Guidance for anticoagulation management in the setting of thrombocytopenia in cancer patients

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Published: 6 Dec 2015
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Dr Gerald Soff - Memorial Sloan Kettering Cancer Center, New York, USA

Dr Soff talks to ecancertv at ASH 2015 about the results of a study that prospectively assessed the efficacy and safety of an algorithm for reducing the dose of low molecular weight heparin (LMWH) in patients with cancer-associated thrombosis who develop chemotherapy-induced thrombocytopenia (CIT).

CIT is a common problem in anticoagulated cancer patients and the current recommendation on how to amend LMWH is based on expert opinion rather published evidence, Dr Soff explains. The present study therefore aimed to address this knowledge gap and considered all 15,000 cancer patients treated with LMWH (enoxaparin) at Memorial Sloan Kettering Cancer Center over a 3-year period.

There were 143 patients who developed CIT and results showed that holding anticoagulant therapy was an appropriate approach if platelet levels fell below 25,000/mcL. Halving the dose of LMWH was appropriate if the platelet count was 25,000/mcL to 50,000/mcL and continuing LMWH at full dose if the platelet count was more than 50,000/mcL.

Read the news story and watch the press conference for more information.

ASH 2015

Guidance for anticoagulation management in the setting of thrombocytopenia in cancer patients

Dr Gerald Soff - Memorial Sloan Kettering Cancer Center, New York, USA


You’ve been looking at the use of low molecular weight heparin dose reductions in the context of thrombocytopenia in patients with cancer. Why did you want to look at dose reductions? Isn’t this just an obvious thing at the moment?

As you know, in cancer patients thrombosis is very common and up until very recently low molecular weight heparins have been the mainstay of therapy. Treating a thrombosis with any anticoagulant, including low molecular weight heparin, is associated with bleeding. In addition, thrombocytopenia from the chemotherapy or other causes is also common in the cancer patients and there has been no guidance on how to balance the need for maintenance of anticoagulation in the setting of thrombocytopenia.

So the big issue was what?

The big issue is there has been no prospective programme to provide guidance on what to do with anticoagulation in the setting of cancer-associated thrombocytopenia. So basically a number of bodies have recommended a dose reduction algorithm which is purely based on judgement, which is perfectly good to start with but they’ve never been validated. So we set up those guidelines at Sloan Kettering and we were able to do a three year cohort analysis, a quality assessment analysis, and basically validated the safety and efficacy of the guidelines.

And you were able to get data originating from 15,000 patients, you got a couple of very good groups, didn’t you?

Yes, we did. So we started with 15,000 patients over a three year period who had a thrombosis and were on therapeutic doses of anticoagulation. From that group we found 143 episodes of thrombocytopenia that lasted at least seven days. For this purpose we’re referring to thrombocytopenia as under 50,000 platelets. In those patients our dosing, our institutional guidelines, called for holding anticoagulation with platelet counts under 25,000, approximately 50% dose reduction between 25,000 and 50,000 and maintenance of full dose over 50,000.

Now those seem reasonable ideas.

Yes. I didn’t come up with them de novo, this was sort of a consensus of what a number of experts, including ourselves, have felt was appropriate but no-one knew if it was good or not.

So what have you been doing now?

We basically took our three years’ experience while we were still using enoxaparin as our primary anticoagulant and were able to demonstrate that in 143 episodes of thrombocytopenia in 102 patients there were no major haemorrhages and there were no recurrent thromboses during that period of time which was extremely gratifying. These were high risk patients, these were patients on chemotherapy with metastatic cancer.

So what is it exactly that you can say now that you couldn’t say before?

The guidance that’s out there from ASCO, NCCN, other organisations, as far as dose reduction seems to be holding. We used the same guidelines, we didn’t come up with a novel strategy, but using that strategy basically there was… you can’t give a per cent when you have no events, but there was clearly no evidence that we were jeopardising safety or efficacy and the patients did well on that regimen. So we believe that this validates and provides reassurance what many doctors have been doing.

So what can you now say to doctors about dose reductions of low molecular weight heparin in thrombocytopenia in patients with cancer?

We basically say these are standard guidelines, we recommend that the thought leaders, the haematologist or the people driving the practice at given institutions, educate their colleagues that this is what should be adhered to. It shouldn’t be just a crap shoot, it should be a planned guidance. When adhered to the risk of failure, the risk of recurrent thrombosis from that brief interruption of anticoagulation, is not high. The risk of major bleeding with the dose reduction is also not high and that provides very important reassurance. We also emphasise that this would have to be independently validated with other anticoagulants. As more of us are shifting to the new direct oral anticoagulants this kind of approach would have to be independently validated; we can’t extrapolate from one class of drug to the next.