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PATH Heme-Onc II > Coagulation Disorders I & II > Flashcards

Coagulation Disorders I & II Flashcards

1
Q

outline the events of primary hemostasis

A

triggered by vessel injury:

  • adhesion phase:
    • vessel injury exposes 1. subendothelial collagen & 2. Von-Willebrand factor (vWF)
    • vWF binds collagen
    • vWF then binds GP-1b receptor on platelets, linking them to injury site.
  • activation phase. :
    • platelets change shape, which causes:
      • conformation change of GP-IIb & GP-IIIa to so that they → fibrinogen
      • binding of neg charged phospholipids to platelets to serve as a site for factors
    • platelets release granules
      • TXA-2: promotes aggregation
      • ADP: promotes aggregation, recruits more factors
    • activation of platelets by PAR, released by thrombin
  • aggregation phase - fibrinogen forms bridges between activated platelets
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2
Q

what is “irreversible” platelet contraction & what causes it?

A
  • = irreversible platelet aggregation
  • caused by stabilization of clot by thrombin, which cleaves fibrinogen to fibrin, which cross links the clot
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3
Q

what are the roles of the GP receptors on platelets?

A
  • GP-Ib: binds vWF on the exposed subendothelial collagen, linking the platelet to the injury site (adhesion phase)
  • GP-IIb & GPIIIa: bind fibrinogen (during activation phase) which is necessary for aggregation phase
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4
Q

what are protease activated receptors & their role in clotting?

A
  • released by thrombin
  • “activate” platelets to that they can aggregate
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5
Q

outline the events of secondary hemostasis

A
  • extrinsic pathway - initiated by tissue factor (TF)
    • TF cleaves VII → VIIa
    • VIIa cleaves IX → IXa
    • IXa cleaves X → Xa (common pathway starter)
  • intrinsic pathway - initiated by XII autoactivation or lab stimulus
    • XIIa cleaves XI → XIa
    • XIa cleaves IX → IXa
    • IXa, with the help of VIIIa, cleaves X → Xa (common path starter)
  • common pathway
    • Xa, with the help of Va, cleaves II (prothrombin) → IIa (thrombin), which
      • cleaves Ia (fibrinogen) to I (fibrin), which forms “stable” (irreversible) clot
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6
Q

outline the intrinsic pathway

A

part of secondary hemostasis

  • XIIa cleaves XI → XIa
  • XIa cleaves IX → IXa
  • IXa, with the help of VIIIa, cleaves X → Xa (common path starter)
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7
Q

outline the extrinsic pathway

A
  • extrinsic pathway - initiated by tissue factor (TF)
    • TF cleaves VII → VIIa
    • VIIa cleaves IX → IXa
    • IXa cleaves X → Xa (common pathway starter)
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8
Q

summarize the key roles of thrombin

A

pro-coagulation effects (at injury site):

  • primary hemostasis: produce PAR → activates platelets
  • secondary hemostasis:
    • fibrinogen → fibrin, making insoluble/stable clot
    • V, VII, XI & XIII activation (take 5 at 7-11 on friday the `3th)

anticoagulant effects (beyond injury site):

  • upon contacting normal endothelium, thrombin becomes prevent clotting from extending byeond injury site
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9
Q

what clotting factors does thrombin activate?

A
  • Ia (fibrin), and
  • Va, VIIa, XIa, XIIIa (take 5 at 7-II)
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10
Q

PAR

  • is produced by?
  • does what?
A
  • release is mediated by thombin
  • activates platelets in the activation phase of _primary hemostasi_s so that they can then aggregate
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11
Q

what clotting factors does thrombin activate?

A
  • Ia (fibrin), and
  • Va, VIIa, XIa, XIIIa (take 5 at 7-II on Friday the 13th)
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12
Q

summarize the counter-regulatory mechanisms are in place to limit the hemostatic process

A
  • induction of fibrinolysis by (t-PA)
  • factor dilution of blood flow past injury
  • restriction of clotting to injury site:
    • requirement of - charged phospholipids on platelets for factor activation
    • platelet inhibitors: they release
      • PGI2
      • NO
      • adenosine diphosphatase (degrades ATP)
    • anti-coagulant affects:
      • thrombomodulin & protein C: when thrombin binds healthy tissue
      • anti-thrombin: bound by heparin & heparin like molecules
      • tissue factor pathway inhibitor (TFPI)
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13
Q

outline fibrinolysis. what factors regulate fibrinolysis?

A
  • activated largely by tissue plasminogen activator (t-PA), which
    • converts plasminogen → plasmin, which:
      • breaks down fibrin & fibrinogen
      • is inhibited by a1-antiplasmin inhibitor
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14
Q

what is the role of plasmin in the coagulation?

A

serves as an counter-regulatory mechanism that limits the hemostatic process (anti-coagulant)

  • breaks down fibrin / fibrinogen
    • activated by tPA
    • inhibited by a2-antiplasmin inhibitor
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15
Q

what is the role of a2-antiplasmin inhibitor in coagulation?

A

inhibits free plasmin to limit excessive fibrinolysis

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16
Q

what pro-coagulant and anti-coagulant factors do platelets release?

A
  • pro-coagulant (activation phase of primary hematopoiesis)
    • ADP
    • TXA-2
  • anti-coagulant:
    • PGI2
    • NO
    • adenosine diphosphatase
17
Q

discuss the role of thrombomodulin the coagulation?

A

counter regulatory mechanism (anti-coagulant)

  • thrombomuodlin + protein C is found on healthy endothelium
    • thrombin binds complex &
      • cleaves protein C into → into active protein C, which
        • binds protein S
        • deactivates factors V & VII
18
Q

what is the role of antithrombin in coagulation?

A

counter regulatory mechanism (anti-coagulant)

  • is activated by
    • heparin (medication), or
    • heparin like agents (endogenous)
  • binds & inactivates several clotting factors, importantly, thrombin
19
Q

what is the role of TFPI in coagulation?

A
  • counter regulatory mechanism (anti-coagulant)
    • inhibits factor (VIIa)-tissue factor (beginning of intrinsic pathway)
20
Q

what is the major differencing in clotting in the lab (in-vitro) vs in vivo (in the body)

A

the intrinsic pathway (initiated by autoactivating XIIa or lab ingredients) is not as important in-vivo. tissue factor most important for in-vivo.

21
Q

to run hemostasis tests, what proper set up must occur?

A
  • blood needs to be in blue tubes: 2.3% citrate, and must have a ratio of:
    • 9:1 whole blood: anti-coagulant
22
Q

what factors does warfarin inhibit?

A
  • VII (initiates common pathway)
  • IX (initiates common pathway)
  • X (starts common pathway)
  • II (thrombin)

(the factors that require vitamin K)

23
Q

pro-thrombin time (PT)

  • requires what ingredients?
  • screens for what factors?
  • is particularly useful clinically for…?
A
  • requires: thromboplastin (phospholipid + TF), Ca++
  • assesses extrinsic + common pathways: i.e, factors:
    • VIIa (extrinsic)
    • Xa, Va, IIa, Ia (common)
  • esp clinically useful to:
    • monitoring warfarin
    • screening for Vitamin K
24
Q

prolonged PT can be caused by?

A
  • deficiency/inhibition of:
    • extinsic path factors (VII)
    • common path factors (X, V, II, I))
  • warfarin - inhibits extrinsic & common
  • heparin - though less usefull than APTT/TT
  • FDP/D-dimer
25
Q

deficiency / inhibition of what factors will NOT significantly prolong the PT?

A
  • intrinsic path factors:
    • XII
    • XI
    • IX
    • VIII
  • HMWK
  • pre-kallikrein
26
Q

what is the purpose of INR? how is INR calculated?

A
  • use to standardize warfarin therapy.
  • INF = patient’s PT / mean reference interval
27
Q

APTT (activated partial thromboplastin time)

  • requires what ingredients?
  • screens for what factors?
  • is particularly useful clinically for…?
A
  • requires: an activator + partial thromboplastin (phospholipid) + Ca++
  • assesses intrinsic + common pathways: i.e, factors:
    • XII, XI, IX, VIII (intrinsic)
    • X, V, II, I (common)
  • is esp useful for:
    • monitoring heparin therapy
    • pre-kalkreinin & HMWK
    • lupus anticoagulant
    • direct thrombin inhibitors
28
Q

what can cause prolonged APTT?

A
  • deficiency/inhibition of:
    • intrinsic path factors (XII, XI, IX, VIII)
    • common path factors (X, V, II, I))
  • heparin - most common cause
  • lupus anti-coagulant
  • thrombin inhibitors
  • improper storage
  • FDP/D-dimer (like PT)
29
Q

what is APTT not affected by?

A
  • extrinsic pathway factors: i.e., factor VII only!!
30
Q

when getting getting an PT or an APTT, what could cause a shortened time (rather than a normal or a prolonged time)

A
  • a traumatic blood draw while obtaining sample that activates the coagulation cascade of blood being tested
    • if no evidence of traumatic blood draw: person might have an increased thrombosis risk
31
Q

thrombin time (TT)

  • requires what ingredients?
  • screens for what factors?
  • is particularly useful clinically for…?
A
  • requires: no ingredients
  • assesses: thrombin - measures time it takes to convert fibrinogen → to fibrin
  • clinical uses:
    • heparin detection: most sensitive test!! too sensitive to used to monitor therapy
    • to dx decreased fibrin: esp good to dx
      • afibrinogenemia
      • hypofibrinogenemia
      • dysfibrinogenemia
32
Q

what can cause a prolonged TT

A
  • thrombin inhibition:
    • heparin: activates antithrombin, which inhibits thrombin (IIa) & many other factors
    • direct thrombin inhibitors
    • FDPs
  • decreased fibrinogen synthesis:
    • afibrinogenemia
    • hypofibrinogenemia
    • dysfibrinogenemia
33
Q

what are FDPs?

  • how are they formed?
  • in what situations are they elevated?
  • what role do they play in coagulation?
  • how do they effect the hemostasis tests?
A

fibrin degradation products

  • formed from degradation of fibrin by plasmin (activated by tPA)
  • are elevated in:
    • hyper-clotting states (lots of clots broken down)
      • DIC
      • thrombosis
    • decreased clearance by liver:
      • cirrhosis
    • some mucous secreting adenocarcinomas
  • compete with thrombin to convert fibrinogen to fibrin & are prolong the:
    • PT
    • aPPT
    • TT
34
Q

what is d-dimer? what is its clinical significance?

A
  • is a type of FDP - tends to break down cross-linked fibrin
  • like all FDPs
    • elevated in
      • DIC, thrombosis (inc clot breakdown)
      • cirrhosis (dec clearance)
      • mucin secreting adeocarcinomas
    • prolongs PT, aPTT, TT
35
Q

mixing studies

  • what is their role?
  • how are they conducted?
  • how are they interpreted?
A
  • distinguishes a factor deficiency from factor inhibition (in either PT or aPPT)
  • pt plasma mixed with donor plasma at 1:1 ratio
  • interpretation:
    • correction of time = deficiency
    • no correction of time = inhibition
36
Q

which clotting factor is seen in highest concentration in the plasma?

A

fibrinogen

37
Q

what is the most commonly inherited bleeding disorder?

A

von willibrand disease

38
Q

von-willebrand disease

  • definition
  • pathogenesis
  • presentation
A
  • common

PATH Heme-Onc II (6 decks)

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