Abstract
Platelet counts in reactive thrombocytosis rarely exceed 1000 × 109/L. We present the case of a male patient, aged 80 years, with quiescent rheumatoid arthritis who was found to have a platelet count of 1011 × 109/L on routine laboratory testing. The patient was initially asymptomatic but developed leukocytosis to 23.1 × 109/L on hospital day 2. Diagnostic work-up revealed obstructive nephrolithiasis and pyelonephritis, and the thrombocytosis and leukocytosis gradually resolved with empiric antibiotic treatment and ureteral stent placement. Tests for myeloproliferative disorders, including JAK-2V617F mutation, BCR-ABL for chronic myeloid leukemia and acute lymphocytic leukemia, and myeloproliferative neoplasms (MPL/CALR), were negative. Physicians should be aware that in rare cases reactive thrombocytosis can exceed 1000 × 109/L, and that markedly elevated platelet counts in the setting of urinary tract infections may be an early sign of obstructive uropathy.
Thrombocytosis can be caused by either reactive or autonomous processes. The mechanism of reactive thrombocytosis secondary to infection and inflammation has been well documented. Platelet production can be driven by interleukin-6, cytokines, and catecholamines in infectious and inflammatory states.1 In particular, interleukin-6 stimulates hepatic production of thrombopoietin, which thereby directly stimulates megakaryocyte proliferation. Moreover, evidence suggests that platelets play a role in amplification of inflammatory and immune responses in chronic inflammation.2 However, infection is not necessarily accompanied by thrombocytosis. A 2019 retrospective study of 421 patients hospitalized with acute infections revealed thrombocytosis occurred in approximately 8% of patients presenting for acute community-acquired pneumonia, urinary tract infections (UTIs), and skin and soft tissue infections, with platelet counts ranging from 401-917 × 109/L.3 We report a case of extreme reactive thrombocytosis with initial platelet count > 1000 × 109/L in a patient with obstructive nephrolithiasis and pyelonephritis.
Case Report
A man, aged 80 years, with a history of rheumatoid arthritis on methotrexate, prostate cancer previously treated with external-beam radiation therapy, and osteoarthritis status post bilateral knee arthroplasties, was referred to the emergency room by his outpatient rheumatologist for a platelet count of 1011 × 109/L (up from 348 × 109 2 months before admission), worsening anemia, and mild acute kidney injury noted on routine laboratory testing. On arrival, the patient was asymptomatic except for his chronic and stable right thigh pain. He had no hand or wrist joint swelling, and less than 30 minutes of morning stiffness. He had self-discontinued the methotrexate 3 weeks prior to admission. On physical examination, vital signs were temperature 98.0°F, respiratory rate 15 breaths per minute, heart rate 83 beats per minute, blood pressure 130/75 mmHg, with no focal findings to suggest infection and no synovitis, lymphadenopathy, or costovertebral angle tenderness. Laboratory results were notable for platelet count 1011 × 109/L, white blood cell count (WBC) 12.6 × 109/L with immature neutrophils on peripheral smear (6 bands, 8 metamyelocytes, 6 myelocytes, and 2 promyeocytes), and hemoglobin 9.3 mg/dL (down from 12.9 mg/dL 2 months before admission) with mean corpuscular volume 95 and red cell distribution width 16.6. The ferritin was 592 ng/mL, and iron studies were consistent with anemia of chronic disease. The reticulocyte count was 1.05%, and markers for hemolysis (total bilirubin, lactate dehydrogenase, and haptoglobin) were normal. Erythrocyte sedimentation rate was 55 mm/hr, blood urea nitrogen 28 mg/dL, creatinine 1.8 mg/dL (baseline 1.3 mg/dL), and carbon dioxide 16 mmol/L. Tests for myeloproliferative disorders, including JAK-2V617F mutation, BCR-ABL for chronic myelogenous leukemia and acute lymphocytic leukemia, and myeloproliferative neoplasms (MPL/CALR), were negative. On hospital day 2 the patient developed worsening leukocytosis (WBC 23.1 × 109/L). Urinalysis was notable for positive leukocyte esterase and 32 WBC/HPF; blood and urine cultures were negative. The patient was started on empiric vancomycin and piperacillin-tazobactam for a possible urinary tract infection. Computed tomography scan of the abdomen and pelvis revealed evidence of left sided pyelonephritis with obstructive uropathy from a 9.8 mm left mid-ureteral stone. The patient then developed gross hematuria with passage of clots, and eventually underwent cystoscopy with clot evacuation and fulguration, laser lithotripsy, and left ureteral stent placement. His platelet count gradually downtrended to the 400-500 × 109 range (Figure 1), and his leukocytosis resolved.
Clinical course in a man, aged 80 years, with reactive thrombocytosis caused by obstructive nephropathy and pyelonephritis.
Discussion
Platelet counts > 1000 × 109/L are traditionally thought to be caused by autonomous processes (i.e., myeloproliferative diseases such as essential thrombocytosis) rather than reactive processes such as infection or inflammation. A few cases of severe thrombocytosis with platelet counts > 1000 × 109/L have been documented in the setting of iron deficiency anemia and pelvic inflammatory disease,4,5 and in rheumatoid arthritis,6 but there are no previous reports of platelet counts > 1000 × 109/L in patients with urinary tract infections. In Schattner’s retrospective study, approximately of 8% of patients admitted with acute infection had reactive thrombocytosis (ranging from 401-917 × 109/L), and these patients had more suppurative complications, more bacteremia, increased length of hospital stay, and increased mortality compared with the majority of patients who did not have reactive thrombocytosis.3 Obstructive uropathy without infection would not be expected to induce the systemic inflammatory response necessary to trigger reactive thrombocytosis. However, UTIs that are caused or complicated by obstructive uropathy can be virulent and rapidly progressive, especially in the elderly, and therefore more likely to cause reactive thrombocytosis. Interestingly, in the setting of UTIs, thrombocytosis may be an early sign of serious obstructive complications. Gofrit et al.7 found 83 patients with upper urinary tract infections and thrombocytosis (mean platelet count 593 × 109/L; range, 501-949 × 109/L), in comparison to a control group of patients with upper urinary tract infections without thrombocytosis, had a significantly higher incidence of obstructive nephropathy (65% vs 18%, P value < 0.00001) and perinephric abscesses (8% vs 0%, P value < 0.003). The finding of thrombocytosis preceded the diagnosis of UTI by a median of 3 days, suggesting thrombocytosis may be an early marker for obstruction and perinephric abscess in the setting of urinary tract infection. This may be especially important in geriatric patients who often present with no fever and atypical symptoms, such as delirium, confusion, and drowsiness, that could make it difficult for them to report classic urinary symptoms.8
In addition to his obstructive uropathy and pyelonephritis, our patient had rheumatoid arthritis, which also could have caused or contributed to his thrombocytosis. In a study of 75 patients with rheumatoid arthritis, Hutchinson et al.6 found 39 (52%) had platelet counts > 450 × 109/L, and 8 (12.5%) had platelet counts > 1000 × 109/L. Hutchinson also observed the height of the platelet count correlated with disease activity. Farr et al.9 noted the same correlation in another cohort of rheumatoid arthritis patients and, also found the rise in platelet counts corresponded with rises in erythrocyte sedimentation rate and C-reactive protein. Of note, our patient’s platelet count was normal at 348 × 109/L two months before hospital admission, and his rheumatoid arthritis symptoms were quiescent at the time of admission. There was also no evidence of iron deficiency anemia; his iron studies were consistent with anemia of chronic disease, and the ferritin level was markedly elevated at 592 ng/mL. This suggests the primary cause of his severe reactive thrombocytosis was the proximal urinary tract infection caused by obstruction from a ureteral stone.
Conclusion
Platelet counts > 1000 × 109/L are traditionally thought to be caused by myeloproliferative diseases rather than reactive processes such as infection, inflammation, and iron deficiency anemia. In rare cases, however, reactive thrombocytosis can exceed 1000 × 109/L. Physicians should be aware that the presence of severe thrombocytosis in urinary tract infections may be an early marker for obstructive uropathy and warrants prompt imaging and intervention to treat the infection and relieve the obstruction.
- Received December 23, 2023.
- Revision received June 16, 2024.
- Accepted June 17, 2024.
References
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