Pre-treatment fibrinogen & bone metastatic burden in new cases.

[pjoshea13]

New study below. [1]

Fibrinogen circulates at normal levels for use in the event that a blood clot is required. In that case, thrombin will convert fibrinogen to the fibrin that forms the clot. Normal levels are OK, although I like to be at the low end of the reference range.

Fibrinogen is also an acute-phase protein & is elevated when there is inflammation. I included it in my series on inflammation markers 3 years ago:

"Inflammation. [3] SedRate, Fibrinogen, IL-6, TNFalpha." [2]

Elevated fibrinogen in the absence of thrombin doesn't mean that there is an increased risk of unwanted clotting.

However, it is not unusual for fibrinogen to be elevated in men with PCa, and cancer alters coagulation factors & risk.

Abnormal coagulation is associated with metastasis.

In the new study:

"Fibrinogen positively correlated with Gleason score ... PSA levels ... and number of metastatic lesions"

"Pre-treatment plasma fibrinogen is positively associated with bone metastatic burden in PCa patients. Our results indicate that fibrinogen might be a potential predictor of" high volume disease.

As I have mentioned before, a D-dimer test can be used to monitor clotting status and nattokinase can be used to accelerate the breakdown of fibrin.

I don't accept the fatalistic view that it is pointless to target metastasis when mets have occurred. I use nattokinase not only to prevent another DVT, but also to eliminate microclots that offer a safe haven to circulating PCa cells.

Once again, we have a study where the authors seem to view the finding in terms of prognosis, rather than a call to action.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/317...

Chin Med J (Engl). 2019 Nov 12. doi: 10.1097/CM9.0000000000000506. [Epub ahead of print]

Clinical association between pre-treatment levels of plasma fibrinogen and bone metastatic burden in newly diagnosed prostate cancer patients.

Xie GS1, Li G, Li Y, Pu JX, Huang YH, Li JH, Yin HM.

Author information

1

Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215031, China.

Abstract

BACKGROUND:

Due to the different treatments for low-volume metastatic prostate cancer (PCa) as well as high-volume ones, evaluation of bone metastatic status is clinically significant. In this study, we evaluated the correlation between pre-treatment plasma fibrinogen and the burden of bone metastasis in newly diagnosed PCa patients.

METHODS:

A single-center retrospective analysis, focusing on prostate biopsies of newly diagnosed PCa patients, was performed. A total of 261 patients were enrolled in this study in a 4-year period. All subjects were submitted to single-photon emission computerized tomography-computed tomography to confirm the status of bone metastasis and, if present, the number of metastatic lesions would then be calculated. Clinical information such as age, prostate-specific antigen (PSA), fibrinogen, clinical T stage, and Gleason score were collected. Patients were divided into three groups: (i) a non-metastatic group, (ii) a high volume disease (HVD) group (>3 metastases with at least one lesion outside the spine), and (iii) a low volume disease (LVD) group (metastatic patients excluding HVD ones). The main statistical methods included non-parametric Mann-Whitney test, Spearman correlation, receiver operating characteristic (ROC) curves, and logistic regression.

RESULTS:

Fibrinogen positively correlated with Gleason score (r = 0.180, P = 0.003), PSA levels (r = 0.216, P < 0.001), and number of metastatic lesions (r = 0.296, P < 0.001). Compared with the non-metastatic and LVD groups, the HVD group showed the highest PSA (104.98 ng/mL, median) and fibrinogen levels (3.39 g/L, median), as well as the largest proportion of Gleason score >7 (86.8%). Both univariate (odds ratio [OR] = 2.16, 95% confidential interval [CI]: 1.536-3.038, P < 0.001) and multivariate (OR = 1.726, 95% CI: 1.206-2.472, P = 0.003) logistic regressions showed that fibrinogen was independently associated with HVD. The ROC curve suggested that fibrinogen acts as a predictor of HVD patients, yielding a cut-off of 3.08 g/L, with a sensitivity of 0.684 and a specificity of 0.760 (area under the curve = 0.739, 95% CI: 0.644-0.833, P < 0.001).

CONCLUSIONS:

Pre-treatment plasma fibrinogen is positively associated with bone metastatic burden in PCa patients. Our results indicate that fibrinogen might be a potential predictor of HVD.

PMID: 31725446 DOI: 10.1097/CM9.0000000000000506

[2] healthunlocked.com/advanced....

[LearnAll]

Interesting correlation. Is there any reason why you do not include CRP and LDH in your inflammation markers ?

[pjoshea13 in reply to LearnAll]

I did include CRP in my inflammation series:

"Inflammation. [2] Albumin & C-Reactive Protein [CRP]" [1]

but I did not include LDH. It wasn't on my radar. Do you track it?

-Patrick

[1] healthunlocked.com/advanced...

[LearnAll in reply to pjoshea13]

Yes, I track albumin, CRP and LDH. I find useful correlation with these markers as mostly they rise and fall in tandem. At present , I am doing well and my LDH is 129 and CRP is 3.4 My PCP who is a family friend says ESR is very non specific and does not give accurate information about degree of systemic inflammation.

BTW, I find similar correlation with Neurophil-Lymphocyte ratio and Neutrophil-platlet ratio.

I keep a chart of each parameter along with PSA , ALP and Hb.

[pjoshea13 in reply to LearnAll]

Looks like you might have material for an interesting post. e.g. the most useful markers & what you are doing to counter inflammation.

Thanks, -Patrick

[LearnAll in reply to pjoshea13]

sure. I will prepare the report to share it with our friends on this forum.

[hansjd]

Thank you for the post, Patrick. As always your diligence in reporting studies is much appreciated.

May I ask you to elaborate on yourvuse of nattokinase? Can you tell me more about it? Where do you source it? How much do you take?

Do you feel it’s ok to take it when taking other supplements? Thanks again.

[pjoshea13 in reply to hansjd]

See:

"Foods/Supplements-Vitamins: Nattokinase"

healthunlocked.com/advanced...

When I could no longer get a steep discount, I switched from Nattozyme to Doctor's Best, which seems to work as well.

I take it before bed with a few other things: Simvastatin, Avodart, melatonin & Iodoral, and I am not aware of an issue.

-Patrick

[hansjd in reply to pjoshea13]

Thanks Patrick for the info and the link. Hadn’t see that post before. It predates my joining the forum. Cheers

[JLS1 in reply to pjoshea13]

I wonder if it's safe to take nattokinase when in bone marrow failure? Does it interfere with platelet development? It seems the later stage of PC, the more concern about microclots. Also, I saw somewhere else here that MCP may have a similar effect - help prevent microclots?

[pjoshea13 in reply to JLS1]

I don't believe that it interferes with platelet development - only with aggregation. But I can't say for sure.

Can't answer your MCP question.

-Patrick

[JLS1 in reply to pjoshea13]

Thank you .

[joekaty]

That’s interesting. When my husband was diagnosed- his metastasis was to his bone marrow. His PSA was in the 500’s but fibrinogen was critically low...D dimer INR PTT all super high.

[pjoshea13 in reply to joekaty]

A very low fibrinogen level will increase clotting time, so a high INR & PTT is consistent with that.

A high D-dimer isn't always due to a clot, but: "Low fibrinogen levels can also cause thrombosis due to an increase in coagulation activity." [1] ???

D-dimer is mostly used to rule out a clot (i.e. when D-dimer is ~zero), but a high D-dimer isn't proof of a clot, so usually leads to more tests.

Did you get an explanation for those test results?

-Patrick

[1] healthline.com/health/fibri...

[joekaty in reply to pjoshea13]

He was in DIC. So...by the time he got to the hospital he wasn’t really clotting at all- he had like 35 blood transfusions. It was horrific. It’s in his bones now but at diagnosis all they saw was bone marrow and lymph node involvement- they actually thought he had leukemia, but when they finally had to do a bone marrow biopsy the cells were prostate cancer cells. It was pretty bizarre...

[pjoshea13 in reply to joekaty]

Scary. So he was using-up fibrinogen at a crazy rate & clots were forming throughout the body (hence the D-dimer.)

Best, -Patrick

[joekaty in reply to pjoshea13]

Yes! I think first you clot like crazy and then you stop and you bleed. That’s my VERY unscientific understanding of it...but I have enjoyed seeing your posts on DIC. It’s such a rare complication and he’s never really recovered from the vascular damage- I try to find post DIC research though and there’s very little.