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Pathology > Hemodynamic Disorders: Hemostasis > Flashcards

Hemodynamic Disorders: Hemostasis Flashcards

1
Q

normal hemostasis includes

A
  • platelets
  • endothelium
  • plasma clotting factors
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2
Q

function of platelets

A
  • maintenance of vascular integrity
  • platelet plug formation
  • platelet phospholipid complex expression (leads to promotion of coagulation cascade)
  • promotion of endothelial repair
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3
Q

name 2 platelet inhibitors

A
  1. cyclooxygenase inhibitors (aspirin)

2. ADP receptor antagonists (ticlopidine and clopidogrel)

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4
Q

what are other platelet inhibitors

A
  1. phosphodiesterase inhibitors (dipyridamole)

2. glycoprotein (GP) IIB/IIIa receptor antagoinsts

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5
Q

mechanism of phophodiesterase inhibitors

A

increases [ ] of cAMP and cGMP

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6
Q

function of endothelium

A
  • metabolic transfer
  • barrier functions
  • synthesis of mediators of interactions between endothelium and blood components
  • thomboresistance - prevents clotting
  • mediation of vascular repair
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7
Q

examples of endothelial thromboresistance

A
  • heparin-like molecules
  • PGI2 and nitric oxide (NO) synthesis
  • plasminogen activation
  • ADP degradation
  • thrombin inactivation
  • thrombomodulin production
  • protein S synthesis
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8
Q

where do heparin-like molecules act at

A

at interface of endothelial cells and plasma

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9
Q

function of heparin-like molecules

A

activate antithrombin III

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10
Q

activated antithrombin II cleaves

A

thrombin, factors Xa and IXa

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11
Q

what is thrombomodulin

A

endothelial surface protein

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12
Q

thrombomodulin is a receptor for

A

thrombin

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13
Q

thrombomodulin binds thrombin and coverts it to an

A

activator of protein C

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14
Q

activated protein C (APC) cleaves factors

A

VA and VIIIa

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15
Q

protein S is a cofactor for

A

activated protein C

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16
Q

other functions of activated protein C

A
  • contributes to significant reduction of mortality in patients with severe sepsis
  • attenuates various deleterious events induced by lipopolysaccharide (LPS)
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17
Q

activated protein C has associated —- and — effects

A

anti-inflammatory

profibrinolytic

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18
Q

activated protein C inhibits

A

tumor necrosis factor-alpha (TNF-alpha) production

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19
Q

events initiated by endothelial disruption

A
  • vasoconstriction (neurogenic, endothelin)
  • platelet adhesion and aggression
  • release of TxA2
  • initiation of coagulation
  • fibrinolysis
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20
Q

what are the 3 distinct phases of the newest representation

A
  • initiation
  • propagation
  • termination
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21
Q

what are initiation

A

-chemical or mechanical damage to tissue

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22
Q

function of initiation

A
  • exposes tissue factor (TF) to the plasma circulation

- induces TF expression by monocytes, activated endothelium

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23
Q

Tissue factors interacts with a small amount of

A

preexistant factor VIIa in the plasma

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24
Q

interaction of TF and preexistant factor VIIa form

A

extrinsic tenase (TF/VIIa/IX/X) on a phospholipid surface

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25
Q

rapid inactivation of the extrinsic tenase by

A

tissue factor pathway inhibitor (TFPI)

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26
Q

extrinsic tenase generates small amounts of factors

A

IXa and Xa

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27
Q

Xa cleaves

A

prothrombin (II) to form small amounts of thrombin (IIa)

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28
Q

initial small amounts of thrombin activates

A

cofactor proteins
factors V and VIII to VA and VIIIa
platelets

29
Q

cofactor activation initiates assembly on

A

platelet phospholipid surface of intrinsic tenase (VIIIa/IX/X) which leads to Xa activation

30
Q

function of prothrominase (Va/Xa/II/Ca++)

A

accelerates thrombin formation (IIa)

31
Q

thrombin and fibrinogen form

A

fibrin

32
Q

function of fibrin

A
  • removal of fibrinopeptide A and B

- cross-linking

33
Q

termination

A

formation of thrombin/thrombomodulin complex activates protein C which inactivates Va and VIIIa

34
Q

how is extrinsic tense inactivated

A

spontaneous decay of TFPI

35
Q

inactivation of Xa and thrombin (IIa) by

A

antithrombin III

36
Q

prothrombin time (PT) is a measure of

A

extrinsic pathway of coagulation

37
Q

Prothrombin Time measures factors

A

VII, X, V, II and fibrinogen

38
Q

prothrombin time is a mixture of

A

thromboplastin (tissue factor) plasma, calcium ion

39
Q

expect a clot to form in —s when using PT

A

12 seconds

40
Q

partial thromboplastin time is a measure of

A

intrinsic pathway of coagulation

41
Q

PTT measures factors

A

XII, XI, IX, VIII, X, V, II, fibrinogen

42
Q

PTT is a mixture of

A

phospholipid platelet substitude (partial thromboplastin), plasma, calcium ions

43
Q

a clot form in —s with PTT

A

25 seconds

44
Q

name 2 disorder of hemostasis

A
  1. antithrombotic (hemorrhagic) disorder

2. prothrombotic (hypercoaguable) states

45
Q

what are the antithrombotic (hemorrhagic) disorders

A
  • classic hemophilia
  • Christmas disease
  • von Willebrand’s disease
  • disseminated intravascular coagulation with consumption coagulopathy etc.
46
Q

what are the prothombotic (hypercoaguable) states

A
  • hereditary thrombophilia
  • lupus anticoagulant
  • HIT syndrome (heparin induced thrombocytopenia and thrombosis syndrome)
  • disseminated intravascular coagulation (DIC)
47
Q

hereditary thrombophilia is most often present in

A

adolescents or young women

48
Q

hereditary thrombophilia presents with

A
  • venous thrombosis

- recurrent thromboembolism

49
Q

name 2 hereditary thrombophilia

A

Factor V Leiden
Prothrombin 20210A transition
Methylene Tetrahydrofolate Reductase Mutation

50
Q

Factor V Leiden has a mutation in

A

factor V

causes resistance to activated protein C

51
Q

what are the 3 Hereditary THrombophilia deficiencies

A
  1. antithrombin III deficiency
  2. protein C deficiency
  3. protein S deficiency
52
Q

Genes implicated in hereditary thrombophilia

A
  • factor V Leiden and other factor V variants
  • prothrombin 20210G-A polymorphism
  • hyperhomocysteinemia and homocystinuria
  • antithrombin 3
  • protein C
  • protein S
  • numerous others
53
Q

lupus anticoagulant has a prolonged — test

A

partial thromboplastin time

54
Q

in lupus anticoagulant what interfers with PTT test

A

antiphopholipid antibodies

55
Q

symptoms of Lupus Anticoagulant

A
  • increased venous and arterial thrombosis

- sometimes associated with autoimmune diseases such as SLE

56
Q

what is HIT syndrome

A

heparin-induced thrombocytopenia (and thrombosis)

57
Q

HIT syndrome is caused by

A

antibodies to the complex of heparin and platelet factor 4 (PF4)

58
Q

HIT syndrome is related to what kind of therapy

A

therapy with high molecular weight heparin (avoided by using low molecular weight heparin)

59
Q

HIT syndrome is clinically characterized by

A

heparin induced thrombocytopenia followed by thrombotic complications (cause too much clotting)

60
Q

disseminated intravascular coagulation (DIC) is caused by

A
  • an obstetric complication caused be:
  • retained dead fetus
  • premature separation of placenta (abruptio placentae)
61
Q

DIC is gram —- species

A

negative

62
Q

DIC can lead to what type of trauma

A
  • leg surgery

- hemolytic transfusion rxns

63
Q

DIC can cause what type of malignancy

A

lung, pancrease, other

64
Q

what is DIC

A

widespread deposition of fibrin in microvasculature

65
Q

what factors are involved with DIC

A

factor VII, V, II and fibrinogen

66
Q

what is consumption of coagulopathy

A
  • depletion of platelets and coagulation factors

- associated with DIC

67
Q

DIC has prolongation of

A
  • prothrombin time (V,II, fibrinogen)
  • PTT (VIII, V, II, fibrinogen)
  • thrombin time (fibrinogen)
68
Q

DIC has presence of

A

fibrin-fibrinogen degradation (split) products (FDP)

Pathology (18 decks)

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