JAK2-positive erythrocytosis presenting with left occipital infarction in a young adult: a case report from a resource‑limited setting

Abstract

Introduction:

Polycythemia-spectrum disorders carry thrombotic risk; in young adults, stroke may be the first manifestation. We report a young male with JAK2-positive erythrocytosis highly suggestive of polycythemia vera, emphasizing diagnostic framing and pragmatic management in a resource-limited setting.

Case presentation:

A 35-year-old former smoker presented with three days of right-sided body tingling. Examination was nonfocal. Laboratory testing revealed hemoglobin 19.3 g/dL and hematocrit 61.4%. Noncontrast computed tomography obtained on Day 3 showed a small, ill-defined hypodensity in the left occipital lobe, consistent with acute infarction. JAK2 V617F mutation was detected; erythropoietin (EPO) was within the normal range (20 mU/L). In the absence of marrow histology and subnormal EPO, the working diagnosis was JAK2-positive erythrocytosis with a syndrome highly suggestive of PV. Treatment comprised phlebotomy, low-dose aspirin, hydroxyurea, and statin therapy.

Discussion:

The case highlights pragmatic stroke evaluation in a young adult, where MRI and comprehensive vascular work-up were not fully available. We discuss pathophysiology, differential diagnoses, and how resource constraints impact certainty and generalizability.

Conclusion:

Ischemic stroke can be the initial presentation of JAK2-positive erythrocytosis consistent with polycythemia vera. Careful framing of diagnostic certainty, early hematocrit control, antithrombotic therapy, and risk-factor optimization are key, especially where resources are limited.

Introduction

Ischemic stroke in younger individuals presents a unique diagnostic challenge, often stemming from etiologies distinct from those observed in older adults. Unlike the predominant atherosclerotic burden in older people, strokes in younger adults are frequently attributed to nonatherosclerotic vasculopathies, arterial dissections, inherited or acquired thrombophilia, and other less common conditions^[1]. A significant proportion of these cases, up to 4%, are linked to underlying hematologic disorders or coagulopathies that predispose patients to cerebral ischemia^[2].

HIGHLIGHTS

• Acute ischemic stroke as the first presentation of JAK2-positive erythrocytosis in a young adult, highlighting an uncommon initial manifestation of polycythemia vera (PV).

• Diagnostic reasoning under resource constraints, where advanced imaging and comprehensive vascular/thrombophilia workup were partially unavailable.

• Importance of cautious diagnostic framing, given subnormal EPO levels and lack of bone marrow histology, demonstrating PV-spectrum disease management.

• Clinical relevance for low- and middle-income settings, illustrating how hematologic and neurologic complications can be recognized and treated with limited resources.

• Pragmatic management approach with phlebotomy, low-dose aspirin, hydroxyurea, and statin therapy, emphasizing hematocrit control and thrombosis prevention.

The JAK2 V617F mutation is a well-recognized driver of clonal erythropoiesis in myeloproliferative neoplasms. While classical polycythemia vera (PV) often presents with panmyelosis (elevated red cells, white cells, and platelets), thrombosis can occur even in cases with isolated erythrocytosis. Studies indicate that JAK2 V617F positivity confers a prothrombotic state independent of leukocytosis or thrombocytosis, likely mediated via endothelial activation, increased blood viscosity, and subtle platelet activation. Thus, isolated JAK2-driven erythrocytosis may be sufficient to predispose young adults to ischemic events such as stroke^[3]. PV is a chronic myeloproliferative neoplasm characterized by the overproduction of red blood cells, white blood cells, and platelets. This hematologic dyscrasia is strongly associated with the JAK2 V617F gene mutation, which drives uncontrolled cellular proliferation, leading to increased blood viscosity and a heightened risk of thrombotic events^[4]. PV can manifest with a variety of symptoms, including fatigue, headache, dizziness, tinnitus, vision changes, and aquagenic pruritus; however, thrombosis remains the leading cause of morbidity and mortality^[5,6]. Thrombotic complications are reported as the initial symptom in 12%–49% of PV patients and contribute to 20%–40% of deaths^[7]. Notably, primary ischemic stroke occurs in approximately 16.2% of PV cases, and cerebral infarction has been reported as the first manifestation of PV in the same proportion^[8,9].

We report a case of young‑onset ischemic infarction in the setting of JAK2‑positive erythrocytosis, highlighting diagnostic framing under contemporary WHO/ICC criteria and pragmatic management where resources are limited.

Methodology

This case has been reported in accordance with the SCARE 2025 checklist^[10].

Case presentation

A 35‑year‑old man from the Terai region of Nepal, a former smoker and former alcohol consumer, with a 2‑year history of seizure disorder on levetiracetam, presented with 3 days of intermittent tingling over the right face and body. Symptoms were sudden in onset, nonprogressive, and subjectively improved over several hours; there was no weakness, no objective sensory loss, and no visual complaints.

On presentation, the patient was alert and oriented. Blood pressure was 130/90 mmHg; other vitals and systemic examination were within normal limits. Neurological examination, including higher functions, cranial nerves, motor, sensory, reflexes, coordination, and gait, was nonfocal; no meningeal signs.

Laboratory results (Table 1): hemoglobin 19.3 g/dL, hematocrit 61.4%, WBC 12 000/mm³, platelets 393 000/mm³, random plasma glucose 142 mg/dL, urea 13 mg/dL, creatinine 0.4 mg/dL, sodium/potassium 143/5.0 mEq/L, total calcium 9.03 mg/dL, ferritin 28.9 ng/mL. Additional testing lipids, liver function tests, thyroid profile, vitamin D, vitamin B12 were within local reference ranges.

Table 1.

Laboratory tests

Test	Result
Hemoglobin	19.3 g/dL
Total leukocyte count (TLC)	12,000/mm3
Platelets	393,000/mm3
Packed cell volume (PCV)	61.4%
Random blood sugar (RBS)	142 mg/dL
Urea	13 mg/dL
Creatinine	0.4 mg/dL
Sodium/Potassium	143/5.0 mEq/L
Total calcium	9.03 mg/dL
Serum ferritin	28.9 ng/mL

Neuroimaging: noncontrast computed tomography (NCCT) of the head performed on Day 3 from symptom onset demonstrated a small, ill-defined cortico-subcortical hypodense focus in the left occipital lobe (≈19 HU), consistent with an acute infarction (Fig. 1a and 1b). Both axial and sagittal reconstructions were obtained, confirming the location and extent of the lesion. Multiplanar or thin-slice imaging beyond these views was not acquired.

Figure 1.

NCCT of the head demonstrating acute infarction in the left occipital lobe. (A) Axial NCCT image showing a small, ill-defined cortico-subcortical hypodense lesion in the left occipital lobe. The black arrow indicates the area of reduced attenuation (≈19 HU), consistent with an acute ischemic infarct. (B) Sagittal reconstruction confirming the location and extent of the occipital hypodensity (black arrow).

Hematologic evaluation: given erythrocytosis, EPO and JAK2 testing were obtained (Table 2). EPO was 20 mU/L (within the local laboratory reference range); JAK2 V617F was detected. Bone marrow biopsy was not pursued due to patient preference and cost/resource considerations.

Table 2.

Confirmatory tests

Test	Result
Erythropoietin	20 mU/L (within normal range)
JAK2 V617F	Positive

Baseline ECG showed sinus rhythm. Transthoracic echocardiography revealed preserved systolic function without significant valvular disease and no intracardiac thrombus by visual assessment; bubble study for patent foramen ovale (PFO) and extended ambulatory rhythm monitoring were unavailable. Carotid and vertebral duplex studies, together with comprehensive inherited and acquired thrombophilia testing, were unremarkable, although the original imaging files were unavailable for review.

The patient underwent therapeutic phlebotomy (total four units over two admissions) targeting hematocrit <45%, and was started on low‑dose aspirin, hydroxyurea, and atorvastatin. He was discharged clinically stable with counseling on hydration, smoking abstinence, and return precautions.

Follow‑up and outcomes: the patient was reviewed at 2 weeks, 6 weeks, and approximately 3 months with no new focal neurologic symptoms. Hematocrit decreased from 61.4% to approximately 45% after phlebotomy and cytoreduction. No major bleeding was reported. Serial hematology monitoring and detailed vascular imaging were variably limited by cost and access. TIMELINE: (Fig. 2)

Figure 2.

Timeline of clinical events and diagnostic evaluation Summary of the patient’s clinical course, including symptom onset (Day 0), neuroimaging on Day 3, initial laboratory evaluation (hemoglobin/hematocrit, JAK2 positivity, and EPO level), therapeutic phlebotomy sessions during weeks 1–2, initiation of aspirin, hydroxyurea, and statin therapy, and follow-up assessments at weeks 2, 6, and 12 demonstrating hematocrit trajectory and clinical stability.

Case timeline: Day 0-symptom onset; Day 3-NCCT (left occipital hypodensity); Week 1-labs (Hb/Hct, JAK2 +, EPO within range); Weeks 1–2 two phlebotomy sessions ×4 units total; start aspirin/hydroxyurea/statin; Week 2, 6, 12-clinic follow‑up and hematocrit trajectory.

Diagnostic reasoning and differentials

In young‑onset ischemic symptoms, our differential included arterial dissection, cardioembolism, hypercoagulable states, vasculitis, toxin‑mediated ischemia, migraine aura, and functional neurologic disorders. Work‑up completeness was constrained by resources. The marked erythrocytosis with JAK2 positivity provided a unifying prothrombotic substrate; however, causality cannot be proven. The normal EPO argues against classic secondary EPO‑driven erythrocytosis; there was no clinical evidence of chronic hypoxia, high‑altitude residence, or overt renal/hepatic neoplasm. Comprehensive thrombophilia and vascular imaging were normal.

Clinicoradiologic correlation

Occipital cortical lesions classically cause contralateral homonymous visual field deficits. The absence of visual symptoms here likely reflects small lesion volume, potentially sparing the primary visual cortex, or represents radiologic–clinical dissociation. We acknowledge this as a limitation of the case’s explanatory power and of NCCT’s modest sensitivity for early/small infarcts.

Management and alignment with guidance

Given the stroke presentation, we pursued phlebotomy to target Hct <45%, low‑dose aspirin for arterial thrombosis prevention, hydroxyurea as a pragmatic first‑line cytoreductive agent in our setting, and a statin for vascular risk modification, acknowledging pleiotropic antithrombotic/anti‑inflammatory effects. These choices align with broad European LeukemiaNet principles for PV‑spectrum disease while recognizing the diagnostic framing (JAK2‑positive erythrocytosis) and resource constraints.

Outcomes and follow‑up plan

Available follow‑up indicates clinical stability without new neurologic deficits over the ensuing months. Ongoing care focuses on hematocrit monitoring (goal <45%), cytoreductive therapy tolerance and dose adjustments, and secondary stroke prevention, including BP, lipids, smoking abstinence, glycemic status with planned HbA1c/fasting glucose given RBS 142 mg/dL, and physical activity.

Patient perspective

The patient expressed concern about stroke recurrence and the financial burden of advanced imaging and tests. He agreed with the management plan, prioritizing hematocrit control and antithrombotic therapy, and consented to share his experience to highlight resource‑related challenges.

Discussion

We present a case of JAK2‑positive erythrocytosis highly suggestive of polycythemia vera that initially presented as an acute ischemic infarct, a rare but significant manifestation of this myeloproliferative neoplasm. Contemporary WHO/ICC frameworks generally require (i) elevated hemoglobin/hematocrit, (ii) bone‑marrow panmyelosis, and (iii) JAK2 mutation; or two major criteria plus subnormal erythropoietin as a minor criterion. In this patient, bone‑marrow histology was not obtained and EPO was not subnormal, precluding formal fulfillment of classic PV thresholds^[11]. We therefore adopt cautious wording and discuss management using PV‑spectrum principles. Acute ischemic cerebrovascular accident was diagnosed via NCCT, which revealed an acute infarct in the left occipital lobe. Although NCCT has a low sensitivity (39%) for detecting acute ischemic changes, its high specificity (100%) makes it a valuable tool for initial assessment^[12].

We considered secondary erythrocytosis from chronic hypoxia (no high‑altitude residence, normal resting oximetry, no clinical cardiopulmonary disease), renal/hepatic neoplasms (no suggestive features; imaging not pursued due to cost), exogenous androgens/EPO (denied), smoking‑related carboxyhemoglobinemia (former smoker >2 years), and obstructive sleep apnea The normal EPO level argues against classic EPO‑driven secondary erythrocytosis, while JAK2 V617F supports a clonal process.

In young adults presenting with ischemic stroke, a thorough evaluation is crucial to exclude other potential etiologies of stroke. PFO is a known contributor to a small percentage of cryptogenic strokes, and cervical artery dissection is another important cause of ischemic stroke in this demographic. Furthermore, substance abuse, particularly cocaine use, is a recognized risk factor for stroke in young adults^[13]. To meticulously rule out these and other pathologies, including carotid artery and cardiac conditions, our patient underwent comprehensive investigations, including carotid artery Doppler ultrasonography and echocardiography. Importantly, the patient denied any history of cocaine or illicit drug use.

Our case shares similarities with previously reported cases of PV presenting with acute neurological events. For example, a comparable case described by Zoraster et al detailed a 57-year-old right-handed Caucasian man who presented with acute right-handed clumsiness and was subsequently diagnosed with PV^[14]. These reports underscore the importance of considering myeloproliferative neoplasms in the differential diagnosis of ischemic stroke, even in the absence of overt hematological abnormalities at initial presentation.

Preventing thrombotic events is a cornerstone of PV management, which is typically achieved by maintaining a hematocrit level below 45%^[15]. Treatment strategies are individualized based on the patient’s thrombotic risk, which is primarily determined by age and history of thrombosis. Low-risk patients are generally managed with phlebotomy and low-dose aspirin therapy. In contrast, high-risk patients require cytoreductive agents, with hydroxyurea and recombinant interferon-alpha serving as first-line therapies. Interferon and ruxolitinib are considered second-line options for patients who are intolerant to or have an inadequate response to hydroxyurea^[16].

In our patient, despite being under 60 years of age, the presentation with an acute ischemic stroke placed him in a higher-risk category for future thrombotic events. Consequently, he received four units of phlebotomy during two hospital admissions to maintain his hemoglobin level at 14.0 g/dL and was initiated on hydroxyurea. Additionally, statins have pleiotropic effects, including antithrombotic, antiproliferative, proapoptotic, and antiangiogenic properties, suggesting their potential benefits in PV management^[17,18].

Limitation

Diagnostic certainty is limited by lack of marrow histology, normal EPO, incomplete vascular/thrombophilia work-up, and absence of MRI. These constraints limit generalizability but mirror realities in many low- and middle-income settings. additional multiplanar reconstructions were not performed.

Conclusion

In a young adult with stroke, JAK2-positive erythrocytosis should prompt consideration of PV-spectrum disease, accompanied by diagnostic humility when marrow and full vascular work-up are unavailable. Early hematocrit control and antithrombotic therapy remain central; transparent documentation of limitations is essential.

Ethical approval

Not applicable.

Consent

Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal upon request.

Sources of funding

The authors received no financial support for the research, authorship, or publication of this case report.

Author contributions

S.P.: study concept or design, interpretation, writing the paper; B.K.: study concept or design, interpretation, writing the paper; S.P.: Study concept or design,interpretation, writing the paper; A.N.: study concept or design, interpretation, writing the paper; U.B.: study concept or design, interpretation.

Conflicts of interest disclosure

The authors have no conflict of interest.

Guarantor

Sandip Pandey.

Research registration unique identifying number (UIN)

Name of registry: NA; UIN: NA; hyperlink to your specific registration (must be publicly accessible and will be checked).

Provenance and peer review

Not commissioned, externally peer-reviewed.

Data availability statement

Datasets are publicly available.