202411021155

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Tags: Obstetrics, Haematology

Peripartum anticoagulation

Venous thromboembolism (VTE) is an important cause of maternal morbidity and mortality

The risk of VTE increases approximately 5x during pregnancy, and 20x in the postpartum period

The main factors associated with VTE during pregnancy are

Indications for anticoagulation during pregnancy include

UFH& LMWH

Unfractionated heparin and LMWHs do not cross the placenta and can be safely used during pregnancy

Unfractionated heparin is a heterogenous mixture of high molecular weight molecules (3000–30,000 Daltons)

LMWHs are derived from UFH, with a molecular weight of 4000–5000 Daltons

The higher ratio of anti-Xa and anti-II activity of LMWH allows their use to balance effective antithrombotic activity with a lower bleeding risk

LMWHs also have a lower associated risk of heparin-induced thrombocytopenia given that they bind platelet factor 4 less and have fewer effects on platelet aggregation, function and activation

UFH is typically only used for thromboprophylaxis if the patient has an allergy to LMWH or has a contraindication such as renal failure.

Typical UFH doses for VTE prophylaxis in pregnancy are

Dosing requirements increase over the course of pregnancy as blood volume, GFR and protein binding of heparin all increase

Therapeutic UFH is used less frequently but is dosed at 10,000 units Q12 h, targeting an activated partial thromboplastin time (aPTT) of 1.5–2.5 times control 6 h after injection

Prophylactic LMWHs, including enoxaparin, dalteparin and tinzaparin, are typically dosed once daily

American College of Obstetricians and Gynecologists (ACOG) recommendations are based on fixed dosing, whereas Royal College of Obstetricians and Gynaecologists (RCOG) recommendations are weight-adjusted

Highlow study

multinational RCT
1110 pregnant women w/ previous Hx of VTE
weight-adjusted intermediate dose LMWH VS fixed low-dose
1° outcome: confirmed VTE event

NO DIFFERENCE

patients in the Highlow study were instructed to stop their anticoagulant dose at the first signs of labour, or at 24 h before planned delivery

19% vs 39% ineligible to receive Neuraxial block due to unplanned onset of labour

Fondaparinux

Fondaparinux is a heparin-like drug that should only be used with advice from a haematologist, and reserved for patients intolerant of heparin-containing medications

Of particular concern is its long (17 h) half-life

Fondaparinux should be held for 36–42 h before neuraxial blockade or catheter removal
6–12 h should elapse after neuraxial blockade or catheter removal before restarting the medication

Warfarin

Warfarin is a vitamin K antagonist less frequently used during pregnancy given its teratogenicity and ability to cross the placenta
use during the 6th to 12th weeks of pregnancy poses the greatest risk

warfarin is superior to LMWH for the prevention of mechanical heart valve thrombosis and may be selected for certain patients with mechanical heart valves after the first trimester, for whom adequate anticoagulation is critical for safety

Reversal of warfarin with either vitamin K or fresh frozen plasma may be needed at the time of delivery, given the risk of maternal retroplacental bleeding and fetal intracerebral haemorrhage near term.

Although warfarin is less frequently encountered in labouring patients, ASRA and ESAIC/ESRA recommend warfarin be stopped for 5 days before a neuraxial procedure, with a normal international normalised ratio (INR) level seen before proceeding

pregnant women with mechanical heart valves on warfarin should switch from warfarin to twice daily LMWH by 36 weeks of pregnancy (or 2 weeks before planned birth, whichever is earlier); LMWH should be monitored with anti-Xa levels

Warfarin is safe for lactating patients

ASRA recommends that epidural catheters should be removed while the INR remains <1.5, ideally within 12–24 h of re-initiating warfarin

DOAC

Safety profile in pregnancy not well established
→ typically avoided during pregnancy

All DOACs can cross into breast milk, and their use during breastfeeding is discouraged because of a relatively unknown safety profile and lack of available studies on the amount of transfer that occurs

Aspirin

Women at risk for PET are recommended to take between 75 and 150 mg of aspirin daily, starting at 12 weeks' gestation, through delivery

Any of the following high-risk conditions are indications for aspirin prophylaxis:

More than one of the following moderate risk factors is also considered an indication for aspirin:

Anaes considerations

Typically, obstetric plans to stop anticoagulant drugs before delivery are related more to the concern for neuraxial haematoma than the risk of bleeding around delivery

Spinal haematoma: neurological recovery was worse if spinal decompression was delayed >12 h after initial presenting symptoms

Neuraxial haematoma most commonly presents with symptoms of spinal cord compression, including progressive sensory block and lower extremity motor weakness or bowel or bladder incontinence

Back pain occurs in a minority of patients, and radicular pain may or may not co-present with back pain

Safety guidelines from the Association of Anaesthetists and the Obstetric Anaesthetists' Association exist to aid in early detection of vertebral canal haematoma and timely escalation of care

These guidelines include recommendations for the anaesthetist to be alerted for abnormal motor block during labour or abnormal recovery from neuraxial blockade, including the inability to raise the heel off the bed against gravity during labour or the inability to perform a straight leg raise at 4 h after the last dose of local anaesthetic.

Neurological symptoms typically evolve 24–48 h after a neuraxial procedure and warrant immediate neurological consultation and imaging, with magnetic resonance imaging being the imaging modality of choice to most sensitively and specifically diagnose neuraxial haematoma

If neuraxial haematoma is detected, emergency neurosurgical consultation and decompressive laminectomy are needed, ideally within 8 h of the onset of symptoms

Societal recommendations for timing of neuraxial anaesthesia with commonly used anticoagulants

Anticoagulant ASRA SOAP ESAIC/ESRA Association of Anaesthetists
Thromboprophylactic
Low-dose UFH (5000 U s.c., b.d. or t.d.s.) Hold for 4–6 h OR assess coagulation status Hold for 4–6 h OR assess coagulation status Hold dose ≤200 IU kg−1 day−1 s.c. for 4 h Hold for 4 h OR assess coagulation status
Low-dose LMWH (enoxaparin ≤40 mg s.c. daily, enoxaparin 30 mg s.c. b.d., dalteparin 5000 U s.c. daily) Hold for 12 h Hold for 12 h Hold for 12 h Hold for 12 h
Intermediate-dose UFH (7500 U s.c. b.d. or 10,000 U s.c. b.d.) Hold for 12 h AND assess coagulation status Hold for 12 h AND assess coagulation status No specific recommendation No specific recommendation
Intermediate-dose LMWH No specific recommendation Insufficient data for a specific interval between 12 and 24 h No specific recommendation No specific recommendation
Aspirin (any dose) No limitations (caution with other medications that might affect clotting) No limitations (caution with other medications that might affect clotting) No limitations No limitations
Therapeutic
High-dose UFH (>10,000 U per dose or >20,000 U day−1) Hold for 24 h AND assess coagulation status Hold for 24 h AND assess coagulation status Wait until the target laboratory value (i.e. aPTT, anti-Xa, ACT) is in normal range (∼6 h if i.v. or 12 h if s.c.) No specific recommendation
I.V. UFH infusion Stop infusion for 4–6 h AND assess coagulation status Stop infusion for 4–6 h AND assess coagulation status Hold dose ≤100 IU kg−1 day−1 i.v. for 4 h Stop infusion for 4 h OR assess coagulation status
High-dose LMWH (enoxaparin 1 mg kg−1 s.c. b.d., enoxaparin 1.5 mg kg−1 s.c. daily, dalteparin 120 U kg−1 s.c. b.d., dalteparin 200 U kg−1 s.c. daily) Hold for 24 h Hold for 24h Hold for 24 h Hold for 24 h
Given the risk of heparin-induced thrombocytopaenia, all patients receiving UFH for >4 days should also have a platelet count assessment before neuraxial placement.

Societal recommendations after neuraxial blockade and epidural catheter removal

Anticoagulant and Action ASRA SOAP ESAIC/ESRA Association of Anaesthetists
Restarting s.c. or i.v. UFH after neuraxial placement or neuraxial catheter removal 1 h 1 h No specific recommendation 1 h
Restarting low-dose UFH thromboprophylaxis with an indwelling neuraxial catheter 4–6 h OR assess coagulation status 4–6 h OR assess coagulation status Hold dose ≤200 IU kg−1 day−1 s.c. for 4 h No specific recommendation; suggest caution
Restarting low-dose LMWH thromboprophylaxis after neuraxial placement or neuraxial catheter removal 12 h (after placement)
4 h (after removal)		 12 h after neuraxial placement and 4 h after catheter removal No specific recommendation 4 h and only 1 dose in the first 24 h after neuraxial blockade
Restarting low-dose LMWH thromboprophylaxis with an indwelling neuraxial catheter 12 h 12 h 12 h No specific recommendation; suggest caution
Restarting intermediate-dose LMWH after neuraxial placement or neuraxial catheter removal Insufficient data for a specific interval between 12 and 24 h Insufficient data for a specific interval between 12 and 24 h No specific recommendation No specific recommendation
Restarting high-dose LMWH after neuraxial placement or neuraxial catheter removal 24 h after the neuraxial placement and 4 h after catheter removal 24 h after the neuraxial placement and 4 h after catheter removal No specific recommendation 4 h; consider 24 h if block performance is traumatic
Aspirin (any dose) No limitations (caution with other medications that might affect clotting) No limitations (caution with other medications that might affect clotting) No limitations No limitations

medications such as non-steroidal anti-inflammatory drugs (NSAIDs) that might increase bleeding risk should be held until the epidural catheter is withdrawn if thromboprophylaxis is continued; women without an epidural catheter in situ do not need to have NSAIDs withheld even if they are receiving thromboprophylaxis after neuraxial blockade

ACOG guideline

The American College of Obstetricians and Gynecologists recommends that anticoagulation therapy be restarted no sooner than 4–6 h after vaginal delivery and no sooner than 6–12 h after Caesarean delivery; timing of the last neuraxial anaesthetic must also be taken into account

Antepartum planning

Patients at particularly high risk for difficult airway, operative delivery, or preterm delivery may be candidates for bridging from LMWH to low-dose UFH at around 36 weeks' gestation

Patients who are hospitalised antenatally and require thromboprophylaxis warrant close consideration by the obstetric and anaesthesia teams as the clinical situation evolves. Such patients often have underlying morbidities, risk for imminent delivery, or both, and use of UFH affords highest flexibility for management of anaesthesia.

There is currently little evidence for the use of point-of-care anticoagulation testing to assess suitability for neuraxial anaesthesia

If patients are receiving neuraxial Neuraxial labour analgesia, using low concentration local anaesthetics may limit the extent of motor block during labour, to allow for concurrent assessment of epidural haematoma.

References

Peripartum Management of the Patient Taking Anticoagulant Medications - BJA Ed