Anticoagulation in Pregnancy and the puerperium

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Anticoagulation in Pregnancy and the puerperium

• Dr. Mohammed Abdalla
• Egypt, Domiat G. Hospital

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• , the optimal use of anticoagulants during
  pregnancy remains controversial because of a lack
  of appropriate prospective randomized clinical
  trials.

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Before Initiating Anticoagulant Therapy

• full thrombophilia screen (provide information
  that can influence the duration and intensity of
  anticoagulation)
• full blood count and a coagulation screen
• urea, electrolytes and liver-function tests, to
  exclude renal or hepatic dysfunction, which are
  cautions for anticoagulant therapy

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Prophylactic Anticoagulation

• 1.    What are the criteria of risk assessment?
• 2.    Who are the patients candidates for
  PROPHYLACTIC anticoagulation ?
• 3.    What are the hazards of anticoagulation
  during pregnancy?
• 4.    Unfractionated or fractionated heparin and
  in which dose?

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what are the criteria of risk assessment?

• increased parity.
• advanced maternal age.
• obesity.
• operative delivery.
• Any persistent and identifiable hypercoagulable
  state .either acquired or inherited.(
  thrombophilia.).

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RISK CATEGORY
Pr.TED thrombophilia Pr.TED family
history. Recurrent TEDs. TED in current
pregnancy Prosthetic mitral valve
HIGH RISK
ONE previous TED.
LOW RISK
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thrombophilia
INHERETED
ACQURED
Protein C deficiency. Protein S deficiency. AT3
deficiency Factor V leiden mutation
Homocystinuria
APhS. Myeloproliferative disease. Malignancy. Neph
rotic syndrome.
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who are the patients candidates for PROPHYLACTIC
anticoagulation ?
1-patients judged at low risk  these patients
are though to be most vulnerable from the time of
delivery throughout the puerperium which is the
period of greatest risk. With low dose asprin
antenatally.
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who are the patients candidates for PROPHYLACTIC
anticoagulation ?

• 2--patients judged at high risk
• these patients receive antenatal ,intranatal
  ,and postnatal anticoagulation. and throughout
  the puerperium,.

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What are the Hazards of anticoagulation during
pregnancy?

• The platelet count should be monitored on a
  monthly basis to detect heparin-induced
  thrombocytopenia, which is associated with
  further thrombotic complications.

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What are the Hazards of anticoagulation during
pregnancy?

• Low molecular weight heparins are a promising
  alternative because of their long half-lives
  which give a more predictable dose-effect and
  reduce the number of daily injections.
• The risk of heparin-induced thrombocytopaenia is
  lower.
• At present, their legal prescription is limited
  to the 2nd and 3rd terms of pregnancy as
  prophylactic treatment.

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Thromboembolic Disease in Pregnancy and the
Puerperium Acute Management

• In women with factors consistent with VTE,
  anticoagulant treatment should be employed until
  an objective diagnosis is made

RCOG guideline A
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Initial treatment of VTE during pregnancy

• In clinically suspected DVT or PTE, treatment
  with unfractionated heparin or low molecular
  weight heparin (LMWH) should be given until the
  diagnosis is excluded by objective testing,
  unless treatment is strongly contraindicated.

RCOG guideline A
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• Two RCTs of unfractionated heparin in acute DVT
  showed that failure to achieve the lower limit of
  the target therapeutic range of the activated
  partial thromboplastin time (APTT) ratio(at least
  twice control ), was associated with a 10-15 fold
  increase in the risk of recurrent VTE..
• Descriptive studies indicate high risks of
  recurrent VTE and death when heparin was withheld
  from patients with suspected or proven VTE,
  compared with low risks when heparin was given.
• (Evidence level 1b supported by levels II III).

Hyers TM, Hull RD, Weg JG. Antithrombotic
therapy for venous thromboembolic disease. Chest
1995 108335-51s.
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, why it may be useful to determine the anti-Xa
level as a measure of heparin dose (target range
0.35-0.7 u/ml)?

• There is an increasing realisation that APTT
  monitoring of unfractionated heparin is
  frequently poorly performed and is technically
  problematic

Hirsh J. Heparin. N Engl J Med
19913241565-74 Wheeler AP, Jaquiss RDB,
Newman JH. Physician practices in the treatment
of pulmonary embolism and deep vein thrombosis.
Arch Intern Med 19881481321-5.
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, why it may be useful to determine the anti-Xa
level as a measure of heparin dose (target range
0. 35-0.7 u/ml)?

• Apparent heparin resistance occurs in late
  pregnancy due to increased fibrinogen and factor
  VIII which influence the APTT.

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Heparin Regimens May Include
Therapeutic Heparinisation

• Continuous intravenous infusion of unfractionated
  heparin,
• Subcutaneous injections of unfractionated heparin
  .
• Subcutaneous injections of LMWH.

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Intravenous unfractionated Heparin
1
2500U in 500ml saline
10 drops/min
7 drops/min
1000u/hour
1500u/hour

• an initial infusion concentration of 1000 iu/ml
  should be employed

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Intravenous unfractionated heparin

• Measure aPTT level six hours after the loading
  dose, then at least daily. The dose should be
  adjusted to achieve a therapeutic target range
  within 24 hours.(60-90sec.).
• The therapeutic target aPTT ratio is usually
  1.5-2.5 times the average laboratory control
  value.. Measure APTT level six hours after the
  loading dose, then at least daily. The dose
  should be adjusted to achieve a therapeutic
  target range within 24 hours. The target range
  for the anti-Xa level in this situation is
  0.35-0.70 iu/ml.

Hyers TM, Hull RD, Weg JG. Antithrombotic
therapy for venous thromboembolic disease. Chest
1995 108335-51s.
20
Subcutaneous unfractionated Heparin
2

• Subcutaneous unfractionated heparin is an
  effective alternative to intravenous
  unfractionated heparin for the initial management
  of DVT.
• .

RCOG Evidence Level I II
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Subcutaneous unfractionated Heparin

• Initial intravenous bolus of 5000 iu and then
  subcutaneous injections of 15,000-20 000 iu, 12
  hourly.

mid-interval aPTT maintained between 1.5-2.5
times the control.
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Low Molecular Weight Heparin
3

• LMWHs are more effective than unfractionated
  heparin with lower mortality and fewer
  haemorrhagic complications in the initial
  treatment of DVT in nonpregnant subjects. LMWHs
  are as effective as unfractionated heparin for
  treatment of PTE.

RCOG evidence level A
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Low Molecular Weight Heparin

• a twice-daily dosage regimen for LMWHs in the
  treatment of VTE in pregnancy IS recommended .

Long-term use of LMWHs may be associated with a
lower risk of osteoporosis and bone fractures
than unfractionated heparin.
Monreal M. Long-term treatment of venous
thromboembolism with low-molecular weight
heparin. Curr Opin Pulm Med 20006326-9.
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Low molecular weight heparin

• Peak anti-Xa activity (three hours
  post-injection) should be measured. The target
  therapeutic range for LMWH (0.6-1.0 units/ml)
  appears satisfactory. And the dose of LMWH should
  be reduced if the target therapeutic range is
  above the upper limit.

The platelet count should be rechecked seven to
nine days after commencing treatment.
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Maintenance Treatment of DVT or PTE

• The simplified therapeutic regimen for LMWH is
  convenient for patients and allows out-patient
  treatmen

oral anticoagulants are generally avoided for
maintenance therapy in pregnancy especially
before 13wk. and after 36wk.
The platelet count should be monitored on a
monthly basis to detect heparin-induced
thrombocytopenia,
Chan WS, Anand S, Ginsberg JS. Anticoagulation
of pregnant women with mechanical heart valves A
systematic review of the literature. Arch Intern
Med 2000160191-6
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Women with antenatal VTE can be managed with an
adjusted-dose regimen of subcutaneous
unfractionated heparin or subcutaneous LMWH for
the remainder of the pregnancy.

• Thomson AJ, Walker ID, Greer IA. Low molecular
  weight heparin for the immediate management of
  thromboembolic disease in pregnancy. Lancet
  19983521904.
• Monreal M. Long-term treatment of venous
  thromboembolism with low-molecular weight
  heparin. Curr Opin Pulm Med 20006326-9.
• Hull RD, Delmore T, Carter C, et al. Adjusted
  subcutaneous heparin versus warfarin sodium in
  the long-term treatment of venous thrombosis. N
  Engl J Med 1982306189-94.
• British Society for Haematology. Guidelines on
  the prevention, investigation, and management of
  thrombosis associated with pregnancy. J Clin
  Pathol 199346489-96.

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Anticoagulant Therapy During Labour and Delivery,
Including the Use of Epidurals

• The dose of heparin should be
  reduced to its thromboprophylactic dose on the
  day prior to induction of labour and continued in
  this dose during labour

unfractionated heparin
5000iu/12h
or
LMWH preparations
Once daily
Thomson AJ, Greer IA. Non-haemorrhagic obstetric
shock. Best Practice and Research in Clinical
Obstetrics and Gynaecology 20001419-41 .
Dahlman TC, Hellgren MS, Blomback M. Thrombosis
prophylaxis in pregnancy with use of subcutaneous
heparin adjusted by monitoring heparin
concentration in plasma. Am J Obstet Gynecol
1989161420-5.40 Toglia MR, Weg JG. Venous
thromboembolism during pregnancy. N Engl J Med
1996335108-14.
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The Treatment Dose (Twice Daily Administration)
Should Be Recommenced Following Delivery.
For delivery by elective caesarean section, the
woman should receive a thromboprophylactic dose
of LMWH on the day prior to delivery and, on the
day of delivery, the morning dose should be
omitted and the operation performed that morning.
The thromboprophylactic dose of LMWH should be
given by three hours post-operatively (over four
hours after removal of the epidural catheter, if
appropriate) and the treatment dose recommenced
that evening.
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Anticoagulant therapy during labour and delivery,
including the use of epidurals

• To minimise or avoid the risk of epidural
  haematoma, regional techniques should not be used
  until at least 12 hours after the previous
  prophylactic dose of LMWH. When a woman presents
  while on a therapeutic regimen of LMWH (i.E. A
  twice-daily regimen), regional techniques should
  not be employed for at least 24 hours after the
  last dose of LMWH.

Checketts MR, Wildsmith JA. Central nerve block
and thromboprophylaxis - is there a problem? Br J
Anaesth 199982164-7.42 Gogarten W, Van Aken H,
Wulf H, et al. Ruckenmarksnahe regionalanassthesie
n und thromboembolieprophylaxe/antikoagulation.
Anasthesiol Intensivmed 199712623-8.
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For Delivery by Elective Caesarean Section

• on the day prior to deliverythe woman should
  receive a thromboprophylactic dose of LMWH
• on the day of deliverythe morning dose should be
  omitted and the operation performed that morning
• The thromboprophylactic dose of LMWH should be
  given by three hours post-operatively (over four
  hours after removal of the epidural catheter, if
  appropriate) and the treatment dose recommenced
  that evening.

RCOG guideline
RCOG guideline
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Postnatal Anticoagulation

• It is recommended that anticoagulant treatment
  should be continued postnatally for 6-12 weeks,
• At three months, the woman should be assessed for
  continuing risk factors for VTE. Warfarin is not
  contraindicated in breastfeeding.
• There are no published data on whether LMWHs are
  secreted in breast milk, although experience of
  enoxaparin in the puerperium reports no problems
  during breastfeeding and other heparins are known
  not to cross the breast.

Prandoni P. Simioni P. Girolami A.
Antiphospholipid antibodies, recurrent
thromboembolism, and intensity of warfarin
anticoagulation. Thromb Haemost 199675859. 46
Nelson-Piercy C. Hazards of heparin. In Greer
IA, editor. Thrombo-embolic disease in obstetrics
and gynaecology. Baillière's Clin Obstet Gynaecol
199711489-509.
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thank you