The significance of JAK2-positive test results in a healthy patient

Here’s how readers responded to a You Make the Call question about the significance of JAK2-positive test results in a healthy patient.

Disclaimer: ASH does not recommend or endorse any specific tests, physicians, products, procedures, or opinions, and disclaims any representation, warranty, or guaranty as to the same. Reliance on any information provided in this article is solely at your own risk.

I think you are obligated to perform a bone marrow biopsy. And a CT scan to look for splenomegaly.

Susan E. Wheaton, MD
Golden Valley, MN

  1. Get a good clinical and family history.
  2. Warn the patient regarding risk of thrombosis.
  3. See the patient once yearly for monitoring.

Kelty R. Baker, MD
Houston, TX

Check complete blood count (CBC) every six months. No other action is needed unless there are significant changes in CBC or a thrombotic event.

Majid Shojania, MD
Winnipeg, Canada

JAK2 mutation should not be present in the normal population; it is a sign of a hematologic condition but not specific. It is more common in patients with polycythemia vera or myelofibrosis but also can be seen in those with myelodysplastic syndromes (MDS) and leukemias. If counts are normal and the patient is asymptomatic, I would perform a general physical exam and basic laboratories, including CBC, every six to 12 months.

William Caceres, MD
San Juan VA Medical Center
Río Piedras, Puerto Rico

A JAK2 mutation confers a higher tendency for thrombosis if the patient is young. I would consider observation in an older patient, with the presumed development of a myeloproliferative neoplasm (MPN) or atypical MDS in the future. I would also consider aspirin.

Antoine Sayegh, MD
Roseville, CA

No treatment necessary. Prognostic significance is unclear. I’d follow the patient, including annual CBC, to see if anything develops.

Alan Feiner, MD
Denver, CO

It is possible to see clonality without disease. I would not do serial genetic testing but would follow symptoms and obtain routine bloodwork. I would also consult with the physician who ordered the JAK2 test.

Russel Kaufman, MD
Durham, NC

I would monitor the counts every six months for a year or two; if normal, I would continue only annual CBC as part of health maintenance.

Mary Klix, MD
Anchorage, AK

Do nothing.

Enrique Davila, MD
Miami, FL


George T. Conklin, MD
Houston, TX

A JAK2 mutation may be a harbinger of a future MPN. I would use an MPN symptom assessment form to carefully document if the patient already has any symptoms. A physical exam to evaluate for splenomegaly should also be done. Assuming no treatment is indicated, I would consider following the patient every six months with an exam and a CBC.

Rahul R. Naik, MD
Santa Clarita, CA

Vascular endothelial expression of JAK2V617F can increase the thrombotic risk through increased p selectin expression. This might be the reason for the increased occurrence of thrombosis, especially in splanchnic vessels, in those with JAK2V617F positivity without an overt MPN. Evidence also suggests that hydroxyurea can effectively reverse the thrombotic risk by reversing the p selectin expression. (Guy A, et al. Vascular endothelial cell expression of JAK2V617F is sufficient to promote a pro-thrombotic state due to increased P-selectin expression. Haematologica. 2019; 104:70-81.)

However, whether hydroxyurea can be used as prophylaxis to prevent thrombosis in such circumstances is controversial, and existing guidelines have not incorporated this practice.

Therefore, I believe management of each patient must be individualized, considering their other vascular risk factors and age. I would use hydroxyurea in selected patients with positive JAK2V617F without thrombosis or MPN.

Thamudika Vithanage, MBBS, MD
Panadura, Sri Lanka

Repeat the test. It may be a false positive. I had such a patient, whose age was 35.

Joel H. Lundberg, MD
Fond du Lac, WI

Don’t act on the abnormal JAK2 immediately. Close monitoring of the patient with CBCs and for thrombotic events is required. Frequency of visits may be influenced by factors such as age and added risk for venous thromboembolism, including obesity.

David Osafo, MD
Ruston, LA

I did this years ago by mis-clicking on the order sheet. Patient informed, no treatment done. All is well at this time.

Rick Grapski, MD
Knoxville, TN

I would consider the age and perhaps the allelic load of the mutation. I believe the patient should be informed and followed every six months and then yearly with a  CBC. If the allelic load is >10 percent and the age >40 years, I would consider this patient at risk of thrombosis, especially if she or he has acquired or inherited thrombophilia, hyperlipidemia, diabetes, hypertension, or has a history of smoking. In that case, I would order a bone marrow biopsy to establish the diagnosis of a myeloproliferative disorder (including pre-MPD). If no contraindications, I would likely advise low-dose aspirin, especially to patients >60 years old. Statin will be an advantage even with mild hyperlipidemia.

And I would study thoroughly the Danish population data on JAK2+ in “healthy” individuals by researchers led by Hans C. Hasselbalch.

Jiri Schwarz, MD, PhD
Prague, Czechia