Coagulation Disorders I & II Flashcards
(38 cards)
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
-
platelets change shape, which causes:
- aggregation phase - fibrinogen forms bridges between activated platelets
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
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
4
Q
what are protease activated receptors & their role in clotting?
A
- released by thrombin
- “activate” platelets to that they can aggregate
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
- Xa, with the help of Va, cleaves II (prothrombin) → IIa (thrombin), which
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)
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)
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
9
Q
what clotting factors does thrombin activate?
A
- Ia (fibrin), and
- Va, VIIa, XIa, XIIIa (take 5 at 7-II)
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
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)
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)
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
- converts plasminogen → plasmin, which:
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
15
Q
what is the role of a2-antiplasmin inhibitor in coagulation?
A
inhibits free plasmin to limit excessive fibrinolysis
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
- cleaves protein C into → into active protein C, which
- thrombin binds complex &
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
deficiency / inhibition of what factors will NOT significantly prolong the PT?
* intrinsic path factors:
* XII
* XI
* IX
* VIII
* HMWK
* pre-kallikrein
26
what is the purpose of INR? how is INR calculated?
* use to standardize warfarin therapy.
* INF = patient's PT / mean reference interval
27
APTT (activated partial thromboplastin time)
* requires what ingredients?
* screens for what factors?
* is particularly useful clinically for…?
* 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
what can cause prolonged APTT?
* **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
what is APTT _not_ affected by?
* extrinsic pathway factors: **i.e., factor VII only!!**
30
when getting getting an PT or an APTT, what could cause a _shortened time_ (rather than a normal or a prolonged time)
* **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
thrombin time (TT)
* requires what ingredients?
* screens for what factors?
* is particularly useful clinically for…?
* 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
what can cause a prolonged TT
* thrombin inhibition:
* heparin: activates antithrombin, which inhibits thrombin (IIa) & many other factors
* direct thrombin inhibitors
* FDPs
* decreased fibrinogen synthesis:
* afibrinogenemia
* hypofibrinogenemia
* dysfibrinogenemia
33
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?
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
what is d-dimer? what is its clinical significance?
* **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
mixing studies
* what is their role?
* how are they conducted?
* how are they interpreted?
* 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
which clotting factor is seen in highest concentration in the plasma?
fibrinogen
37
what is the most commonly inherited bleeding disorder?
von willibrand disease
38
von-willebrand disease
* definition
* pathogenesis
* presentation
* common
