Platelets Flashcards
1
Q
During platelet plug formation, what proteins trigger aggregation?
A
GPIIb-IIIa
2
Q
What binds to vWF?
A
GPIb-IX-V
3
Q
Where is vWF?
A
Endothelial cells
4
Q
Order the intrinsic pathway
A
12–>11–>9 (+8) –> 10 (5) then common pathway
5
Q
Order the common pathway
A
10 (+5) –> II (thrombin) –> I (fibrin) –> 13
6
Q
Active Protein C inhibits
A
Factor 8 and 5
7
Q
Not a necessary part of pathway
A
factor 12
8
Q
measures intrinsic pathway
A
PTT
9
Q
measures extrinsic pathway
A
PT
10
Q
Thrombin activates
A
5, 7, 8, 11, 13 (almost all odds in a row except 8)
- *platelet aggregation
- **activates protein C pathway
11
Q
How does protein C get activated?
A
- Thrombin (II) binds to thrombomodulin
- That complex binds to protein C
- Protein S then activates it
12
Q
Heparin MOA
A
activates antithrombin
13
Q
____ + _____ form mesh clot
A
fibrin (1) + factor 13
14
Q
______ breaks up mesh clot once activated by ______
A
plasmin,
tPA and plasminogen
15
Q
Antithrombin inhibits
A
Factor 10 and 2 (thrombin)
16
Q
Why do we use PT to for warfarin monitoring when it inhibits factors in both pathways?
A
Factor 7, in the extrinsic pathway, had a short half life
17
Q
3 roles of fibrin
A
- stabilize platelet plug
- induces platelet aggregation
- starts fibrinolysis process
18
Q
Vitamin K dependent factors, warfarin inhibits
A
10 9 7 2 (year 1972)
CS
19
Q
Dense granules contain
A
serotonin, ADP, Ca, ATP
20
Q
Alpha granules contain
A
platelet growth factor, trans-growth factor beta, fibrinogen, vWF, platelet factor 4, factor V
21
Q
Von-Willebrand Factor
A
large protein stored in endothelial cells/platelets
Functions:
1. bind to endothelium, promote platelet adhesion at injury site
2. plasma carrier for factor 8, prevents its degradation
22
Q
Glycoprotein IIb/IIIa
A
fibrinogen receptor
23
Q
GlycoproteinIb-IX
A
VWF receptor
24
Q
Glycoprotein Ia/IIa
Glycoprotein VI
A
collagen receptor
25
Endothelial cells: Anticoagulant properties
1. thrombomodulin binds thrombin, activates protein C
2. Protein S
3. tissue factor pathway inhibitors
4. tissue plasminogen activator
5. prostacyclin/nitric oxide inhibit aggregation
6. Heparin activates antithrombin
26
Endothelial cells: Procoagulant properties
1. injury
2. down regulated thrombomodulin
3. tissue factor expression
4. PAI-1 expression
5. vWF
27
PTT
Ref: 25-35 s
Intrinsic Pathway
*UFH monitoring
28
Reasons for prolonged PTT?
1. Factor VIII or IX deficiency
aka hemophilia A/B
2. On heparin
29
PT
Ref: 10-14 s
Extrinsic Pathway
*warfarin monitoring
30
Reasons for prolonged PT?
1. on warfarin
2. vitamin K deficiency
3. Amyloidosis: factor X bound up
4. Homocystinuria: VII deficiency
31
Reasons for Vitamin K deficiency
drugs, newbown, low leafys, malabsorption, pancreatitis
32
Thrombin time
Ref: 14-16 s
good if on direct thrombin inhibitor
measures fibrinogen-->fibrin time
33
Vitamin K antagonist
warfarin
34
Factor Xa inhibitors
Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Endoxaban (Savaysa)
35
LMWH
Enoxaparin (Lovenox)
Dalteparin (Fragmin)
Tinzaparin (Innohep)
36
Bernard-Soulier Syndrome
autosomal recessive
defect/loss platelet ADHESION receptors
thrombocytopenia
LARGE PLATELETS
37
Glanzmann Thrombasthenia
autosomal recessive
| defect/loss receptors LINKING platelets
38
Storage Pool Defects
Lack DENSE granules, can't package
| Hermansky, Wiskott, Chediak Diseases
39
Aspirin-like defects
COX deficient, thromboxane synthetase deficient
40
Released and activates other platelets
| Also inhibitied when taking ASA/NSAIDS
thromboxane
41
Gray Platelet Syndrome
abnormal ALPHA granule formation/secretion
| smear is colorless w/o granules
42
Irreversible drugs
aspirin
| clopidogrel
43
reversible drugs
NSAIDS 12-24 hours
44
Thrombocytopenia presentation
low platelets
mucous membranes bleed (epistaxis, gums, GI)
cerebral hemorrage
petechial rash
45
Destructive thrombocytopenia
-Ab mediated (ITP)
-Drug related (Heparin)
Splenomegaly/Hypersplenism (trapped)
46
Consumptive thrombocytopenia
- massive trauma
- dilutional (during transfusion of fluids)
- complicated surgery
- consume to stop bleeds
47
ITP
autoantibodies against antigen on platelet surface, eventual splenic destruction
48
ITP treatment
prednisone 3-6 months, IVIG if severe, then splenectomy if chronic
49
Drug related destruction
increased clearance and platelet destruction
Ab forms against drug and it cross reacts with platelets
-Antibiotics
-Heparin
50
HIT
hepatin + PF4 forms neoantigen on platelet surface
antibodies attack it
leads to hypercoaguability and clotting
51
Cases of hypoproliferation
```
BM fails to produce mature platelets
1. leukemia/lymphoma
2. metastatic CA
3. severe viral infection
4. radiation/chemo
could get stem cell transplant
```
52
Causes of arterial thrombosis
platelet plug problem
1. MI
2. stroke
3. peripheral artery vasculitis
4. antiphos ab syndrome
5. HIT
5. hyperhomocyteinemia
53
Factor V Leiden
hypercoag-inherited
Factor V is resistant to active protein C
strong association with estrogen, stop OCPs
un-coagulate in pregnancy
54
Prothrombin gene mutation G20210A
hypercoag-inherited
upregulate prothrombin expression
cerebral vein thrombosis or stroke
55
Protein C deficiency
hypercoag-inherited
decreased synthesis and activitiy
warfarin skin necrosis
56
Protein S deficiency
hypercoag-inherited
decreased synthesis and activitiy
warfarin skin necrosis
57
HIT
Acquired thrombophilia
heparin induced clot- Ab mediated
switch to direct thrombin inhibitor in future
58
Antiphospholipid syndrome
```
Acquired thrombophilia
Need one: recurrent miscarraige, VTE, MI, microvascular thrombosis w/ multi organ failure
Need two 12 week apart:
1. Lupus anticoag
2. anticardilipid Ab
2. B2 glycoprotein Ab
```
59
Antithrombin deficiency
hypercoag-inherited
| heparin resistance, low antithrombin
60
VTE Risk factors
```
immobilization
personal/family history
unexplained miscarriages
cigarettes
OCPs
cancer
recent surgery
central venous catheter
trauma
heparin exposure
```
61
Fibrinolysis
conversion of plasminogen to plasmin mediated by tissue plasminogen activator (tpa)
62
Virchow's Triad
Endothelial injury
venous stasis
hypercoagability
(perfect situation for a clot!)
63
DVT long term complication
post thrombotic syndrome: perm venous valve damage and long term swelling
64
PE long term complications
thromboembolic pulmonary HTN
| greater risk of death than DVT
65
DVT symptoms
Homan's sign
pain, swelling, tender
palpable cord
prominent superficial veins
66
PE symptoms
SOB, tachycardia, pleuritic chest pain, cough, hemopytsis, hypotension, syncope, death, R side heart failure
67
VTE treatment steps
1. anticoagulate acutely (UFH/LMWH/DOAC)
2. risk-stratify for thrombolysis (tPA)
3. convert to chronic anticoagulants (warfarin/DOAC)
68
Bridging to warfarin
d/t hypercoaguable state at start, overlap with UFH/LMWH until PT/INR is therapeutic
69
Contraindications for warfarin
IVC filter
70
Diagnosing PE
VQ Scan: ventilation normal, perfusion altered
| PECT w/ contract
71
Treatment for mild hemophilia
DDAVP
Prior to surgeries
Releases factor 8 stores
Hemophilia A only
72
Inherited causes of prolonged PTT
VWF
| Factor VIII, IX, XI, XIII deficiencies
73
Acquired causes of prolonged PTT
Heparin
| Antiphospholipid antibody
74
Inherited causes of prolonged PT
Factor VII deficiency
75
Acquired causes of prolonged PT
Vit K deficiency
Liver disease
Warfarin
Factor VIII inhibitor
76
Inherited causes for prolonged PT and PTT
Prothrombin, fibrinogen, factor V, factor X, or combined factor deficiencies
77
Acquired causes of prolonged PT and PTT
```
Vitamin K deficiency
Liver disease
DIC****
Supratherapeutic heparin or warfarin
Combined heparin or warfarin use
Direct thrombin inhibitors
Inhibitor of prothrombin, fibrinogen, or factored V or X
```
78
Oozing at venapuncture site could indicate
K deficiency
79
How does liver disease cause coagulopathy?
It has decreased production of clotting factors
| (Factor 8 and vWF are not made in liver)*
