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  • Nathan Riley, MD

Obgyno Wino Podcast Episode 58 - Prevention of Deep Vein Thrombosis and Pulmonary Embolism

"One could say that man sneaks through the crack where paradox exists. So, here we are - all part of this great hologram called Creation, which is everybody else's SELF. It's all a cosmic play, and there is nothing but you! The Soul is repository of information that we gather during a lifetime." - Itzhak Bentov


2019 Les Quatre Cepages from Domaine de Pajot

PB#84 - Published August 2007 (Reaffirmed 2018)


Five Pearls

1. Most patients who die from PE do so within 30 minutes of the event, so prevention is key.

2. If a patient is known to have Factor V Leiden mutation or prothrombin gene mutation 20210A, they should be considered high risk and managed appropriately intra- and post-operatively and in pregnancy

3. Compression stockings, pneumatic compression devices, and pharmacologic prophylaxis are all safe and useful in preventing VTE

4. Highest risk patients benefit most from a combined approach of mechanical or stocking prophylaxis combined with pharmacologic prophylaxis

5. Platelet inhibitors should be stopped 14 days before spinal or epidural anesthesia, unfractionated heparin or twice daily low molecular weight heparin 8-12 hours before, and low molecular weight heparin 18 hours before


Why do we care?

- Venous thromboembolic events (VTE) occur in 15-40% of gynecologic surgeries in the absence of thromboprophylaxis

- VTE include both deep vein thrombosis (DVT) and pulmonary embolism (PE)

- 50% of postop VTE occur within 24 hrs, 75% within 72 hrs

- asymptomatic DVT can easily become a very problematic PE

- most patients who die from PE do so within 30 minutes of the event

- prevention is key, especially for high-risk patients

- DVT is diagnosed in 2 million Americans every year, and 30% (~60,000) will die from resulting PE

- incidence of first VTE for all-comers in ~0.1%

- risk of dying from a PE is 10-12% (lower in younger patients; higher in patients with cancer)

- 9x higher risk of VTE in bedbound/bedrested patients

- Odds ratio of 11 for hospitalized patients and 6 for patients undergoing surgery


- in a study of 2000 patients undergoing surgery, ~2% risk of VTE (80% of the patients received thromboprophylaxis)

- 1.7% chance mortality within 35 days of surgery; 46% of the deaths were due to VTE



Who is at risk?

- risk factors are found in the box to the right

- recall Virchow's triad: stasis of blood flow, vessel wall injury, and hypercoagulable state (any of the risk factors in that box can fit into one of these categories!)

- everybody is at risk, some more than others

- risk stratification details are found in Table 1 (below)

- most common thrombophilias are listed in Table 2 (below)


Pearl: in patients diagnosed with VTE, Factor V Leiden mutation and prothrombin gene mutation 20210A are the most common genetic mutations found; if these conditions are known prior to surgery or pregnancy, the patient would be considered high risk

A few notes on specific hypercoagulable states...


Factor V Leiden mutation

- results in resistance to Protein C

- recall that Protein C works as an anticoagulant by regulating the activity of Factor VIIIa and Factor Va in the clotting cascade - the most common inherited thrombophilia, affecting 5% of caucasians

- 20% of people diagnosed with VTE have the mutation

- heterozygotes have 3-8x higher risk over baseline; homozygotes have 50-80x increased risk!!

- diagnosed by DNA analysis


Prothrombin gene mutation 20210A

- 2nd most common

- found in 6% of patients diagnosed with VTE

- mutation results in abnormally high levels of prothrombin

- 3x increased risk of VTE above baseline

- diagnosed by activated Protein C resistance assay

Source: http://www.pathophys.org/vte/


Antithrombin-III, Protein C, and Protein S deficiencies

- all natural anticoagulants, deficiencies in which would obviously result in excess coagulation

- much more rare, but still should be considered if a patient has a strong personal or family history of VTE but are negative for Factor V Leiden and Prothrombin gene mutation 20210A

- heterozygotes for any of the three have 10x increased risk of VTE above baseline

- homozygotes usually have severe thrombotic events early in infancy

- all three are diagnosed by serum assay, but these assays aren't accurate during acute VTE or while on anticoagulation

Hyperhomocysteinemia

- can result from genetic or acquired conditions

- homozygotes of the methylenetetrahydrofolate reductase variant 677T have mildly elevated homocysteine levels w/ associated moderately increased risk for VTE above baseline

- deficiencies in folate, vitamin B6, and vitamin B12 also can cause hyperhomocysteinemia

- it's unclear if elevated homocysteine is the causative agent of increased VTE risk or merely a marker


Antiphospholipid syndrome

- acquired thrombophilia

- 50% of patients with systemic lupus erythematous (SLE) test positive for antiphospholipid antibodies

- diagnosed by serum assays for lupus anticoagulant and anticardiolipin antibodies

- the former is more relevant because it detects B2-glycoprotein-1 antibodies, which correlate closely with thromboembolic complications and pregnancy morbidity

- reasonable to offer testing for any patient with VTE, SLE, recurrent pregnancy loss, early or severe preeclampsia, or thrombocytopenia




Prevention

- early ambulation and raising the feet/legs of post-op patients are universal recommendations


Graduated compression stockings

- reduces risk of DVT by 50%

- even better when combined with other methods

- low cost and simple

- knee-length is just as effective as thigh-length


Pneumatic compression (aka sequential compression devices - SCDs)

- sleeves the cover the lower legs that squeeze in regular intervals to help to circulate blood

- just as effective a heparin products when used during and after major gynecologic surgery

- use continuously until ambulatory

- in patients with malignancy, studies have shown 3x decrease risk of VTE if SCDs are used for 5 days following surgery


Low-dose unfractionated heparin

- compared with placebo or no prophylaxis, unfractionated heparin at 5000 units administered two hours prior to major general surgery and every 8 hours after surgery reduced fatal PE by two-thirds

- similar benefit for patients undergoing surgery for gyn cancer

- for patients undergoing gyn surgery for benign indications, q12 dosing post-operatively is sufficient

- low cost

- pre-op administration helps decreases VTE risk but may also increase risk for minor post-op hematoma (likely not clinically significant)

- if used for longer than 4 days post-op, monitor for heparin-induced thrombocytopenia (affects 6% of patients)

- combined with graduated compression stockings results in 4x decreased risk over unfractionated heparin alone


Low molecular weight heparin

- advantages is once daily use but also more expensive

- more activity against Factor Xa and less activation of anti-thrombin than unfractionated heparin

- heparin-induced thrombocytopenia is exceedingly rare so monitoring is not required

- treatment for 4 weeks post-op has been shown to reduce risk of fatal PE by 60% (compared to only 1 week of therapy) without increasing the risk for severe post-op bleeding or thrombocytopenia

- highest risk patients (>60 years old, malignancy, prior VTE, and prolonged surgery or bedrest) may benefit from longer course


Pearl: highest risk patients (2 of 3: >60 years old, malignancy, or prior VTE) benefit most from combined approach of mechanical or stocking prophylaxis combined with pharmacologic prophylaxis


Anesthesia considerations

- regional anesthesia carries 50% reduced risk of VTE over general anesthesia

- spinal or epidural anesthesia, however, is challenged by the use of low molecular weight heparin

- there is an increased risk of spinal hematoma, especially if patient is using multiple anti-thrombotic agents or in the presence of spinal or anatomic abnormalities (additional risk factors include: underlying coagulopathy, traumatic or need for repeat needle insertion, advanced age, female sex, and catheter removal while on thromboprophylaxis)

- side note: no increased risk if patient is using NSAID

- platelet inhibitors should be stopped 14 days before spinal or epidural anesthesia, unfractionated heparin 8-12 hours before, and low molecular weight heparin 18 hours before

- spinal or epidural catheters should be removed at the nadir of anticoagulant effect (right before next dose is due), and next dose should be held until 2 hours after catheter removal


How long should I wait post-op to begin pharmacologic

thromboprophylaxis?

- 6-12 hrs: less than 6 hours may increase risk of post-op bleeding; more than 12 hours may decrease benefit of thromboprophylaxis


Should my patient continue combined oral contraceptives (COC) or hormone replacement therapy (HRT) before surgery?

- the Women's Health Initiative found that estrogen + progesterone HRT together increases the risk of venous thrombosis x2; estrogen alone HRT increases the risk x1.3

- data looking specifically at COCs does show an increased risk of postoperative VTE from 0.5% to 1% for patients taking COCs

- having said that, there is no evidence that stopping COC or HRT before surgery decreases risk of VTE (besides: the prothrombotic effects last for 4-6 weeks after discontinuation, so even a tiny increased risk of VTE needs to be balanced against risk of unwanted pregnancy)





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