Thrombosis, ASPHO Flashcards
3 parts of virchow’s triad?
endothelial injury
hypercoagulability
venous stasis
–> blood clot
what are the vit k dep factors?
2,7,9,10
bimodal distribution of clots..peaks?
<1 year (particularly <1 month) and during adolescenece 11-18
acquired rfs for thrombosis…top 3? give 8 others
top 3= central venous catheters, cancer, cardiac disease…renal disease, liver diseae, rheum disease like lupus, IBD, DM, obesity, surgery, trauma, immonbility, infection, estrogen, dehydration, antiphospholipid syndrome
what does fondaprinux target?
Xa
what does heparin target?
Xa, IIa= thrombin
3 times when you should eval for thrombophilia?
- non CVL-related clot
- recurrent clot
- acquired RF in pts with strong family hx of VTE (first degree relative <40 yrs or multiple relatives)
what should you check for thrombophilia eval?
AT def Prot C def Prot S def Factor V Leiden mutation prothrombin G20210A mutation
mild common thrombphilias?
Factor V Leiden, prothormbin gene mut
severe rare thrombophilias?
prot c def, prot s def, at def
explain fvl
factor 5 mutant becomes insensitive to activated protein c= a natural anticoagulant–> f5 becomes overly active…most common thrombophilia we see, 5% in white population
explain G2021A mutatio in prothrombin
–> increase in prothrombin levels
factor v ledin: what % don’t get a clot?
95% of hetero
FVL: increase risk of clot from baseline?
4x higher
FVL and obsetrics?
may play a role in some cases of unexplained recurrent late preg loss
FVL hetero have a ___ recurrence risk
LOW…shouldn’t alter decision-making re: duration of AC
PT mutation: increase risk of clot over baseline?
4x higher
PT mutaiton: risk of VTE recurrence is ___
low
what does protein s do?
helper protein for protein C
what’s the most common? prot c, prot s, or at def?
Prot c def>prot s def> AT def
high -very high risk of recurrence for pts with what thrombophilias?
prot c def
prot s def
at def
typical prot c levels?
70-150%…<55%= problem
typical prot s levels?
60-120%…<35%= problem
typical AT levels?
110-140%…<40-60%= problem
which disorders are associate with warfarin skin necrosis? (2)
prot c def and protein s def
which disorder is asscoaited with hep resistance?
AT def
of protein c def, protein s def, adn AT def, which is most likely asscoaited iwth arterial clot?
prot c def
of protein c def, protein s def, adn AT def, which is most associate with preg-related VTE?
AT def
of protein c def, protein s def, adn AT def, which is most associated with fetal loss?
prot c def
of protein c def, protein s def, adn AT def, whihc is most asscoiated with VERY high risk of clot recurrence?
AT def
when does AT reach normal level?
age 6-12 mos
when does prot c reach normal level?
late teens/early 20s
when does prot S reach adult level?
6-12 months
how does homozygous prot c/prot s def present?
purpura fulminans
manage purpura fulmianns how?
- send off prot c and s!
- aggressive FFP replacment at time of presentation
- long term AC, prot C replacmenet (we can’t replace prot S)
consier antiphospholipid antibody syndrome when?
- unprovoked VTE
- new VTE in patient with underlying autoimmune disease
def’in of AAS?
persistent presence of antiphospholipid abs or lupus AC for at least 12 weeks in context of an acute thrombotic event
lab eval for AAS?
LAC, anticardiolipin abs, anti-beta 2 glycoprotein
how do you manage AAS?
long term ac
LAC: dx how?
dilute Russell viper venom tire (dRVVT), activated PTT or StaClot test…LA are characterized by correction fo the prolonged clotting time when you add phospholipid to the patient sample but NOT when you add control palsma, confirming that the coagulation inhibitor is phospholipid-dependent
4 signs/sx of DVT
acute swelling
pain/tenderness
red/purple discoloration
warmth
4 acute signs/sx of catheter related clots?
extremity sewlling
extremity pain
discoloration
line malfucntion
chronic signs of catheter-related clot? (3)
catheter occlusion
prominent chest wall veins
recurrent bacteremia
triad for PE?
chest pain, SOB, hypoxia…but only seen in 20% of kids with PE….also can get fever, cough, hemoptysis, rapid/irreg pulse
4 signs/sx of cerebral sinovenous thrombosis?
h/a
sz
cranial nerve palsies
papilledema
RFs for CSVT? 5
dehydration lymphadenitis ear infection--> mastoiditis jugualr vein catheterization neonatal age group
3 anatomic variants associated with unprovoked VTE?
May Thurner syndrome
Thoracic outlet syndrome
IVC atresia/anomalies
May Thurnder: increased risk of VTE where?
left sided iliofemoral clots
what is May Thurner?
narrowed left iliac vein due to compression from right iliac artery
most commonly see May Thurner in which pts?
females in the 2nd adn 3rd decade of life
throacic outlet syndrome aka?
paget-schroetter syndrome
Thoracic outlet syndrome associated with DVTs where?
axillary, subclavian
TOS due to?
compression of veins by extra rib, muscle group
TOS associated with?
repeititve activity: baseball, softball, swimming, volleyball
TOS: management?
first rib resection
5 tx options for VTE?
UFH LMWH fondaparinux parenteral direct thormbin inhibitors vit k antagonists direct oral anticoagnats thrombolysis
UFH: binds reversibly to ___; after binding, increases ___’s ability to inhibit ___ and ____…does it bind other palsma proteins?
AT; AT; thrombin; Factor Xa; yes
UFH: chains of varying lengths: sizes?
5k-40k Da
LMWH size chains?
<8k Da
LMWH binds to and accelerates the activity of ____ but with a preferenctial and longer-lasting effect on ___
AT; Xa…less able to inhibit thombin and bind to other plasma proteins thn UFH!
fondaparinux binds to enhances activity of ___ by ___-fold…does it bind to other plasma proteins? does it have direct effect on thrombin?
AT; 300; no; no
explain the mech of UFH
binds to and increases AT inhbiition of Factor 10A and thrombin
explain the mech of LMWH
binds to and increases AT inhibition of 10 a and thormbin, BUT with a preferential and longer-lasting effect on Xa
explain teh mech of fondaparinux
binds to adn STRONGLY enhances actvity of AT, only inhibits 10A with NO DIRECT EFFECT on THROMBIN
other activity of UFH?
binds non-specifically to a variteyt of other palsma protiens
other activity of LMWH?
less able to bind other plasma proteins
other activity of fondaparinux?
does not bind to tohter plasma proteins
UFH: monitoring?
PTT, ACT, anti-Xa
LMWH monitoring?
Anti-Xa
fondaparinux monintroing?
anti-Xa that’s calibrated for fonda
act stands for?
activated clotting time
Adv of UFH?
good first choice for pt who is unstable or may need a procedure soon; short half life of 30 min; reversible with protamine
disadv of UFH?
continuous infusion
LMWH advs?
SC injection
easier to use in stable pt
more predictable pharmacokinetics
longer half life: 4-7 hrs
disadv of LMWH?
requires good renal functon
incomplete reversal with protamine
monitor UFH how often?
daily, and 4 hours after any dose changes
PTT target in UFH?
65-80, or 1.5-2.5x baseline
PTT sensitive to what?
improper collection, anemia, low plts, factor defs, LAC, pt age
preferred way to monitor UFH?
anti-xa, has most consistnet results
ACT: sensitive to?
plt counts and function, factor defs, ambient temp, hypothermia, LAC
anti-10a target?
0.3-0.7
anti-10a affected by?
hemolysis, high bili, high triglycerides
LMWH: obtain anti-10a level how many hours after dose? goal range? goal range for ppx?
4-6 hours
- 5-1
- 1-0.3
infant <3 months need ___ doses of heparin and more ___ ___ due to a ___ ___ __ ____
higher; frequent monitoring; larger volume of distribution
heparin affects what when drawing sample from central cath? (2)
thrombin time, PTT…you could do a PTT HEPARINASE to see if that PTT prolongation was due to heparin
RFs for HIT?
PICU, NICU, heart surgery…has been receiving heparin for several days
what causes HIT?
due to formation of auto-antibodies against endogenous platelet factor 4…development of auto-ab takes about 5 days
do what if suspect HIT?
stop heparin! start direct thrombin inhibitor…test for HIT Ab (ELISA) and confirm with functional assay= serotonin release…AVOID plt transfusions unless severe hemorrahge
give 2 direct thrombin inhibitors. do they have reversal agents?
argatroban, bivalirudin…no
argatroban and bival: bind thrombin reversibly or no?
arg: reversible; bival: partially reversible
half life of argatroban?
45 min
bival half life?
25 min
elimination argatroban?
hepatic
bival elim?
renal
monitor bival how?
aPTT, ACT
argatroban: monitor how?
aPTT, ACT
antidote for bival and argatroban?
none
mech of warfarin?
inhibitors hte synth of vit k dependent clotting factors= 2, 7, 9, 10…..will also inhibit prot c and s because also vit k dependent–> actually leads to HYPERCOAGULABLE state at first because protein c and s decrease FIRST! this is why you need bridging
warfarin must be given with another AC for at lesat __ days until a therpeutic inr is reached
5
typical dose of warfarin?
0.1 mg/kg/day
what is INR?
ratio fo the patient’s pt= prothrobin time and the rnomal mean PT
what can interact with warfarin? 8
antibiotics, gastroenteritis, anticonvulsants, anti-fungals, antacids, febrile illness, liver disease, vit k containing foods, infant formulas (have lots of vit k), mango, avocado, fish oil, soy milk, grapefruit
how to reverse warfarin?
vit k, FFP, PCC= prothormbin complex concentrate
adv of direct oral anticoag?
less bleeding than warfarin with similar efficacy
Xa inhibiting doacs to know?
apixaban, rivaroxaban
direct thrombin inhibitor?
dabigatran
which doac has phase 3 in kids?
rivaroxaban…liquid not yet available
give half lives of dabigatran, rivaroxaba, apixaban
dab: 11-14 hours (BID)
riva: 5-9 hours (QD)
apix: 9-14 (BID)
clearance of dabigatran?
renal
clearance of riva?
renal
clearance of apix?
mainly liver
provoked VTE: tx for how long?
if RF is reversbile, 3 months (6 weeks in neonataes)…if RF is chronic: 12 mos to lifelong
idiopathic VTE tx for how long?
6-12 mos
recurrent VTE tx for how long?
reversible RF: 6-12 mos
chronic RF: 12 mos- lifelong
4 reasons for thrombolysis?
life threatening art thormb
intracardiac thrombus
PE with right heart strain or hypotension
extensive DVT (SVC syndrome, occlusive IVC thrombosis with renal compromise, large iliofemoral clot)
when NOT to do thrombolysis?
- active major bleeding
- significant potential for uncontrolled local bleeding
- surgery within preceding 10 days (neurosurgery 60 days)
- neurosurgery
- intracranial neoplasm/cerebral vascular lesion
- seizures within 48 hours
- sepsis
- uncontrolled severe htn
- contrast allergy
ways to give tPA?
catheter-driected
low-dose systemic 24-96 hours
high-dose systemic 6 hours
laboratory monitoring and goals in thrombolysis?
- fibirnogen: 100-200 (hsould decrease by 20-50%)
- d-dimer (elevatd)
- PTT (50-70), becuase give UFH at same time usually
- hgb stable
- plts >100k…think of thrombolysis= just like DIC!
post-thrombotic syndrome causes? 2
residual venous outflow, venous valvular insufficiency
RFs for PTS? (5)
adolescents obesity extesnive DVT (multiple vessels) idiopathic or efffort-related upper extrem DVT lack fo DVT resolution
PTS incidence?
25% in thsoe with extremity DVT
symptoms/signs of PTS?
pain, paresthesia, dialted vessels, swelling….also decreased QoL if mod-severe
how to prevent PTS?
- consider thromboprophylaxis is those with prolong hospitalization/immobilization/prescence of CVL/infection/chronic inflamm/prothromb chronic disease
- timely dx and initiation of therapy for VTE
4 ways to manage PTS?
- elastic compression stockings
- phys therpay
- elevating the affected extrem at rest
- mantaining a healthy wt
