Antithrombin III Thromboprophylaxis

[periopdoc]

---

Members do not see this ad.

Saw a pretty basic, but still somewhat interesting case in pre-anesthesia clinic today and thought I would seek your opinion.

57 yo woman with usual comorbidities for bilateral knee replacements. She has a familial history of significant ATIII deficiency with multiple family members on lifelong anticoagulation and a couple with IVC filters in situ. She had a DVT several years ago while on combined oral contraceptives and was admitted for heparin therapy followed by several weeks of coumadin. She has had great difficulty getting pregnant.

The usual Ortho plan for joint replacement is to start coumadin the day before surgery and give empirically dosed, unfractionated heparin for thromboprophylaxis until coumadin is therapeutic.

I am trying to figure out the best way to provide appropriate post-operative thromboprophylaxis for a patient with Antithrombin III deficiency, short of having a non-ortho team start a heparin drip with modest anticoagulation goals. (We can also discuss the likelihood of this patient actually being AT III deficient but that is beside the point)

I used to place my pregnant patients on Lovenox and follow Anti Xa activity. This would not really work in this situation given the length of time to get Anti factor Xa results.

Any thoughts?

pod

 

[militarymd]

uhhhh......heparin doesn't work when you have ATIII deficiency.

If you want to use heparin...you have to replace ATIII..with

- the concentrate
- or ffp.

 

[periopdoc]

uhhhh......heparin doesn't work when you have ATIII deficiency.

If you want to use heparin...you have to replace ATIII..with

- the concentrate
- or ffp.

Mil... I am surprised to hear that kind of academic dogma coming from you. The use of low molecular weight and unfractionated heparin can certainly be used in cases of Antithrombin deficiency without antithrombin replacement, but it may requires higher dosing.

Most of the data that I am familiar with is in the obstetric literature because of my background. Given the obvious contraindication to coumadin use in this population, heparin has been reasonably well studied and used to good effect for antithrombin deficiency in pregnancy. While the data on improving pregnancy outcomes is somewhat suspect, there is certainly good evidence of increased anti Xa activity and elevation of PTT in these studies to suggest that heparin is in fact working in these individuals.


The American College of Chest Physicians Clinical Based Guidelines Statement on Venous Thromboembolism, Thrombophilia, Antithrombotic Therapy and Pregnancy recommends low molecular weight and unfractionated heparin in AT deficiency, without the mention of plasma derived antithrombin concentrate administration. (Chest. 2008; 133:844S-886)


More to the point "It might seem strange that heparins remain fully effective despite inherited antithrombin (heparin cofactor) deficiency, but antithrombin becomes rate-limiting for heparin effect only at very low levels that are rarely seen except during severe disseminated intravascular coagulation, or with the very high heparin doses given during cardiopulmonary bypass." Gallus, Alexander (S. Semin Thromb Hemost 2005; 31: 118-126)


Per The British Committee for Standards in Haematology, The initial treatment of VTE in these patients should be no different than in non-affected individuals. Occasionally, if the thrombosis is severe or heparin resistance develops, antithrombin supplementation can be considered. (Br J Haematol 2001 Sep; 114 (3): 512-28)



For some great reading on the subject check out this article.

Hereditary and Acquired Antithrombin Deficiency: Epidemiology, Pathogenesis and Treatment Options. Maclean PS; Tait RC. (DRUGS), 2007; 67(10): 1429-40

Isn't that a great name for a journal BTW? DRUGS

There is an especially interesting discussion of plasma derived antithrombin concentrate and pooled plasma and the paucity of evidence for their use.

If anyone is interested in that last article, PM me and I can provide a limited number of PDFs of the article.

In this case I will likely recommend standard empirically dosed low molecular weight heparin for this patient given that she is on the ortho service and the coumadin will be starting to take effect. Still interested in other constructive ideas.

 

[Planktonmd]

🙂
You seem to know the answer to your question and already have a plan in place.
I would let them do their protocol without any modification (Coumadin + Heparin bridge), put in bilateral femoral nerve catheters to make it possible to start physical therapy and mobilization as early as possible.
I am not sure if starting a heparin infusion and achieving therapeutic anticoagulation immediately after surgery is a good idea or if the Ortho guy would let you do it.
Anticoagulants are only one part of DVT prophylaxis, early mobilization, compression stockings, hydration are all important elements as well.

 

[militarymd]

you got me dude....

Learned something new...

I was thinking in terms of DIC and CPB only...those are the patient populations that I'm familiar with.

 

[militarymd]

Is this what you are looking for?

 

[militarymd]

And there is an accompanying article that studies total knees.

How effective is heparin in ATIII deficiency?

Any comparative studies in the OB population....or any other population.

I only know of the problem in critically ill patients and those undergoing CPB requiring intense anticoagulation.

 

[pd4emergence]

I would talk to the ortho guys and see when they were comfortable starting lovenox. If they were good with it on the day of surgery she will probably be ok. The question remains does she have decreased levels of ATIII? If she does how long does she need to be anticoagulated? You can't answer these questions. If your ortho guys are anything like ours, she will be on coumadin the standard time and they will not have a second thought about when to stop it. I would get some hematology help to answer these questions. She may need coumadin for longer than usual she may not.

pd4

 

[periopdoc]

🙂
You seem to know the answer to your question and already have a plan in place.
I would let them do their protocol without any modification (Coumadin + Heparin bridge), put in bilateral femoral nerve catheters to make it possible to start physical therapy and mobilization as early as possible.
I am not sure if starting a heparin infusion and achieving therapeutic anticoagulation immediately after surgery is a good idea or if the Ortho guy would let you do it.
Anticoagulants are only one part of DVT prophylaxis, early mobilization, compression stockings, hydration are all important elements as well.

I certainly developed a plan and discussed it with the Ortho Docs office, but I was wondering if anyone else had something more elegant or had some better experience. I implied therapeutic anticoagulation in my post, but did not mean to. If I were going to use a heparin drip, I would aim for a small elevation in PTT but not full anticoagulation. I fully agree with the last statement that thromboprophylaxis is only a portion of the total picture. So here is the plan I presented to the Ortho doc.

1: Preop - Heme consult to manage thromboprophylaxis. While I believe that I and my anesthetic colleagues can come up with a viable perioperative anticoagulation plan, I will not be directly managing this patient on the floor or post discharge. Her risk is significant enough that I don't think that her thromboprophylaxis should be managed by my Ortho colleagues and I am sure they would agree. The heme anticoag team can set up a plan for post-discharge follow up in their clinic and decide on an appropriate duration of prophylaxis. Personally I would recommend prophylaxis for 4-6 weeks depending on how well she meets mobility and PT goals.

2: Intraop - Bilateral femoral nerve catheters and SAB. Intraoperative sedation vs GA per patient preference. Before I get the for placing SAB and catheters in a patient on coumadin for a day, they do it all the time at the institution I am currently visiting. My response was , but they do it all the time without complication so I am going with it. It does make pharmacological sense, but I am still a bit nervous about it.

3: Intraop part 2 - Aggressive non-pharmacologic thromboprophylaxis as outlined by Plankton.

3: Post-op aggressive pain control and PT to maximize early mobility.

pod

 

[periopdoc]

Is this what you are looking for?

Exactly the type of thing I am wondering about. Anyone have experience with this?

pod

 

[Planktonmd]

It might be a good idea to give this patient a dose Antithrombin III concentrate preop which I think has a half life of 2-3 days and should make your prophylactic heparin or LMWH more effective without having to increase the dose until the Coumadin becomes therapeutic.
You should not be nervous about a spinal after 1 day of Coumadin, get a PT, INR and proceed.