Recently Diagnosed or Relapsed? Stop Looking For a Miracle Cure, and Use Evidence-Based Therapies To Enhance Your Treatment and Prolong Your Remission
Multiple Myeloma an incurable disease, but I have spent the last 25 years in remission using a blend of conventional oncology and evidence-based nutrition, supplementation, and lifestyle therapies from peer-reviewed studies that your oncologist probably hasn't told you about.
Click the orange button to the right to learn more about what you can start doing today.
- You are here:
- Home »
- Blog »
- Multiple Myeloma »
- Protease Inhibitor Cause Blood Clots?
Protease Inhibitor Cause Blood Clots?
Can protease inhibitors cause blood clots? Yes. More to the point PIs can cause tiny blood clots (thrombotic microangiopathy) that can damage organs.
I understand that all forms of chemo regimens come with side effects. Fine. I have two questions regarding PI thrombotic microangiopathy.
- First, velcade has been FDA approved since 2003. How can MM patients and survivors be learning about this serious side effect 20 plus years after the fact?
- Sec9nd, how does a MM patient about to undergo a PI, prevent or even reduce the risk of a TMA?
I am a long-term MM survivor. I live with a host of treatment-related long-term and late stage side effects. I say this to encourage you to be aware of treatment related side effects.
According to the research linked below, up to 16% of MM patients undergoing a PI can develop one or more TMA. Though the video above talks about diagnostic testing and possible therapies, I have to admit that I couldn’t really follow the content well enough to be able to write about them here.
All to say, TMAs are a risk for MM patients and we all should be aware of this side effect and should discuss the possibility with our oncologists.
Email me with questions about MM- David.PeopleBeatingCancer@gmail.com
Thank you,
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
Proteasome inhibitors related thrombotic microangiopathy: a systematic and comprehensive review
“Proteasome inhibitors (PIs) are crucial in treating multiple myeloma but carry a risk of thrombotic microangiopathy (TMA), especially with carfilzomib use. This systematic review includes 44 studies with 115 cases of PI-induced TMA, where carfilzomib was implicated in 101 cases…
The need for dialysis emerged as a significant predictor of outcomes, often indicating a poor prognosis. For patients suspected of having PI-TMA, it is advisable to discontinue the offending medication promptly, even without definitive laboratory confirmation…
Comprehensive evaluation of the complement system, including
- genetic mutations,
- function,
- and associated complement inhibitory factor antibodies,
should be included in the assessment of PI-TMA…
Carfilzomib, a significant therapeutic option for multiple myeloma, is potentially linked to TMA as a severe side effect [4]. Prospective clinical studies show that the incidence of carfilzomib-related TMA ranges from about 1–10% [5,6,7,8,9], while retrospective studies report an incidence between 0.89% and 16.7% [4, 10,11,12], suggesting that carfilzomib-related TMA is more common than once believed.
Importantly, the occurrence of MAHA following carfilzomib treatment is notably high. Two retrospective studies found that carfilzomib-related MAHA occurred in 64.5% (20/31) [4] and 66.7% (16/24) [13] of cases. This underscores the need for vigilant monitoring for TMA during carfilzomib treatment…
Increasingly, clinical studies on carfilzomib are recognizing the higher incidence of proteasome inhibitor-related TMA and have adjusted dosing to mitigate this risk…
Additionally, apart from the poor prognostic outcomes, TMA significantly elevates healthcare costs. A cost-analysis from the MYX.1/MCRN003 study reported that the development of TMA in three patients resulted in an average cost of $18,863.32 per patient, encompassing expenses related to hospitalizations and therapeutic plasma exchange [14].
Consequently, PI-related TMA demands heightened vigilance from clinicians. In this systematic review, we surveyed all available literature on PI-related TMA…
This review included a total of 44 studies, consisting of 33 case reports or case series, 6 studies from clinical trials, and 5 retrospective studies (Supplementary Fig. S1).
The analysis covered 115 cases of TMA linked to PIs. Specifically,
- Bortezomib was implicated in 12 cases,
- Ixazomib in 2,
- and Carfilzomib in 101 cases.
We propose a potential management strategy for PI-TMA (Fig. 2). Symptoms such as hypertension, which is commonly noted in the history of patients with PI-related TMA and was present in over half of the patients at diagnosis, should prompt increased vigilance. New-onset or exacerbated hypertension could serve as an early diagnostic indicator of TMA [35]…
For patients suspected of PI-TMA, it is advisable to test for schistocytes in peripheral blood. In a few cases of PI-TMA, peripheral blood tests may not detect schistocytes, yet there is a strong clinical suspicion of PI-TMA, and symptoms improve post-discontinuation of the therapy [36]…
Conclusion
As the clinical use of carfilzomib increases, reports of PI-TMA are rising, underscoring the need for heightened vigilance. Early detection and intervention are crucial to improving patient outcomes. Given that most research on PI-TMA stems primarily from case reports, our review largely depends on these reports for data extraction.
Our objective is to systematically describe the clinical manifestations, treatment strategies, and prognosis associated with PI-TMA.
Our literature review indicates an approximate 14.9% rate of adverse outcomes in PI-TMA, though this figure may underestimate the true prevalence, as some cases likely go undiagnosed or unrecognized.
There is increasing evidence that abnormalities in the complement system are frequently linked with carfilzomib-induced TMA. As such, patients with mutations in complement genes should be considered at high risk for PI-TMA.
Designing prospective studies to screen for complement gene defects can significantly benefit clinical practice by identifying these high-risk patients. Additionally, certain clinical indicators, such as new or worsening hypertension during PI treatment or preceding viral infection, may signal a heightened risk of PI-TMA.
These patients could potentially benefit from more rigorous management strategies, particularly during the initial treatment cycles, typically from the first to the third. Effective approaches could include using peripheral blood smears to identify schistocytes and performing complement function tests.
Testing for Sc5b-9 may also be helpful in diagnosing suspected cases of PI-TMA. In light of the rising reports of complement gene deficiencies linked to carfilzomib-related TMA, it is advisable to plan prospective studies aimed at developing tailored management protocols for affected patients, especially those receiving carfilzomib therapy.
Patients requiring dialysis typically face poorer prognoses, emphasizing the need for more robust interventions. Early administration of ECU in patients suspected of having complement activation abnormalities.”
protease inhibitors cause blood clots
protease inhibitors cause blood clots
protease inhibitors cause blood clots