« The present study reveals a JAK2V617F mutation prevalence (12.2%) in a stroke population that is substantially higher compared to the background population (GESUS) in the same region of Denmark, using the same assay.
The GESUS study showed a JAK2V617F mutation prevalence of 3.1% and for individuals above age 60 a prevalence of 4.1%. Given the fact that the JAK2V617F mutation is present in patients with and without cytosis, our results highly suggest that the JAK2V617F mutation per se is a thrombogenic factor in ischemic stroke.
This calls for an exploration of the pathophysiological mechanisms and potential treatments to prevent future thrombotic events in individuals with and without cytosis »
Consistent with our known risk for stroke, TIA etc. But they suggest the risk is for even super low VAF, down to 0.002%.
-A glaring item in there is " Only three (of 6) patients (with elevated MPN like bloods) had continuously elevated blood cell levels after 1 month." One had VAF of 14%. So these three got a sort of CHR (complete hem response) with no treatment at all.
My HCT and WBC was resolving over 1 month after Dx before I started HU, and I had blood VAF of 14% like one of the patients above. Maybe it was this sort of thing. But PLT did not resolve without HU.
It seems that the allele burden is not a direct causative factor for stroke. Some other factors are involved, especially endothelial cells.
“In summary, our data show that the bleeding diathesis seen in a number of MPN patients may be due to the expression of JAK2V617F in Endothelial Cells (ECs), in addition to hematopoietic cells. We have identified a potential mechanism whereby mutant JAK2 may contribute to the bleeding phenotype via regulation of VWF. However, it is highly likely that a number of other, as yet unidentified, mechanisms contribute to EC-mediated thrombohemorrhagic events in pnas.org/doi/10.1073/pnas.1...
It may be the answer to a question I have had, but have never asked nor seen addressed prior to this, which is:
Why do MPN patients appear to be at higher risk for both bleeding events [hemorrhage] and clotting events [thrombosis]?
Usually, the increased propensity for developing spontaneous clots would also prevent bleeding incidents, but somehow it doesn't seem to be the case in MPN patients.
Speaking of which, I have fallen twice in past few months, both of which injured my right shoulder, and both of which caused ecchymosis [blood loose in the subcutaneous tissues] and pain in different areas of my shoulder. Ecchymosis is different from bruising- which is localized in the subcutaneous tissue underlying of an impact injury, because ecchymosis can be observed to progress dependently under the influence of gravity, and because it is an artifact or effect of bleeding in deeper tissues [muscle, periosteum, or in my case joint, it can take several days to present.
In both cases, I was injured on a Saturday, and the discoloration only became evident on the following Monday or Tuesday, and evolved [both in the area affected and in color- from red-purple to brownish-green and yellowish] over the course of approximately a week to 10 days before slowly fading away.
The only reason I'm bring this up in response to Manouche's post is that I have had more than a few similar injuries in the past- some of which were markedly more severe, and yet I never had anywhere the degree or apparent duration of the resultant ecchymosis.
In fact, until 7/2020 [ not long prior to my PV diagnosis], when I injured my right knee, the only time I ever had ecchymosis was post-operatively after my left knee replacement.
Has anyone else noticed an increased amount of bleeding, bruising, or ecchymosis occurring with minor injuries, which seems like it might be related to their MPN diagnosis ?
BTW, it's not because of taking aspirin because I started doing that long before my diagnosis.
« Why do MPN patients appear to be at higher risk for both bleeding events [hemorrhage] and clotting events [thrombosis]? »
We are at higher risk of all types of bleeding aneurysms. Some may leak while others may rupture. Clotting events could therefore be associated with bleeding events.
Too right, but honestly, it is really bizarre to be at risk for both at the same time, because the hypercoagulation [coagulopathy w/ increased clotting] disorder should preclude us from also having increased risk of hemorrhagic complications.
Thus it's not just our blood that is broken, although it seems to start there- it is becoming more and more evident that that's just the starting [or tipping] point,
From Manouche's article that implicates endothelial cells, to mine, wherein the subtext for Figure 1 states: "Somatic JAK2 V617F mutations are acquired in the bone marrow at the hematopoietic stem cell (HSC) level. The resulting bone marrow-derived JAK2 V617F-mutated macrophages infiltrate the abdominal aorta, where they demonstrate increased levels of two genes critical for aortic aneurysm formation, matrix metalloproteins 2 and 9 (MMP-2, MMP-9). This expression and the resulting AAA are decreased upon treatment with a JAK inhibitor (JAK2i), ruxolitinib, confirming that the development of AAA is mediated by JAK2 V617F", and also that MPN's are closely associated with atherosclerotic disease [ASCVD], more evidence that we have a fully systemic disorder [not just a blood or bone marrow dysfunction] continues to surface.
This has implications on what other tests [like abdominal ultrasounds] we should have on a more regularly scheduled basis to monitor for the changes involved in them.
If a Jak-i helps, it should follow that reducing Jak2 alleles also helps since both improvements leave some Jak2 allele effects in place, if fewer. But the article seems to say that having even vanishingly small VAF loads leads to the cardio risk.
On the AAA, I'm at double risk since my mother had a severe one and has a sort of fabric artery. I do ask Drs to check; this thread makes it more pressing. My Dr has said that on a slim person it is easy to check manually. But I always hear about modern medical training having less of this type of hands on experience.
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ASH paper re younger MPN patients, dx age <= 40
Specialist 2nd visit 
Gene mutations positive or not? 
