B) Acute VTE(not to be confused with prophylaxis) :- Treatment of Venous Thromboembolism
• When VTE is suspected, till diag is
confirmed , Early initiation of anticoagulation
: Best choice is Unfractionated heparin. Cheap, easy to administer and follow
up, Doctors & nurses are comfortable with this drug in the ICU/ Wad sings. with unfractionated heparin (UFH) or
low-molecular-weight heparin (LMWH) should be initiated until the diagnosis is
excluded.
What about
in RPL as a prophylaxis UFH /costly LMWH or very cheap easy to monitor Warfarin?
Which one to choose? Member’s opinion??
Benefits
common to UFH/ LMWH :-Neither of these anticoagulants cross the
placenta nor are secreted into breast milk; thus, there is no risk for
teratogenicity or fetal hemorrhage, although bleeding at the uteroplacental junction is possible.
Few salient points
on LMWH: We need to remember !! Dose of LMWH in diagnosed cases of VTE?? Ans;-Weight-adjusted LMWH should be used for the treatment of VTE. Advantages of LMWH
include fewer bleeding complications, lower risk of heparin-induced
thrombocytopenia (HIT) and osteoporosis, longer plasma half- life, and more
predictable dose-response relationships.
D) IN preg: should we offer B D schedule as renal clearance is high??
Some experts recommend twice daily dosing of enoxaparin secondary to
pharmacokinetic properties of LMWH in pregnancy; however, comparison data are
lacking. Additionally, women at the extremes of weight may require different
dosing. Theoretical concerns have been raised regarding once daily dosing compared to twice daily
dosing (i.e., prophylactic or therapeutic) secondary to the increased renal
clearance in pregnancy possibly prolonging trough LMWH levels. However,
no comparison data of the two regimens are available. Additionally, recent data
suggest daily dosing in the treatment of acute VTE is effective. E)
How to monitor the women while on Inj LMWH?? Ans: Current guidelines do not provide
definitive monitoring recommendations; however, some researchers advocate
checking levels periodically (every 1 to 3 months).
-Monitoring
of LMWH levels remains controversial. To
remember that LMWH cannot be monitored
using activated partial thromboplastin time (aPTT), as it will likely be
normal. But “Anti-factor Xa activity
levels”- may be measured 4 hours after subcutaneous injection, with a
therapeutic peak goal of 0.6 to 1.0 U/mL (slightly higher if once daily dosing
is used); however, frequent monitoring is not typically recommended, except at
extremes of body weight. If trough levels are evaluated with therapeutic dosing
(i.e., 12 hours after dosing), goal level is 0.2 to 0.4 IU/mL.
Do we need to stratify
women regarding possibility of risk of abortion /VTE and adjust the dose of
LMWH/ heparin schedule accordingly- say Low risk, medium
risk high risk & do the clinicians
have to consider weight of concerned woman about dose adjustments ??
Heparin
titration & follow up in VTE/ Pulm embolism not for prophylaxis of RPL :-How
to adjust dose of what an obstetrician need to know & memorize on Unfractionated Heparin –very cheap and users friendly too. UFH(unfractionated heparin
which is much cheaper). Ans:-UFH is administered either IV or subcutaneously (SC). IV UFH may be
a better initial therapeutic option in unstable patients (e.g., large PE with
hypoxia or extensive iliofemoral disease) or patients with significant renal
impairment (i.e., creatinine clearance <30 mL/min). The goal of the initial
bolus dose (typically 80 U/kg) and subsequent maintenance dosing (typically 18
U/kg/hr) is to achieve a
midinterval (6 hours postinjection) therapeutic aPTT (often described as an
aPTT ratio of 1.5 to
2.5 times normal).
Measuring
anti-factor Xa heparin levels may assist in evaluating heparin dosing (target
level 0.3 to 0.7 IU/mL). Many facilities have standard protocols for heparin
titration. IV treatment should be maintained in the therapeutic range for at
least 5 days, and therapy may then be continued with either adjusted-dose SC
heparin injections or LMWH. If maintained on UFH, the aPTT should be monitored
every 1 to 2 weeks.
Although UFH
has been standard treatment for the prevention and treatment of VTE during
pregnancy, recent evidence-based clinical practice guidelines now recommend
LMWH. Compression stockings and leg
elevation should be used for DVT.
9) How to monitor a woman while on heparin?? Why and
how the aPTT response to heparin in pregnant women is often attenuated??
Ans: aPTT response to heparin in pregnant women is often attenuated -secondary
to elevated heparin-binding proteins and increased factor VIII and fibrinogen.
The therapeutic dose may need to be adjusted. Thus, it may be difficult to
achieve target aPTT levels late in pregnancy.
Point 1:-Measure
platelate 10 days after initiation of UFH. Must .A great caution!!! What are
the risks of cheap anticoagulants in pregancy?? Ans:- The major concerns with
UFH use during pregnancy are bleeding, osteopenia, and thrombocytopenia. The
risk of major bleeding with UFH is approximately 1) 2% Bone density reductions have been reported in
30% of patients on heparin for over 1 month.2) Thrombocytopenia :- HIT occurs
in up to 3% of nonpregnant patients and should be suspected when platelet count decreases to
<100,000/p.L or <50% of baseline value.
J) How early platelate be monitored??
Ans:-Typical
onset is between 5 and 10 days after starting heparin. In 25% to 30% of
patients who develop HIT, onset occurs rapidly (within 24 hours) after starting
heparin and is related to recent exposure to heparin. After obtaining a
starting platelet level, ACOG recommends checking platelets again on day 5 and then periodically for
the first 2 weeks of therapy. Others suggest platelets be monitored at 24 hours
and then every 2 to 3 days for the first 2 weeks or weekly for the first 3
weeks. If HIT is acquired and ongoing anticoagulant therapy is required,
danaparoid sodium (factor Xa inhibitor,
not currency available in the United States) or argatroban (direct thrombin
inhibitor) can be used.
Can we
prescribe cheapest anticoagulant in pregancy?? What about oral anticoagulant??
Ans:-Warfarin sodium crosses
the placenta and, therefore, is a potential teratogen and may cause fetal
bleeding. Warfarin is likely safe during
the first 6 weeks’ gestation, but between 6 and 12 weeks’ gestation, a risk
of skeletal embryopathy exists, consisting of stippled epiphyses and nasal and
limb hypoplasia. One third of fetuses
a)
Enoxaparin 40 mg
SC q 24 hr Enoxaparin 30 mg SC q 12 hr
b) Dalteparin 5,000 U SC q 24 hr
c)
c) Tinzaparin
4,500 U SC q 24 hr UFH
B) UFH?? Dosage?? UFH 5,000 U SC q 12 hr Alternative or UFH
5,000-7,500 U SC q 12 hr in first trimester
UFH 7,500-10,000 U SC q 12
hr in second trimester”::UFH 10,000 U SC q 12 hr in third trimester (unless
aPTT elevated)
LMWH
Enoxaparin 40 mg SC q 12
hr Dalteparin 5,000 U SC q 12 hr UFH
UFH SC q 12 hr; doses
adjusted to target peak antifactor Xa levels (4 hr after injection) of 0.1 to
0.3 U/mL
Treatment
(weight-adjusted) dose
LMWH
Enoxaparin 1 mg/kg SC q 12
hr (or enoxaparin 1.5 mg/kg SC q 24 hr6)
heparin; aPTT, activated
partial thromboplastin time; INR, international normalized ratio.
What about embryopathy
induced by warfarin?? Ans Embryos exposed
to warfarin late in pregnancy develop central nervous system injuries,
hemorrhage, or ophthalmologic abnormalities. Warfarin may be used postpartum
and may be given to nursing mothers, as it does not enter breast milk. Antepartum
use is indicated for women with mechanical heart valves, for which neither
Lovenox nor heparin provide adequate anticoagulation.
All obstetricians
must have a spouse who is a vascular surgeon!!!! An advice from eldest member of
this group!!!! Temporary inferior
vena cava filters are
indicated in women in whom anticoagulants are contraindicated. They may be
inserted within a week of elective induction or cesarean section and removed
postpartum.
The balance sheet of
prescribing anticoagulants as “Prophylaxis
for Venous Thromboembolism in
Pregnancy in women who had
had VTE earlier” : The edge is in favour
of probably benefit from UFH or LMWH throughout pregnancy and postpartum.
A) at Antepartum
period??
Limited data exist
regarding the use of prophylactic anticoagulation for VTE during pregnancy.
Women need to be stratified by risk and clinical judgment applied when making
recommendations for prophylaxis. Although recommendations vary, women at very
high risk for VTE probably benefit from UFH or LMWH throughout pregnancy and
postpartum. At a minimum, postpartum prophylaxis is usually recommended in
women at elevated risk for VTE.
What prophylaxis
at delivery in women who had had VTE in nonpreg state earlier?? Ans:-
The risk of
maternal hemorrhage may be minimized with carefully planned delivery. If
possible, induction of labor or scheduled cesarean section should be considered
in women on therapeutic anticoagulation dosing regimens, so therapy may be
discontinued at an appropriate time. When used in therapeutic doses, LMWH
should be discontinued 24 hours before elective induction of labor or cesarean
delivery. Epidural or spinal anesthesia should not be administered within 24
hours of the last therapeutic dose of LMWH. A common approach is to transition
from LMWH to UFH at 36 to 38 weeks’ gestation. If the patient goes into
spontaneous labor and is receiving SC UFH, she should be able to receive
regional analgesia if the aPTT is normal. If significantly prolonged, protamine
sulfate may be administered at 1 mg/100 U of UFH. If the patient is at very
high risk for VTE, IV UFH can be started and then discontinued 4 to 6 hours
before expected delivery. When receiving LMWH once daily for prophylaxis,
regional anesthesia can be administered 12 hours after the last dose. LMWH
should be withheld for at least 2 to 4 hours after the removal of an epidural
catheter.
Postpartum: How to adjust dose in women who had had
VTE in nonpregnant state ??
Postpartum anticoagulation may be resumed within 12 hours of cesarean delivery
and 4 to 6 hours after vaginal delivery. If at high risk of bleeding
postpartum, IV UFH may be chosen initially because its effect dissipates more
rapidly and may be reversed with protamine sulfate. Once adequate hemostasis is
assured, warfarin can be started by initial overlap with UFH or LMWH until
international normalized ratio (INR) is
for 2 consecutive days,
with a target INR of 2.0 to 3.0. Anticoagulation should be administered for at
least 6 weeks postpartum for DVT and 4 to 6 months for PE.
Birth control options for
women with a history of VTE or those with high-risk thrombophilias:
Due to the thrombogenic
potential of estrogen-containing contraceptives, progestin-only or nonhormonal
contraceptive methods are recommended. Natural family planning, condoms,
progestin-only pills, Levonorgestrel-releasing IUD, copper IUD, or tubal
ligation/occasion are methods that can be discussed with patients at high risk
for VTE.
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