Neutrophil-to-Lymphocyte Ratio May Predict Thrombotic Events in Polycythemia Vera

[PhysAssist]

Neutrophil-to-Lymphocyte Ratio May Predict Thrombotic Events in Polycythemia Vera

Vicki Moore, PhD

A new study suggests that the neutrophil-to-lymphocyte ratio (NLR) in patients with polycythemia vera (PV) at the time of diagnosis may serve as a predictor of thrombotic events. The study’s findings were reported in the journal BioMed Research International.

PV and other myeloproliferative neoplasms carry risks of thrombotic events, which may result in mortality. NLR has previously demonstrated utility in assessing systemic inflammation, and evidence suggests it can aid in predicting progression of thrombotic events in patients with essential thrombocytosis, the study investigators explained in their report. However, research on a possible role of NLR in patients with PVs is limited.

The study included hospitalized patients receiving an initial diagnosis of PV who had not received prior antiplatelet, anticoagulant, or blood cell-lowering related medications. Patient demographic and clinical data were obtained from electronic medical records and follow-up visits that occurred either in person or by telephone. The research team conducting the study analyzed data for risk factors involved with the occurrence and development of thrombotic events.

There were 170 patients evaluated in this study, and they had a median age at onset of PV of 56 years. A history of prior thrombosis was present in 31.8% of patients. Most (62.9%) patients tested positive for the presence of the JAK2V617F mutation.

A multifactorial analysis identified a few independent risk factors for thrombotic events at the time of initial diagnosis. These included a history of prior thrombosis (P <.001), NLR (P =.030), and white blood cell count (P =.045).

The median follow-up time for this population was 20.33 months, with 30.0% of patients having progressed to thrombotic events. Multifactorial analysis identified independent risk factors for the progression of future thrombotic events. These were a history of prior thrombosis (P <.001), age ≥60 years (P =.004), NLR (P =.025), and fibrinogen level (P =.042).

Additionally, NLR demonstrated greater diagnostic efficacy regarding the progression of future thrombotic events than did age, history of prior thrombosis, JAK2V617F mutation, and fibrinogen level in a receiver operating characteristic curve analysis. The sensitivity of NLR as a predictor of the progression of thrombotic events was 74.5%, and the specificity was 79.8%, when the NLR was set to 4.713 in this analysis.

In a survival analysis of patients split into categories by high NLR (≥4.713) and low NLR (<4.713), those with high NLR had a median overall survival duration of 22.033 months (95% CI, 4.226-35.840). This was significantly below the median overall survival duration of 66.000 months (95% CI, 50.670-81.330) for the patients with low NLR (P <.001). Progression-free survival rates at 60 months were 32.8% with high NLR and 58.8% with low NLR.

“Peripheral blood NLR levels at the time of initial diagnosis and treatment had better diagnostic and predictive value for the progression of future thrombotic events in patients with PV than age ≥ 60 years, history of previous thrombosis, and fibrinogen,” the study investigators concluded in their report.

Study source article: downloads.hindawi.com/journ...

[PhysAssist]

Study limitations included: small population size, its retrospective nature, and by the author's report:

"The study’s border is that it only looked at NLR levels at the time of the first diagnosis and therapy; nevertheless, NLR levels alter over time as illness progresses. Furthermore, because the inflammatory process is complicated, NLR alone is insufficient to determine the amount of inflammatory response."

[EPguy]

I recently came across a version of this one too. The most important item that's not fully clear is repeated several time "Peripheral blood NLR levels at the time of initial diagnosis and treatment ..."

If treatment means what it appears to it says doing normal cytoreduction should bring the NLR well into the low risk range. ie we normally have control of this risk factor in same way we control HCT risk. I wish they were more explicit there.

They use the term "progression" to mean -progression to- a thrombotic event best I can tell. "Progression" is a heavily loaded word to us.

[PhysAssist in reply to EPguy]

Hi EPguy,

I agree on all counts- and as you well know, avoiding progression [in any use or sense] is my primary goal [as a means to living well].

Thanks,

PA

[FG251 in reply to EPguy]

How does one do the calculation oneself from a CBC?

My final CBC as part of my work-up two years ago showed Neutrophils of 5.66 and Lymphocytes of 2.42.

5.66/2.42 = 2.34. Is that the correct way round?

[mhos61 in reply to FG251]

There are online calculators. If you type in neutrophil to lymphocyte ratio.

I think it might be a prognostic biomarker in many diseases, probably in relation to inflammation?.?

[FG251 in reply to mhos61]

Thanks - and, yes, undoubtedly in relation to inflammation.

Just found one. It came out at ‘2’ - which is normal. That was before treatment. My neutrophils are lower now.

[EPguy in reply to FG251]

That is how I did it, and it seemed to match the method in the report.

Yours is well in the good zone per this report. Did you have different results in your tests near the time of Dx? I did.

[FG251 in reply to EPguy]

I did - some were 3, some 2. The neutrophils seemed to vary quite a bit, between 4 and 6-ish! Cytoreduction keeps my neutrophils (and I’m assuming the other white blood cells, too) within range. I only seem to get the total white count and neutrophils on my forms, following a CBC, plus of course the platelets, Hb, LFTs, etc.

Clearly controlling inflammation is key, since cardiovascular events are, by their very nature, a form of inflammation. That’s also why I’m happy to be on Atorvastatin, for its ‘pleiotropic,’ anti-inflammatory properties. This was mentioned by Dr Hasselbalch, in the context of statins being potential enhancers of IFN-a therapy. Anyway, I have to be on them, following my MI, so if it turns out that statins have a key part to play in enhancing the effect of immunotherapy, so much the better!

[EPguy in reply to FG251]

The result you had of 2.34 was before taking any meds, is that right? I was near the limit here at Dx but on Bes it's at 1.8 now.

I agree on the statins. I had a cardio calcium CAT scan and was half hoping I'd need some. But it came out all zeros, I guess that is for the best. In at least one report, NAC supplement is considered another good way to reduce inflam. I've been on it.

[FG251 in reply to EPguy]

Correct - it was my last CBC before my haem put me on HU.

Couldn’t you request a low-dose statin for primary prevention? So many doctors consider them ‘risk-reduction’ meds, rather than simply ‘cholesterol-lowering’ ones.

[EPguy in reply to FG251]

That is a good idea, I can ask dr, I do see the results that statins are good in general. But with the NAC I'm taking it might be redundant or additive, of course no easy answers.

[FG251 in reply to EPguy]

Let us know what s/he says!

[EPguy in reply to FG251]

I asked Dr about statins. He agreed it's a good anti-inflam, which is nice to hear. But he reminded that statins have plenty of potential side effects so there is a trade off. I think he might Rx if I pushed it, but I think he'd like to hold it for when it's actually needed for heart issues. As above I'm ok for now with the NAC.

[mhos61 in reply to EPguy]

I’ve just put my NLR numbers in the calculator at diagnosis (before treatment) and recent NLR (on hydrea) both are 1.

I’m assuming that is an indicator of low inflammation?

[EPguy in reply to mhos61]

a 1:1 ratio is within their study results (3:344 ± 2:353 for the low risk group), and also is possible within normal limits of each, so it should be a very good thing. But they didn't divide it that well, only at 4.7. Could be a 1 ratio has an even higher blue line in this plot. "survival" means no thrombotic event.

One notable is at 5 years it didn't matter that much, but is it possible a really low ratio like you had would help more at 5 years? As I noted above, I'm at 1.8 now with meds, so it would be nice if they had provided results at lower than 4.7 also.

NLR

[mhos61 in reply to EPguy]

Thanks

[Bluetop]

Interesting. No one has ever mentioned NLR to me before and I had wondered why not when it seems to be a key measure for other patients with other diseases at risk of thrombosis. Looking back, my NLR was indeed high at diagnosis but apparently controlled since I started hydroxy. Thanks for posting. I will enquire at my next appointment.

[PhysAssist in reply to Bluetop]

Hi Bluetop,

I had never even heard it referenced before, and since my prior exposure to hematology had mostly been limited to referring patients for things like anemia work-ups, if I had run across it, I wouldn't have known that it was related to thrombosis at all.

I was tied up all day yesterday in training, so I haven't had a chance to look back at my NLR yet, but it will be interesting to see where it fell, and if it changed with my HU tx, and then to see what happens as I transition to IFN and d/c HU.

Thanks,

PA