Transcript Thromboembolism Panel

Thromboembolism Panel
 Dr Hommam
 Dr Jalilian
 Dr Moosavi
 Dr Torkestani
 Dr Vafaei
Significance of VTE
 Highest risk during pregnancy and peurperium
 Incidence : 1/10000 ( nonpregnant) …….1/1600
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( pregnant)
6 - 22 X
Antepartum = postpartum
DVT …..Antepartum ( 74%)
PE………Postpartum (60.5%)
Cesarean section : 30.3 RR for PE
50% due to thrombophilia
Responsible for 20% of pregnancy- related
deaths
Aims of this panel
 Oral presentation
 Who needs thromboprophylaxy?
 Who needs screening for thrombophilia?
 Review of guideline for thromboprophylaxy
 Thromboprophylaxy in cases with previous history
of VTE
 Thromboprophylaxy in cases with thrombophilia.
 Thromboprophylaxy in cases with ART
 Peripartum thromboprophylaxy
 Early diagnosis of VTE
 Treatment of VTE
‫ارا‌‌ئه‌گزارش‌وضع‌موجود‌در‌کشور‬
‫خانم‌دکتر‌ترکستانی‬
Risk Factors
Pregnancy as a prothrombotic state
 Virchow triad: stasis, local trauma to the
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vessel wall, and hypercoagulability
Increased level of factor I, VII, VIII, IX, X , XIII
, VWB ( 20-1000%)
Decreased activity of Pr S ( 39%)
Decreased level of Pr S after cesarean section
and infection
Venous statsis due to compression
Increased in deep vein capacitance ( prog.,
Prostacycline and nitric oxide)
Risk factors
Risk factors
Risk factors
 Obstetrics:
Thrombophilia
 Reduction in inhibitory proteins for
coagulation
 15% white people
 50% TE events in pregnancy ((Lockwood,
2002; Pierangeli, 2011)
 Inherited
 Acquired
Inherited thrombophilia
 Family history
 VTE before 45 y/o
 VTE without risk factor
 VTE with minimal provocation ( long flight,
estrogen)
 Family history of sudden dead due to PE
 History of multiple family members requiring
long-term anticoagulation therapy because of
recurrent thrombosis (Anderson, 2011)
Inherited thrombophilia
 Antithrombin Deficiency:
 Type I
 Type II
 Autosomal Dominant
 Most thrombogenic of the heritable coagulopathies
 Homozygous antithrombin deficiency is lethal
Inherited thrombophilia
 Protein C Deficiency:
 >100 different AD mutations
 prevalence : 2 to 3 per 1000, but many of these
individuals do not have a thrombosis history because
the phenotypic expression is highly variable
(Anderson, 2011).
Inherited thrombophilia
 Protein S Deficiency:
Decreased in pregnancy ( 30-24%)
Decreased after cesarean and infection
Inherited thrombophilia
 Factor V Leiden Mutation:
 Most prevalent of the known thrombophilia
 Heterozygous inheritance for factor V Leiden is the
most common ; 3 to 15 percent of selected European
populations and 3 percent of African Americans, but it is
virtually absent in African blacks and Asians (Lockwood,
2012).
 Diagnosis during pregnancy : DNA analysis for the
mutant factor V gene. This is because bioassay is
confounded by the fact that resistance is normally
increased after early pregnancy because of alterations
in other coagulation proteins
Factor V Leiden Mutation
*****Universal prenatal screening for the
Leiden mutation and prophylaxis for
carriers without a prior venous
thromboembolism is not indicated***
Inherited thrombophilia
 Prothrombin G20210A Mutation:
Excessive accumulation of prothrombin
Inherited thrombophilia
 Hyperhomocysteinemia:
 Most common cause : C667T thermolabile mutation
of the enzyme 5, 10-methylene-tetrahydrofolate
reductase (MTHFR)
 Deficiency of several enzymes involved in methionine
metabolism ( correctible nutritional deficiencies of
folic acid, vitamin B6, or vitamin B12)
 Autosomal recessive
 Decreased in normal pregnancy
 fasting threshold of > 12 μmol/L
Hyperhomocysteinemia:
 Elevated homocysteine level is actually a weak
risk factor (ACOG, 2013).
 The ACOG (2013) has concluded that there is
insufficient evidence to support assessment of
MTHFR polymorphisms or measurement of
fasting homocysteine levels in the evaluation for
venous thromboembolism.
Other Inherited thrombophilia
 Protein Z
 plasminogen activator inhibitor type 1 (PAI-1)
 *****a paternal thrombophilia could increase the
risk of a maternal thromboembolism. (Galanaud
(2010).
 Paternal thrombophilia—the PROCR 6936G
allele—affects the endothelial protein C receptor.
This receptor is expressed by villous trophoblast
and thus is exposed to maternal blood.
Acquired thrombophilia
 Anticardiolipin
 Lupus anticoagulant
 β2-glycoprotein I
 ***In addition to vascular thromboses, these include:
 (1) at least one otherwise unexplained fetal death at or
beyond 10 weeks;
 (2) at least one preterm birth before 34 weeks because
of eclampsia, severe preeclampsia, or placental
insufficiency; or
 (3) at least three unexplained consecutive spontaneous
abortions before 10 weeks.
Acquired thrombophilia
 Arterial
 Venous
 Unusual sites
Thrombophilias and Pregnancy
Complications
 ACOG(2013) : Definitive causal link cannot be
made between inherited thrombophilias and
adverse pregnancy outcomes.
 In contrast, the association between
antiphospholipid syndrome and adverse
pregnancy outcomes—including fetal loss,
recurrent pregnancy loss, and
preeclampsia—is much stronger.
Thrombophilia Screening
 Given the high incidence of thrombophilia in the
population and the low incidence of venous
thromboembolism, universal screening during
pregnancy is not cost effective
*** If thrombophilia testing is performed, it is
done before anticoagulation because heparin
induces a decline in antithrombin levels, and
warfarin decreases protein C and S
concentrations (Lockwood, 2002).
Thrombophilia Screening
SELECTIVE SCREENING:
 (1) a personal history of venous
thromboembolism that was associated with a
non recurrent risk factor such as fractures,
surgery, and/or prolonged immobilization
 (2) a first-degree relative (parent or sibling) with a
history of high-risk thrombophilia or venous
thromboembolism before age 50 years in the
absence of other risk factors.
Do we need to test IT in cases with
adverse pregnancy outcome?
 ACOG(2013) : Testing for inherited thrombophilias
in women who have experienced recurrent fetal loss
or placental abruption is not recommended because
there is insufficient clinical evidence that
antepartum heparin prophylaxis prevents
recurrence. Similarly, testing is not recommended
for women with a history of fetal-growth restriction
or preeclampsia
 Screening for antiphospholipid antibodies may be
appropriate in women who have experienced a fetal
loss.
Screening Tests
 Should be performed at least 6 weeks after the
thrombotic event, while the patient is not
pregnant, and when she is not receiving
anticoagulation or hormonal therapy.
 Lack of association between
methylenetetrahydrofolate reductase (MTHFR)
gene mutations—the most common cause of
hyperhomocysteinemia—and adverse pregnancy
outcomes, screening with fasting homocysteine
levels or MTHFR mutation analyses is not
recommended (ACOG 2013).
Screening Tests
Thromboprophylaxis
Thromboprophylaxis
There is a lack of overall agreement about which
groups of women should be offered
thromboprophylaxis during or after pregnancy or
offered testing for thrombophilias
All women should undergo a documented
assessment of risk factors for VTE in early
pregnancy or before pregnancy.
Basic rules in thromboprophylaxy
Basic rules in thromboprophylaxy
Basic rules in thromboprophylaxy
Post NVD prophylaxy
Post C/S thromboprophylaxy
Thromboprophylaxy in lactation
Thromboprophylaxy in ART
Venous Thrombo -Embli
Early diagnosis of VTE
 70% iliofemoral veins in pregnancy
 Left sided ( 90- 97%) [compression of the left iliac
vein by the right iliac and ovarian artery, both of
which cross the vein only on the left side]
 Abrupt in onset, Pain, edema
 Reflex arterial spasm causes a pale, cool
extremity with diminished pulsations.
 Calf pain, either spontaneous or in response to
squeezing or to Achilles tendon stretching—
Homans sign
 30 - 60 percent may be asymptomatic …PE
Diagnosis of DVT
 Compression US: Noninvasive technique is currently
the most-used first-line test; noncompressibility and
typical echoarchitecture of a thrombosed vein.
 MRI : Excellent delineation of anatomical detail above
the inguinal ligament, The venous system can also be
reconstructed using MR Venography
 D-Dimer Screening Tests: increases in nl
pregnancy, multifetal, cesarean , abruption, PET,
sepsis;
***** Negative D-dimer test should be considered
reassuring (Lockwood, 2012; Marik, 2008).****
***Normal findings with venous ultrasonography
results do not always exclude a pulmonary embolism.
This is because the thrombosis may have already
embolized or because it arose from iliac or other deeppelvic veins, which are less accessible to ultrasound
evaluation
 Venography: The gold standard to exclude lower
extremity deep-vein thrombosis, NPV = 98%
 Fetal radiation exposure without shielding is
approximately 3 mGy (Nijkeuter, 2006).
***venography is associated with significant
complications, including thrombosis, and it
is time consuming and cumbersome
Treatment of VTE
 Bed Rest ( 60% chance of PE reduced to 5% with Rx)
 LMWH/ UFH
 ACCP Recommend LMWH:
 Better bioavailability,
 Longer plasma half-life,
 More predictable dose response,
 Reduced risks of osteoporosis and thrombocytopenia,
 Less frequent dosing (Bates, 2012).
 Safe in pregnancy and lactation
 Increased risk of hematoma ( < 2 hr of cesarean)
Treatment of VTE
 After symptoms have abated ( almost 7 days), graded
ambulation should be started.
 Elastic stockings are fitted
 Graduated compression stockings should be
continued for 2 years after the diagnosis to reduce the
incidence of postthrombotic syndrome. This
syndrome can include chronic leg paresthesias or pain,
intractable edema, skin changes, and leg ulcers.
 Duration of RX: 20 weeks therapeutic and then
prophylaxis if still pregnant
 DVT postpartum : 6 months
Unfractionated Heparin
 Initial treatment of thromboembolism
 Delivery
 Surgery
 Thrombolysis may be necessary (ACOG 2011).
 (1) Initial intravenous therapy followed by adjusted-
dose subcutaneous UFH given every 12 hours;
 (2) Twice-daily, adjusted dose subcutaneous UFH with
doses adjusted to prolong the activated partial
thromboplastin time (aPTT) into the therapeutic
range 6 hours postinjection (Bates, 2012)
 Bolus intravenous dose of 70 to 100 U/kg( 5000 to 10,000
U) followed by
 continuous intravenous infusions beginning at 1000 U/hr
or 15 to 20 U/kg/hr, titrated to
 achieve an aPTT of 1.5 to 2.5 times control values (Brown,
2010).
 Intravenous anticoagulation should be maintained for at
least 5 to 7 days, after which treatment is converted to
subcutaneous heparin to maintain the aPTT to at
 least 1.5 to 2.5 times control throughout the dosing
interval.
 APS : aPTT does not accurately assess heparin
anticoagulation, and thus anti-factor Xa levels are
preferred.
Low-Molecular-Weight
Heparin
 4000 to 5000 daltons
 unfractionated heparin has equivalent activity against
factor Xa and thrombin, but LMWH have greater
activity against factor Xa than thrombin
 More predictable anticoagulant response
 Fewer bleeding complications (because of their better
bioavailability, longer half-life, dose-independent
clearance, and decreased interference with platelets
(Tapson, 2008).
 cleared by the kidneys
LMWH (enoxaparin, tinzaparin, and
dalteparin.
 1 mg/kg ( wt of early pregnancy)
 Target therapeutic level: peak anti-factor Xa activity 3
hours post- injection, with a target therapeutic range
of 0.4–1.0 U/mL.
 Assay measurement accuracy and reliability are
uncertain; correlations with bleeding and recurrence
risks are lacking; and assay costs are high.
So ACCP:
Routine monitoring with anti-Xa levels
is difficult to justify.
Labor and Delivery
 Therapeutic or prophylactic anticoagulation should be
converted from LMWH to the shorter half-life UFH in
the last month of pregnancy or sooner if delivery
appears imminent
 ACOG (2013): Twice-daily adjusted-dose subcutaneous
UFH or LMWH discontinue their heparin 24-36 hours
before labor induction or cesarean delivery.
 Patients receiving once-daily LMWH should take only
50 percent of their normal dose on the morning of the
day before delivery (Bates, 2012).
Labor and Delivery
 The American Society of Regional Anesthesia and
Pain Medicine advises withholding neuraxial blockade
for 10 to 12 hours after the last prophylactic dose of
LMWH or 24 hours after the last therapeutic dose
(Horlocker, 2010).
Anticoagulation with Warfarin Compounds
 Warfarin derivatives are generally contraindicated
because they readily cross the placenta and may cause
fetal death and malformations from hemorrhages (. 12
wks)
 Warfarin <12 weeks: nasal hypolasia, Stippled
epiphyses,ACC, Dandy walker, cerebral atrophy, optic
atrophy
 To avoid paradoxical thrombosis and skin necrosis
from the early anti-protein C effect of warfarin, these
women are maintained on therapeutic doses of UFH or
LMWH for 5 days and until the INR is in a therapeutic
range (2.0–3.0) for 2 consecutive days (ACOG 2013;
Stewart, 2010).
Thromboprophylaxy in mechanical
heart Valve
Complications of
Anticoagulation
 Heparin-Induced Thrombocytopenia
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Nonimmune :Benign, reversible , within the first
few days of therapy and resolves in approximately 5
days without therapy cessation.
Immune reaction: paradoxically causes
thrombosis ; monitoring every 2 or 3 days from day 4
until day 14
 Replace by danaparoid,
Complications of Anticoagulation
 Heparin-Induced Osteoporosis:
 Long term users: 6 mo or >
 Bleeding
SUPERFICIAL VENOUS
THROMBOPHLEBITIS
 Analgesia
 Elastic support
 Heat
 Rest
Pulmonary Embolism
PULMONARY EMBOLISM
 Dyspnea :82 percent,
 Chest pain: 49 percent,
 Cough : 20 percent,
 Syncope 14 percent,
 Hemoptysis: 7 percent
 Tachypnea, apprehension, and tachycardia
 Massive Pulmonary Embolism: hemodynamic
instability
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Nonspecific diagnostic tests
 CXR: Normal, atelectasis , effusion
 ECG: S1Q3T3, Right axis deviation, p pulmonale ,
and T-wave inversion in the anterior chest leads
may be evident on the ECG ( mimic nl
physiologic changes in Preg.)
 ABG: normal, hypoxic
 Echocardiograpy (TEE):
Specific diagnostic tests
 V/Q scan: preferred to CTPA in pregnancy (
avoiding
breast irradiation), normal V/Q scan
findings do not exclude pulmonary embolism
a fourth of V/Q scans in pregnant women were
nondiagnostic
 CTPA: first –line in nonpregnant, more accurate
 MRA ( gadolinium): Relatively contraindicated,
high sensitivity for detection of central
pulmonary emboli, the sensitivity for detection of
subsegmental emboli is less precise
 Pulmonary angiography:
Treatment of PE: Vena Caval Filters
 The woman who has very recently suffered a
pulmonary embolism and who must undergo
cesarean delivery presents a particularly serious
problem
 Heparin therapy fails to prevent recurrent pulmonary
embolism from the pelvis or legs, or
 when embolism develops from these sites despite
heparin treatment
Treatment of PE
 Thrombolysis: risk of recurrence or death was
significantly lower in patients given thrombolytic
agents and heparin compared with those given
heparin alone
 Embolectomy
 Anticoagulant
Many thanks for your attention
Many thanks to panelist
Previous VTE
Previous > 1 VTE
No prior VTE
Antiphospholipid antibody
Antiphospholipid antibody