the complex increases with the presence of Heparin
27
What plasma glycoprotein becomes an anticoagulant when it is activated by thrombin? It also enhances the activation efficiency of the thrombin-thrombomodulin complex
Protein C
28
What is a transmembrane proteoglycan-binding site for thrombin on endothelial cell surfaces?
Thrombomodulin
29
How does protein C act as an anticoagulant? And what is its cofactor?
by cleaving and inactivating Factors V and VIII | Protein S
30
Quantitative or qualitative deficiencies of Protein C or S, or resistance to the activation of protein C by a specific mutation at its target cleavage site in factor Va leads to..
Hypercoagulability states
31
This is a plasma protease inhibitor that regulates the TF-induced extrinsic pathway of coagulation
Tissue Factor Pathway Inhibitor (TFPI)
32
What is activated to dispose of intravascular fibrin and thereby maintain or reestablish the patency of circulation?
Endogenous Fibrolytic System
33
What is the major protease enzyme of the fibrinolytic system?
Plasmin
34
What enzymes cleave the Arg60-Val561 bond of plasminogen to generate the active enzyme plasmin?
Tissue Type Plasminogen Activator (tPA) and Urokinase-type Plasminogen Activator (uPA)
35
The physiologic fibrinolysis is termed "_____" because the lysine-binding sites of plasmin permit it to bind to fibrin
Fibrin-specific
36
The ternary complex is composed of...
fibrin, plasminogen, and tPA
37
This complex promotes localized interaction between plaminogen and tPA and greatly accelerates the rate of plasminogen activation to plasmin
Ternary Complex
38
What is released when plasmin acts on covalently cross-linked fibrin?
D-dimers
39
D-dimers can be measured in plasma as a relative specific test of ______ degradation and has been validated for clincal use to exclude DVT and pulmonary embolism.
Fibrin
40
Physiologic regulation of fibrinolysis occurs primarily at what levels? (3)
1. plasminogen activator inhibitors inhibit physiological plasminogen activators 2. thrombin-activatable fibrinolysis inhibitor (TAFI) limits fibrinolysis 3. alpha 2-antiplasmin inhibits plasmin
41
What is the hallmark of moderate and severe factor VIII and IX deficiency
hemarthroses
42
These symptoms are more suggestive of underlying platelet disorders or vW disease
Mucosal Bleeding
43
What has been validated as a tool to predict patients more likely to have type 1 VWD?
Bleeding Score
44
A low bleeding score (less than/equal to 3) and a normal aPTT had 99% negative predictive value for the diagnosis of what disease?
von Willebrand Disease
45
If there is posttraumatic bleeding and a history of hyperextensibility, what is the disease?
Ehlers-Danlos Syndrome
46
Chronic steroid and aging result in changes in skin and subcutaneous tissue, subcutaneous bleeding occurs in response to minor trauma. This is seen in what syndrome
Cushing's Syndrome
47
It is the most common symptom in hereditary hemorrhagic telangiectasia and in BOYS with VWD
Epistaxis
48
Quantitative loss of >80ml of blood per mestruation cycle
Menorrhagia
49
What are the predictors of menorrhagia?
Bleeding resulting in Iron Deficiency Anemia/ need for blood transfusion, passage of clots >1inch in diameter, and changing pad/tampon more than once hourly.
50
What substances impair primary hemostasis and may exacerbate bleeding from another cause or even unmask a previously occult mild bleeding disorder such as VWD?
Aspirin and NSAIDs
51
What supplement can impare platelet function?
Fish-oil or concentrated omega-3 fatty acid supplements
52
What Vitamin inhibits protein kinase C-mediated aggregation and nitric oxide production?
Vitamin E
53
Factors II, VII, IX, and X and proteins C and S are dependent on what Vitamin?
Vitamin K
54
Vitamin K deficiency results in
Bleeding
55
This results from decreased productiopn, increase destruction, and or sequestration of platelet
Thrombocytopenia
56
What are the normal levels of platelet in blood?
150,000-450,000/uL
57
bleeding occurs in what levels of platlet count?
10,000-20,000/uL
58
What is the level of platelet count needed for surgery?
80,000/uL
59
What is the major risk factor for arterial thrombosis?
Atherosclerosis
60
What are the risk factors for venous thrombosis?
immobility, surgery, underlying medical conditions such as malignancy, medications such as hormonal therapy, obesity, and genetic predisposition
61
In patient without underlying malignancy, having _____ is the strongest predictor of recurrence of Venous Thrombus Embolism
Idiopathic Event
62
what are symptoms of hemarthroses?
severe pain and swelling, loss of function, (rarely) discoloration from bruising around the joint
63
What is the essential cofactor in conversion of prothrombin to thrombin?
Factor Va
64
What is the size of petechiae?
65
What is the size of purpura?
2mm-1cm
66
What is the size of ecchymoses?
>1cm
67
Rupture of ovarian cysts with intraabdominal hemorrhage results to
Postpartum bleeding
68
Give examples of ACQUIRED bleeding disorders
Liver disease, Severe Renal Impairement, Hypothyroidism, Paraproteinemias or amyloidosis, Bone marrow failure
69
History of what drug may suggest past DVT?
Warfarin
70
What is assessed when Prothrombin Time is requested for a patient?
Function of Extrinsic and Common Pathway
71
What is assessed when Activated Partial Thromboplastin Time is requested for the patient?
Intrinsic and common pathway
72
What is assessed in Thrombin time?
Intrinsic and Extrinsic Pathways
73
Hereditary disorders diagnosed with the use of aPTT
``` Hemophilia a (Factor VIII deficiency) Hemophilia b (Factor IX deficiency) ```
74
This assesses anticoagulation due to reduction of Vit K-dependent coagulation factors. Roughly predicts the bleeding risk in liver disease
International Normalized Ratio (INR)
75
Prolonged Prothrombin time is seen in what diseases?
Factor VII deficiency, early Vit K deficiency, Warfarin anticoagulation
76
Prolonged aPTT and PT is seen in?
Factor II, V, or X deficiency, late Vit K deficiency, direct thrombin inhibitors
77
This is used to distinguish bet a factor deficiency and an inhibitor
Mixing studies
78
Predictors for recurrent thrombosis
D-dimer assay, thrombin generation test
79
For minor surgeries, what is the minimum platelet count required?
50,000/uL

Internal Medicine I (4 decks)

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