Thread by @runthelistpod

Let's HIT the topic 💊 Heparin-induced Thrombocytopenia (HIT)🩸!

This #tweetorial is a deep dive into Episode 43 of Run the List (RTL) on Thrombocytopenia: bit.ly/32feVfQ

Thanks @LeelaChock for covering this week’s topic!

Thrombocytopenia is a broad topic!

In Ep. 43 of RTL, Dr. Robert Stern, @NavinKumarMD, & @sonorato11 go over a general approach to thrombocytopenia 👇

Broadly, there are THREE umbrellas:

1. ⬆️ destruction

2. Splenic sequestration 💪

3. ⬇️ production

runthelistpodcast.com/s/RTL_Thromboc…

HIT (Heparin-induced thrombocytopenia), is classified under “⬆️ destruction”

HIT in-depth:

✨It is *common*, occurring in 1 out of 5,000 hospitalized patients✨

💥It’s a can’t miss dx! 50% of patients w/ HIT who are not appropriately treated go on to develop a thrombosis💥

HIT risk factors?

⬆️ duration/dose of heparin administration (can even happen w/ simple heparin flush!)

Type of heparin used: UFH > LMWH > fondaparinux💊

🩹Surgical, trauma, cardiopulm bypass pts at ⬆️ risk (maybe 2/2 increased heparin use, but MoA unknown)

Patient sex (F>M)

HIT mechanism:

▶ Heparin 💊 complexes w/ platelet factor 4 (PF-4), a protein released by platelets

▶ B-cells make IgG antibodies (~5-7 days after heparin exposure) to the PF4-heparin complex 🧪

▶ IgG then binds these heparin-PF4 complexes to platelets and then…

(HIT MoA cont.):

IgG-PF4-heparin complexes bind platelets causing BOTH:

1⃣Thrombocytopenia by marking the platelets for ☠️destruction☠️ via splenic macrophages (type II hypersensitivity rxn)

AND

2⃣Paradoxical PRO-thrombotic state by IgG Ab complexes 💥activating💥 platelets!

Sequelae include:

🔴Thrombocytopenia to ~50-80k (usually >20K)

🟠Paradoxical thrombosis (venous > arterial), despite thrombocytopenia!

🟡(Rarely) anaphylaxis; HIT Ab may activate leukocytes

🟢Skin necrosis at *heparin injection sites* (seen below) immediately suggests HIT! 🩺

Let’s review timing ⏰ of HIT!

Suppose heparin is given on day 0:

🔸d0-d1 = Rapid 50% drop (pt already has IgG Ab 2/2 heparin exposure w/i last 3 months)

🔹d5-d7 = Rapid 50% drop (no prior heparin exposure)

🔸d7-d14 after heparin withdrawal = Rapid drop ("delayed-onset HIT")

If suspecting HIT calculate a "4-T score"

The 4 T's are:

📌Thrombocytopenia

📌Timing ⌚️ of Onset

📌Thrombosis

📌oTher causes of Thrombocytopenia.

A LOW score (<4 points) has a very HIGH negative predictive value (NPV) of 97 to 99%, and essentially *rules out* HIT

The positive predictive value (PPV) of a 4-T score of 4-5 is 10-20%, but a score >=6 is 40-80%

A 4-T score >=4 requires:

1⃣Stopping all heparin products immediately 🛑!

2⃣An Anti–PF4–heparin ELISA test 🧪

3⃣Starting therapeutic NON-heparin anticoagulation (e.g. Argatroban 💊)

Anti-PF4 test has high NPV (98-99%), but low PPV

a ➕ anti-PF4 result requires confirmation w/ *gold standard functional test*: serotonin release assay (SRA)

How does SRA work?

If pt's serum has active heparin-PF4 IgG Ab ➡️ activate donor platelets ➡️ 💥 releasing serotonin 💥

All pts w/ suspected or confirmed HIT need therapeutic (non-heparin) anticoagulation (AC)!

Why💊?

HIT Abs activate platelets➡️clots despite thrombocytopenia

For HIT: continue AC until platelet count >150K

For HIT-related clot: continue AC for 3 months (like any provoked clot)

[on AC]

@ASH_hematology suggests the following tx as initial anticoagulants in acute HIT🩸:

📝Argatroban, bivalirudin, fondiparinux, danaparoid, or a DOAC

💊Argatroban or bivalirudin = short half-lives (!)

⌛️Short half-lives = indicated for critically ill or bleeding risk pts

If pt is on warfarin, 🛑hold warfarin🛑 & reverse with IV Vitamin K 🥦

Seems strange right?

◾️Warfarin has been shown to paradoxically WORSEN the hypercoagulable state in HIT 😱

◽️Once platelet count stabilizes, can re-start warfarin 👍

in SUM:

1) HIT complexes both activate *and* deplete platelets (thrombocytopenia)

2) Use the 4-T score🧮 to assess for HIT

3) If >=4 🛑heparin products, start non-heparin anticoagulation (not warfarin!), & send labs

4) Have a low threshold to look for thrombotic complications

REFs (1/2):

[1]theawkwardyeti.com/comic/blood-cl…
[2]runthelistpodcast.com/s/RTL_Thromboc…
[3]
[4]aruplab.com/testing/HIT
[5]nejm.org/doi/full/10.10…
[6]semanticscholar.org/paper/Heparin-…
[7]uptodate.com/contents/clini…
[8]nejm.org/doi/full/10.10…
[9]nejm.org/doi/full/10.10…

REFs (2/2):

[11]slideshare.net/skyecreativeon…
[12]
[13a]ashpublications.org/bloodadvances/…
[13b]jahjournal.org/viewimage.asp?…
[15]runthelistpodcast.com/s/RTL_Thromboc…

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