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Nothing can happen unless you first dream
Carl Sandburg
Anticoagulation in
Prosthetic valves
with Pregnancy
A Dilemma !
• Dr Shahid Abbas
• Consultant Interventional Cardiologist
INTRODUCTION
Less than 1% of pregnant women have
prosthetic heart valves
They are an important group as they require
specialist care during pregnancy
Cardiovascular Physiology of Pregnancy;
• Normal pregnancy is associated with of 30 to 50
percent increase blood volume and CO
• These increases begin during the first trimester; the
levels peak by 20 to 24 weeks of pregnancy and then
are eithersustained until term or decrease.
• The heart rateincreases by 10 to 20 beats per minute,
the stroke volume increases,and there is a substantial
reduction in systemic vascular resistance,with
decreases in blood pressure.
Cardiovascular Physiology of Pregnancy
• During labor, cardiac output increases & the blood
pressure increases
• Immediately after delivery, the cardiac filling
pressure mayincrease dramatically due to the
decompression of the vena cava and the return of
uterine blood
• The cardiovascular adaptations associated with
pregnancy regress by approximately six weeks after
delivery
Cardiovascular Physiology of Pregnancy
• Functional Murmurs develop in nearly all women
during pregnancy
• Echocardiography is warranted when diastolic
murmurs, continuous murmurs, or loud systolic
murmurs (louder than grade 2 on the 6-point scale)
are detected or when murmurs are associated with
symptoms or an abnormal electrocardiogram
Other physiologic change
• Hypercoaguble state.
• Hypoalbumineamia.
• Insulin resistant state.
• Increased red c.ell mass
• Increased ESR.
• Increased renal blood flow ( 30 % ).
• Increased hepatic clearance of medications.
Etiology of thrombosis in pregnancy
• Increased serum levels of procoagulants:
fibrinogen and factors II, VII, VIII, X, and XII
• Decreased protein S levels
• Increased resistance to activated protein C
second and third trimesters of pregnancy
• Increased serum plasminogen activator
inhibitor-1 (PAI-1) and placental PAI-2 levels
• Venous stasis
Risk of Thrombosis
• History of a prior thromboembolic event
• Atrial fibrillation
• Prosthesis in the mitral position
• Multiple prosthetic valves
• Mechanical prosthetic valves
• Pregnancy etc
Pregnant Patients With Valvular Heart
Disease
Poorly tolerate
• Aortic stenosis
• Mitral regurgitation
• Aortic regurgitation with New York Heart
Association (NYHA) class 3-4 symptoms
• Mitral stenosis with NYHA class 2-4 symptoms
• Valvular heart disease that results in severe
pulmonary hypertension
• Left ventricular (LV) dysfunction with an ejection
fraction (EF) less than 40%
Evolution of Prosthetic Heart Valves
The development of the
original ball-and-cage
valve design can be
attributed to the bottle
stopper in 1858
In the early 1950’s, it led to
the idea of a prosthetic
heart valve
First implanted in a human in
a closed procedure in
September of 1952
VALVE TYPES
• Mechanical Valves
• Bioprosthetic Valves
Mechanical Valves
High risk of valve thrombosis
Lifelong anticoagulation .
Valve type, size and position all
influence thrombotic risk.
St Jude’s tilting disc mechanical
valve
Bioprosthetic Valves
Tissue valves
porcine bioprosthesis
eliminate the need
for anticoagulation A Porcine Bioprostheses
COMPLICATIONS OF MECHANICAL
VALVES
Thrombus
formation
Systemic
embolization
Bleeding due to
anticoagulation
Endocarditis
Problems in pregnancy
Maternal Complications
• Increased risk of valve thromboembolism
• 25% risk of significant maternal morbidity,
such as myocardial infarction and stroke
• Estimated 3% risk of maternal mortality
Fetal Complication
• As a result of anticoagulation therapy
Miscarriage, growth restriction,
Prematurity, low birth weight
Care Before and during pregnancy
1. Preconception Counselling
2. Anticoagulation during pregnancy
3.Intrapartum and postpartum
management
Preconception Counselling
1. General Advice
2. Specific Advice
General Advice
Lifestyle advice
Avoid smoking & drinking,
Diet and exercise
Advise high dose Folic
Acid (5mg)
Specific Advice
Meeting with cardiologist
before stopping Contraception
Possible changes to their
anticoagulation regimen
Contact doctor after first
positive pregnancy test
Anticoagulation in prosthatic valves  with pregnancy
ANTENATAL MANAGEMENT
• Folic acid and iron
• Frequent antenatal visits
• Anti-coagulants to prevent valve
thrombosis
• Periodic hospitalization for,
– Cardiac decompensation
– Infection etc.
Anticoagulation Therapy
Classification
A. Parenteral Anti-Coagulants
1. Indirect Thrombin Inhibitors
a) Heparins
i) High Molecular Weight Heparin (UFH)
ii) Low Molecular Weight Heparins
Enoxaparin Dalteparin
Tinzaparin Reviparin
Danaparoid
2. Direct Thrombin Inhibitors,
Hirudin Lepirudin
Bivalirudin Argatroban
Classification (Cont)
B. Oral Anti-Coagulants
1. Coumarins,
Warfarin
Dicumarol
2. Indanediones,
Phenindione
warfarin
• Inhibit Factor 2,7,9,10, protein C &S.
• Dose, < 5mg/day
• Monitoring INR ( Target 2-3).
• Complication. Cross placenta so causing both
maternal and fetal complication.
• Excreation,92% urine. 8% Bile
• Half Life, 20-60 hr
Anticoagulation in pregnant patients
with valvular heart disease
• Warfarin is more efficacious than unfractionated
heparin (UFH) for thromboembolic prophylaxis of
pregnant women with mechanical valves
• Warfarin therapy in the first trimester of
pregnancy is associated with a substantial
increase in fetal anomalies
1. Fetal wastage (approximately 30%)
2. Prematurity (approximately 45%)
3. Low birth weight (approximately 50%)
Antidote of Warfarin
• Vitamin K (Antidote)
• Fresh frozen plasma
• Prothrombin complex concentrates
• Recombinant factor VIIa
Heparin
• Activate Anti Thrombin III.
• Monitoring , APTT for High MW Heparin and
Anti X a level for LMWH ( 0.7-1.2IU/ml).
• Half life 1.5hr
• Excretion, Bile and Urine
• Antidote, Protamine sulphate , 1mg/100
units heparin.
Maternal complications of
anticoagulants during pregnancy
• The rate of major bleeding in patients treated
with UFH therapy is 2%
• Approximately 3% of patients receiving UFH
develop HIT
• Heparin-induced osteoporosis causes vertebral
fracture in 2-3% of patients
• Significant reduction in bone density in 30%
• LMWH causes less osteoporosis and HIT than
UFH
Fetal complications
• Warfarin crosses the placenta and can cause
fetal bleeding and teratogenicity esp in first
trimester.
• UFH & low LMWH does not cross the placenta
Although bleeding at the uteroplacental
junction and fetal wastage are possible
ACCP Recommendations (2012)
Option 1
Adjusted-dose, twice-daily (bid) LMWH throughout
pregnancy, adjusted to reach the manufacturer's peak anti-
Xa LMWH level 4 hours after subcutaneous (SC) injection
Option 2
Adjusted-dose bid SC UFH every 12 hours (q12h)
throughout pregnancy, adjusted so the mid interval aPTT
remains at least twice control or to achieve an anti-Xa
heparin level of 0.35-0.70 U/mL
Option 3
UFH or LMWH (as above) until 13 weeks' gestation, THEN
change to vitamin K antagonists until the patient is close to
delivery, and THEN restart UFH or LMWH
Regimens of Anticoagulant
• Regimen 1-Warfarin sodium through out
pregnancy with unfractionated heparin
sodium near term
• Regimen 2-Substitution of warfarin with
unfractionated heparin between 6-12 weeks
and near term
• Regimen 3-Unfractionated heparin
throughout pregnancy
Prosthetic heart valves and
anticoagulation
Regimen withlowest risk of valve thrombosis (3.9%)
• warfarin throughout pregnancy
• At cost of warfarin embryopathy in 6.4% of live
births
• This risk was eliminated when heparin was
substituted for warfarin at or prior to 6 weeks and
continued until 12 weeks
• Although using heparin only from 6-12 weeks'
gestation was associated with an increased risk of
valve thrombosis (9.2%)
Fetal Complications
0
5
10
15
20
25
30
Abortion Anomalies
Regimen 1
Regimen 2
Regimen 3
%
Chan WS. Arch Intern Med 2000;160:191
Maternal Complications
0
5
10
15
20
25
30
35
Thrombus Death
Regimen 1
Regimen 2
Regimen 3
%
Chan WS. Arch Intern Med 2000;160:191
Treatment
• Warfarin, should be stop before 06 weeks of
pregnancy.
• 06-13 weeks Heparin.
• 13-36 weeks Warfarin.
• 36weeks to birth Heparin.
• Heparin should be stop 06 hr before birth and
resume 06 hr after birth and continue for 24
to 72 hrs than switch to warfarin.
Treatment of Stuck valve
• Heparin may be considered for small,
nonobstructive thrombi.
• For obstructive valve thrombosis, the
treatment options are surgical thrombectomy
and thrombolysis, both of which carry
substantial fetal and maternal risks.
Treatment of Stuck valve
• cardiac surgery during pregnancyPerioperative
maternal and fetal mortality were 6 and 30 %
respectively.
• thrombolysis during pregnancy Maternal
mortality, hemorrhagic complications, and
fetal mortality rates were 1.2, 8, and 5,8%
respectively.
CONCLUSION
• Pregnant women with mechanical heart valves
require careful, adequate anticoagulation with
frequent monitoring
• Warfarin provides better maternal protection against
thromboembolism but may be harmful to the fetus
• Heparin is less protective against maternal
thromboembolism but is safer for the fetus
Thank You
Anticoagulation in prosthatic valves  with pregnancy

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Anticoagulation in prosthatic valves with pregnancy

  • 1. Nothing can happen unless you first dream Carl Sandburg
  • 2. Anticoagulation in Prosthetic valves with Pregnancy A Dilemma ! • Dr Shahid Abbas • Consultant Interventional Cardiologist
  • 3. INTRODUCTION Less than 1% of pregnant women have prosthetic heart valves They are an important group as they require specialist care during pregnancy
  • 4. Cardiovascular Physiology of Pregnancy; • Normal pregnancy is associated with of 30 to 50 percent increase blood volume and CO • These increases begin during the first trimester; the levels peak by 20 to 24 weeks of pregnancy and then are eithersustained until term or decrease. • The heart rateincreases by 10 to 20 beats per minute, the stroke volume increases,and there is a substantial reduction in systemic vascular resistance,with decreases in blood pressure.
  • 5. Cardiovascular Physiology of Pregnancy • During labor, cardiac output increases & the blood pressure increases • Immediately after delivery, the cardiac filling pressure mayincrease dramatically due to the decompression of the vena cava and the return of uterine blood • The cardiovascular adaptations associated with pregnancy regress by approximately six weeks after delivery
  • 6. Cardiovascular Physiology of Pregnancy • Functional Murmurs develop in nearly all women during pregnancy • Echocardiography is warranted when diastolic murmurs, continuous murmurs, or loud systolic murmurs (louder than grade 2 on the 6-point scale) are detected or when murmurs are associated with symptoms or an abnormal electrocardiogram
  • 7. Other physiologic change • Hypercoaguble state. • Hypoalbumineamia. • Insulin resistant state. • Increased red c.ell mass • Increased ESR. • Increased renal blood flow ( 30 % ). • Increased hepatic clearance of medications.
  • 8. Etiology of thrombosis in pregnancy • Increased serum levels of procoagulants: fibrinogen and factors II, VII, VIII, X, and XII • Decreased protein S levels • Increased resistance to activated protein C second and third trimesters of pregnancy • Increased serum plasminogen activator inhibitor-1 (PAI-1) and placental PAI-2 levels • Venous stasis
  • 9. Risk of Thrombosis • History of a prior thromboembolic event • Atrial fibrillation • Prosthesis in the mitral position • Multiple prosthetic valves • Mechanical prosthetic valves • Pregnancy etc
  • 10. Pregnant Patients With Valvular Heart Disease Poorly tolerate • Aortic stenosis • Mitral regurgitation • Aortic regurgitation with New York Heart Association (NYHA) class 3-4 symptoms • Mitral stenosis with NYHA class 2-4 symptoms • Valvular heart disease that results in severe pulmonary hypertension • Left ventricular (LV) dysfunction with an ejection fraction (EF) less than 40%
  • 11. Evolution of Prosthetic Heart Valves The development of the original ball-and-cage valve design can be attributed to the bottle stopper in 1858 In the early 1950’s, it led to the idea of a prosthetic heart valve First implanted in a human in a closed procedure in September of 1952
  • 12. VALVE TYPES • Mechanical Valves • Bioprosthetic Valves
  • 13. Mechanical Valves High risk of valve thrombosis Lifelong anticoagulation . Valve type, size and position all influence thrombotic risk. St Jude’s tilting disc mechanical valve
  • 14. Bioprosthetic Valves Tissue valves porcine bioprosthesis eliminate the need for anticoagulation A Porcine Bioprostheses
  • 16. Problems in pregnancy Maternal Complications • Increased risk of valve thromboembolism • 25% risk of significant maternal morbidity, such as myocardial infarction and stroke • Estimated 3% risk of maternal mortality Fetal Complication • As a result of anticoagulation therapy Miscarriage, growth restriction, Prematurity, low birth weight
  • 17. Care Before and during pregnancy 1. Preconception Counselling 2. Anticoagulation during pregnancy 3.Intrapartum and postpartum management
  • 18. Preconception Counselling 1. General Advice 2. Specific Advice
  • 19. General Advice Lifestyle advice Avoid smoking & drinking, Diet and exercise Advise high dose Folic Acid (5mg)
  • 20. Specific Advice Meeting with cardiologist before stopping Contraception Possible changes to their anticoagulation regimen Contact doctor after first positive pregnancy test
  • 22. ANTENATAL MANAGEMENT • Folic acid and iron • Frequent antenatal visits • Anti-coagulants to prevent valve thrombosis • Periodic hospitalization for, – Cardiac decompensation – Infection etc.
  • 24. Classification A. Parenteral Anti-Coagulants 1. Indirect Thrombin Inhibitors a) Heparins i) High Molecular Weight Heparin (UFH) ii) Low Molecular Weight Heparins Enoxaparin Dalteparin Tinzaparin Reviparin Danaparoid 2. Direct Thrombin Inhibitors, Hirudin Lepirudin Bivalirudin Argatroban
  • 25. Classification (Cont) B. Oral Anti-Coagulants 1. Coumarins, Warfarin Dicumarol 2. Indanediones, Phenindione
  • 26. warfarin • Inhibit Factor 2,7,9,10, protein C &S. • Dose, < 5mg/day • Monitoring INR ( Target 2-3). • Complication. Cross placenta so causing both maternal and fetal complication. • Excreation,92% urine. 8% Bile • Half Life, 20-60 hr
  • 27. Anticoagulation in pregnant patients with valvular heart disease • Warfarin is more efficacious than unfractionated heparin (UFH) for thromboembolic prophylaxis of pregnant women with mechanical valves • Warfarin therapy in the first trimester of pregnancy is associated with a substantial increase in fetal anomalies 1. Fetal wastage (approximately 30%) 2. Prematurity (approximately 45%) 3. Low birth weight (approximately 50%)
  • 28. Antidote of Warfarin • Vitamin K (Antidote) • Fresh frozen plasma • Prothrombin complex concentrates • Recombinant factor VIIa
  • 29. Heparin • Activate Anti Thrombin III. • Monitoring , APTT for High MW Heparin and Anti X a level for LMWH ( 0.7-1.2IU/ml). • Half life 1.5hr • Excretion, Bile and Urine • Antidote, Protamine sulphate , 1mg/100 units heparin.
  • 30. Maternal complications of anticoagulants during pregnancy • The rate of major bleeding in patients treated with UFH therapy is 2% • Approximately 3% of patients receiving UFH develop HIT • Heparin-induced osteoporosis causes vertebral fracture in 2-3% of patients • Significant reduction in bone density in 30% • LMWH causes less osteoporosis and HIT than UFH
  • 31. Fetal complications • Warfarin crosses the placenta and can cause fetal bleeding and teratogenicity esp in first trimester. • UFH & low LMWH does not cross the placenta Although bleeding at the uteroplacental junction and fetal wastage are possible
  • 32. ACCP Recommendations (2012) Option 1 Adjusted-dose, twice-daily (bid) LMWH throughout pregnancy, adjusted to reach the manufacturer's peak anti- Xa LMWH level 4 hours after subcutaneous (SC) injection Option 2 Adjusted-dose bid SC UFH every 12 hours (q12h) throughout pregnancy, adjusted so the mid interval aPTT remains at least twice control or to achieve an anti-Xa heparin level of 0.35-0.70 U/mL Option 3 UFH or LMWH (as above) until 13 weeks' gestation, THEN change to vitamin K antagonists until the patient is close to delivery, and THEN restart UFH or LMWH
  • 33. Regimens of Anticoagulant • Regimen 1-Warfarin sodium through out pregnancy with unfractionated heparin sodium near term • Regimen 2-Substitution of warfarin with unfractionated heparin between 6-12 weeks and near term • Regimen 3-Unfractionated heparin throughout pregnancy
  • 34. Prosthetic heart valves and anticoagulation Regimen withlowest risk of valve thrombosis (3.9%) • warfarin throughout pregnancy • At cost of warfarin embryopathy in 6.4% of live births • This risk was eliminated when heparin was substituted for warfarin at or prior to 6 weeks and continued until 12 weeks • Although using heparin only from 6-12 weeks' gestation was associated with an increased risk of valve thrombosis (9.2%)
  • 35. Fetal Complications 0 5 10 15 20 25 30 Abortion Anomalies Regimen 1 Regimen 2 Regimen 3 % Chan WS. Arch Intern Med 2000;160:191
  • 36. Maternal Complications 0 5 10 15 20 25 30 35 Thrombus Death Regimen 1 Regimen 2 Regimen 3 % Chan WS. Arch Intern Med 2000;160:191
  • 37. Treatment • Warfarin, should be stop before 06 weeks of pregnancy. • 06-13 weeks Heparin. • 13-36 weeks Warfarin. • 36weeks to birth Heparin. • Heparin should be stop 06 hr before birth and resume 06 hr after birth and continue for 24 to 72 hrs than switch to warfarin.
  • 38. Treatment of Stuck valve • Heparin may be considered for small, nonobstructive thrombi. • For obstructive valve thrombosis, the treatment options are surgical thrombectomy and thrombolysis, both of which carry substantial fetal and maternal risks.
  • 39. Treatment of Stuck valve • cardiac surgery during pregnancyPerioperative maternal and fetal mortality were 6 and 30 % respectively. • thrombolysis during pregnancy Maternal mortality, hemorrhagic complications, and fetal mortality rates were 1.2, 8, and 5,8% respectively.
  • 40. CONCLUSION • Pregnant women with mechanical heart valves require careful, adequate anticoagulation with frequent monitoring • Warfarin provides better maternal protection against thromboembolism but may be harmful to the fetus • Heparin is less protective against maternal thromboembolism but is safer for the fetus