Hematology Week 2: Introduction to Thrombophilia Flashcards
(90 cards)
1
Q
Virchow’s Triad
3 listed
A
- Alteration of blood flow
- Endothelial injury
- Hypercoagulable state (inherent/acquired)
2
Q
VTE AKA
A
Venous Thromboembolism
3
Q
Thrombosis High-Risk Patients
3 listed
A
- Males
- >55
- recently hospitalized
4
Q
DVT AKA
A
Deep Venous Thrombosis
5
Q
circulatory stasis involves
A
alteration of blood flow
6
Q
Circulatory stasis: Things that contribute to a clot in arteries
A
Turbulence
7
Q
Circulatory stasis: Things that contribute to a clot in venous
A
Stasis
8
Q
Circulatory stasis
A
Arterial: turbulence
Venous: Stasis
9
Q
Alteration of blood flow consequences
A
Disruption of laminar flow via stasis or turbulence
- allows platelets to interact with endothelium
- activates endothelium
- prolongs exposure of activated clotting factors
10
Q
Common Causes of Alteration of blood flow in the arteries/cardiac/aortic
3 listed
A
- Aneurysms
- Dilated atrium
- Ulcerated atherosclerotic plaques
11
Q
Causes of Altered blood flow in the venous system
9 listed
A
- Prolonged immobilization
- Paget-Schroetter syndrome axial or subclavian vein can be compressed
- Clot in iliac veins (pregnancy) left iliac vein is compressed by the right iliac artery
12
Q
Common Causes of Hyperviscosity
3 listed
A
- polycythemia (primary, secondary)
- Sickle Cell Anemia
- Increased plasma proteins
13
Q
Causes of arterial endothelial injury
12 listed
A
commonly affected due to high flow rates
14
Q
Indications for inheritable Hypercoagulable States
5 listed
A
age <40
unprovoked thrombosis
FHx of thrombosis
Thrombosis at an unusual site
15
Q
Contraindicators of inherited hypercoagulable states
A
NOT associated with arterial thrombosis (Stroke, TIA, MI, etc)
16
Q
Inherited hypercoagulability conditions
5 listed
A
- Factor V Leiden
- Factor II hyperprothrombinemia
- AT deficiency
- Protein C deficiency
- Protein S deficiency
17
Q
Procoagulant gains of function conditions
2 listed
A
- Factor V Leiden
- Factor II hyperprothrombinemia
18
Q
inherited conditions with a weaker risk of VTE
2 listed
A
- Factor V Leiden
- Factor II hyperprothrombinemia
19
Q
Factor V Leiden Genetic inheritance pattern
A
- Autosomal Dominant
- can be traced back to a single mutational event 25k years ago
20
Q
accounts for half of all heritable thrombophilias
A
Factor V Leiden
21
Q
Found in 12-18% of all patients with VTE
A
Factor V Leiden
22
Q
Factor V Leiden subtype increased risks
A
Heterozygotes patients with a NON-O BLOOD TYPE have more FVIII and have 2-4x more risk of VTE
23
Q
Risk of recurrence of VTE with Factor V Leiden
A
Negligible recurrence risk
24
Q
Risks of heterozygotes of Factor V Leiden
A
5% will have VTE
non-O blood type has increased risks
25
What does Factor 5 do?
factor 5 associated with factor 10 to link the intrinsic and extrinsic pathways
26
Factor V in Factor V Leiden
Factor V is less susceptible to the inhibition of the anticoagulant protein Protein C
27
Factor V Leiden Etiology
arginine to glutamine substitution at R506
28
Factor II Hyperprothrominemia Genetic inheritance and consequences
* Autosomal dominant
* nearly exclusively caucasian
* 3-4 fold increased risk of thrombosis
29
Factor II Hyperprothrombinemia Genetics
Autosomal Dominant
30
Factor II Hyperprothrombinemia VTE recurrence risk
Negligible recurrence risk
31
Factor II Hyperprothrombinemia Pathophysiology
gain of function mutation in 3' unstranslated region resulting in increased plasma prothrombin levels by 25%
32
Factor II Hyperprothrombinemia gene
prothrombin 20210A untranslated region causing high efficiency mRNA
33
More rare inherited conditions of hypercoagulability
3 listed
* AT Deficiency
* Protein C deficiency
* Protein S Deficiency
34
inherited conditions of hypercoagulability with greater risk of VTE
3 listed
* At Deficiency
* Protein C Deficiency
* Protein S Deficiency
35
Inherited conditions of hypercoagulability that are measured by activity or antigen levels
3 listed
At Deficiency
Protein C Deficiency
Protein S Deficiency
36
Protein C Deficiency Genetics
Autosomal Dominant \>160 mutations
37
Protein C Deficiency epidemiology
3 listed
* .2-.5% of population
* 2-5% of all VTE patients
* initial VTE episode is spontaneous in 2/3 of patients
38
Protein C deficiency Caveats
* Homozygotes are rare but typically fatal (born with purpura fulminans)
* Heterozygotes Risk of warfarin skin necrosis because it is a vitamin K antagonist
39
Protein S deficiency Genetics
Autosomal Dominant
40
Protein S deficiency epidemiology
rare \<1% of population
41
most difficult to Dx Inherited condition of hypercoagulability
Protein S deficiency
42
Protein S deficiency Homozygotes
Rare but typically fatal (born with purpura fulminans
43
Protein S deficiency Caveat
* can be a physiologic phenomenon during pregnancy
* Risk of Warfarin skin necrosis
44
Protein S deficiency pathophysiology
Protein S is a cofactor for Protein C to put the brakes on Factor V
45
Antithrombin Deficiency Genetics
Autosomal Dominant (mostly)
46
Antithrombin Deficiency Epidemiology
0.02% of population
1% of all VTE cases particularly in pregnancy
Half of affected patients have spontaneous VTE
Much higher o
47
Antithrombin Deficiency Acquired form
Nephrotic Syndrome (more common than Antithrombin Deficiency)
48
Which inherited hypercoagulable condition carries the highest risk for VTE?
Antithrombin Deficiency
49
Antithrombin Function
Antithrombin inhibits thrombin
50
Inherited Conditions of hypercoagulability association with pregnancy morbidity
No significant association
51
Inherited Conditions of hypercoagulability association with arterial thrombosis
No significant association
52
Heritable thrombophilias Overview
53
Clots usually occur in a vein where?
Around a valve
54
Tissue Factor can also be expressed on\_\_\_\_\_\_\_\_ to contribute to \_\_\_\_\_\_\_\_\_
White Cells, clotting
55
Neutrophils NETs can contribute to?
Clotting
56
Hypoxia in valve areas can contribute to?
Clotting
57
Treatment of unprovoked clots
nowhere does thrombophilia affect treatment decisions, if a patient has a clot they have a pretty high risk to have another clot regardless of how they got it
58
Acquired Hypercoagulable Conditions
5 listed
59
Acquired Hypercoagulable Conditions Arterial Thrombosis possible
* Heparin-induced thrombocytopenia
* Antiphospholipid syndrome
* Cancer
60
Heparin-induced Thrombocytopenia
1/5000 patients typically using unfractionated heparin and cardiac surgery
61
Heparin-induced thrombocytopenia pathophysiology
* prothrombotic, potentially fatal complication of heparin treatment
* demonstrate anti-PF4/heparin antibodies
62
Heparin-induced thrombocytopenia mechanism
positively charged PF4 molecules are stored in alpha granules of platelet interact with negatively charged heparin polysaccharide causing a conformational change of the PF4 molecule that is immunogenic quickly developing IgG antibodies within 4-5 days
antibodies complex with platelets which have Fc receptors which cause antibody activation of platelets which release more PF4 causing a cycle
63
HIT AKA
Heparin-induced Thrombocytopenia
64
HIT Treatment
stop heparin and put them on another anticoagulant
65
Antiphospholipid Syndrome in vitro vs in vivo
* autoimmune hypercoagulable state
* causes prolongation of PTT in vitro
* In vivo causes clotting
66
Antiphospholipid syndrome antibody to
ß2GP1
67
Antiphospholipid syndrome pathophysiology
ß2GP1 conformational change can become immunogenic which can upregulate complement activity, upregulating endothelial proteins, increasing tissue factor expression, activates platelets, interferes with trophoblasts (pregnancy morbidity)
68
Antiphospholipid syndrome how is it diagnosed
Clinicopathologic diagnosis
patient with thrombotic episode or a pregnancy morbidity by the loss of pregnancy after 10 wks gestation or lost 3 pregnancies before 10 weeks gestation, preterm labor before 34 weeks gestations eclampsia or preeclampsia
69
Antiphospholipid syndrome Transiency
need to prove that the antibodies are persistent because 10% of healthy subjects need to have transient antibodies 12 weeks apart the same type of the 3
70
Antiphospholipid syndrome clinical presentation
3 listed
DVT in lower extremity but PE is less common
arterial thrombosis
microvascular clotting: least common and the most deadly woul be called catastrophic Antiphospholipid syndrome)
71
Catastrophic Antiphospholipid syndrome
microvascular clotting in Antiphospholipid syndrome
72
Cancer and thrombosis epidemiology
73
Hypercoagulability Estrogen and hormone replacement therapy
* also true for testosterone
* confers increased risk for thrombosis
* most risk in the first year
74
Hypercoagulability and pregnancy
can increase risk of clot by 10x
75
Hypercoagulability and pregnancy how many thromosis occur post partum?
1/3
76
Hypercoagulability and pregnancy thrombosis prevalence
0.86 per 1000 deliveries
77
Hypercoagulability and pregnancy mechanism of increased risk
5 listed
* decreased protein S levels
* Increased fibrinogen and prothrombin
* increased estrogen
* impaired fibrinolysis
* vascular congestion
78
Symptoms of DVT
4 listed
* swelling
* pain
* redness
* heat
79
Symptoms for pulmonary embolism
5 listed
tachypnea is the most reliable symptom
80
Symptoms for pulmonary embolism most reliable symptom
Tachypnea
81
Symptoms for pulmonary embolism most common symptoms
chest pain and tachypnea
82
pulmonary embolism picture
83
D-Dimer Test
best test for thrombosis
84
Clinical and pathophysiologic aspects of thrombosis
5 listed
85
How are D-dimers formed?
86
d-dimer is only detectable if?
Factor XIIIa has crosslinked fibrin
87
Arterial vs venous thrombosis
88
Arterial vs venous thrombosis
89
Clot in iliac veins (pregnancy) the ____________ is compressed by the \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
left iliac vein is compressed by the right iliac artery
90
Clotting in Paget–Schroetter
axial or subclavian vein can be compressed
