Thread by @mghmedres

1/ We have a special tweetorial by PGY-1 @kevincmillerMD !

We are here to talk about @DGlaucomflecken 's favorite organ: THE SPLEEN! ♥️Or rather, what happens in its absence!

Is having a splenectomy a risk factor for thrombosis ❓🤔

@MedTweetorials #MedTwitter

2/ First, the spleen is a complex, beautiful & underrated organ. There, we said it. 🤷

It’s so great that 15% of people have an extra accessory spleen

The spleen has 3 general components: A marginal zone & 2 pulps.

3/ ↔️Marginal Zone: Free-flowing transit space for immune cells, where antigens are captured by dendritic cells and B cells (i.e. as APCs) prior to migration to white pulp.

⚪️White Pulp: Physically exclusive lymphoid tissue where T and B cells mature 👶👧👩👵

4/ 🔴Red Pulp:
(1) Diverse immune effector cells reside & intercept pathogens 🗡️
(2) Plasma cells (after graduation from white pulp 🎓) make IgG
(3) Senescent RBCs are squeezed between cords & venous sinuses, then eaten by macrophages if they get stuck
(4) Iron is recycled ♻️

5/ Okay, so the spleen does a lot.

When it’s removed or dysfunctional, we are keenly aware of the risk for overwhelming infection with encapsulated bacteria like S. pneumoniae 🦠, or even more rare organisms like Capnocytophaga canimorsus 🐶.

But what about thrombosis?

6/ There is a well-documented increased risk of portal vein thrombosis in the short-term after splenectomy (PMID: 15650628).

This is easy to envision; perhaps it’s related to local inflammation and/or venous stasis post-op.

7/ But there is also data showing splenectomy increases the risk of both arterial & venous thrombosis, including later after the spleen is but a distant memory (PMID: 19636061 & 23637127).

8/ This thrombosis risk been reported in several disease states where splenectomy is commonly performed:
✅thalassemia
✅sickle cell disease
✅hereditary spherocytosis
✅hereditary stomatocytosis
✅immune thrombocytopenic purpura

9/ One could argue that these patient populations are unique, as they have a dysfunctional hematologic system 🩸.

Perhaps those who medically require splenectomy have an elevated risk of thrombosis for other reasons (i.e. splenectomy is a confounder 🧐).

10/ However, there is a host of data showing that splenectomy is associated with increased risk of thrombosis even for people w/o underlying hematologic disorders!

11/ The 1st report suggesting this was in 1977 Lancet paper by Robinette & Fraumeni (Yes the one behind Li-Fraumeni syndrome). This paper described excess mortality from ischemic heart disease in American soldiers who underwent splenectomy for trauma in WWII. (PMID: 69206)

12/ A more recent study of 8149 veterans who underwent splenectomy showed an ⬆️ incidence of DVT/PE, including when examining only a subset of patients who had splenectomy in the setting of trauma. However, the data for arterial thrombosis was so-so.
(PMID: 24056815)

13/ So why could splenectomy potentially elevate thrombosis risk?

A review by Crary & Buchanan suggests there could be many factors, including thrombocytosis, hemoconcentration, lack of clearance of senescent RBCs, ⬇️ of protein C/S, & ⬆️ thrombin, to name a few.

14/ Interestingly, a recent study using a mouse model 🐭showed splenectomy
⬆️ procoagulant platelet microparticles
⬆️ leukocyte–platelet aggregates
⬆️ anionic phospholipids in thrombi, which was associated with delayed thrombus resolution. (PMID: 24584745)

15/ In summary

🔴A Splenectomy has been associated with an ⬆️ risk of thrombosis (even in the absence of a known underlying heme dz)
🔴A possible mechanism is ⬆️ procoagulant platelet microparticles & ⬇️ thrombus resolution.