How does PCa affect Venous Thromboembolism risk?

[pjoshea13]

New study below [1].

In Sweden, PCa isassociated with a ~50% increase in the risk of a deep vein thrombosis [DVT] or pulmonary embolism.

This is much lower than some studies have reported, e.g.:

"In a larger study from the UK using linked primary care, secondary care and National Statistic Cause of Death data, Walker et al found a 2.6 ... increased rate of VTE among 10,238 men with prostate cancer compared with a non- cancer comparison cohort ..." ... from the Discussion section, below ...

Large study: "92,105 {Swedish} men with prostate cancer and 466,241 men without prostate cancer ... matched 5:1 by birth year and residential region."

"Swedish men with prostate cancer had a mean 50% increased risk of VTE {venous thromboembolism} during the 5 years following their cancer diagnosis compared with matched men free of prostate cancer."

Cancer is a known risk factor for unwanted blood clots. D-dimer can be monitored - when zero, there is no clot. Nattokinase can be used to speed up clot removal.

Unfortunately, many men only hear of the risk while in the ER.

Even though we have increased risk, doctors do not monitor since treatment protocols call for anticoagulants only after a blood clot has caused a trip to the ER.

"DISCUSSION

"In our nationwide study in Sweden, men with prostate cancer had a 50% increased risk of a first VTE in the 5 years following cancer diagnosis compared with men free of prostate cancer in the general population, after adjusting for age and other confounders. The risk was mostly increased in the first 6 months of prostate cancer diagnosis, decreasing steadily thereafter, and the average time to develop a first VTE was shorter in men with prostate cancer than in men free of prostate cancer of a similar age (3.1 years vs 3.4 years).

"Adjusted HRs differed only marginally from crude estimates, indicating that this excess risk is likely due to effects of the prostate cancer itself and/or residual confounding.

"Additionally, VTE incidence increased in both study cohorts over time, reflecting an increased incidence with age irrespective of cancer status.

Our findings support previous findings on this topic, although the magnitude of increased risk among men with prostate cancer in our study was lower than those in other reports. This could be explained by the inclusion of both inpatient and outpatient VTE cases—the latter likely representing less serious events. In a previous study using PCBaSe, incidence rates of DVT and PE were twofold higher in men with prostate cancer (2.5 higher in those on endocrine therapy or who received curative treatment) compared with the expected rates from the general male Swedish population. In a registry study from Denmark, Cronin-Fenton et al reported a threefold increased risk of hospitalised VTE among 4457 men with prostate cancer compared with matched general popu- lation controls after adjusting for confounders (median follow-up 1.23 and 3.5 years in the all-cancer and general population cohorts, respectively). In a larger study from the UK using linked primary care, secondary care and National Statistic Cause of Death data, Walker et al8 found a 2.6 (95% CI 2.4 to 2.9) increased rate of VTE among 10238 men with prostate cancer compared with a non- cancer comparison cohort, after adjusting for age and calendar year (median follow-up of 2.0 and 2.6 years in the all-cancer cohort and comparison cohort, respec- tively). Their exclusion of patients with other cancers in their comparison cohort would have meant this group was probably healthier than our comparison cohort that did not exclude men with other cancers, and thus could also be a reason for their observed higher relative risk. Furthermore, the smaller relative increase in VTE risk seen in our study occurred over a longer follow-up duration (median 4.5 years) than the two aforemen- tioned studies. As we observed a higher relative incidence of VTE in the first 6 months from cancer diagnosis—as seen previously—it is logical that higher relative risks would be observed in shorter studies. The higher risk in the months after prostate cancer may reflect the higher risks of VTE associated with surgical interventions such as radical prostatectomy.

In addition to being a leading cause of death in patients with cancer, VTE adversely affects patients’ quality of life, bringing anxiety about the risk of recurrence, and potentially interrupting cancer treatment. Furthermore, decisions about treating the VTE can be challenging, as risks of recurrent VTE and anticoagulant-associated bleeding are higher in patients with cancer. For most patients, clinical guidelines currently recommend long-term anticoagulant therapy with low-molecular weight heparin or a DOAC to help prevent VTE recurrence, although some recommend a duration of at least 3 months, while others recommend 6 months16 or more. Ageing populations with increasing life expectancy means that more men will be living with prostate cancer and at risk of VTE for many years. Our findings quantifying the increased risks of VTE in men with prostate cancer suggest that physicians should be particularly vigilant of these patients in the first 6 months following diagnosis."

...

"The magnitude of increased VTE risk among men with prostate cancer seen in our study is lower than that seen for other cancer types as seen in previous studies, and is likely attributable to the high proportion of men with localised disease and at low risk of cancer progression. Not withstanding this, physicians treating men with prostate cancer should be aware of the marked increase in VTE risk in these men, particularly in the first 6 months following cancer diagnosis, to help ensure timely VTE diagnosis."

{You can't ensure timely diagnosis without D-dimer tests - IMO.}

-Patrick

[1] full text: bmjopen.bmj.com/content/bmj...

pubmed.ncbi.nlm.nih.gov/356...

BMJ Open

. 2022 May 23;12(5):e055485. doi: 10.1136/bmjopen-2021-055485.

Risk of venous thromboembolism in men with prostate cancer compared with men in the general population: a nationwide population-based cohort study in Sweden

Yanina Balabanova 1 , Bahman Farahmand 2 , Hans Garmo 3 , Pär Stattin 3 , Gunnar Brobert 2

Affiliations expand

PMID: 35606159 DOI: 10.1136/bmjopen-2021-055485

Abstract

Objective: To estimate the additional risk of venous thromboembolism (VTE) in men with prostate cancer compared with men without prostate cancer in Sweden.

Design: Nationwide cohort study following 92 105 men with prostate cancer and 466 241 men without prostate cancer (comparison cohort) matched 5:1 by birth year and residential region.

Setting: The male general population of Sweden (using the Nationwide Prostate Cancer data Base Sweden).

Primary and secondary outcome measures: Crude incidence proportion ratios (IPRs) comparing the incidence of VTE in men with prostate cancer and men in the comparison cohort. Cox regression was used to calculate HRs for VTE adjusted for confounders.

Results: 2955 men with prostate cancer and 9774 men in the comparison cohort experienced a first VTE during a median of 4.5 years' follow-up. Deep vein thrombosis (DVT) accounted for 52% of VTE cases in both cohorts. Median time from start of follow-up to VTE was 2.5 years (IQR 0.9-4.7) in the prostate cancer cohort and 2.9 years (IQR 1.3-5.0) in the comparison cohort. Crude incidence rates of VTE per 1000 person-years were 6.54 (95% CI 6.31 to 6.78) in the prostate cancer cohort (n=2955 events) and 4.27 (95% CI 4.18 to 4.35) in the comparison cohort (n=9774 events). The IPR decreased from 2.53 (95% CI 2.26 to 2.83) at 6 months to 1.59 (95% CI 1.52 to 1.67) at 5 years' follow-up. Adjusted HRs were 1.48 (95% CI 1.39 to 1.57) for DVT and 1.47 (95% CI 1.39 to 1.56) for pulmonary embolism after adjustment for patient characteristics.

Conclusions: Swedish men with prostate cancer had a mean 50% increased risk of VTE during the 5 years following their cancer diagnosis compared with matched men free of prostate cancer. Physicians should be mindful of this marked increase in VTE risk in men with prostate cancer to help ensure timely diagnosis.

Keywords: epidemiology; thromboembolism.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

[LearnAll]

Prostate cancer just like any other cancer is a hypercoagulable state. This means that the tendency form mini clots are increased and these clots can lodge into various organs. If these clots lodge in an eye vessel, they are capable of causing retinal detachment. if in heart arteries, then myocardial infarction or heart attack, if in brain arteries, then a stroke and if in legs..they can circulate and lodge in lung tissue and cause partial dead lung tissue.

So this clotting abnormality needs to prevented.

A very effective way to reduce risk of venous thrombosis is walking multiple times a day and pump leg muscles. Eating Ginger, turmeric ,garlic etc reduce clotting tendency. Careful use of 81 mg Aspirin a day or even once a week can be protective.

[Hidden]

Do you think low dose aspirin, natto, and estrogen replacement during ADT reduce your risk?

[pjoshea13 in reply to Hidden]

I believe that nattokinase alone is probably sufficient to eliminate the risk, provided that the dose is periodically validated via a D-dimer test.

-Patrick

[MateoBeach]

In order to put relative risk increases into perspective it is necessary to consider the Absolute risk levels (“crude”) from which the relative are calculated. In this case the observed incidence of VTE was 6.5 cases per 1000 person-years with PC, vs 4.3 without PC. That is an absolute risk per year for PC was 0.65% vs 0.43 % without PC ( % of 100 men affected). This is important for perspective, as relative risk ratios always magnify the differences. Both are statistically true.

One question I have is total additional cardiovascular risk increase when we consider arterial side: heart attack and stroke risk, plus venous side: DVT and PE? Do you have any data or insight into that, Patrick?

As for protection (prevention) besides frequent movement, I now take Nattokinase per your making me aware of this. 200,000 iu, though perhaps twice that might be optimal? I have also taken to wearing knee-high compression stockings, first for support while walking (they feel good) and now just everyday. Especially important on flights and long car rides. Also take low dose enteric aspirin 3X per week.

[GreenStreet]

Thanks Patrick. Glad I am taking Natto x 3 and enteric baby aspirin every third day

[Hawk56]

In December 2010 (age 53) I had PEs to both lungs coming back on a flight from San Antonio to Kansas City. I was in good shape, weight, BP, diet and exercise so it was a "surprise!". They could not find any cause for the PEs. My GP had just completed a CEMU which discussed the link between clots and cancer. She started with a colonoscopy which did show polyps though benign.

Because of those polyps, I was scheduled for another colonoscopy in three years vice 10 (which my wife was based on her negative colonoscopy.) In December 2013 during my next colonoscopy my gastrologist "examined" my prostate while I was under anesthesia and found a nodule. When I came to, he recommended I see my urologist. The rest is history.

I am not saying that the PEs I experienced were a harbinger of my PCA diagnosis in 2013 but MY GP felt there may be a link after attending a CEMU which discussed linkages between PEs and cancer and took action though diagnostic testing.

Kevin

Clinical History

[pjoshea13 in reply to Hawk56]

There are a number of study papers that end with advice to doctors to look for cancer following an abnormal coagulation event.

Even in men with a low PSA, a DVT or PE might be a symptom of occult PCa. No harm in treating it as a harbinger. I believe that the risk drops to normal in about 6 months.

Here is an interesting twist on risk for men on an anticoagulent. The risk of metastatic PCa is lower with long-term use - but higher with short-term use. Micro-clots allow circulating tumor cells to hide & safely lodge somewhere hospitable. If the cancer has developed sufficiently to affect coagulation, there might circulating cells.

-Patrick

[TylexGP]

Thank you for sharing. The silver lining for me may be that I am on Xarelto for Afib Maybe it will lessen my risk.

[pjoshea13 in reply to TylexGP]

Tyler,

Agree, but:

"Compared with rivaroxaban [Xarelto], the use of dabigatran [Pradaxa] may be associated with a lower risk of cancer-related death and all-cause mortality."

pubmed.ncbi.nlm.nih.gov/344...

-Patrick

[TylexGP]

Thank you for sharing, I will talk with my Cardiologist and EP doc. Curious if apixaban[Eliquis] would have similar outcome as rivaroxaban? Now you have peaked my curiosity.😀

[j-o-h-n]

Blame it all on that Swedish fish candy....................

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 05/25/2022 7:13 PM DST

[Currumpaw]

You have been busy again! Well shared!

Currumpaw

[Spyder54]

Thanks Patrick, still taking my 81mg St Joseph baby aspirin every morning, along with high dose Tumeric-Curcumin, plus NATTOKINASE every other night. Blood seems thin, but better than a DVT ! Mike

[farmanerd]

I know this is an old thread, but having been to an ER last Friday for chest pain and getting a D-dimer test result of 2.99ug/ml with no PE detected on CTA, I decided to learn more about D-dimer and PCA. Not exactly happy about what I've read so far. I'm still searching to see if any studies have been done on elevated D-dimer predicting existence of currently undetected or of future mets. PSA test result was <0.02 last Tuesday. D-dimer's sensitivity but lack of specificity is giving me a bit of anxiety.

[lcfcpolo]

Firstly, it is great that your PSA is so low and that the CTA did not show anything.

You are correct that a higher D-dimmer can be indicative of cancer, including prostate cancer. Indeed my own Advanced Prostate Cancer was only found after having a high D-dimmer for a 2nd time. My PSA was off the charts though, at 1,311. No PSA was checked after my first high D-dimmer after I had a DVT, so yes it is possible that a high reading could be the first signs of something worse. However, the fact that your PSA is so low appears really positive and hopefully means that there is no spread.

Can you discuss this with your medical team and request more regular checkups for PSA tests but also additional scans to monitor, just incase. Hopefully you have been given a anticoagulant to take. I'm on Apixaban for life.