Hyperfibrinogen & ADT

[pjoshea13]

New study [1] below.

I recently posted a paper on the role of platelets & abnormal coagulation factors in metastasis. The current paper looks at fibrinogen.

In the coagulation cascade, platelets clump together to form a plug, & fibrin is deposited around it to form the body of the clot. This can happen on a large scale in a fixed location (e.g. DVT) or on a very small scale in circulation (microclot). The latter is associated with metastasis.

Fibrinogen circulates along with prothrombin in the healthy body, so that they are at hand in the event of injury involving blood vessels. During the clotting cascade, prothrombin converts to thrombin, which acts on the soluble fibrinogen to form fibrin strands.

Fibrinogen represents clotting potential. When fibrinogen is elevated, the reason is likely to be systemic inflammation. Other markers of inflammation are likely to affected too (e.g. depressed albumin & elevated C-reactive protein). These are all modifiable, since inflammation can be controlled (IMO, by polyphenols).

Nattokinase can also lower fibrinogen [2].

"All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months."

"After 2 months of administration, fibrinogen ... decreased 9%, ... for the Healthy Group; 7% ... for the Cardiovascular Group; and 10% ... for the Dialysis Group, whereas blood lipids were unaffected by nattokinase."

From the new study:

"Hyperfibrinogen is thought to be associated with a higher risk of invasion and metastasis, as well as a worse outcome for multiple types of cancer. However, the prognostic significance of plasma fibrinogen has not been investigated in prostate cancer with hormonal therapy."

"Compared with patients with a lower fibrinogen level <3.225 g l−1), patients with a higher fibrinogen level were more likely to have higher PSA, Gleason score, risk stratification and incidence of metastasis ..."

"The pretreatment plasma fibrinogen level was associated with tumor progression and might have a significant role in the prognosis of the prostate cancer patients treated with ADT."

Cancer is an inflammatory disease, but it also interferes with normal coagulation. Fibrinogen elevation is perhaps not the only change to coagulation factors, since fibrinogen itself is fairly innocuous. Anyway, my feeling is that is is prudent to target (a) inflammation & (b) fibrin. A simple D-dimer test will indicate whether the body's plasmin is degrading a fibrin clot, & nattokinase can speed up the process.

The cutoff used in the analysis was "3.225 g l−1", a clumsy way of saying 3.225 g/L, which would appear on most U.S. lab reports as 322.5 mg/dL. It seems likely that a different reference range is being used, than LabCorp's: 193-507. In any case, there doesn't seem to be much "hyper" about that number.

Whatever the ref. range, the target should be low-normal.

-Patrick

[1] nature.com/pcan/journal/v19...

Prostate Cancer and Prostatic Diseases (2016) 19, 209–215; doi:10.1038/pcan.2016.6; published online 8 March 2016

Pretreatment plasma fibrinogen as an independent prognostic indicator of prostate cancer patients treated with androgen deprivation therapy

Y Wang1,5, W Yin2,5, Z Wang3, J Huang1, J Pan1, Y Zhu1, F Xu1, X Shao1, J Sha1, Y Cai3, Q Liu4, B Dong1, W Xue1 and Y Huang1

1Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

2Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

3School of Public Health, Shanghai Jiao Tong University, Shanghai, China

4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Correspondence: Dr B Dong or Dr W Xue, Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Pudong District, Shanghai 200127, China. E-mail: [e-mail] or [e-mail]

5These authors contributed equally to this work.

Received 22 October 2015; Revised 13 January 2016; Accepted 19 January 2016

Advance online publication 8 March 2016

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Abstract

Background: Hyperfibrinogen is thought to be associated with a higher risk of invasion and metastasis, as well as a worse outcome for multiple types of cancer. However, the prognostic significance of plasma fibrinogen has not been investigated in prostate cancer with hormonal therapy. The objective of this study was to evaluate its roles in prostate cancer patients treated with androgen deprivation therapy (ADT).

Methods: A total of 290 patients who underwent ADT as first-line therapy for prostate cancer were retrospectively analyzed. The fibrinogen level was measured at the time of diagnosis. Patients were categorized using a cutoff point of 3.225 g l−1 according to a calculation by the receiver operating curve analysis. Correlations between the fibrinogen and clinical characteristics were analyzed. Meanwhile, univariable and multivariable cox regression analyses were performed to determine the associations of fibrinogen with progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). Prognostic accuracy was evaluated with the Harrell concordance index.

Results: Compared with patients with a lower fibrinogen level (<3.225 g l−1), patients with a higher fibrinogen level were more likely to have higher PSA, Gleason score, risk stratification and incidence of metastasis (P<0.05). Multivariable analyses identified hyperfibrinogen as an independent prognostic factor for PFS (hazard ratio (HR)=2.000, P<0.001), CSS (HR=2.209, P=0.006) and OS (HR=1.965, P=0.009). The final models built by the addition of fibrinogen improved predictive accuracy (c-index: 0.750, 0.799 and 0.767) for PFS, CSS and OS compared with the clinicopathological base models (c-index: 0.730, 0.778 and 0.746), which included Gleason score and metastasis.

Conclusions: The pretreatment plasma fibrinogen level was associated with tumor progression and might have a significant role in the prognosis of the prostate cancer patients treated with ADT. Thus, we recommend adding fibrinogen to traditional prognostic model, which may improve its predictive accuracy.

[2] ncbi.nlm.nih.gov/pubmed/193...

[Live2day]

Great article. This website is awesome. It gives hope of new treatments and diagnostics. That being said, as a layman, I need help figuring out which new modalities I should bring up with my oncologist at Dana Farber. Should I ask him to test for plasma fibrinogen level? Tia and best wishes. Paul

[pjoshea13 in reply to Live2day]

Hi Paul,

I find it convenient to monitor my coagulation status privately. The annual LEF Blood Test sale is still on, & the fibrinogen test is only $23.25 to members:

lifeextension.com/Vitamins-...

The D-dimer test is $60:

lifeextension.com/Vitamins-...

Not sure that many doctors would know how to respond if either was elevated.

As I mentioned, I would react to a highish fibrinogen result by looking at inflammation markers. A basic blood chemistry panel will include albumin. 4.5 or higher is very good, while <4.0 is worrisome IMO. C-reactive protein [CRP] is usually a separate test. Whatever the result, being closer to zero is always better - falling within the reference range is not good enough.

I use polyphenols to control inflammation.

An elevated D-dimer doesn't necessarily mean that there is clotting, but a zero result rules out a clot. Having cancer increases the risk of clots, so a non-zero result would be suggestive of a clot IMO.

Nattokinase dissolves fibrin faster than plasmin, so D-dimer - which is a metabolite of fibrin breakdown - might increase in the short-term, but quickly approach zero (depending on the dose).

You could print out the study & discuss with your oncologist. Hopefully, your doctor is open to such a dialogue. He might not know about nattokinase.

For obvious reasons, there has been no clinical trial of nattokinase against a DVT, but there have been limited trials (see PubMed & clinicaltrials.gov).

-Patrick