Intro:
TMA syndromes are extraordinarily diverse❗️
They may be
-hereditary or acquired
-occur in children and adults
-onset can be sudden or gradual
BUT
despite their diversity, they are united by common, defining clinical and pathological features
2/16
Pathology:
-For all primary TMA syndromes the same
- -renal arteriole occlusion with endotheliosis as well as lumen and vessel-wall fibrin
- -Proliferation in the myocyte layer (“onion skinning”) may also be present
5/16
Think first before you act:
Before you start sophisticated lab tests and hypotheses, exclude common causes of MAHA and thrombocytopenia❗️
Remember, any condition associated with DIC can occur with MAHA and thrombocytopenia
👉rule out first
Evaluate MAHA and thrombopenia:
-severity of kidney injury as distinguishing feature
-severe acute kidney injury
👉consider complement-mediated (acquired/hereditary)
-idiopathic disease in + 20%
-TTP is also called ADAMTS13 deficiency–mediated TMA
7/16
Thrombotic thrombocytopenic purpura:
-rare systemic form of TMA
👉severe deficiency in ADAMTS13
👉disintegrin + metalloprotease with thrombospondin type 1 motif 13, which cleaves von Willebrand factor
For more, I refer to the legend @nihardesai7
Complement-mediated aHUS:
-0.4 cases per Mio per year
-acquired or inherited defects in the alternative pathway
-Extra-renal manifestations in 10-20%
-AKI more prominent than in TTP
-Genetic screening (CFH, CFI, C3, CFB, CD46, CFHR1) is essential, incl DGKE & MMACHC
9/16
Shigatoxin-associated TMA:
-most common form, mainly occurring in children <5 years
-accounts for 90% of cases of HUS in children
-transmission
👉undercooked meat, unpasteurised dairy produce, direct contact, ingesting contaminated🥦🍅
-majority is self-limiting
10/16
Pregnancy-associated TMA:
-Pregnancy + postpartum high-risk periods for TTP and complement-mediated aHUS❗️
-typically in the 2nd + 3rd trimesters
-cause: maybe VWF production⬆️
-experience of caplacizumab limited
For more👉legend @nihardesai7
11/16
Transplant-associated (TA-) TMA:
-high mortality❗️
-etiology is myriad
-~8% of BMT patients
-historically, plasma exchange was mainstay of treatment
BUT
-with recognition that ADAMTS13 levels in TA-TMA are mostly normal, strategies have shifted away from this approach
12/16
TA-TMA treatment:
-Elucidation of complement in development of TA-TMA shifted treatment toward terminal complement inhibition with eculizumab and MASP-2 inhibition with narsoplimab
-Prospective data on eculizumab still limited to children
-more evidence needed
13/16
Narsoplimab for TA-TMA:
-IV once weekly for 4-8 weeks
-Response rate: 61%, similar across subgroups
-Improvement in organ function in 74%
-100-day survival after TA-TMA diagnosis was 94% in responders
14/16
Autoimmune TMA:
-SLE, scleroderma renal crisis or catastrophic antiphospholipid syndrome (CAPS)
-Case reports describe use of eculizumab in SLE-TMA
-~30% of CAPS show renal TMA with 36% morality 👉glucocorticoids, anticoagulants + IVIG
For more👉legend @PanktiMehta24
15/16
Summary of TMA:
❗️Array of manifestations, CHALLENGING
❗️High morbidity + mortality
❗️Renal involvement is common
❗️Suspect: MAHA, thrombopenia
❗️rule out other causes
❗️rapid assessment, diagnosis + treatment essential
❗️TA-TMA very serious
❗️Eculizumab, narsoplimab new options
Relations between us are often poisoned by fights for the best spotlight, position and papers.
Here are 10 things we should say to one another more often.
A 🧵
1️⃣ "You're not alone." Remember, everyone goes through ups and downs in research. Reach out to your peers, share your struggles, and lean on each other. Together, we can overcome challenges and celebrate successes.
2️⃣ "You belong here." Doubting your abilities is common, especially when starting out. Remember, you earned your place through hard work and dedication. Believe in yourself and trust in your unique contributions.
Intro DIC:
-systemic activation of coagulation
👉resulting in microvascular thrombosis & haemorrhage
-devastating condition, poor prognosis
-clinic variable, depends on ⚖️of clot formation in microvasculature & consumption of coagulation factors, inhibitors, platelets
2/20
History I:
-Dupuy in 1834: described effect of IV injection of brain material in animals👉almost immediately died and at autopsy widespread clots in the circulation, 👉due to what we would now call tissue factor–dependent systemic activation of coagulation
3/20
What's TLS?
-major comorbidity in the management of hematologic malignancies and one of the major conditions young colleagues should
👉know to detect and to handle❗️
-modern definition of TLS is based on the Cairo–Bishop criteria for laboratory and clinical TLS
2/19
Clinical TLS:
-simply defined as laboratory TLS with the addition of an elevated creatinine not attributable to
- - another cause
- - 🫀arrhythmia/sudden death
- - seizures
-given newer treatment/preventive measures, both forms of TLS may have clinical implications
3/19
1/ Medical societies exist to serve their members, promote their evolution and excellence in patient care. Through that you become more than the sum of your members. Always keep this at the forefront of all initiatives.
2/ It's all about your members, not about your sponsors or leaders. Be as democratic as possible. Stay responsive to their needs. Listen to their feedback and suggestions, and use this information to continuously improve your offerings and services.
3/ Embrace diversity and inclusivity in all aspects of your society. Encourage participation and representation from all members, regardless of their background. Avoid favoritism and foster representation and engagement from all levels.
Veno-occlusive disease (VOD) is one of the worst and a potentially life-threatening complication that can occur after blood or marrow transplantation (BMT).
VOD:
-clinical syndrome which can occur after BMTand, less commonly, after chemo, toxic alkaloids, high doses of radiotherapy, or liver transplant
-incidence varies from 2-60% because of different setting, application of different diagnostic criteria and BMT procedures
2/15
Clinic:
-rapid weight gain, often unresponsive to diuretics, hyperbilirubinemia, painful hepatomegaly, & ascites
-within 21 days after BMT
-late-onset VOD a distinct feature, occurring in 39.3% and 16.7%, respectively, in the adult and pediatric setting
-@TheEBMT criteria👇
3/15