Leading transformational change: inner and outer skills
Lect 9 VTE- DVT-PE .pptx
1. Venous Thromboembolism (VTE)
(ICD-9 = 453; ICD-10 = 182-184):
• Superficial phlebitis with or
without thrombosis
• Deep venous thrombosis (DVT)
• Pulmonary Embolism (PE)
2. Superficial Phlebitis
• common in the lower extremities; causes discomfort but
generally do not cause serious consequences, can
progress to the deep veins through the perforator veins;
• Etiology: often with previous trauma or contusion,
– most commonly due to stasis
• Signs and symptoms: distal edema, erythema, localized
mild pain and swelling; no systemic effects
Tx: many options:
• NSAIDs, hot wet towels- 20 minutes tid, anti-platelet Rx
(ASA, persantine, Aggrenox, cilostazol) or
anticoagulants(heparin, coumadin, LMWH, factor Xa
inhibitors, direct thrombin inhibitors.)
3. Venous Thromboembolism (VTE):
life threatening (15-25% of all cases of sudden
death are due to PE)
Thus the Dx, prophylaxis, Tx critical
Incidence: DVT/PE estimates range from
300,000 to 600,000 (1 to 2 per 1,000, and in
those over 80 years of age, as high as 1 in 100)
each year in the United States.
5. DVT and PE
Estimates suggest that 60,000-100,000 Americans die
of DVT/PE
10 to 30% of people will die within one month of
diagnosis.
Sudden death is the first symptom in about one-
quarter (25%) of people who have a PE.
PE - 630,000/yr. (of which 200,000 are fatal)
11% (67,000) fatal in the first hour
DVT - 2.5 million cases/yr.;
7. ↓↓↓VTE: Risk Factors
1. pregnancy/postpartum/ miscarriage (5-6 X)
increased clotting factors (1.5%)- placental separation
and tissue thromboplastin III ; factors VII, VIII, IX in
pregnancy and fibrinolytic activity is ↓ in the last
trimester of pregnancy
2. estrogens (increased thrombotic tendency 4-7 X)
BCP, HRT, or estrogen chemotherapy-
↓ anti-thrombin III levels ; increase the plasma
concentration of clotting factors I, II, VII, VIII, X, XII
due to increasing gene transcription.
3. Hx of previous DVT (3-5 X) high incidence of
recurrence
8. VTE: many Risk Factors
• 4. paralysis; prolonged bed rest (3X) (e.g. p
CVA; post-op) prolonged immobilization
(casts and splints)
• 5. surgery alone (5 X )- venous stasis even
while the patient is on the operating room
table and worse in Podiatric surgery with
the use of tourniquets for hemostasis.
9. VTE: More Risk Factors
• 6. chronic venous insufficiency
(venous stasis disease) and varicose
veins- #1 risk factor
• 7. cardiac disease or CHF
• 8. advancing age- aged related increase in
factor IX (FIX)
• 9. malignancy- any type of cancer;
chemotherapy
10. VTE:More risk factors
10. Obesity- ↑ levels of Plasminogen activator
inhibitor-1, (PAI-1) an inhibitor of fibrinolysis,
↑ in Platelet aggregation;
↑ levels of coagulation factors I, VII, VIII, vWF
11. trauma
11. VTE: Even more Risk Factors
12. infection (including viral e.g. HIV )
13. myeloproliferative disorders (e.g.
polycythemia, essential thrombocytosis,
sickle-cell =hyperviscosity)
14. inflammatory diseases (especially the
auto-immune e.g. anti-phoshpolipid syndrome)
15. Nephrotic syndrome (CRF)
16. thrombophilia- hypercoagulable syndromes
and hyperviscosity states (see previous lecture 7
and below) e.g FV Leiden; prothrombin Mutation
12. Resistance to Thrombosis
a. cells arranged longitudinally
b. endodothelial surface- covered with glycosaminoglycans =
80% heparin sulfate
c. (-) surface charge = decreased platelet adhesion
d. endothelial synthesis=
nitric oxide ( EDRF)
prostacyclin
tPA
antithrombin III
Protein C
lipoprotein lipase
13. DVT
Thrombophlebitis (i.e.
inflammation is present) vs
Phlebothrombosis (know
the distinction)
function of the veins:
capacitance vessels
innervation? yes--can
have venospasm
15. B. Thrombosis (DVT)- Causes of….
Etiology: Virchow’s Triad
chemical trauma: sclerosing agents; antibiotics; iodides;
venipuncture and IVs
mechanical trauma: contusions; lacerations; Fx; anatomical;
damage - exposes subendothelial collagen -
1. activates (Kallilrein) coagulation cascade → intrinsic pathway
factor XII→IX→IX
2. activates (GP IV receptor) platelet degranulation → adhesion,
aggregation
3. activates C1→CB3 (inflammation and WBC chemotaxis)
obstructions: May-Thurner Syndrome; crossing of legs,
pregnancy, abdominal or pelvic masses
other: inflammation/infection; vasculitis;
erythema nodosum;
suppurative thrombophlebitis, ischemia;
varicose veins and stasis
16. May–Thurner syndrome
• a rare condition
in which
compression of
the left common
iliac vein by the
overlying right
common iliac
artery.
17. May- Thurner Syndrome
• resultant obstruction of venous return
causes peripheral edema, pain, venous
hypertension, varicose veins, and
potentially deep venous thrombosis (DVT)
in the illio-femoral veins
• Prevalence- 2-5% of lower-extremity
venous disorders; 3 X F> M in 2-4 decade
• May–Thurner syndrome is often
undiagnosed;
18. Hypercoagulability: Common causes
overactivity of coagulation system (due to stasis and the blood does
not get mixed with inhibitors such as antithrombin III or increased
levels of activated clotting factors
1. Antithrombin deficiency- rare but often with nephrotic syndrome-
leads to overactivity of factors II and X and resistance to heparin and
LMWH
19. Hypercoagulability: common causes
2. Protein C deficiency- a Vit K dependent factor;
rare;
Activated protein C (aPC) acts as a natural
anticoagulant to limit the extent of clotting by
cleaving and degrading factor Va and VIIIa.
type 1= quantitatively low levels of protein C,
and its resultant effect on factor V
type 2 which is abnormally low functioning
protein C
20. Inherited Hyperviscosity Syndromes
2. Protein S deficiency ( PSD three types)
– A form of thrombophilia
• Has been associated with DIC; VTE
– a vitamin K dependent factor;
– less common than aPC deficiency;
– cofactor for the activation of protein C
21. 3. Factor V Leiden
• most common inheritable hypercoagulability in Caucasians
• prevalence estimated at 5% in US; inherited as an
autosomal dominant with incomplete penetrance;
• the excessive clotting that occurs in this disorder is almost
always restricted to the veins (not arterial) up to 30% of
patients who have had VTE have this condition- will cause
a 20 fold ↑ in forming clots
• results in a factor V variant that cannot be as easily
degraded by aPC (activated Protein C).
• Normally, factor V functions as a cofactor to allow factor Xa
to activate thrombin;
22. More Thrombophilia
3. Prothrombin G20210A- (aka prothrombin
20210 mutation; factor II mutation;
prothrombin mutation); 2nd most common
genetic hypercoagulopathy due to abnormal ↑
prothrombin levels (II)
a genetic variant that causes 2-3 X ↑ in risk of
forming blood clots in veins (VTE) and with
concomittent use of BCP, ↑ to 15%.
almost exclusively present in Caucasians,
2 to 3% of Caucasians carry the variant
23. 5. Other causes of Thrombophilia:
• Hyperfibrinogenemia (I)- fibrin binds to
GpIIb/IIIa platelet surface membrane
proteins; But, studies reveal no significant
effect of hyperfibrinogenemia on platelet-
dependent thrombus formation; but, an
increase in baseline plasma fibrinogen of
approximately 0.7 g/L (70 mg/dL) being
associated with a 39% increase in cardiac
death and a 60% increase in nonfatal
myocardial infarction.
24. Hypercoagulable Syndromes
High factor VIII levels- (aka the AHF) is encoded
by the F8 gene on the X-chromosome;
• it is a cofactor for factor IXa which, in the
presence of V, Ca2+ and phospholipids forms a
complex that converts factor X to the activated
form Xa.
• High plasma levels predisposes to VTE; FVIII
is non-functional in the blood while bound to
vWF;
• FVIII is proteolytically inactivated by activated
protein C and factor IXa.
25. Hypercoagulable Syndromes
• High F IX levels- aka the Christmas Factor and deficiency
causes Hemophilia B; the opposite can occur with gene
for FIX is also on the X-chromosome; rare mutations of
factor IX result in elevated clotting activity, VTE; factor
IXa, with Ca2+, and VIII cofactor →hydrolyses one
arginine-isoleucine bond in factor X to form factor Xa;
Factor IX is inhibited by antithrombin.
• High factor XI levels- aka the plasma thromboplastin
antecedent (PTA) and a deficiency causes hemophilia C
(rare); High levels of factor XI have been implicated in
VTE, although it is uncertain what determines these
levels and how serious the procoagulant state is.
• Hyperhomocysteinemia
26. hypercoaguopathy
• Hyperhomocysteinemia- deficiencies of the
vitamins B6, B9, and B12 can lead to high
homocysteine levels, a known risk factor for
cardiovascular disease and thrombosis;
homocysteine auto-oxidizes reactive oxygen
intermediates, damaging endothelial cells
and increasing the risk of thrombosis
27. DVT- Thrombophlebitis
Where: Generally the lower legs; Large venous sinuses & behind
valve cusps (pockets) 1974 - Browse and Thomas in Lancet 430
venograms - 42% begin in calf veins, 35% extend proximally in
popliteal are and only 23% in in the high thigh alone.
Clinical Appearance:
H & P will discover in 50% of cases; 50% of cases are asymptomatic
symptoms: (in calf) night cramps; acute onset; (1-3 weeks)
pain - 50%; tenderness (palpable firm cord) - 75%
erythema (overlying skin) and local warmth
swelling- lower leg and feet
dilated engorged superficial veins
positive Homan's (forcible dorsiflexion) + in
33% of out + 50% are false positive
fever (102 degrees = 39 c.)
30. DVT- Diagnosis
1. Doppler 80-85% accurate; (B
mode imaging); color flow
imaging- Doppler
2. D-dimer- is a fibrin
degradation product (FDP),
a small protein fragment
present in the blood after a
blood clot is degraded by
fibrinolysis;
93-95% sensitivity;
50% specificity in the
diagnosis of thrombotic disease
31. Doppler-(hand-held or analog waveform
“ANNA” compression test:
With the Doppler probe on a distal vein (e.g. post tibial veins)
apply distal compression
to the foot (apply continued pressure to the sole of the foot) the
venous flow will be Augmented with normal pushing of venous blood
up (and no proximal obstruction) then release the compression,
there will be No increased in sound (i.e. no flow reversal due to bad
venous valves)
Apply proximal compression (e.g. to the calve or thigh) the venous
should be
No augmentation of sound (i.e. no flow reversal with good valves)
then release the compression and there should be
Augmented sound (i.e. increased venous outflow due to the build up
of venous pressure and release of the compression, if there is no prox
obstruction such as DVT).
•
32. Venous Doppler-MVO
Doppler Maximum Venous Outflow (MVO): the test
measures how quickly venous blood flows out of
the limb after a venous tourniquet has been
removed. If there is a proximal obstruction such as a
soleal or popliteal vein thrombosis (DVT) the MVO
will be very low.
With the Doppler probe on a distal vein (e.g. post
tibial veins) a venous tourniquet (70-90 mm Hg) is
placed around the calve or thigh for 60 sec.; the air
filled cuff is the released and the venous flow volume
and velocity is recorded. ( normally without a
proximal obstruction the venous flow will escape the
limb as if air is being released from a balloon.)
33. Venous return with Breathing
Venous Doppler- Phasicity with Respiration-
audibly recorded or recorded with analog
waveform
the augmention of sound with normal breathing,
i.e. venous return velocity with intra-thoracic
pressure changes. Normal CVP is 2-6 mm Hg
which fluctuates2 mm Hg—inhalation, 6 mm
Hg—exhalation; Blood flows faster with
inhalation
•
34. D-Dimer
• False positive readings: can be due to various
causes: liver disease, high rheumatoid factor,
inflammation, malignancy, trauma, pregnancy,
recent surgery advanced age
• False negative readings: can occur if the sample is
taken either too early after thrombus formation; if
testing is delayed for several days; the presence of
anti-coagulation can render the test negative
because it prevents thrombus extension.
•
35. DVT- Dx Test
3. Venogram 95-100% accurate; know the problems
associated with a venography
4. Impedance plethysmography (IPG) meas. venous
capacitance; max. venous outflow (MVO)
5. I-125 labeled fibrinogen scan (i.e. radionucleotide
scan) accumulates in the fibrin of a thrombus;
many false neg.; considered positive only if one leg
shows 20% greater uptake than the other
6. thermography or infrared photography
37. Complications of DVT:
1. Post-phlebitis syndrome
2. Phlegmasia cerulea dolens, tends to develop in
association with a life-threatening illness; characterized
by an acute and nearly total venous occlusion of the
entire extremity outflow, including the iliac and femoral
veins; leg is painful, cyanotic, and edematous ; aka
“Venous gangrene”
3. Phlegmasia Alba Dolans (milk leg) a variant of DVT -
pale or white leg characterized by the occurrence of
arterial occlusion secondary to the profound edema of
venous thrombosis; leg appears white due to pallor of
ischemia.
4. Illio-femoral vein or lymphatic obstruction
38. DVT-prophylaxis:
Begin warfarin within 1-3 days of therapy
• enoxaparin (Lovenox) 30 mg every 12 hours, with
initial dose within 12 to 24 hours after surgery,
and every 12 hours for at least 10 days or until
risk of DVT has diminished or the patient is
adequately anti-coagulated on warfarin. The
American College of Chest Physicians
recommends initiation ≥12 hours preoperatively
or ≥12 hours postoperatively; extended duration
of up to 35 days suggested (Guyatt, 2012).
• dalteparin (Fragmin) 200 IU SQ q d
• tinzaparin (Innohep) 175 IU SQ qd
39. DVT Prophylaxis- Out-patient
• warfarin (Coumadin)vitamin K antagonists 2-10 mg po q d
• rivaroxaban (Xarelto) a factor Xa inhibitor 10 mg po q d
with food (prophy)
DVT/PE prophylaxis: 10 mg po q d x 12-35 days
DVT/PE Tx: 20 mg q d x 21 d
Alternatives:
• apixaban (Eliquis) 2.5 mg twice daily beginning 12 to
24 hours postoperatively; duration: 12 days
• dabigatran Etexilate (Pradaxa)- direct thrombin inhibitor;
110 mg given 1 to 4 hours aftter surgery OR 220 mg as 1
dose in postoperative patients maintenance: 220 mg once
daily (total duration of therapy: 10 days; ACCP
recommendation [Guyatt, 2012]: Minimum of 10 to 14 days;
extended duration of up to 35 days suggested)
40. DVT Prophylaxis
ASA?
2. intermittent pneumatic calf compression
(IPCC)
mechanical - intermittent compression
chemical - induces plasminogen activity
(i.e. fibrinolysis)
3. anti-embolism stockings “TED” if CBR > 3
days
4. early ambulation
41. Tx (Acute Tx of DVT and PE)
• American College of Chest
Physicians February 2012 for the
treatment of VTE.
• what are the goals of Tx;
–note: if DVT is untreated-25% will
develop a PE (of which 35% will be
fatal)
• 1. Immediate anticoagulation
42. Acute VTE-Anticoagulation
• Preferred- enoxaparin (Lovenox)1 mg/kg
bid (preferred over UFH or dalteparen)
After day 1 of Tx, begin oral anticoagulation.
Run platelet Ct. q o d
• Coumarin (Warfarin)- vitamin K
antagonists2-10 mg po q d; Start warfarin
on the first or second treatment day and
continue enoxaparin until INR is ≥2 for at
least 24 hours (usually 5 to 7 days)
(Guyatt, 2012).
43. Acute VTE-Other po options (instead
of warfarin):
rivaroxaban (Xarelto) – a factor Xa inhibitor
DVT/PE prophylaxis: 10 mg po q d x 12-35 days
DVT/PE Tx: 20 mg q d x 21 d
• apixaban (Eliquis) 10 mg twice daily for 7 days
followed by 5 mg twice daily
• dabigatran (Pradaxa) 150 mg twice daily (after 5
to 10 days of parenteral anticoagulation)
44. Acute Tx of DVT
2. CBR; do not use compression stockings
3. elevation of affected extremity
4. hot packs or hot wet towels - AK (Aqua- K pad) a
hot water circulating pad
5. analgesics/anti-inflammatory
6. Pharmacological thrombolysis :
tPAS/Urokinase
7. Thrombectomy; venous cut-down and manual
thrombectomy or a balloon tipped Fogarty
catheter;
8. caval interruption device- Greenfield cage
45. Fate of the venous thrombosis:
extension
lysis
organize
recanalize
embolize
post-phlebitic
syndrome
46. Pulmonary Embolism (PE) Tulpius 1641
One of the four most common causes of sudden death in U.S.
Even with appropriate treatment 6% mortality; increased if not Tx
25-35%
1. Definition (P.E.): A thrombotic occlusion of the pulmonary
arteries
2. Etiology (P.E.): Most originate from deep veins of the legs (DVT)
3. Pathophysiol: major occlusion of pulmonary arteries occlusion:
47. Pulmonary Embolus (PE)
4. Where: lower lobes of
lungs, i.e. posterobasilar and
apical segments of lower
lobes. "Saddle embolus" -
large embolus at bifurcation
of pulmonary artery
5. Diff. Dx:chest pain; MI;
angina; palpitations;
pulmonary edema; pleuritis;
48. PE- S and SX:
may be silent - (sudden onset)
tachypnea/hyperventilation
pleuritic type chest pain (a few hours - 2-3 days)
dyspnea (85%)
hemoptysis (50%)
fever, low (occasionally; will subside 2-3 days
rales/poss. pleural friction rub
shock: pallor sweating; weakness; (hypotension, syncope) RSHF ;
tachycardia
distension of the neck veins-JVD (RVH)
decreased Sa02
cyanosis
tachypnea
50. PE: Dx:
1. Blood Work: D-dimer and enzymes:
triad w/PE: increased LDH
hyper-bilirubinemia
normal SGOT
2. chest x-ray: (radiographic densities) elevation of the
diaphragm; enlargement of the hilar shadow;
best view- right ant./oblique; may show pleural effusion
- 50% = elevation of hemi-diaphragm; “Hamptons Hump” –
triangular shaped density
52. PE: Dx:
CT pulmonary angiography (CTPA) aka Spiral CT with contrast
a non-invasive; pulmonary angiogram obtained using computed
tomography (CT) with radiocontrast
demonstrating a saddle embolus.
The white area above the center is the
pulmonary artery, opacified by
radiocontrast. Inside it, the grey matter is
blood clot.
53. PE: EKG and Echocardiogram
to rule out cardiac disease : check for RVH; hypokinetic,
dilated heart but LV is normal; R/O myocardial infarctions;
ECG may show signs of right heart strain or acute cor pulmonale
in cases of large PEs —
the classic signs are a large S wave in lead I, a large Q wave in
lead III and an inverted- T wave in lead III ;
most commonly seen signs in the ECG is sinus tachycardia,
right axis deviation, and right bundle branch block.
Sinus tachycardia is found in 8–69% of people with PE
54. PE Dx:
Echocardiogram- appearance of the right
ventricle on echocardiography is referred to as
McConnell's sign. This is the finding of akinesia
of the mid-free wall but normal motion of the
apex. This phenomenon has a 77% sensitivity
and a 94% specificity.
specificity for the diagnosis of acute pulmonary
embolism in the setting of right ventricular
dysfunction.
55. PE DX: V/Q Scan
Ventilation/perfusion scan (or V/Q scan or lung scintigraphy
“scan”), which shows that some areas of the lung are being
ventilated but not perfused with blood (due to obstruction by a
clot) also called perfusion lung scan- good screening test;
56. PE: V/Q scan
IV albumen labeled Iodine - 131; or Tc-99 check for "cold" spots
(i.e. areas of avascularity); ventilation lung scan- labeled Xe gas
• It is particularly useful in people who have an allergy to
iodinated contrast,impaired renal function, or in pregnancy
due to lower radiation exposure than CT.
57. PE Dx: pulmonary angiogram
-invasive, involves right sided heart catheterization;
most diagnostic (gold Standard) must be done w/in 24
hours after symptoms begin; reference standard; utiliz
contrast media which is injected through a catheter
passed through the medial basilic (or axillary, jugular, or
femoral) into the main pul. artery and then selectively
through the R or L main pul artery;
check for intraluminal filling defect
defect or sharp cut-off of a pull vessel. “knuckle-sign”
59. V/Q scan
• After inhalation of 20.1 mCi of Xenon-133 gas, scintigraphic
images were obtained in the posterior projection, showing
uniform ventilation to lungs.. (B) After intravenous injection of
4.1 mCi of Technetium-99m-labeled macroaggregated
albumin, scintigraphic images were obtained, shown here in
the posterior projection. This and other views showed
decreased activity in the following regions: apical segment of
right upper lobe, anterior segment of right upper lobe,
superior segment of right lower lobe, posterior basal segment
of right lower lobe, anteromedial basal segment of left lower
lobe, and lateral basal segment of left lower lobe.
61. PE Dx -Arterial Blood Gases (ABGs):
pH= 7.35-7.45 (normal) may be acidotic
Pa02 = 75-100 (normal) less than 80
PaCO2= 35-45 (normal) > 45 = hypercarbia
HCO3 = 24-28 meq/L. .
62. PE Tx:
1. heparin only: study 124 patients on
heparin (500 units/kg/d) alone vs no Tx at
all; with heparin there was a 86% survival ;
followed by warfarin (Coumadin) x 3-6
months
2. thrombolysis: (rarely done and nearly
abandoned) the UPET study results:
160 patients with PE; after 2 weeks there
was no significant difference between
theheparin only Tx group and the UK group;
63. PE Tx
• surgical caval interruption-prophylactic if
indicated vena caval interruption device.i.e. VC
umbrella or the Kimray-Greenfield cage.
(a metal cage placed within the vena cava usually
via femoral cut-down under local anesthesia in
OR under floro.; Placed distal to the renal veins at
about the level of L2-L3.
