Fibrinogen

New Shanghei study below.

The formation of a clot involves (a) the clumping of platelets around the wound, & (b) the action of thrombin on fibrinogen to produce fibrin, the substance of the clot.

Fibrinogen would seem to be a fairly benign entity. It requires thrombin to turn it into a clot. LabCorp has the reference range as 193-507 mg/dL. Since higher levels represent higher clotting potential, is it best to be low-normal?

According to the Mayo Clinic:

"Fibrinogen is an acute phase reactant, so a number of acquired conditions can result in an increase in its plasma level:

-Acute or chronic inflammatory illnesses

-Nephrotic syndrome

-Liver disease and cirrhosis

-Pregnancy or estrogen therapy

-Compensated intravascular coagulation"

Nuclear Factor-kappaB [NFkB] is chronically activated in PCa, making that a "chronic inflammatory illness". Which makes fibrinogen a possible marker for the extent of inflammation in PCa.

In the new study, a cutoff of 3.225 g/L was determined. i.e. 322.5 mg/dL.

"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 ... Multivariable analyses identified hyperfibrinogen as an independent prognostic factor for" progression-free survival (risk factor = 2.000), cancer-specific survival (risk = 2.209) & overall survival (1.965).

Now, 350 mg/dL is the midpoint of the "normal" range, & the authors are defining >322.5 mg/dL as "hyperfibrinogen". Would that make 200-250 mg/dL a decent place to be, perhaps?

As I mentioned on the old site, polyphenols commonly used by men with PCa are NFkB inhibitors & thereby reduce inflammation. In my view, inflammation is not so much predictive of outcome, as a signal for intervention.

{The LEF blood test sale should be coming up. LEF has a coagulation test that includes fibrinogen & D-dimer. D-dimer should be zero (LabCorp returns <0.20 mg/L). A higher number could mean that there is an active clot. I use D-dimer to guess at a good dose of nattokinase. Nattokinase disolves fibrin faster than the body does via plasmin. It also lowered fibrinogen in a human study.}

-Patrick

ncbi.nlm.nih.gov/pubmed/269...

Prostate Cancer Prostatic Dis. 2016 Mar 8. doi: 10.1038/pcan.2016.6. [Epub ahead of print]

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

Wang Y1, Yin W2, Wang Z3, Huang J1, Pan J1, Zhu Y1, Xu F1, Shao X1, Sha J1, Cai Y3, Liu Q4, Dong B1, Xue W1, Huang Y1.

Author information

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.

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.Prostate Cancer and Prostatic Diseases advance online publication, 8 March 2016; doi:10.1038/pcan.2016.6.

PMID: 26951714 [PubMed - as supplied by publisher]

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