Thrombophilia in pregnancy: Whom to screen, when to treat

THROMBOPHILIA has been widely investigated—and that may be one of the main challenges in detecting and managing it during pregnancy: Numerous studies have yielded different estimates of the incidence of various clotting disorders in pregnancy —itself a hyper coagul able state—and conflicting screening and prevention recommendations.

SELECTION OF PATIENTS FOR TESTING Routine testing for inherited thrombophilias in unselected populations is not recommended (ACOG) suggests: screening for thrombophilia when the results will affect pregnancy/postpartum management, and suggests avoiding screening when treatment is indicated because of patient-specific risk factors

(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.

When to test There are a number of tests that can be performed when evaluating for inherited thrombophilias. Ideally, laboratory testing is performed at least six weeks from the thrombotic event and while the patient is not pregnant and not taking an anticoagulant or hormonal therapy

PREVENTION OF VTE

high-risk thrombophilias AT deficiency, homozygotes for the FVL mutation, homozygotes for the PGM mutation, double heterozygotes for FVL and PGM)

lower-risk thrombophilias heterozygotes for FVL and PGM deficiencies of protein C or protein S

Antepartum/intrapartum Anticoagulation should ideally be initiated in the first trimester Anticoagulation should be discontinued at onset of labor or before scheduled induction or cesarean delivery to minimize risk of hemorrhagic complications, including those related to placement of neuraxial anesthesia; timing depends on the type and dose of anticoagulant.

We use the following terminology to describe heparin anticoagulation dosing Prophylactic dose anticoagulation refers to the use of low doses of anticoagulants, which aims to reduce the risk of thromboembolism while minimizing bleeding complications. Intermediate dose anticoagulation refers to the adjustment of prophylactic dose anticoagulation with weight gain during pregnancy Therapeutic dose anticoagulation refers to the use of anticoagulants at doses typically reserved for treatment of thromboembolic disease

Monitoring of prophylactic or intermediate dose LMW heparin is not required. Unfractionated heparin is monitored using the aPTT, measured six hours after injection. The dose should be adjusted to maintain the aPTT at 1.5 to 2.5 times the mean of the control value or the patient's baseline aPTT value We do not monitor laboratory values (eg, anti-factor Xa activity levels) in pregnant women treated with therapeutic dose LMW heparin in routine clinical practice, although some experts do recommend such monitoring. If monitoring is done, peak anti-factor Xa activity levels are tested four to six hours after dosing,

Women with high-risk thrombophilias We suggest that women with high-risk thrombo philias receive anticoagulation antepartum and postpartum , whether or not they have a personal or family history of VTE.

HIGH RISK THROMBOPHILIA without a history of VTE who are not chronically on anticoagulation, single daily intermediate dose of LMWH rather than a prophylactic dose administer therapeutic doses of LMWH to women who are considered to be at high risk for recurrence

Women with lower-risk thrombophilias WITH PRIOR VTE WITH OUT RIOR VTE should receive antepartum and postpartum anticoagulation the choice of regimen needs to be individualized and discussed with the patient. In women with an unprovoked episode of VTE who are not chronically on anticoagulation, we will generally employ a single daily intermediate dose of LMWH rather than a prophylactic dose

Low RISK WITH OUT PRIOR VTE asymptomatic women (no prior VTE) who are heterozygotes for FVL or PGM or have deficiencies of protein C or protein S do not routinely require antepartum anticoagulation, but should undergo individualized risk assessment and monitoring for clinical signs and symptoms of VTE. We use a once daily intermediate dose of LMWH

ACOG suggests postpartum surveillance without anticoagulation therapy except in women with additional risk factors for thrombosis (eg, obesity, prolonged immobility, first degree relative with VTE before age 50 years)

The ACCP recommends postpartum anticoagulation for women with lower-risk thrombo philias if there is a positive family history of VTE or delivery is by cesarean; clinical vigilance without anticoagulation is adequate if there is no family history of VTE The RCOG recommends seven days postpartum thrombo prophylaxis, but six weeks if the patient has a family history of VTE or other risk factors for VTE

Fetal surveillance and timing of delivery Given that there may be a small increased risk of stillbirth in thrombo philic pregnant women who are receiving or not receiving prophylactic anticoagulation, we suggest weekly fetal assessment with non stress tests beginning at ≥36 weeks of gestation and delivery at 39 weeks of gestation in the absence of an obstetrical complication such as preeclampsia, abruption, or fetal growth restriction.

1.women receiving unfractionated heparin therapy should be able to receive regional analgesia if they have a normal activated partial thromboplastin time (aPTT) 2. Women receiving prophylactic doses of unfractionated heparin or low-dose aspirin are not at increased risk and can be offered regional analgesia 3. For women receiving once-daily low-dose low-molecularweight heparin, regional analgesia should not be placed until 12 hours after the last injection

4. Low-molecular-weight heparin should be withheld for at least 2 hours after epidural catheter removal 5. The safety of regional analgesia in women receiving twice daily low-molecular-weight heparin has not been studied sufficiently. It is not known whether delaying regional analgesia for 24 hours after the last injection is adequate.

Postpartum Because postpartum risk of VTE is as high or higher than antepartum risk, postpartum treatment dosing regimens should be as, or even more, aggressive than antepartum regimens and postpartum treatment is sometimes indicated for women who did not receive antepartum anticoagulation. Postpartum heparin can be started 4 to 6 hours after a vaginal delivery or 6 to 12 hours after a cesarean delivery in patients with normal postpartum bleeding