Thrombocytosis: Not Always a Benign Finding

Introduction

An abnormal platelet count should never be underestimated and a broad differential diagnosis must arise in our mind to avoid later complications. We will present a patient with a long standing thrombocytosis who was discharged from hospital after an ischemic stroke and readmitted 3 weeks later with portal/superior mesenteric vein thrombosis.

Case Report

A 51 year old female with hypertension, recently admitted to the hospital due to left thrombotic stroke, complained of 5 days of severe upper abdominal pain associated with nausea and multiple episodes of non-bloody vomiting. The patient also complained of productive cough, with yellowish sputum associated with pleuritic chest pain. She denied fever, shortness of breath, palpitations, visual disturbances, diarrhea or constipation.

Physical Exam

Ill appearing female, in moderate distress, febrile with epigastric tenderness, bowel sounds present, no guarding or rebound. Awake, alert and oriented, right upper /lower extremity weakness 4/5.

Labs

WBC: 36.5×10³ cells/mm³ with neutrophils 90%, hemoglobin/hematocrit 9.7/31.7, platelets 1.247×10³ cells/mm³.

Radiology

ct abdomen/pelvis C+: portal/superior mesenteric vein thrombosis. Chest XRay: not apparent infiltrates.

Hospital Course

The patient was admitted to the floor with a diagnostic impression of sepsis versus myeloproliferative disorder. Pancultures were taken, and she was started on empiric antibiotic therapy with Vancomycin, Zosyn and Flagyl. Anti-coagulation due to portal/superior mesenteric vein thrombosis was also initiated. After a consultation with hematology, laboratory work up including LAP (leukocyte alkaline phosphatase) score and JAK2 V617F mutation analysis was sent. Hematology recommended cytoreduction therapy with hydroxyurea and bone marrow biopsy for definitive diagnosis. During the next few days the platelet count improved but the WBC and hemoglobin dropped significantly secondary to chemotherapy-induced myelosupression. Hydroxyurea was subsequently discontinued. The patient was started on GCSF (granulocyte colony stimulating factor) and transfused with 4 packed red blood cells. Blood cultures grew Bacteroides Fragilis, so the infectious disease consult changed the antibiotics to Meropenem and continued Flagyl to complete 10 days. The patient clinically improved. The JAK2 V617F mutation was present, LAP score was high and bone marrow biopsy was hypercellular with a dramatic increase in the number of megakaryocytes. Large numbers of platelet clumps were seen throughout the specimen. Stainable iron was present. The findings are highly suggestive of the diagnosis of chronic myeloproliferative disease, most likely Essential Thrombocytosis. The patient was discharged on Coumadin 4 mg to complete 6-9 months of anticoagulation. She was not started on aspirin at this time since she was being anticoagulated, but will definitely need long term aspirin after completion of coumadin. Long term therapy with hydroxyurea to maintain platelets below 600.000 cell/mm³ will be determined by the hematologist in the future.

Discussion

Essential thrombocytosis (ET) is an uncommon myeloproliferative disorder of unknown etiology involving a multipotent hematopoietic progenitor cell manifested clinically by overproduction of platelets without a definable cause with an incidence of 1-2/100.000 and a distinct female predominance with a ratio of 2:1, ^{1 2}   affecting patients between the ages of 50 and 70 years. The majority of these patients have a normal life expectancy. ET is most often identified incidentally when a platelet count is obtained during the course of a routine medical evaluation. Occasionally, review of previous blood counts will reveal that an elevated platelet count was present but overlooked for many years. Signs and symptoms are non-specific for ET, but these patients have an increased risk for hemorrhagic and thrombotic events. Venous thrombosis may occur in unusual sites such as mesenteric, hepatic or portal vein as in the case described above. ^{1 2}   Whenever we encounter a patient with increased platelets we must distinguish primary (myeloproliferative disorders) from secondary causes (infections, iron deficiency, malignancy, inflammatory, etc). ET is a diagnosis of exclusion, the criteria includes a platelet count of >600.000, adequate iron stores, absence of Philadelphia chromosome, no evidence in the bone marrow of myelofibrosis or myelodysplastic syndrome, and no secondary cause. Megakaryocyte hyperplasia, often in clumps, is usually identified on bone marrow biopsy. JAK 2 gene mutation is present in 50% of patients. ⁴   Treatment is individualized based on risk stratification, starting from low dose aspirin to chemotherapy and platelet pheresis. ⁴

Optimal identification and management of ET is a challenge to the practicing clinician. Thrombocytosis shouldn’t be ignored since it’s not always a benign finding as demonstrated in this case. Early diagnosis and treatment is paramount to prevent severe complications.