thrombophilia Flashcards
1
Q
arterial thrombosis accounts for what fraction of deaths in the US
A
1/3
2
Q
if there are platelets and vessel wall injury, what type of thrombosis is it?
A
arterial thrombosis
due to adhesion, activation and then aggregation of platelets
3
Q
vessel wall abnormalities can result from ?
how?
A
- trauma/injury
- infection - may induce release of procoagulants from endothelial cells
- inflammation - endothelial cell damage due to multiple etiologies - activated leukocytes, chemokine release, TNF, etc
4
Q
what are some abnormalities of blood vessels that could happen
A
- vessel injury/trauma
- atherosclerosis
5
Q
what is the primary form of venous thrombosis?
A
deep vein thrombosis (DVT)
6
Q
DVTs can subsequently embolize to ?
A
the lungs = pulmonary embolism (PE)
7
Q
venous thrombosis is most commonly caused by ?
A
activation of coagulation cascade, due to stasis or hypercoagulability
can be due to heritable or acquired causes
8
Q
why are DVTs most commonly found in the lower leg/calf?
A
further away from the heart
veins more prone to stasis bc can’t contract as strong as arteries
9
Q
some abnormalities that can affect blood flow/stasis (8)
A
- a-fib
- LVD
- immobility (severe)
- vessel obstruction
- hyperviscosity (ex. polycythemia vera)
- sickle cell anemia
- heart valve disease/replacement (usually mitral)
- indwelling catheters (ex. PIC, femoral)
10
Q
abnormalities of circulating coagulation proteins/hypercoagulation (6)
A
- protein C/S deficiency
- activated protein C resistance
- antithrombin (AT) deficiency
- antiphospholipid antibodies
- malignancy (tumor cell procoagulants)
- high dose estrogen therapy/pregnancy (BCs too)
11
Q
differences between arterial vs venous thrombosis
A
- started differently and follow distinct pathways
- contribution of hypercoagulability to arterial thrombus formation is not well defined
- common risk factors - age, smoking, obesity, DM, HTN, HLP
- may both be triggered by inflammatory pathways
12
Q
causes of venous thromboembolism
A
- inherited thrombophilia
- acquired disorders
13
Q
6 inherited thrombophilia that can cause venous thromboembolism
A
- factor V Leiden mutation
- prothrombin gene mutation
- protein S def.
- protein C def.
- antithrombin (AT) def.
- dysfibrinogenemia (rare)
14
Q
acquired disorders that can cause venous thromboembolism (18)
A
- malignancy
- presence of central venous catheter
- surgery
- trauma
- pregnancy
- OCs
- hormone replacement therapy
- estrogen meds - tamoxifen, bevacizumab, thalidomide, lenalidoide
- immobilization
- CHF
- antiphospholipid antibody syndrome
- myeloproliferative disorders
- paroxysmal nocturnal hemoglobinuria
- inflammatory bowel disease
- nephrotic syndrome
- marked leukocytosis in acute leukemia
- sickle cella nemia
- HIV/AIDS
15
Q
what is the MC inherited thrombophilia
A
favtor V Leiden
16
Q
factor V Leiden is a risk factor for what types of thrombosis?
A
cerebral, mesenteric, and portal vein thrombosis
17
Q
factor V Leiden is most commonly seen in what demographic
A
white ppl
18
Q
women who are FV Leiden carriers are more likely to clot if ?
A
they take OC
19
Q
what circulates in the plasma as an inactive cofactor and is activated by thrombin?
A
FV
turns into Va, serving as a cofactor in conversion of prothrombin to thrombin
20
Q
what are the mechanisms of FV Leiden hypercoagulability
A
- increased coagulation
- decreased anticoagulation
21
Q
a vitamin K-dependent protein that is the precursor of thrombin, made in the liver and circulates with a half-life of 3-5d
A
prothrombin
(prothrombin gene mutation)
22
Q
what disorder can cause purpura fulminans neonatalis, widespread venous thrombosis, and skin necrosis
A
protein C def
23
Q
1-9% of pts with venous thrombosis have ?
A
protein C def
24
Q
pts with protein C deficiency are at risk for ?
A
warfarin-induced skin necrosis
25
how do you treat a pt with protein C deficiency with warfarin-induced skin necrosis?
1. stop warfarin
2. start vit. K + heparin + protein C concentrate/FFP
(if labs are normal with warfarin, most likely protein c deficieincy)
26
pts with heterozygous protein C def with show what lab values? homozygous?
hetero - normal PT and aPTT
homo - abnormal coagulation tests consistent with DIC
27
any disorder associated with vit. K deficiency may result in protein C def, including ? (5)
1. warfarin use
2. liver disease
3. malnutrition
4. DIC
5. nephrotic syndrome
28
what is a cofactor for activated protein C
protein S
29
2 forms of protein S
1. free (40%) - ACTIVE form
2. bound (60%) - to C4b binding protein
30
acquired protein S deficiency is commonly seen in ? (6)
1. pregnancy
2. OC use
3. sickle cell anemia
4. inflammation
5. nephrotic syndrome
6. coumadin therapy
31
what is the only one that can act as a cofactor for the inhibition of FVa and FVIIIa by APC
free protein S
32
why does protein S activity decrease in pts on warfarin?
it is a vitamin K-dependent protein
33
Protein S levels are lower in ? (4)
1. women - esp. pregnant or OC use
2. liver disease
3. inflammatory bowel disease
4. nephrotic syndrome
34
what inactivates thrombin and FIXa, FXa, FXIa, and FXIIa
antithrombin
35
antithrombin III deficiency can be caused by ?
42% spontaneously
___
1. pregnancy
2. parturition
3. OC use
4. surgery
5. trauma
(58%)
36
what is associated with about sixfold increased risk of venous thromboembolism
pregnancy
37
what is the 6wk period following delivery that is associated with a higher rate of thrombosis
puerperium
38
risk factors for thrombosis in pregnancy
1. age
2. c-section
3. prolonged immobilizatin
4. obesity
5. previous thromboembolism
6. coexistent thrombophilia
39
mechanisms of thrombosis in pregnancy (4)
1. gravid uterus = alternations in hemostasis and venous stasis in lower extremities
2. trauma to pelvic veins
3. alternations in pro/anti coagulation factors
4. compression of the left iliac vein by crossing right iliac artery
40
what mechanism of thrombosis in pregnancy leads to a threefold higher incidence of DVT in left leg compared to the right
compression of left iliac vein by crossing right iliac artery
41
what 7 pro coagulant factors increases during pregnancy that increases the chance of thrombosis
1. thrombin
2. fibrinogen
3. platelet activation
4. vWF
5. FVII
6. FVIII
7. FX
42
what anti coagulant factors decreases during pregnancy that increases the chance of thrombosis (2)
1. protein S
2. ATIII
43
an acquired hypercoagulable condition that results in recurrent venous/arterial thrombosis and/or pregnancy mortality
antiphospholipid syndrome
44
what occurs either as a primary condition or in the setting of an underlying autoimmune disease, such as SLE (MC)
antiphospholipid syndrome
45
what can "trigger" antiphospholipid syndrome
exposure to infectious agents
46
antiphospholipid syndrome is a result from ?
variety of aPL effects upon pathways of coagulation
47
hallmarks of APS
1. thrombotic events
- venous or arterial
2. pregnancy complications
- fetal death after 10wks gestations
- premature birth due to severe preeclampsia or placental insufficiency
- embryonic losses (<10wks gestation)
48
___ is the most common site of thrombosis
DVT
49
___ are the most common in cerebrovascular circulation
arterial occlusions
50
other clinical manifestations of APS
1. CV disease
2. pulmonary HTN
3. avascular hypertension
4. cutaneous ulcers and/or Livedo reicularis (image)
5. adrenal insuffiency
6. cognitive deficits
7. thrombocytopenia
8. ocular complications
9. Libman-Sacks verrucous endocarditis
51
what begins with virchow's traid, than spirals own coagulation cascade to thrombus formation
DVT
52
describe the embolization of DVT to PE
1. detaches from site of formation, travels through IVC, RA, RV, then lodges in pulmonary arterial circulation
- If there is a PFO/ASD = emboli can travel to system arterial circulation
- many with PFO show no evidence of DVT
53
clinical presentation of DVT
1. swelling, pain, discoloration in extremity
2. unilateral or bilateral
3. asx, mild to severe
4. tenderness in calf or along deep veins in medial thigh
5. warmth and erythema over area of thrombosis
54
PE findings of DVT
1. palpable cord
2. ipsilateral edema, warmth, and/or superficial venous dilation
3. tenderness on deep palpation of the calf muscles (suggestive)
4. dusky cyanosis
5. Homan's sign unreliable
55
how to differentiate DVT from cellulitis
look for skin breakage
56
what is known as the "great masquerader" and what are the s/s
PE
1. SOB - sudden onset
2. tachypnea
3. pleuritic chest pain
4. cough, hemoptysis
5. pleural effusion
6. pulmonary infiltrates
7. Right sided HF
8. hypotension
9. syncope
10. sudden death (10% are fatal)
57
how do you test for probability of PE?
Wells score
>3 = high probability
1-2 = moderate
<0 = low
58
diagnostic testing for DVT
1. **compression venous doppler ultrasonography**
2. D-dimer serum testing
3. impedance plethysmography (IPG) (never used)
4. contrast venography (invasive)
5. MRI (costly)
59
what does the D-dimer test for?
1. byproduct of degradation of blood clots of fibrin within a thrombin
- elevated = thrombus is being degradated
2. often first test - negative test MOST helpful where pretest probability of DVT is low
60
why is d-dimer not highly specific for DVT
may be false positive in many situations such as:
1. pregnancy
2. infection
3. cancer
4. recent surgery
5. inflammatory disease processes
61
how to workup a PE
1. **CT scan w/IV contrast** - high probability
2. ventilation/perfusion scan (V/Q scan)
3. angiography
4. D-dimer - order with low probability
62
what are the main goals of DVT tx?
1. prevent further clot extension
2. prevention of acute pulmonary embolism
3. reducing the risk of recurrent thrombosis
63
tx for DVT
anticoagulant therapy - since PE will occur in approx. 50% of untreated ppl (days or wks of event)
1. LMW heparin or unfractionated IV heparin PLUS
2. oral anticoagulation - warfarin
OR
3. DOACs - pradaxa, xarelto, eliquis, savaysa
(tx for acute)
64
why do you need heparin with warfarin?
warfarin takes a few days to be effective
65
pt with DVT is continued on heparin for minimum 5d and DC until ?
what is the next step of therapy after?
INR has been therapeutic for two days (2.0-3.0, target 2.5)
pt is continued on oral therapy
66
if a pt cannot be on anticoagulants and has had recurrent thromboembolisms, what is the alternative tx?
inferior vena caval filter (IVC filter)
67
if a pt is suspected of having a hypercoagulable state, what labs are you considering?
1. antithrombin
2. protein C
3. protein S
4. FV Leiden
5. prothrombin gene mutations
6. APL antibodies
68
any abnormal lab results should be repeated when? why?
2-3 months after initial test
esp in setting of acute thromboembolic event
there are certain medications and diseases that can affect coagulant factors
69
what are some thrombophilia workup constraints
1. warfarin reduces protein C and protein S levels
2. heparin can reduce antithrombin levels
3. acute medical illness can reduce levels of any natural anticoagulants
70
massive acute venous thrombosis and PE/unstable event are strong indications for ?
thrombolytic therapy
71
pts are considered high-risk and require long-term anticoagulation if they meet these criterias:
1. 2+ spontaneous events for all high-risk pts
2. 1 spontaneous life-threatening thrombosis
3. 1 spontaneous thrombosis in association with
- APL antibody syndrome
- active cancer
- ATIII def.
- more than one genetic allelic abnormality
