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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 ( pregnant) 6 - 22 X Antepartum = postpartum DVT …..Antepartum ( 74%) - PowerPoint PPT Presentation
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Thromboembolism PanelDr HommamDr JalilianDr MoosaviDr TorkestaniDr Vafaei
Significance of VTEHighest risk during pregnancy and peurperiumIncidence : 1/10000 ( nonpregnant) …….1/1600 (
pregnant) 6 - 22 XAntepartum = postpartumDVT …..Antepartum ( 74%)PE………Postpartum (60.5%)Cesarean section : 30.3 RR for PE50% due to thrombophiliaResponsible for 20% of pregnancy- related
deaths
Aims of this panelOral presentation Who needs thromboprophylaxy?Who needs screening for thrombophilia?Review of guideline for thromboprophylaxyThromboprophylaxy in cases with previous
history of VTEThromboprophylaxy in cases with
thrombophilia.Thromboprophylaxy in cases with ARTPeripartum thromboprophylaxyEarly diagnosis of VTETreatment of VTE
کشور در موجود گزارشوضع ارائهترکستانی دکتر خانم
Risk Factors
Pregnancy as a prothrombotic state
Virchow triad: stasis, local trauma to the 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
infectionVenous statsis due to compressionIncreased in deep vein capacitance ( prog.,
Prostacycline and nitric oxide)
Risk factors
Risk factors
Risk factorsObstetrics:
ThrombophiliaReduction in inhibitory proteins for
coagulation15% white people50% TE events in pregnancy ((Lockwood,
2002; Pierangeli, 2011)InheritedAcquired
Inherited thrombophiliaFamily historyVTE before 45 y/oVTE without risk factor VTE with minimal provocation ( long flight,
estrogen)Family history of sudden dead due to PEHistory of multiple family members requiring
long-term anticoagulation therapy because of recurrent thrombosis (Anderson, 2011)
Inherited thrombophiliaAntithrombin Deficiency:Type IType II Autosomal Dominant
Most thrombogenic of the heritable coagulopathiesHomozygous antithrombin deficiency is lethal
Inherited thrombophiliaProtein 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 thrombophiliaProtein S Deficiency: Decreased in pregnancy ( 30-24%) Decreased after cesarean and infection
Inherited thrombophiliaFactor V Leiden Mutation:Most prevalent of the known thrombophiliaHeterozygous 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 thrombophiliaProthrombin G20210A Mutation:
Excessive accumulation of prothrombin
Inherited thrombophiliaHyperhomocysteinemia: 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 recessiveDecreased in normal pregnancyfasting 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 Zplasminogen 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 thrombophiliaAnticardiolipinLupus anticoagulantβ2-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 thrombophiliaArterial VenousUnusual 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 ScreeningGiven 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 ScreeningSELECTIVE 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 TestsShould 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
ThromboprophylaxisThere 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 VTE70% iliofemoral veins in pregnancyLeft 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 deep-pelvic 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 VTEBed Rest ( 60% chance of PE reduced to 5% with Rx)LMWH/ UFHACCP 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 lactationIncreased risk of hematoma ( < 2 hr of cesarean)
Treatment of VTEAfter symptoms have abated ( almost 7 days), graded
ambulation should be started.Elastic stockings are fittedGraduated 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 HeparinInitial treatment of thromboembolismDelivery 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 Heparin4000 to 5000 daltonsunfractionated 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, anddalteparin.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 DeliveryTherapeutic 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 DeliveryThe 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 CompoundsWarfarin 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 AnticoagulationHeparin-Induced Thrombocytopenia 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 AnticoagulationHeparin-Induced Osteoporosis: Long term users: 6 mo or >
Bleeding
SUPERFICIAL VENOUS THROMBOPHLEBITISAnalgesiaElastic support Heat Rest
Pulmonary Embolism
PULMONARY EMBOLISMDyspnea :82 percent, Chest pain: 49 percent, Cough : 20 percent, Syncope 14 percent, Hemoptysis: 7 percentTachypnea, apprehension, and tachycardiaMassive Pulmonary Embolism:
hemodynamic instability
Nonspecific diagnostic testsCXR: Normal, atelectasis , effusionECG: 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, hypoxicEchocardiograpy (TEE):
Specific diagnostic testsV/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 accurateMRA ( 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 FiltersThe 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 PEThrombolysis: risk of recurrence or death was
significantly lower in patients given thrombolytic agents and heparin compared with those given heparin alone
EmbolectomyAnticoagulant
Many thanks for your attention
Many thanks to panelist
Previous VTE
Previous > 1 VTE
No prior VTE
Antiphospholipid antibody
Antiphospholipid antibody