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

Lec 4: Bleeding & Thrombosis Flashcards

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
Q

Give examples of substances that activate fibrolytic mechanisms

A

Tissue Plasminogen Activator 1, Urokinase, Annexin-2

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26
Q

How does Antithrombin neutralize Thrombin?

A

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

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27
Q

What plasma glycoprotein becomes an anticoagulant when it is activated by thrombin?

It also enhances the activation efficiency of the thrombin-thrombomodulin complex

A

Protein C

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28
Q

What is a transmembrane proteoglycan-binding site for thrombin on endothelial cell surfaces?

A

Thrombomodulin

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29
Q

How does protein C act as an anticoagulant? And what is its cofactor?

A

by cleaving and inactivating Factors V and VIII

Protein S

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30
Q

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..

A

Hypercoagulability states

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31
Q

This is a plasma protease inhibitor that regulates the TF-induced extrinsic pathway of coagulation

A

Tissue Factor Pathway Inhibitor (TFPI)

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32
Q

What is activated to dispose of intravascular fibrin and thereby maintain or reestablish the patency of circulation?

A

Endogenous Fibrolytic System

33
Q

What is the major protease enzyme of the fibrinolytic system?

34
Q

What enzymes cleave the Arg60-Val561 bond of plasminogen to generate the active enzyme plasmin?

A

Tissue Type Plasminogen Activator (tPA) and Urokinase-type Plasminogen Activator (uPA)

35
Q

The physiologic fibrinolysis is termed “_____” because the lysine-binding sites of plasmin permit it to bind to fibrin

A

Fibrin-specific

36
Q

The ternary complex is composed of…

A

fibrin, plasminogen, and tPA

37
Q

This complex promotes localized interaction between plaminogen and tPA and greatly accelerates the rate of plasminogen activation to plasmin

A

Ternary Complex

38
Q

What is released when plasmin acts on covalently cross-linked fibrin?

39
Q

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.

40
Q

Physiologic regulation of fibrinolysis occurs primarily at what levels? (3)

A
  1. plasminogen activator inhibitors inhibit physiological plasminogen activators
  2. thrombin-activatable fibrinolysis inhibitor (TAFI) limits fibrinolysis
  3. alpha 2-antiplasmin inhibits plasmin
41
Q

What is the hallmark of moderate and severe factor VIII and IX deficiency

A

hemarthroses

42
Q

These symptoms are more suggestive of underlying platelet disorders or vW disease

A

Mucosal Bleeding

43
Q

What has been validated as a tool to predict patients more likely to have type 1 VWD?

A

Bleeding Score

44
Q

A low bleeding score (less than/equal to 3) and a normal aPTT had 99% negative predictive value for the diagnosis of what disease?

A

von Willebrand Disease

45
Q

If there is posttraumatic bleeding and a history of hyperextensibility, what is the disease?

A

Ehlers-Danlos Syndrome

46
Q

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

A

Cushing’s Syndrome

47
Q

It is the most common symptom in hereditary hemorrhagic telangiectasia and in BOYS with VWD

48
Q

Quantitative loss of >80ml of blood per mestruation cycle

A

Menorrhagia

49
Q

What are the predictors of menorrhagia?

A

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
Q

What substances impair primary hemostasis and may exacerbate bleeding from another cause or even unmask a previously occult mild bleeding disorder such as VWD?

A

Aspirin and NSAIDs

51
Q

What supplement can impare platelet function?

A

Fish-oil or concentrated omega-3 fatty acid supplements

52
Q

What Vitamin inhibits protein kinase C-mediated aggregation and nitric oxide production?

53
Q

Factors II, VII, IX, and X and proteins C and S are dependent on what Vitamin?

54
Q

Vitamin K deficiency results in

55
Q

This results from decreased productiopn, increase destruction, and or sequestration of platelet

A

Thrombocytopenia

56
Q

What are the normal levels of platelet in blood?

A

150,000-450,000/uL

57
Q

bleeding occurs in what levels of platlet count?

A

10,000-20,000/uL

58
Q

What is the level of platelet count needed for surgery?

59
Q

What is the major risk factor for arterial thrombosis?

A

Atherosclerosis

60
Q

What are the risk factors for venous thrombosis?

A

immobility, surgery, underlying medical conditions such as malignancy, medications such as hormonal therapy, obesity, and genetic predisposition

61
Q

In patient without underlying malignancy, having _____ is the strongest predictor of recurrence of Venous Thrombus Embolism

A

Idiopathic Event

62
Q

what are symptoms of hemarthroses?

A

severe pain and swelling, loss of function, (rarely) discoloration from bruising around the joint

63
Q

What is the essential cofactor in conversion of prothrombin to thrombin?

64
Q

What is the size of petechiae?

65
Q

What is the size of purpura?

66
Q

What is the size of ecchymoses?

67
Q

Rupture of ovarian cysts with intraabdominal hemorrhage results to

A

Postpartum bleeding

68
Q

Give examples of ACQUIRED bleeding disorders

A

Liver disease, Severe Renal Impairement, Hypothyroidism, Paraproteinemias or amyloidosis, Bone marrow failure

69
Q

History of what drug may suggest past DVT?

70
Q

What is assessed when Prothrombin Time is requested for a patient?

A

Function of Extrinsic and Common Pathway

71
Q

What is assessed when Activated Partial Thromboplastin Time is requested for the patient?

A

Intrinsic and common pathway

72
Q

What is assessed in Thrombin time?

A

Intrinsic and Extrinsic Pathways

73
Q

Hereditary disorders diagnosed with the use of aPTT

A 
Hemophilia a (Factor VIII deficiency)
Hemophilia b (Factor IX deficiency)
74
Q

This assesses anticoagulation due to reduction of Vit K-dependent coagulation factors. Roughly predicts the bleeding risk in liver disease

A

International Normalized Ratio (INR)

75
Q

Prolonged Prothrombin time is seen in what diseases?

A

Factor VII deficiency, early Vit K deficiency, Warfarin anticoagulation

76
Q

Prolonged aPTT and PT is seen in?

A

Factor II, V, or X deficiency, late Vit K deficiency, direct thrombin inhibitors

77
Q

This is used to distinguish bet a factor deficiency and an inhibitor

A

Mixing studies

78
Q

Predictors for recurrent thrombosis

A

D-dimer assay, thrombin generation test

79
Q

For minor surgeries, what is the minimum platelet count required?

Internal Medicine I (4 decks)

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