Hypercoagulability in pregnancy

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Hypercoagulability in pregnancy
SpecialtyObstetrics

Hypercoagulability in pregnancy is the propensity of

post partum bleeding.[1] However, when combined with an additional underlying hypercoagulable states, the risk of thrombosis or embolism may become substantial.[1]

Causes

Pregnancy-induced hypercoagulability is probably a physiologically adaptive mechanism to prevent post partum hemorrhage.

first trimester, due to enhanced compliance of the vessel walls by a hormonal effect.[2]

Also, pregnancy can cause hypercoagulability by other factors, e.g. the

vacuum extractor or Caesarean section.[2][4]

A study of more than 200,000 women came to the result that admission to

venous thromboembolism (VTE) during the stay, and a 6-fold increase in risk in the four weeks after discharge, compared with pregnant women who did not require hospitalization.[5] The study included women admitted to hospital for one or more days for reasons other than delivery or venous thromboembolism.[5]

Pregnancy after the age of 35 augments the risk of VTE, as does

multigravidity of more than four pregnancies.[2]

Pregnancy in itself causes approximately a five-fold increased risk of

deep venous thrombosis.[6] Several pregnancy complications, such as pre-eclampsia, cause substantial hypercoagulability.[2]

Hypercoagulability states as a

prothrombin mutation, proteins C and S deficiencies, and antithrombin III deficiency
.

Complications

Hypercoagulability in pregnancy, particularly due to inheritable thrombophilia, can lead to placental vascular thrombosis.[7] This can in turn lead to complications like early-onset hypertensive disorders of pregnancy, pre-eclampsia and small for gestational age infants (SGA).[7] Among other causes of hypercoagulability, Antiphospholipid syndrome has been associated with adverse pregnancy outcomes including recurrent miscarriage.[8] Deep vein thrombosis has an incidence of one in 1,000 to 2,000 pregnancies in the United States,[2] and is the second most common cause of maternal death in developed countries after bleeding.[9]

Prevention

Main article:
Thrombosis prophylaxis

Unfractionated

low molecular weight heparin, warfarin (not to be used during pregnancy) and aspirin remain the basis of antithrombotic treatment and prophylaxis both before and during pregnancy.[10]

While the consensus among physicians is the safety of the mother supersedes the safety of the developing

anticoagulation
regimen during pregnancy can be performed to minimize the risks to the developing fetus while maintaining therapeutic levels of anticoagulants in the mother.

The main issue with anticoagulation in pregnancy is that warfarin, the most commonly used anticoagulant in chronic administration, is known to have

weeks of gestation.[13] However, unfractionated heparin and low molecular weight heparin do not cross the placenta.[13]

Indications

In general, the indications for anticoagulation during pregnancy are the same as the general population. This includes (but is not limited to) a recent history of

deep venous thrombosis (DVT) or pulmonary embolism, a metallic prosthetic heart valve, and atrial fibrillation
in the setting of structural heart disease.

In addition to these indications, anticoagulation may be of benefit in individuals with lupus erythematosus, individuals who have a history of DVT or PE associated with a previous pregnancy, and even with individuals with a history of coagulation factor deficiencies and DVT not associated with a previous pregnancy.[14]

In pregnant women with a history of

live birth rate among those with antiphospholipid syndrome and perhaps those with congenital thrombophilia but not in those with unexplained recurrent miscarriage.[15]

Strategies

A consensus on the correct anticoagulation regimen during pregnancy is lacking. Treatment is tailored to the particular individual based on her risk of complications. Warfarin and other

platelets and a clotting screen should be performed prior to administration of anticoagulant regimens in pregnancy.[13]

Subcutaneous tinzaparin may be given at doses of 175 units of antifactor Xa activity per kg,[13] based on prepregnancy or booking weight at approximately 16 weeks, and not the current weight.[13] While unfractionated heparin is otherwise typically given in an intravenous formulation, this is inconvenient for the prolonged period of administration required in pregnancy.[citation needed
]

Whether warfarin can be reinitiated after the 12th week of pregnancy is unclear. In a recent retrospective analysis, resumption of warfarin after the first trimester is completed is associated with increased risk of loss of the fetus.[18] However, this analysis included only individuals who were treated with anticoagulants for mechanical heart valves, who generally require high levels of anticoagulation.

In pregnant women with mechanical heart valves, the optimal anticoagulation regimen is particularly unclear. Anticoagulation with subcutaneous heparin in this setting is associated with a high incidence of

enoxaparin (a LMWH) in these high-risk individuals.[21]

Risk score

Prevention of DVT and other types of venous thrombosis may be required if certain predisposing risk factors are present. One example from Sweden is based on the point system below, where points are summed to give the appropriate prophylaxis regimen.[9]

Points Risk factors
1 point
Minor factors
2 points
Intermediate risk factors
3 points
Intermediate risk factors
  • Homozygous
    for factor V Leiden mutation
  • Homozygous for factor II mutation
4 points
Severe risk factors
Very high risk

After adding any risk factors together, a total of one point or less indicates no preventive action is needed.

post partum prophylaxis to six weeks.[9]

A risk score of four points or higher means prophylaxis in the

proximal DVT or pulmonary embolism requires a minimum of 26 weeks (6.5 months) of therapy[13] If the therapy duration reaches delivery time, the remaining duration may be given after delivery, possibly extending the minimum of six weeks of post partum therapy.[13] In a very high risk, high-dose ante partum prophylaxis should be continued at least 12 weeks after delivery.[9]

Women with antiphospholipid syndrome should have an additional low-dose prophylactic treatment of aspirin.[9]

Cautions

All anticoagulants (including LMWH) should be used with caution in women with suspected

nephropathy.[13]

Major side effects of

haemorrhage, hair loss and drug allergy.[13] Still, LMWHs are much less likely to cause heparin-induced thrombocytopenia than unfractionated heparin.[13]

Regional anaesthesia is contraindicated in women on therapeutic anticoagulation, and should not be used within 24 hours of the last dose of tinzaparin.[13]

Monitoring

Anticoagulant therapy with LMWH is not usually monitored.

INR, and anti-Xa levels are not reliable.[13] It can prolong the partial thromboplastin time (APTT) in some women, but still, the APTT is not useful for monitoring.[13]

To check for any thrombocytopenia,

platelet count should be checked prior to commencing anticoagulant therapy, then seven to ten days after commencement, and monthly thereafter.[13] Platelet count should also be checked if unexpected bruising or bleeding occurs.[13]

Reversal

anti-Xa activity, but the clinical effect of the residual anti-Xa activity is not known.[13] Both anti-IIa and anti-Xa activity may return up to three hours after protamine reversal, possibly due to release of additional LMWH from depot tissues.[13]

See also

  • Valvular heart disease and pregnancy

References

  1. ^
    ISBN 978-0-521-88115-9
    .
  2. ^ a b c d e f g h Hypercoagulability during Pregnancy Lab Lines. A publication of the Department of Pathology and Laboratory Medicine at the University of Cincinnati. September/October 2002 Volume 8, Issue 5
  3. PMID 2521425
    .
  4. ^ "Venous Thromboembolism (Blood Clots) and Pregnancy". Centers for Disease Control and Prevention. 20 August 2020. Retrieved 24 October 2020.
  5. ^
    PMID 24201164
    .
  6. PMID 23825156
    .
  7. ^
    PMID 22118560
    .
  8. PMID 22729089
    .
  9. ^ a b c d e f g h i "Hemostasrubbningar inom obstetrik och gynekologi" (Disorders of hemostasis in obstetrics and gynecology), from ARG (work and reference group) from SFOG (Swedish association of obstetrics and gynecology). Intro available at [1]. Updated 2012.
  10. PMID 22876895
    .
  11. PMID 16856447
    .
  12. S2CID 33278534
    .
  13. ^ a b c d e f g h i j k l m n o p q r s t u v w [2] Archived 12 June 2010 at the Wayback Machine Therapeutic anticoagulation in pregnancy. Norfolk and Norwich University Hospital (NHS Trust). Reference number CA3017. 9 June 2006 [review June 2009]
  14. PMID 16444389
    .
  15. PMID 23766357
    .
  16. PMID 1121966
    .
  17. PMID 17531898
    .
  18. PMID 16967636
    .
  19. PMID 3773964
    .
  20. PMID 8636556
    .
  21. PMID 12639202
    .

External links

  • [3] Therapeutic anticoagulation in pregnancy. Norfolk and Norwich University Hospital (NHS Trust). Reference number CA3017. 9 June 2006 [review June 2009]
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