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Assessment Spring > Coagulation > Flashcards

Coagulation Flashcards

Exam 4 (92 cards)

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1
Q

What is hemostasis?

A

the balance between clot generation, thrombus formation and regulation to inhibit uncontrolled thrombogenesis.

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2
Q

What are the two stages of hemostasis?

A

primary hemostasis: immediate platelet deposition at site of injury-> plt plug formation

secondary hemostasis: clotting factors are activated and clot secured w/ fibrin

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3
Q

Name a few anti-clotting mechanisms of endothelial cells…

A
  1. negative charge to repel plt
  2. produce prostacyclin and NO
  3. excrete adenosine diphosphatase
  4. increase protein C
  5. produce TFPI
  6. synthesize tPa
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4
Q

where are Plt derived from?

A

megakaryocytes in bone marrow

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5
Q

what is the lifespan of inactive plts?

A

8-12 days

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6
Q

How many plts are formed daily?

A

120-150 billion

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7
Q

Describe what happens at the site of injury during primary hemostasis…

A

Endothelium is damages which exposes the extracellular matrix containing collagen and vWF. This triggers adhesion, activation and aggregation of the plts.

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8
Q

What causes platelet activation?

A

the interaction b/w the plt and the collagen and TF which causes the release of granular proteins.

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9
Q

What are the two types of storage granules that platelets contain?

A
  1. alpha granules
  2. dense bodies
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10
Q

what do alpha granules contain?

A

fibrinogen, factor V, VIII, vWF and platelet derived growth factor

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11
Q

what do dense bodies contain?

A

ADP, ATP, Ca, 5HT, histamine, Epi

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12
Q

What triggers aggregation of platelets?

A

the release of granular contents which activate additional plts.

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13
Q

what are the 4 components of tenase-complexes?

A
  1. a substrate
  2. an enzyme
  3. a cofactor
  4. calcium
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14
Q

what is the extrinsic pathway responsible for?

A

-initiation of plasma-mediated hemostasis
-tissue factor forms active complex w/ VIIa
-this complex can activate factor X (common pathway) and IX (intrinsic pathway)

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15
Q

what is the intrinsic pathway responsible for?

A

-responsible for amplification and propagation of thrombin generated by the extrinsic pathway
-lab coag studies rely in the intrinsic pathway to acitivate the clotting cascade

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16
Q

Describe the major components of the intrinsic pathway…

A

factor XIIa is activated by negatively charged surface which converts XI-> XIa which activates IXa which interacts w/ VIIIa to activate factor Xa

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17
Q

What factor is used to propagate the intrinsic pathway to further amplify thrombin generation?

A

Thrombin or factor IIa

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18
Q

Describe the common pathway…

A

Factor X becomes Xa which binds w/ Va to form a prothrombinase complex. This complex rapidly converts prothrombin to thrombin (IIa)
Thrombin attaches to the plts and converting fibrinogen to fibrin (Ia) Fibrin strands are used to stabilize clot

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19
Q

what factor is responsible for forming crosslinks between fibrin strands?

A

factor XIIIa

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20
Q

What is the key step in regulating hemostasis?

A

Thrombin generation

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21
Q

what are the two tenase-complexes that facilitate the formation of prothrombinase complexes?

A

intrinsic tenase complex: activator + IXa + VIIIa + Ca
extrinsic tenase complex: injury + TF + VIIa + Ca

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22
Q

What are the 4 major coagulation counter-mechanisms of anticoagulation?

A
  1. fibrinolysis
  2. tissue factor pathway inhibitor (TFPI)
  3. protein C system
  4. serine protease inhibitors (SERPINS)
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23
Q

What factors are involved in the protein C system?

A

Protein C inhibits factor II, Va and VIIIa

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24
Q

What are three examples of SERPINs?

A
  1. antithrombin
  2. heparin
  3. heparin cofactor II
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25
which factors does antithrombin inhibit?
factors 9a, 10a, 11a, and 12a and thrombin
26
How does heparin work?
binds to antithrombin (AT) causing a conformational change that accelerates AT activity
27
If a bleeding disorder is suspected what are the first line labs to be ordered?
PT and aPTT
28
What is Von Willebrand's disease?
-the most common inherited bleeding disorder -caused by a deficiency in vWF causing defective plt adhesion and aggregation
29
vWF prevents degradation of which factor?
VIII
30
Which labs do you need to order if VWD is suspected?
vWF level, vWF-plt binding activity, factor VIII level and a plt function assay routine platelets and PT will be normal
31
What is the treatment for VWD?
DDAVP (increases vWF)
32
What is the difference between hemophilia A and B?
A: factor 8 deficiency B: factor 9 deficiency (more rare)
33
Which lab is normally affected with hemophilia?
PTT is normally prolonged PT, plts and BT are usually normal
34
What products may be indicated prior to surgery for a patient with a bleeding disorder like VWD or hemophilia?
DDAVP Factors 8 or 9
35
What are a few drugs that can cause increased bleeding?
heparin warfarin DOACs Beta lactam ABx nitroprusside NTG NO SSRIs
36
What are a few homeopathic drugs that can increase the risk of bleeding?
cayenne garlic ginger gingko biloba grapeseed oil St. John's wort turmeric vitamin E
37
Which factors is the liver the primary source for?
5,7,9,10, 11,12
38
What other components of the coagulation cascade is the liver the primary source for?
proteins C and S and antithrombin
39
What causes CKD patients to be anemic?
-lack of EPO -plt dysfunction
40
What are the treatment options for plt dysfunction r/t CKD?
-cryo -DDAVP -conjugated estrogens can be given 5 days preoperatively
41
What is DIC?
-the pathological hemostatic response to TF/7a complex causing excessive activation of the extrinsic pathway which overwhelms the anticoagulant mechanisms -Coag factors and plts become depleted leading to MSOD
42
What are a few causes for DIC?
trauma, amniotic fluid embolus, malignancy, sepsis or incompatible blood transfusion
43
Which labs with be affected if you are in DIC?
decreased plts, prolonged PT/ PTT/TT, increased fibrin and increased fibrin degradation products
44
What is trauma induced coagulopathy?
acute coagulopathy seen in trauma patients r/t activated protein C which decreases thrombin generation--> increased bleeding
45
What is the driving force for protein C activation with trauma-induced coagulopathy?
hypoperfusion
46
What is the most common inherited prothrombotic disease?
factor V leiden mutation
47
what is factor V leiden?
genetic mutation of factor V the leads to activated protein C resistance leading to increased risk of clot formation
48
what does prothrombin mutation cause?
increases prothrombin concentration which leads to hypercoagulation
49
What is thrombophilia?
an inherited predisposition for thrombotic events like DVTs. These patients are highly susceptible to Virchow's Triad
50
What is antiphospholipid syndrome?
an autoimmune disorder w/ antibodies against the phospholipid-binding proteins in the coagulation system. This disease is characterized by recurrent thrombosis and pregnancy loss
51
What is heparin induced thrombocytopenia?
a mild-moderate thrombocytopenia associated with Heparin that occurs about 5-14 days after heparin treatment is initiated
52
How long does it take to clear the HIT antibodies from circulation?
about 3 months
53
How is prothrombin time (PT) performed and what does it measure?
plasma is mixed with tissue factor and the seconds until a clot forms is measured Assesses the integrity of the extrinsic and common pathways good at measuring vit. K antagonists like Warfarin
54
What is the aPTT and what does it measure?
the activated partial thromboplastin time measures the sec until clot forms after mixing plasma w/ phospholipid, Ca, and an activator of the intrinsic pathway Assesses the intrinsic and common pathways Useful for measuring Heparin
55
What does an anti-Xa measure?
provides a functional assessment of heparin's anticoagulant effect. Can also be used to assess LMWH and fondaparinux
56
What is a normal plt count?
greater the 100,000 plts/microliter
57
What is an ACT and what does it measure?
activated clotting time measures responsiveness to heparin. Assesses intrinsic and common pathways.
58
What is a normal ACT?
>107s +/- 13 seconds
59
how much protamine do you need to neutralize 1 mg of heparin?
1 mg of protamine
60
What is a normal R time? What is the treatment?
5-10 min FFP
61
What is a normal K time? What is the treatment?
1-3 min Cryo
62
What is the normal alpha angle? What is the treatment?
53-72 degrees cryo
63
What is the normal value for maximum amplitude? What is the treatment?
50-70mm plts or DDAVP
64
What is the normal lysis at 30 minutes (LY30)? What is the treatment?
0-8% TXA or amicar
65
What are the three main classes of antiplatelets?
1. COX inhibitors (aspirin, nsaids) 2. P2Y12 receptor antagonists (clopidogrel, ticagrelor, ticlopidine) 3. Plt GIIa/IIIa receptor antagonists (abciximad, eptifibatide)
66
Warfarin is the DOC for what pathologies and how does it work?
DOC for valvular afib and valve replacements inhibits the synthesis of vitamin K dependent factors
67
What are the vitamin K dependent factors?
2, 7, 9, 10 also, protein C and S
68
How does Heparin work?
binds to antithrombin and directly inhibits soluble thrombin and Xa
69
What are some differences between unfractionated heparin and LMWH?
UFH: shorter HL, fully reversible w/ protamine, coag testing needed LMWH: longer HL, no caogs needed, only partially reversible w/ protamine
70
How do direct thrombin inhibitors work?
they bind to thrombin in both soluble and fibrin-bound states
71
Give some examples of direct thrombin inhibitors (DTI) ...
Hirudin, Argatroban, Bivalirudin, and Dabigatran
72
Which DTI has the shortest HL and is the DOC for renal and liver impaired patients?
Bivalirudin
73
What are direct oral anticoagulants (DOAC)?
These are a newer class of drugs that have more predictable pharmacokinetics and dynamics. They have a similar efficacy to Warfarin but fewer drug interactions, embolic events, ICH, and mortality than Warfarin.
74
Give three examples of DOAC's...
DTI: Dabigatran Xa inhibitors: Xarelto, Eliquis and Savaysa
75
How do thrombolytics work?
these dissolve clots directly. They are usually serine proteases that convert plasminogen to plasmin (which breaks down fibrin).
76
What are the two categories of thrombolytics?
fibrin specific: alteplase (tPA), tenecteplase non-fibrin specific: streptokinase
77
How long does surgery need to wait after giving a thrombolytic?
10 days
78
What are some contraindications for thrombolytics?
vascular lesions, uncontrolled HTN, recent cranial surgery or trauma, brain tumors, recent ischemic stroke (w/i 3 mos), peptic ulcers, pregnancy, major surgery in the last 3wks
79
Name a few antifibrinolytics...
1. Lysine analogues (EACA, TXA) 2. SERPINs (removed from the market d/t cardiotoxicity)
80
What are some factor replacements?
- recombinant VIIa - prothrombin complex concentrate (PCC)--> contain vit. K factors - fibrinogen (from pooled plasma) - cryo and FFP (cheaper but less specific)
81
When should patients stop taking Warfarin?
dc 5 days prior to surgery low risk: restart 12-24h postop high risk: bridge to UFH or LMWH
82
When should patients stop taking heparins?
UFH: dc 4-6hr prior to surgery LMWH: dc 24hr prior to surgery
83
When should surgical patients stop taking aspirin?
low risk patients dc 7-10 days prior mod/high risk: do NOT dc
84
How long should surgery be delayed for patients with bare metal stents?
6 weeks after placement
85
How long should surgery be delayed for patients with drug-eluding stents (DES)?
6 months after placement
86
How long do you need to wait to do neuraxial anesthesia on patients who are on NSAIDS? Aspirin? Heparin BID? TID?
NSAIDS/aspirin: no restrictions Heparin SQ BID: no restrictions Heparin SQ TID: 4hr
87
How long do you need to wait to given neuraxial anesthesia to patients who are on Lovenox? Warfarin?
Lovenox: 12 hr Warfarin: 5 days (INR <1.5)
88
What is the DOC for warfarin reversal?
Give PCC's first for emergent coumadin reversal (short HL) Give vit. K for sustained correction
89
What is the reversal drug for Dabigatran?
Idarucizumab
90
What is the reversal agent for Factor Xa Inhibitors?
Andexanet (a derivative of factor Xa)
91
What is the reversal agent for antiplatelet drugs like aspirin, clopidogrel, or cangrelor?
Platelets :)
92
What factors make up the prothrombinase complex?
Xa + Va + Ca

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