Essential Thrombocythemia with Renal Infarction: A Case-Based Review

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Essential Thrombocythemia with Renal Infarction: A Case-Based Review

Introduction

Essential thrombocythemia (ET), also known as essential thrombocytosis, is a rare chronic myeloproliferative neoplasm characterized by persistent elevation in platelet count without an identifiable reactive cause. Patients are often asymptomatic but may present with thrombotic or hemorrhagic complications. This column reviews a real-life case of renal infarction secondary to ET in a 72-year-old female, followed by an in-depth discussion on its etiology, pathophysiology, imaging findings, diagnosis, treatment, and prognosis.

Case Presentation

Patient: 72-year-old female
Chief Complaint: Left flank pain for 2 days
Physical Exam: Unremarkable
Lab Findings:

  • Platelet count: 652,000/µL (normal: 150,000–400,000/µL)

  • WBC and RBC: Within normal range

  • Previous platelet count: Unknown

Imaging:
Contrast-enhanced abdominal CT revealed a filling defect in the left renal artery and a perfusion defect in the left renal cortex, consistent with renal artery thrombosis and renal infarction.
→ [See Figure 1]

Genetic Testing: Positive for JAK2 V617F mutation

Final Diagnosis: Essential Thrombocythemia (ET) with renal infarction

Treatment: Initiation of hydroxyurea and aspirin. After 2 months, the patient reported improvement and normalization of platelet counts.

Figure

Figure 1. Axial contrast-enhanced CT demonstrating a filling defect (thrombosis) in the left renal artery and a wedge-shaped perfusion defect in the renal cortex, consistent with renal infarction.

Discussion

1. Cause and Etiology of Essential Thrombocythemia

Essential thrombocythemia is classified among the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), which also include polycythemia vera and primary myelofibrosis. It is driven primarily by mutations in hematopoietic stem cells leading to excessive megakaryocytic proliferation.

  • Common driver mutations:

    • JAK2 V617F (~60%)

    • CALR (~20–25%)

    • MPL (~5–10%)

Reactive thrombocytosis due to inflammation, iron deficiency, infection, or malignancy must be ruled out before making a diagnosis of ET.

2. Pathophysiology

The central pathophysiologic mechanism involves:

  • Hyperproliferation of megakaryocytes

  • Increased platelet production and turnover

  • Aberrant platelet activation, leading to:

    • Arterial thrombosis (e.g., stroke, myocardial infarction, renal infarction)

    • Venous thrombosis (e.g., deep vein thrombosis, portal vein thrombosis)

    • Microvascular disturbances (e.g., erythromelalgia, transient ischemic attacks)

The JAK2 mutation results in constitutive activation of the JAK-STAT signaling pathway, promoting unchecked hematopoietic proliferation.

3. Epidemiology

  • Incidence: ~1.2–3.0 per 100,000 persons annually

  • Peak Age: 50–70 years (but can affect younger adults)

  • Sex: Female predominance (2:1)

  • Thrombotic Risk: High in patients >60 years or with prior thrombosis

4. Clinical Presentation

While many patients are asymptomatic, symptomatic individuals may present with:

  • Thrombosis (e.g., stroke, coronary artery disease, renal infarction)

  • Hemorrhagic episodes (especially mucocutaneous)

  • Microvascular symptoms: Headache, dizziness, visual disturbances

  • Splenomegaly (30–40%)

  • Constitutional symptoms: Fatigue, weight loss

In this case, the patient presented with left flank pain due to renal infarction, a less common but recognized complication of ET-related thrombosis.

5. Imaging Features

Imaging studies are not diagnostic for ET but help identify complications:

  • CT with contrast is crucial for identifying arterial or venous thrombosis, as in this case.

  • MRI may assist in the evaluation of splenomegaly or cerebral infarcts.

  • Ultrasound/Doppler: Useful in assessing blood flow and ruling out portal or hepatic vein thrombosis.

6. Diagnosis

Diagnosis of ET is based on the 2016 WHO criteria:

  1. Platelet count >450,000/µL

  2. Bone marrow biopsy showing proliferation of megakaryocytes

  3. Exclusion of BCR-ABL1 (to rule out chronic myeloid leukemia)

  4. Presence of JAK2, CALR, or MPL mutation

Supporting tests:

  • Peripheral smear

  • Iron studies

  • JAK2 mutation analysis

  • BCR-ABL1 PCR

7. Treatment

The goals of treatment are to prevent thrombosis and hemorrhage while minimizing therapy-related side effects.

Risk Stratification:

  • Low risk: Age <60, no history of thrombosis, and no JAK2 mutation

  • Intermediate: Age >60 with no thrombosis

  • High risk: Age >60 with thrombosis or JAK2 mutation

Therapeutic Approaches:

  • Low-dose aspirin: All patients, unless contraindicated

  • Cytoreductive therapy:

    • Hydroxyurea (first-line in high-risk)

    • Anagrelide

    • Interferon-α (preferred in younger patients or during pregnancy)

8. Prognosis

  • Median survival: Over 20 years in low-risk patients

  • Risk of transformation:

    • To myelofibrosis: ~10–15%

    • To acute leukemia: <5%

Regular monitoring of platelet counts, thrombotic events, and medication side effects is essential.

Quiz

1. Which genetic mutation is most closely associated with the diagnosis in this patient?

A. BCR-ABL1
B. CTLA4
C. FLT3
D. JAK2
E. MYC

2. What is the most likely complication of untreated essential thrombocythemia?

A. Acute leukemia
B. Deep vein thrombosis
C. Osteoporosis
D. Iron overload
E. Hyperparathyroidism

3. What is the primary goal of treatment in essential thrombocythemia?

A. Cure the disease
B. Normalize bone marrow histology
C. Suppress all blood cell lines
D. Prevent thrombotic events
E. Increase white blood cell count

Answer & Explanation

1. Answer: D. JAK2
Explanation: The JAK2 V617F mutation is found in ~60% of ET cases and leads to constitutive activation of the JAK-STAT pathway, contributing to increased megakaryocytic proliferation and platelet production. 

2. Answer: B. Deep vein thrombosis
Explanation: Thrombosis is the most common complication in ET, occurring in both arteries and veins, including DVT, portal vein thrombosis, and myocardial infarction.

3. Answer: D. Prevent thrombotic events
Explanation: The main goal in managing ET is reducing thrombotic and hemorrhagic risk. Treatment is tailored according to risk stratification.

Conclusion

Essential thrombocythemia is a chronic but manageable hematologic malignancy. Though often indolent, serious complications like renal infarction, as illustrated in this case, can occur. Early recognition and appropriate therapy with aspirin and cytoreductive agents such as hydroxyurea can significantly improve outcomes. Integration of genetic testing, particularly for JAK2, is critical for diagnosis and management.

References

[1] T. Barbui, A. Finazzi, and A. Falanga, “Myeloproliferative neoplasms and thrombosis,” Blood, vol. 117, no. 22, pp. 5399–5407, 2011.
[2] R. Tefferi and A. Vainchenker, “Myeloproliferative neoplasms: Molecular pathophysiology, essential thrombocythemia, and therapeutic management,” The New England Journal of Medicine, vol. 371, pp. 2319–2331, 2014.
[3] S. Rumi et al., “Clinical effect of JAK2 V617F versus CALR mutation in essential thrombocythemia,” Blood, vol. 123, no. 10, pp. 1552–1555, 2014.
[4] A. Cervantes, “Modern management of myeloproliferative neoplasms,” Hematology Am Soc Hematol Educ Program, pp. 284–291, 2011.
[5] M. Griesshammer, “Essential thrombocythemia: Diagnosis, clinical course, and treatment,” Transfusion Medicine and Hemotherapy, vol. 40, pp. 731–740, 2013.
[6] E. Reilly and B. Mesa, “Current challenges in essential thrombocythemia and polycythemia vera: risk stratification and management,” Leukemia & Lymphoma, vol. 55, pp. 2062–2071, 2014.
[7] D. C. Silver, “Essential thrombocythemia: 2023 update on diagnosis, risk stratification, and treatment,” Leukemia Research, vol. 122, 106987, 2023.

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