Thread by @sigman_md

1/ 42 yo patient presents with 3 hours of left hemiparesis found to have right M1 thrombus. Platelets are 24,000/uL!

Welcome to a CANNOT MISS #EmoryNCCTweetorials @EmoryNeuroCrit on a rare etiology of #acuteischemicstroke

#Neurotwitter #FOAMncc #stroketwitter

2/ 🚨Goals for the scroll:

✅Discuss a rare cause of acute ischemic stroke
✅ Review thrombectomy safety w thrombocytopenia (tcp)
✅Review dx and pathophys of thrombotic thrombocytopenic purpura (TTP)
✅Review the treatment of TTP

3/ Our patient with plt of 24,000 /uL is taken for #thrombectomy. Would you send your pt w/ severe thrombocytopenia for thrombectomy?

4/ Many thrombectomy trials exclude patients with thrombocytopenia:

🧐MERCI, multi-MERCI:<30,000 /uL
🧐MR CLEAN: <40,000 /uL
🧐SWIFT PRIME and EXTEND IA: <100,000/mL
🧐DAWN and DEFUSE-3: <50,000/mL

5/ Data suggest thrombectomy for pts w/ thrombocytopenia is safe:

✅ No⬆️ risk of ICH
✅ No⬆️ risk of groin complications

pubmed.ncbi.nlm.nih.gov/19095994/
pubmed.ncbi.nlm.nih.gov/30980980/

🤔 Few pts in these studies had plt <50,000 /uL

Thoughts? @feras_akbik @rwregenhardt @DrAjithThomas

6/ Re platelets: how low can you go?

✅ Data from ITP pts: bleed when plt <10,000
✅ Data from chemo pts: bleed when plt <5,000

pubmed.ncbi.nlm.nih.gov/13897369/
pubmed.ncbi.nlm.nih.gov/4052629/

7/ The patient is admitted to #neuroICU after thrombectomy: the platelets are now your problem.

🚨Thrombocytopenia + acute stroke should TRIGGER you

✅ Nice algorithm for thrombocytopenia work-up here: pubmed.ncbi.nlm.nih.gov/29989621/
✅ Adapted algorithm attached

8/ What are diagnoses I should be thinking about for patients w/ thrombocytopenia + thrombosis?

✅ #DIC
✅ #HUS
✅ #TTP
✅ Other thrombotic microangiopathies: tinyurl.com/ycm3k65m

9/ So, in your patient with thrombocytopenia and stroke, some of the first steps are:

Thoughts? @acweyand @HollisViray

10/ Back to our case. The initial labs are in:

PT/PTT: normal
LDH ⬆️
Indirect bili ⬆️
Schistocytes: ✅
Haptoglobin ⬇️
Fibrinogen ⬆️
HIT assay: negative

What's the diagnosis?

11/ What is TTP?

✅ It's a problem with ADAMTS13, an enzyme that ⬇️ protein-platelet complexes
✅ Von Willebrand factor (vWF) multimers form protein-plt complexes on endothelium
✅ If ADAMTS13 ⬇️ vWF + plt aggregate -> thrombus formation ⬆️-> ischemia

tinyurl.com/3n2bn3jr

12/ TTP is an emergency!

✅ There's a scoring system to assess probablity of TTP
✅ PLASMIC score created by Bendapudi et al.
✅ mdcalc.com/plasmic-score-…
✅ Score >5 suggests high probability of TTP

tinyurl.com/fabjx7y6

13/ Our patient's score is 7! We send for ADAMTS13 activity. Let's review the facts:

💡TTP has ⬆️ mortality if untreated (>90%)
💡 We use PLASMIC score to assess probability given gold standard ADAMTS13 activity won't result for 3-5 days
💡 TTP needs to be treated early

14/ You place a pheresis catheter and start plasma exchange (PLEX) because:

✅ PLEX removes pts plasma (and thus autoantibodies to ADAMTS13) + ultralarge vWF multimers
✅ Donor plasma restores functional ADAMTS13

tinyurl.com/fabjx7y6

15/ Assessing the treatment?

✅ W/in 3-4 sessions, ⬆️ platelets
✅ If no response, consider alt dx or refractory disease
✅ Continue to appreciate #hematology recs 😂😂

See our patients platelet trend:

16/ Our patient improves from NIHSS 6->3.

✅ MRI is done. See photo attached. There are addt left frontal and cerebellar infarcts.
✅ ADAMTS13 activity results: <5%

17/ Although TTP pathophys suggests microangiopathy, large vessel strokes are reported in the literature!

💡TTP related strokes are often multifocal
💡Large vessel occlusion can be seen w/ TTP

pubmed.ncbi.nlm.nih.gov/29437728/

18/ Be sure to think about the cause of TTP:

✅Acquired (antibodies to ADAMTS13)
✅Genetic (ADAMTS13 mutations lead to ⬇️activity) = Upshaw-Shulman syndrome
✅Secondary causes (cancer, transplant, pregnancy, medications, HIV)

Nice review:
pubmed.ncbi.nlm.nih.gov/30862697/

19/ What are the long term outcomes of stroke from TTP?

💡Unclear, data is lacking
💡TTP is rare! Incidence is ~3 in a million
💡 Up to 40% of pts can have disease relapse
💡 Immunotherapies ⬇️ relapse

@TTP_Network

20/ What about secondary stroke prevention. Would you put your TTP-related stroke patient on aspirin?

💡Data free zone
💡Mainstay is to treat underlying cause

Interested to hear your thoughts @JenHarrisMD

21/ Scary facts:

🚨 Neuro sx can be the initial presentation of TTP w/ low normal or normal plt = atypical TTP
🚨 All classic 5 features of TTP (fever, tcp, hemolytic anemia, neuro sx and renal dz) present in <10% of patients with TTP

doi.org/10.1155/2019/7…

22/ 💡Remember other neuro manifestations of TTP:

🧠 Headache
🧠 Confusion
🧠 Seizures
🧠 Strokes
🧠 Other focal signs (transient or otherwise)

23/ What about platelet transfusions in TTP?

💡Generally, not recommended...unless you have to (bleeding, invasive procedure)
💡The antibody to ADAMTS13 will continue to wreak havoc
💡But...it may be safe

pubmed.ncbi.nlm.nih.gov/19210323/

24/ What have we learned about TTP!?

✅ TTP can cause stroke
✅ Thrombectomy is likely safe w/ tcp
✅ Early dx of TTP is 🔑
✅ Plt can be normal in early TTP
✅ PLASMIC score + heme c/s -> PLEX

🚨🚨 Today is the eve of International TTP Day (on 3rd Sat of September annually) !

🚨Special thanks to @caseyalbin 🚨

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