Thromboembolic Disease in Pregnancy – The Silent Disorder

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Thromboembolic Disease in Pregnancy – The Silent Disorder Hassan Nasrat FRCS, RCOG Professor of Obstetric and Gynecology Fetal and Maternal Medicine Faculty of Medicine King Abdul Aziz university Jeddah – Saudi Arabia

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Thromboembolic Disease in Pregnancy – The Silent Disorder. Hassan Nasrat FRCS, RCOG Professor of Obstetric and Gynecology Fetal and Maternal Medicine Faculty of Medicine King Abdul Aziz university Jeddah – Saudi Arabia. Thromboembolic Disease (VTE) Refer to - PowerPoint PPT Presentation

Transcript of Thromboembolic Disease in Pregnancy – The Silent Disorder

Page 1: Thromboembolic Disease in Pregnancy – The Silent Disorder

Thromboembolic

Disease in Pregnancy –

The Silent DisorderHassan Nasrat FRCS, RCOG

Professor of Obstetric and Gynecology Fetal and Maternal MedicineFaculty of Medicine King Abdul Aziz university Jeddah – Saudi Arabia

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Anticoagulation Is Highly Effective Therapy For Both Conditions

Tests Designed To Diagnose DVT Are Also Of Importance For The Diagnosis Of Acute PE. 

Thromboembolic Disease (VTE) Refer to Deep Vein Thrombosis (DVT) And Pulmonary Embolism (PE)

Over 90 % Of Acute PE Are Emanating From Emboli Of The Lower Extremities.

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Incidence And Incidence And EpidemiologyEpidemiology Incidence And Incidence And EpidemiologyEpidemiology

Pulmonary Embolism (PE) Is Responsible For

Approximately 150,000 To 200,000 Deaths

Per Year In The USA.

PE Remains The Most Common

Preventable Cause Of Hospital Death

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The Incidence: 4 To 50 Times Higher In Pregnant Versus Non-pregnant Women (Age-adjusted)

Absolute Incidence: 1 In 500 To 2000 Pregnancies (0.025 To 0.10 Percent)

Pregnancy and Pregnancy and VTE VTE

Pregnancy and Pregnancy and VTE VTE

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VTE in Pregnancy: A Major Cause of Maternal Death

VTE in Pregnancy: A Major Cause of Maternal Death

VTE Is The Leading Direct Cause Of

Maternal Death In Western Obstetric

Practice (11 cases = 27% Of Cases)

“Confidential enquiries into maternal death in UK”

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VTE in Pregnancy: A Major CauseVenous Insufficiency

and VTE in Young Women

VTE in Pregnancy: A Major CauseVenous Insufficiency

and VTE in Young Women

71 women (mean age 35.5 years) with VTE

Assessed about 4 years after event – 52 DVT & 19 PTE– 79% mild / moderate post thrombotic

syndrome

Risk of VI after DVT: OR 10.9 (95% CI 4.2-28.0)

Risk of VI after PTE: OR 3.8 (95% CI 1.2-12.3)

McColl, Ellison, Greer et al 1999

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PATHOGENESIS AND RISK PATHOGENESIS AND RISK FACTORSFACTORS

PATHOGENESIS AND RISK PATHOGENESIS AND RISK FACTORSFACTORS

Part IPart IPart IPart I

Antithrombotic Strategies Antithrombotic Strategies

Part Part IIII

Part Part IIII

Part Part IIIIII

Part Part IIIIIIUse of LMWHs in PregnancyUse of LMWHs in Pregnancy

Part Part IVIV

Part Part IVIVSummary and RecommendationsSummary and Recommendations

Thromboembolic Disease in Pregnancy – The Silent

Disorder

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PATHOGENESIS AND RISK PATHOGENESIS AND RISK FACTORSFACTORS

PATHOGENESIS AND RISK PATHOGENESIS AND RISK FACTORSFACTORS

Part IPart IPart IPart I

Antithrombotic Strategies Antithrombotic Strategies

Part Part IIII

Part Part IIII

Part Part IIIIII

Part Part IIIIIIUse of LMWHs in PregnancyUse of LMWHs in Pregnancy

Part Part IVIV

Part Part IVIVSummary and RecommendationsSummary and Recommendations

Thromboembolic Disease in Pregnancy – The Silent

Disorder

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PATHOGENESIS PATHOGENESIS AND PregnancyAND PregnancyPATHOGENESIS PATHOGENESIS AND PregnancyAND Pregnancy

Proper Blood Proper Blood FlowFlow

Balance Balance between between

coagulation coagulation and and

anticoagulatianticoagulation on

mechanism: mechanism:

Healthy Vessel Healthy Vessel wallswalls

Increases Increases coagulaticoagulati

ononReduces Reduces fibrinolysfibrinolys

isis

Increases Increases coagulaticoagulati

ononReduces Reduces fibrinolysfibrinolys

isis

Vessel Wall Vessel Wall Trauma At Trauma At deliverydelivery

Vessel Wall Vessel Wall Trauma At Trauma At deliverydelivery

> 30% > 30% reducreduction tion by 15 by 15 weekweek

ss> 60% > 60% reducreduction tion

by 36 by 36 weekweek

ss

> 30% > 30% reducreduction tion by 15 by 15 weekweek

ss> 60% > 60% reducreduction tion

by 36 by 36 weekweek

ss

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A longitudinal Follow Up of 24 pregnant women with monthly Doppler ultrasound examinations found:

Progressive dilation of the deep veins of the legs.

Decreased flow velocity in the left common femoral vein and inferior vena cava that was most severe in the supine position.

The left lateral decubitus position significantly increased the velocity in both lower extremities

An ultrasound study of gestational and postural changes in the deep venous system of the leg in pregnancy. Macklon NS; BrJOG1997, 104]

Circulatory stasisCirculatory stasis

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The Incidence Of Is Nearly Twice As Many Postpartum Than Antepartum Events.

Pelvic Vein DVT Is More Likely In Pregnancy.

More Common In The Left Than The Right Leg.  

Antepartum VTE Is Roughly Equally Distributed Across Trimester’s.

Features of DVT in PregnancyFeatures of DVT in Pregnancy

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Among 5451 Patients With Ultrasound-confirmed DVT.

1 % Had DVT Confined To The Pelvis.

While 12 % Of Pregnant And 11 % Of Post-partum Women Had Isolated Pelvic DVT

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Conclusion -Conclusion - Part I Part IConclusion -Conclusion - Part I Part I

A Serious Disease

High Mortality Rate

Serious Morbidities

Appropriate Prophylactic Measures

Appropriate Diagnosis

Appropriate Treatement

VTE

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PATHOGENESIS AND RISK PATHOGENESIS AND RISK FACTORSFACTORS

PATHOGENESIS AND RISK PATHOGENESIS AND RISK FACTORSFACTORS

Part IPart IPart IPart I

Antithrombotic Strategies Antithrombotic Strategies

Part Part IIII

Part Part IIII

Part Part IIIIII

Part Part IIIIIIUse of LMWHs in PregnancyUse of LMWHs in Pregnancy

Part Part IVIV

Part Part IVIVSummary and RecommendationsSummary and Recommendations

Thromboembolic Disease in Pregnancy – The Silent

Disorder

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Antithrombotic Strategies

Antithrombotic Strategies

Vitamin K Antagonists

Un-Fractionated Heparin

Low-Molecular-Weight Heparins

Physical methods Vena Cava Filter

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Mechanical ThromboprophylaxisMechanical Thromboprophylaxis

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Antithrombotic Antithrombotic

Safety (Maternal and Fetal)

Effectiveness

Compliance

Cost

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Safety (Maternal and Fetal)

Safety (Maternal and Fetal)

Two potential fetal complications of maternal anticoagulant therapy:

Teratogenicity

Bleeding

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Vitamin K AntagonistsVitamin K Antagonists

Cross the placenta

Risk of maternal and fetal bleeding throughout gestation

Embryopathy: 6-12 wks of gestation - 4-5% Chondrodysplasia punctata Nasal (midface) hypoplasia Stippled epiphyses, short proximal limbs, short phalanges,

scoliosis

Central nervous system abnormalities Adverse fetal outcomes if Warfarin > 5 mg/day

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Warfarin EmbryopathyWarfarin Embryopathy

Embryopathy– chondrodysplasia punctata– midface hypoplasia– short proximal limbs– short phalanges– scoliosis Increased risk of low

IQ and neurological dysfunction (RR 7.6 for 2 or more defects)1

Maternal and foetal haemorrhage

X-ray: Wellesley D, et al. Br J Obstet Gynecol. 1998;105:805. 1Wesseling J, et al. Thromb Haemost. 2001;85:609-13.

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UFH in pregnancy:no placental transfer but…

UFH in pregnancy:no placental transfer but…

AllergySkin Necrosis

Heparin-induced thrombocytopenia

Osteoporosis

Frequent monitoringFrequent monitoring

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UF-Heparin Induced Osteoporosis

UF-Heparin Induced Osteoporosis

• >30% of women on prolonged UFH therapy will lose ≥10% of bone mass

• 2% symptomatic vertebral fractures on UFH thromboprophylaxis (Dahlman 1993)

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Potential Advantages of LMWH over UFH

Potential Advantages of LMWH over UFH

Like UFH: Do not cross

the placenta Safe in nursing

mother

less monitoring Ease of administration Efficacy comparable Greater safety: allergy

and HIT, bleeding, and osteoporosis

less monitoring Ease of administration Efficacy comparable Greater safety: allergy

and HIT, bleeding, and osteoporosis

But Also

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Safety & Effectiveness of LMWHSystematic Review of LMWH in

Pregnancy81 reports

2931

2777 11reports heart valvePul hypertension

2 reports duplicate 3 reports methodological

Most Common: Enoxaparin 1287, Dalteparin 789Least Common: Rivaparin 40, Tinzaparin 3.

Greer & Nelson Piercy Blood 2005

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ComplicationsComplications Rate% 95% C.I.

Thrombosis VTE Arterial

1.370.860.50

0.97-1.870.55-1.280.28-0.84

Bleeding Antenatal PPH > 500ml Wound haematoma

1.980.430.940.61

1.50-2.570.22-0.750.61-1.370.36-0.98

Allergy 1.80 1.37-2.34

Thrombocytopaenia Platelet HIT

0.110.00

0.02-0.320.00-0.11

osteoporosis 0.04 < 0.01-0.20

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Conclusion - Part IIConclusion - Part II

The Two Major Concerns with

Pharmacologic Antithrombotic Agents

Are (1) Teratogenicity And (2)

Bleeding.

Currently The evidence that LMWH Is

The Antithrombotic Agent Of Choice. It

Confer: Safety (Maternal And Fetal)

And Efficacy.

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PATHOGENESIS AND RISK PATHOGENESIS AND RISK FACTORSFACTORS

PATHOGENESIS AND RISK PATHOGENESIS AND RISK FACTORSFACTORS

Part IPart IPart IPart I

Antithrombotic Strategies Antithrombotic Strategies

Part Part IIII

Part Part IIII

Part Part IIIIII

Part Part IIIIIIUse of LMWHs in PregnancyUse of LMWHs in Pregnancy

Part Part IVIV

Part Part IVIVSummary and RecommendationsSummary and Recommendations

Thromboembolic Disease in Pregnancy – The Silent

Disorder

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Use of LMWHs in Use of LMWHs in PregnancyPregnancy

Use of LMWHs in Use of LMWHs in PregnancyPregnancy

Thromboprophylaxis

Treatment of VTE

Women with artificial heart valves

Fetal survival

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8/13 (62%) women with Fatal Antenatal PTE died in the first Trimester.

8/14 (71%) of postpartum deaths followed vaginal delivery.

There is a need for guideline on thromboprophylaxis after normal delivery

Pregnancy and Pregnancy and VTE VTE

Pregnancy and Pregnancy and VTE VTE

“Confidential enquiries into maternal death in UK”

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Risk Assessment In PregnancyRisk Assessment In Pregnancy

All women should undergo an All women should undergo an assessment of risk factors for VTE in assessment of risk factors for VTE in early pregnancy or before pregnancy. early pregnancy or before pregnancy.

It should be repeated if the woman is It should be repeated if the woman is admitted to hospital or develops other admitted to hospital or develops other intercurrent problems (Grade C)intercurrent problems (Grade C)

Women with VTE should be screened Women with VTE should be screened for inherited and acquired for inherited and acquired Thrombophilia ideally before Thrombophilia ideally before pregnancy (Grade B)pregnancy (Grade B)

Royal College of Obstetricians and Gynecologists Guidelines No 37 (January Royal College of Obstetricians and Gynecologists Guidelines No 37 (January 2004)2004)

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Risk Factors for VTE in pregnancy and the Risk Factors for VTE in pregnancy and the PuerperiumPuerperium

Risk Factors for VTE in pregnancy and the Risk Factors for VTE in pregnancy and the PuerperiumPuerperium

RCOG guidelinesRCOG guidelines

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Risk Factors in PregnancyRisk Factors in Pregnancy

Pregnancy: 10 fold increase in risk of VTE beginning from 1st trimester

ImmobilizationSurgery-CS

Prior VTE

Thrombophilia (Congenital and acquired)

Obesity And Advanced Age:All women dying from PTE following vaginal delivery were either obese or > 35 years of age. Only 1/10 deaths followed operative delivery.

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Role of Age and Delivery in the Incidence of Postpartum VTE

Macklon et al. Scott Med J 1996;41:83-6.

Role of Age and Delivery in the Incidence of Postpartum VTE

Macklon et al. Scott Med J 1996;41:83-6.

Vaginal delivery

Emergency CSElective CS

Rate

per

1,0

00 e

ven

ts

Age (years)

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Obesity and DVTObesity and DVT

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A retrospective cohort study of 159 women who had at least one pregnancy after an episode of VTE

6% VTE among women who did not receive antepartum thromboprophylaxis.

50 to 100 times higher than the overall incidence of antepartum VTE (0.6 to 1.3 of every 1000 deliveries)

Prior VTE and Prior VTE and pregnancypregnancy

Prior VTE and Prior VTE and pregnancypregnancy

Women with a history of VTE (with or without thrombophilia) are believed to have a higher risk of recurrence in subsequent pregnancies.)

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Higher Risk Thrombophilia

Low Risk Thrombophilia

Antithrombin Deficiency.

Persistent Antiphospholipid Antibodies.

compound heterozygotes for prothrombin G20210A and factor V Leiden, and homozygotes for these conditions

e.g. Protein C, Protein S Deficiency, And Hyperhomocysteinemia

ThrombophiliaThrombophiliaThrombophiliaThrombophilia

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Pharmacologic Thromboprophylaxis

Timing

Pharmacologic Thromboprophylaxis

Timing

PostpartumPostpartum

AntepartumAntepartum

Intrapartum- Cesarean SectionIntrapartum- Cesarean Section

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Single prior episode of VTE plus a higher risk thrombophilia Single idiopathic episode of VTE who are not receiving long-term anticoagulants Multiple prior episodes of VTE Antithrombin deficiency Single prior episode of VTE that was related to pregnancy or estrogen use (e.g., contraceptives)

Single episode of VTE associated with a transient risk factor that is no longer present Single prior episode of VTE in a patient with thrombophilia that is not considered higher risk

Antepartum

Antepartum Thromboprophylaxis Should be AdministeredThromboprophylaxis Should be Administered

Thromboprophylaxis on Case by Case Basis:Thromboprophylaxis on Case by Case Basis:

The 2008 American College of Chest Physicians guidelines on VTE and pregnancy The 2008 American College of Chest Physicians guidelines on VTE and pregnancy

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Postpartum Thromboprophylaxis Is Indicated For Women Who Have Had One Or More Episodes Of VTE Or Who Have Any Type Of Thrombophilia, Even Those That Are Not Considered Higher Risk

Postpartum

Postpartum

The 2008 American College of Chest Physicians guidelines on VTE and pregnancy The 2008 American College of Chest Physicians guidelines on VTE and pregnancy

Women who receive Epidural: LMWH may be initiated 4-6 hours after insertion or removal of the catheter

In High Risk women Postpartum Thromboprophylaxis should be continued for at least 6 weeks

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For most postpartum women who are unwilling to receive subcutaneous injections, a Warfarin-based regimen, rather than no pharmacologic thromboprophylaxis (Grade 2B).

For most postpartum women who are willing to receive subcutaneous injections, a LMWH-based regimen, rather than an UFH- or Warfarin-based regimen (Grade 2B). thromboprophylaxis be continued for four to six weeks

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Thromboprophylaxis Is NOT Recommended For Women Whose Only Risk Factors For VTE Are The Pregnancy And CS.

Intrapartum – Cesarean Section

Intrapartum – Cesarean Section

The 2008 American College of Chest Physicians guidelines on VTE and pregnancy The 2008 American College of Chest Physicians guidelines on VTE and pregnancy

Women Who Have Only One Additional Risk Factor For VTE Should Receive Either Pharmacological or Mechanical Thromboprophylaxis

Women who have multiple additional risk factors should receive Pharmacological Plus Mechanical Thromboprophylaxis

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Antenatal throboprophylaxis should Antenatal throboprophylaxis should begin as early in pregnancy as practical.begin as early in pregnancy as practical.

Postpartum prophylaxis should begin Postpartum prophylaxis should begin as soon as possible after delivery. as soon as possible after delivery. (Grade B)(Grade B)

Low Molecular Weight Heparins are Low Molecular Weight Heparins are the agents of choice for antenatal the agents of choice for antenatal thromboprophylaxis. They are as thromboprophylaxis. They are as effective as and safer than effective as and safer than Unfractionated heparin in pregnancy. Unfractionated heparin in pregnancy. (Grade B)(Grade B)

Royal College of Royal College of Obstetricians and Obstetricians and

Gynecologists Guidelines Gynecologists Guidelines No 37 (January 2004)No 37 (January 2004)

Royal College of Royal College of Obstetricians and Obstetricians and

Gynecologists Guidelines Gynecologists Guidelines No 37 (January 2004)No 37 (January 2004)

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RCOG guidelinesRCOG guidelines

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Antenatal Prophylactic and Therapeutic Doses of LMWH

Antenatal Prophylactic and Therapeutic Doses of LMWH

BMI > 30 in early pregnancyBMI > 30 in early pregnancy

RCOG guidelinesRCOG guidelines

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Use of LMWHs in Use of LMWHs in PregnancyPregnancy

Use of LMWHs in Use of LMWHs in PregnancyPregnancy

Thromboprophylaxis

Treatment of VTE

Women with artificial heart valves

Fetal survival

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Two Ways to Reduce Maternal mortality from PE:

•by investigating women aggressively when they present with a clinical suspicion of deep vein thrombosis (DVT) or PE, and treating those with a diagnosis of venous thromboembolism (VTE)

•by prophylaxis of those who have an increased risk for DVT and/or PE.

Both approaches are problematic

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The S&S Compatible With DVT And PE Are Common and Usually Nonthrombotic In Origin During Pregnancy.

Dilemmas in Clinical Diagnosis of DVT in pregnancy

The compressive effects of the gravid alter the interpretation and sensitivity of the tests.

Concern about performing procedures that expose the fetus to radiation

The Significance of Identifiable Laboratory Abnormality Associated With Thrombophilia And Its Management Remain Controversial.

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Diagnosis Of DVT in Diagnosis Of DVT in PregnancyPregnancy

Diagnosis Of DVT in Diagnosis Of DVT in PregnancyPregnancy

High ProbabilityHigh Probability2 (1.8%)2 (1.8%)

113 Patients suspected PE113 Patients suspected PEVentilation Perfusion Lung Ventilation Perfusion Lung

ScanScanNormalNormal

83 (73%)83 (73%)Non DiagnosticNon Diagnostic

28 (25%) 28 (25%)

Hull et al Ann Int Med 1990, 112chan et Arch Int. Med. 2002, 162l

PregnantPregnant

Non-PregnantNon-Pregnant High ProbabilityHigh Probability10 - 30%10 - 30%

Diagnosis Of PE in PregnancyDiagnosis Of PE in PregnancyDiagnosis Of PE in PregnancyDiagnosis Of PE in Pregnancy

PregnantPregnant Non-PregnantNon-Pregnant

Clinical DVTClinical DVT < 10%< 10% > 25%> 25%

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Diagnosis of VTE – Importance of Confirming the Diagnosis

Diagnosis of VTE – Importance of Confirming the Diagnosis

Long Term Treatment

Implication on Future pregnancy

Implications on Hormonal OC

Implications on HRT

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Risk Factors For DVT

Diagnosis of VTE - Clinical Examination

Diagnosis of VTE - Clinical Examination

Non Invasive TestsNon Invasive Tests

Clinical Symptoms and signs

Serum D-DimerSerum D-Dimer::

Invasive Test: Contrast Invasive Test: Contrast VenographyVenography

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Diagnosis of VTE - Serum D-dimer

Diagnosis of VTE - Serum D-dimer

A product of the degradation of fibrin by plasmin Has A High Sensitivity But Rather Low Specificity.

Elevations In D-dimer Are Found In: Uncomplicated Pregnancy. Increase With Gestational Age And Peaking At The Time Of Delivery And In The Early Postpartum Period.

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Compression Ultrasonography Compression Ultrasonography (Doppler ultrasound)(Doppler ultrasound)

Compression Ultrasonography Compression Ultrasonography (Doppler ultrasound)(Doppler ultrasound)

Accuracy:   Sensitivity And Specificity Of 100 And 99 Percent, Respectively.

Limitation:  

Does Not Detect Isolated Thrombi In The Iliac Vein Or The Femoral Vein Within The Adductor Canal.

Approximately 2 % With Initially Negative Us Develop A Positive Study When Retested Seven Days Later.

False Positive Test Patients With Pelvic Neoplasms Or Abscesses A systematic review of the accuracy of ultrasound in the diagnosis of deep venous thrombosis in asymptomatic patients. Kassai B; et al, Thromb Haemost 2004; 91

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Abnormal change in diameter during the Valsalva Abnormal change in diameter during the Valsalva maneuver: maneuver:

Compression Ultrasonography Compression Ultrasonography (Doppler ultrasound)(Doppler ultrasound)

Compression Ultrasonography Compression Ultrasonography (Doppler ultrasound)(Doppler ultrasound)

Abnormal compressibility of the Abnormal compressibility of the

veinvein: :

Abnormal Doppler color flowAbnormal Doppler color flow: :

The presence of an echogenic bandThe presence of an echogenic band::

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Magnetic resonance imaging Magnetic resonance imaging (MRI)(MRI)

Magnetic resonance imaging Magnetic resonance imaging (MRI)(MRI)

Can Detect Both Thigh And Pelvic Vein DVT With A Sensitivity That Approaches 100 Percent In The Non-pregnant Population.

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Is the gold standard for the diagnosis of lower extremity DVT

Diagnosis of VTE - Contrast Venography

Diagnosis of VTE - Contrast Venography

Reserved For Situations If Non Invasive Studies Are:

Not Feasible Equivocal,

Discordant With A Strong Clinical Impression

Requires Ionizing Radiation And Percutaneous Requires Ionizing Radiation And Percutaneous Veins Cannulation Veins Cannulation

Fetal Radiation (<500 Mcgy) With Abdominal-Fetal Radiation (<500 Mcgy) With Abdominal-pelvic Shielding, Shielding Renders The Test pelvic Shielding, Shielding Renders The Test Relatively Insensitive To Isolated Iliofemoral Relatively Insensitive To Isolated Iliofemoral Thrombosis.Thrombosis.

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Diagnostic algorithm for deep venous thrombosisDiagnostic algorithm for deep venous thrombosis

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PULMONARY EMBOLISMPULMONARY EMBOLISM PULMONARY EMBOLISMPULMONARY EMBOLISM

In Many Cases Of Proximal DVT, Silent PE Has Already Occurred By The Time That The Patient Is Seen (Meignan M; Et Al Arch Intern Med 2000 Jan 24).

Thus negative studies for DVT are not definitive In unselected population less that 30% of patients with PE have radiologic evidence of DVT

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PULMONARY EMBOLISMPULMONARY EMBOLISM PULMONARY EMBOLISMPULMONARY EMBOLISM

Because the treatments for DVT and submassive PE are identical, documentation of a DVT is sufficient to terminate the diagnostic evaluation and institute therapy.

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Pulmonary Embolus - Pulmonary Embolus - DiagnosisDiagnosisPulmonary Embolus - Pulmonary Embolus - DiagnosisDiagnosis

Clinical Signs and SymptomsTachypnea (>20 breaths per minute) and tachycardia (>100 bpm) are present in 90 percent of patients with acute PEPresyncope and syncope are rarer symptoms and indicate a massive embolus

Scoring Scoring systemssystemsScoring Scoring systemssystemsRISK OR SIGN POINT

S

Clinical signs and symptoms of DVT

+3

Alternative diagnosis deemed less likely than PE

+3

Heart rate > 100bpm + 1.5

Immobilization or surgery in previous 4 weeks

+ 1.5

Prior VTE + 1.5

Hemoptysis + 1

Active Cancer + 1

““PE unlikely” PE unlikely” score is ≤4score is ≤4

““PE unlikely” PE unlikely” score is ≤4score is ≤4

““PE likely” PE likely” score > 4score > 4

““PE likely” PE likely” score > 4score > 4

2/3 of Patients

N Engl J Med 349:1247, 2003

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Nonspecific StudiesNonspecific StudiesNonspecific StudiesNonspecific Studies•electrocardiographic changes

•Chest Radiograph

Pulmonary Arteriography

Ventilation-Perfusion Scanning

Spiral Computed Tomographic Pulmonary Angiography (Spiral Computed Tomography)

Magnetic Resonance Angiography

Pulmonary Embolus - Pulmonary Embolus - Diagnostic TestsDiagnostic TestsPulmonary Embolus - Pulmonary Embolus - Diagnostic TestsDiagnostic Tests

Specific Studies Specific Studies Specific Studies Specific Studies

As with evaluation of DVT, D-dimer is a very sensitive, but not specific, test for PE

D-Dimer AssaysD-Dimer AssaysD-Dimer AssaysD-Dimer Assays

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Diagnostic algorithm for PEDiagnostic algorithm for PE

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Radiation Exposure in PregnancyRadiation Exposure in PregnancyRadiation Exposure in PregnancyRadiation Exposure in Pregnancy

Exposure to < 5 rads has not been associated with

increases in pregnancy loss or fetal anomalies.

However exposure to ionizing radiation doses

above 1 rad increase risk of childhood leukemia from

1/3000 baseline to 1/2000

A combination of chest radiograph, V/Q scan and

pulmonary angiography exposes the fetus to less than

0.5 rads. The American College of Obstetricians and Gynecologists

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Investigations Fetal Exposure RADS

Chest X-ray <0.01

Limited venography (shielded) <0.05

Unilat venography without shield 0.31

Perfusion lung scan 0.006 – 0.012

Ventilation lung scan Xenon-133 0.001- 0.019

Pul. Angiography via Brachial 0.05

Pul. Angiography via Femoral 0.22 – 0.37

Spiral CT 0.013

Estimated radiationEstimated radiation

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Diagnosis and Treatment of VTEDiagnosis and Treatment of VTE

High Index Of Clinical Suspicion

High Risk Index

Initiate Therapy Diagnostic Studies

LOW Risk Index

Diagnostic Studies

Initiate Therapy

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Use of LMWHs in Use of LMWHs in PregnancyPregnancy

Use of LMWHs in Use of LMWHs in PregnancyPregnancy

Thromboprophylaxis

Treatment of VTE

Women with artificial heart valves

Fetal survival

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Anticoagulation of pregnant women with mechanical Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. heart valves: a systematic review of the literature.

Chan, et al, Arch Intern Med 2000;160.Chan, et al, Arch Intern Med 2000;160.

Anticoagulation of pregnant women with mechanical Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. heart valves: a systematic review of the literature.

Chan, et al, Arch Intern Med 2000;160.Chan, et al, Arch Intern Med 2000;160.

Pregnant women with prosthetic heart valves

pose a problem because of the lack of reliable

RCT

The overview consisted of prospective and

retrospective cohort studies.

Women with artificial heart Women with artificial heart valvesvalves

Women with artificial heart Women with artificial heart valvesvalves

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(1)use of VKAs throughout pregnancy (in widespread use in Europe)

(2)replacement of VKAs with UFH from 6 to 12 weeks, and

(3) UFH use throughout pregnancy.

Outcomes Measures: pregnancy loss, fetopathic effects (including Warfarin embryopathy), maternal bleeding, thromboembolic complications, and death.

Three commonly used approaches:

Anticoagulation of pregnant women with mechanical heart valves: a Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. systematic review of the literature. Chan, et al, Arch Intern Med 2000;160.Chan, et al, Arch Intern Med 2000;160.Anticoagulation of pregnant women with mechanical heart valves: a Anticoagulation of pregnant women with mechanical heart valves: a

systematic review of the literature. systematic review of the literature. Chan, et al, Arch Intern Med 2000;160.Chan, et al, Arch Intern Med 2000;160.

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Warfarin embryopathy occurred in 6.4% if used throughout pregnancy

The substitution of heparin at or prior to 6 weeks eliminate this risk .

The Overall rate of fetal wastage were similar in all groups.

The overall maternal mortality was 2.9 %.

Major bleeding: occurred in 2.5% of all pregnancies

Use of VKAS throughout was associated with the lowest risk of valve thrombosis/systemic embolism (3.9%)

The reported high rates of Thromboembolism with UFH The reported high rates of Thromboembolism with UFH might be explained by inadequate dosing and/or the use might be explained by inadequate dosing and/or the use of an inappropriate target therapeutic range.of an inappropriate target therapeutic range.

The reported high rates of Thromboembolism with UFH The reported high rates of Thromboembolism with UFH might be explained by inadequate dosing and/or the use might be explained by inadequate dosing and/or the use of an inappropriate target therapeutic range.of an inappropriate target therapeutic range.

ResultsResultsResultsResults

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VKAs are more efficacious than UFH for thromboembolic prophylaxis of women with mechanical heart valves in pregnancy; however,

However it increases the risk of embryopathy(6.3%)

Substituting VKAs with heparin between 6 weeks and 12 weeks reduces the risk of fetopathic effects but possibly subjects the woman to an increased risk of thromboembolic complications.

ConclusionConclusionConclusionConclusion

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Adjusted-dose bid LMWH throughout pregnancy in doses adjusted according to weight (Grade 1C),

Aggressive adjusted-dose UFH throughout pregnancy, (Grade 1C)

UFH or LMWH (as above) until the thirteenth week, change to Warfarin until the middle of the third trimester, and then restart UFH or LMWH (Grade 1C)

Long-term anticoagulants should be resumed postpartum with all regimens.

In women with prosthetic heart valves at high risk, suggest the addition of low-dose aspirin, 75 to 162 mg/d (Grade 1C)

RecommendationsRecommendationsRecommendationsRecommendations

The 2008 American College of Chest Physicians guidelines on VTE and pregnancy The 2008 American College of Chest Physicians guidelines on VTE and pregnancy

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Women Requiring Long-term Vitamin K Antagonist Therapy Who Are Attempting Pregnancy,

Should Perform Frequent Pregnancy Tests And Substituting Unfractionated Heparin (UFH) Or Low Molecular Weight Heparin (LMWH) For Warfarin When Pregnancy Is Achieved (Grade 2C)

Women Requiring Long-term Vitamin Women Requiring Long-term Vitamin K Antagonist Therapy K Antagonist Therapy

Women Requiring Long-term Vitamin Women Requiring Long-term Vitamin K Antagonist Therapy K Antagonist Therapy

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Use of LMWHs in Use of LMWHs in PregnancyPregnancy

Use of LMWHs in Use of LMWHs in PregnancyPregnancy

Thromboprophylaxis

Treatment of VTE

Women with artificial heart valves

Fetal survival

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MATERNAL THROMBOPHILIAS ARE ASSOCIATED WITH: INCLUDING FETAL LOSS IUGR PREECLAMPSIA ABRUPTION INTRAUTERINE DEATH.

Fetal survivalThrombophilia and Pregnancy

Complications

Fetal survivalThrombophilia and Pregnancy

Complications

KUPFERMINC ET AL NEJM, 1999, 341

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Women With Recurrent Pregnancy Loss ( > Miscarriages) And Women With Prior Severe Or Recurrent PET, Abruptions, Or Otherwise Unexplained IUFD, Should Receive Screening For Congenital Thrombophilia And APLAS (Grade 2C).

Women With APLAS And A History Of Multiple (>) Early Pregnancy Losses Or One Or More Late Pregnancy Losses, PET, IUGR, Or Abruption, Antepartum Aspirin Plus Minidose Or Moderate-dose UFH Or Prophylactic LMWH May Be Administered (Grade 2B).

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For women with a congenital thrombophilic

deficit and recurrent miscarriages, a second-

trimester or later loss, severe or recurrent

PET, or abruption, low-dose aspirin therapy

plus either minidose heparin or prophylactic

LMWH therapy (Grade 2C).

In addition to postpartum anticoagulants

should be administered to these women (Grade

2C)

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Patients with APLAS and NO PRIOR VTE OR

PREGNANCY LOSS should be considered to

have an increased risk for the development of

venous thrombosis and, perhaps, pregnancy

loss.

One of the following approaches for these

women: Surveillance. Minidose heparin, prophylactic LMWH, and/or low-dose aspirin, 75 to 162 mg/d (all Grade 2C).

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Key PointsKey Points

Complication And Pathogenesis:

VTE Is A Leading Cause Of Mortality And Serious Long Term Morbidity Among Pregnant Women

VTE Is A Leading Cause Of Mortality And Serious Long Term Morbidity Among Pregnant Women

Pregnancy Is A Leading Risk Factor For VTE Attention Should Be Paid To The Presence And / Or Development Of Additional Risk Factor (S)

Pregnancy Is A Leading Risk Factor For VTE Attention Should Be Paid To The Presence And / Or Development Of Additional Risk Factor (S)

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Key Points (cont.)Key Points (cont.)

Diagnosis:

D-dimer because of its high negative predictive value given the higher rate of false-positive D-dimer results in pregnancy.

Venous compression US has sensitivity of 90 – 100 % for proximal vein thrombosis.

Spiral computed tomographic pulmonary angiography (spiral CT) is now the preferred screening and diagnostic modality for PE

D-dimer because of its high negative predictive value given the higher rate of false-positive D-dimer results in pregnancy.

Venous compression US has sensitivity of 90 – 100 % for proximal vein thrombosis.

Spiral computed tomographic pulmonary angiography (spiral CT) is now the preferred screening and diagnostic modality for PE

The diagnosis of either DVT or PE in pregnancy is a challenging.

the PPV of a test increase with the prevalence of the disease to be detected The Key To Accurate Diagnosis Of Either DVT Or PE Is Initial Risk Assessment

The diagnosis of either DVT or PE in pregnancy is a challenging.

the PPV of a test increase with the prevalence of the disease to be detected The Key To Accurate Diagnosis Of Either DVT Or PE Is Initial Risk Assessment

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LMWH is as effective but safer than Unfractionated heparin

Further Studies are needed for defining:

oAppropriate / individualized Dose.

oDuration of prophylaxis / Treatment

oThe High risk groups who likely to get the most benefit

Key Points (cont.)Key Points (cont.)

Prophylaxis and Treatment:

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ThanksThanksFor Great AudienceFor Great Audience