Tuesday, 4 February 2020

Prevention & tr of thrombo embolism in pregancy and postpartum period



 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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