Heme @tony_breu-style tweetorial (part 2):
Thrombocytopenia in #COVID19
While lymphopenia takes most of the hematology spotlight on the #COVID stage (80+%), accompanied #thrombocytopenia is also seen in ~36% of cases.
Why it occurs is equally as interesting.
Thrombocytopenia in #COVID19
While lymphopenia takes most of the hematology spotlight on the #COVID stage (80+%), accompanied #thrombocytopenia is also seen in ~36% of cases.
Why it occurs is equally as interesting.
Why does thrombocytopenia occur in SARS Cov2?
Again, let’s review.
Platelets aren’t just little clotty bits that only serve to stop hemorrhage.
These little guys are mighty in a number of different ways.
#clottybits
Platelets aren’t just little clotty bits that only serve to stop hemorrhage.
These little guys are mighty in a number of different ways.
#clottybits
From what cells do platelets arise?
Right! Megakaryocytes (MK) are the mother of all platelets.
As the name implies, these cells are HUGE and easily identified by their large granular cytoplasm and lobulated nucleus.
As the name implies, these cells are HUGE and easily identified by their large granular cytoplasm and lobulated nucleus.
How long does it take for a platelet to mature?
Right again. Platelets take approximately 5-7 days to mature in circulation.
This is why we typically wait 5-7 days post-aspirin for an elective procedure.
It’s also why stored platelets have a shelf-life of ~5 days.
This is why we typically wait 5-7 days post-aspirin for an elective procedure.
It’s also why stored platelets have a shelf-life of ~5 days.
Where do platelets mature?
Platelets don’t only mature within the bone marrow.
Immature platelets can be released early in times of physiological stress or thrombocytopenia. This is partly why giant platelets are seen in conditions like ITP!
Some of maturation is also thought to occur in the lung:
Immature platelets can be released early in times of physiological stress or thrombocytopenia. This is partly why giant platelets are seen in conditions like ITP!
Some of maturation is also thought to occur in the lung:
MK travel to the lung, where they form proplatelets.
Platelet release occurs in the bone marrow, but evidence suggests that platelet release from proplatelets occurs mainly in the pulmonary circulation.
...this makes the lungs the birthplace of many of your body’s platelets!
Platelet release occurs in the bone marrow, but evidence suggests that platelet release from proplatelets occurs mainly in the pulmonary circulation.
...this makes the lungs the birthplace of many of your body’s platelets!
Additionally, young platelets have the ability to cleave themselves and form more platelets.
This is why older platelets tend to be smaller than young, giant platelets!
Therefore part of the maturation process also occurs in the peripheral circulation as well.
This is why older platelets tend to be smaller than young, giant platelets!
Therefore part of the maturation process also occurs in the peripheral circulation as well.
Other platelet functions (future tweetorial):
1. An important role in immunity (via Toll-like receptors)
2. Autophagy (cell self-clearance)
3. Microparticle secretion (>95% of micro-particles from plts)→alter / modulate function of other cells
4. Cancer metastasis/spread (!)
1. An important role in immunity (via Toll-like receptors)
2. Autophagy (cell self-clearance)
3. Microparticle secretion (>95% of micro-particles from plts)→alter / modulate function of other cells
4. Cancer metastasis/spread (!)
In my previous tweetorial, we discussed how SARS Cov2 infects cells via the ACE2 receptor.
One cell that expresses ACE2 in high amounts is the vascular endothelium.
Thus vascular endothelial infection and destruction may compound oxidant-stress-induced endothelial injury:
One cell that expresses ACE2 in high amounts is the vascular endothelium.
Thus vascular endothelial infection and destruction may compound oxidant-stress-induced endothelial injury:
Endothelial infection/injury → subendothelial collagen exposure → platelet aggregation → thrombosis → platelet consumption
Therefore, given what we’ve discussed, in COVID-19 the mechanism for thrombocytopenia patients is likely multifactorial:
Therefore, given what we’ve discussed, in COVID-19 the mechanism for thrombocytopenia patients is likely multifactorial:
1. Endothelial damage → plt activation → aggregation/thrombosis → plt consumption / low grade DIC (⬆️fibrin deposition/dissolution = why D-dimer elevated)→ chronic thrombocytopenia
2. Lungs = site of platelet release + lung injury / ARDS → decreased MK and proplatelets
2. Lungs = site of platelet release + lung injury / ARDS → decreased MK and proplatelets
The more these occur, the more likely severe disease is present.
Thus, like lymphopenia, the presence of thrombocytopenia portends an increased risk of severe disease.
Lippi et al. observed that thrombocytopenia is associated with a >3-fold enhanced risk of severe COVID-19.
Thus, like lymphopenia, the presence of thrombocytopenia portends an increased risk of severe disease.
Lippi et al. observed that thrombocytopenia is associated with a >3-fold enhanced risk of severe COVID-19.
Predictably, more severe thrombocytopenia (~50k) or less was also shown to be associated with mortality.
A subgroup analysis comparing patients by survival, found an even lower platelet count was observed with mortality.
(WMD, −48 × 109/L; 95% CI, −57 to −39 × 109/L)
A subgroup analysis comparing patients by survival, found an even lower platelet count was observed with mortality.
(WMD, −48 × 109/L; 95% CI, −57 to −39 × 109/L)
So, to summarize:
Why does thrombocytopenia occur in SARS Cov2?
Why does thrombocytopenia occur in SARS Cov2?
From what cells do platelets arise?
How long does it take for a platelet to mature?
Where do platelets mature?
TL;DR:
▶️Platelets = more than clotty bits
▶️Platelets take 5-7 days to mature; this partly occurs in the lungs
▶️Mechanism = multifactorial: decreased pulmonary MK, capillary injury / DIC / consumption
▶️Thrombocytopenia is associated with a >3-fold risk of severe COVID-19
▶️Platelets = more than clotty bits
▶️Platelets take 5-7 days to mature; this partly occurs in the lungs
▶️Mechanism = multifactorial: decreased pulmonary MK, capillary injury / DIC / consumption
▶️Thrombocytopenia is associated with a >3-fold risk of severe COVID-19
