Dr. Moths gave a great noon report of a younger patient without significant past medical history who initially presented in septic shock and developed thrombocytosis.
What is thrombocytosis?
Thrombocytosis is defined as a platelet count about 350-450 K. Thrombocytosis can either be a primary or secondary process.
What is reactive thrombocytosis?
Thrombocytosis caused by a secondary process is known as reactive thrombocytosis.
There is an extensive list of causes of reactive thrombocytosis (taken from UptoDate):
-Nonmalignant hematologic conditions
Acute blood loss
Acute hemolytic anemia
Iron deficiency anemia
Treatment of vitamin B12 deficiency
Rebound effect after treatment of ITP or ethanol-induced thrombocytopenia
-Nonhematologic Malignant conditions
Metastatic cancer
Lymphoma
Rebound effect following use of myelosuppressive agents
-Acute and chronic inflammatory conditions
Rheumatologic disorders, vasculitides
Inflammatory bowel disease
Celiac disease
Kawasaki disease
Nephrotic syndrome
POEMS syndrome (osteosclerotic myeloma)
-Tissue damage
Thermal burns
MI
Severe trauma
Acute pancreatitis
Post-surgical period, especially post-splenectomy
-Infections
Chronic infections
Tuberculosis
Acute bacterial and viral infections
-Exercise
-Allergic reactions
-Functional and surgical asplenia
-Reaction to medications
Vincristine
Epinephrine, glucocorticoids
Interleukin-1B
All-trans retinoic acid
Thrombopoietin, thrombopoietin receptor agonists
Notice that inflammation is a common theme: inflammation is the most common cause for secondary thrombocytosis because a multitude of inflammatory cytokines augment platelet production and release from megakaryocytes.
What about primary thrombocytosis?
Primary thrombocytosis can be familial or secondary to clonal proliferation. We will review Essential Thrombocytosis (ET) here.
ET can be suspected when a patient has a platelet count of at least 600,000 on two occasions separated by at least one month without any secondary causes present.
Patients are generally asymptomatic, but can present with thrombotic events which primarily are arterial (i.e. CVA/TIA, MI, digital ischemia). Patients can also present with erythromelalgia. Finally, bleeding may be seen, either from dysfunctional platelets or from acquired VonWillebrand Disease.
How do I work up a patient with persistent thrombocytosis?
A peripheral blood smear is always a good place to start. If there are worrisome findings, get hematology involved immediately.
Next, evaluate the patient for findings suggestive of a myeloproliferative neoplasm. Suggestive symptoms include vasomotor or constitutional symptoms, unusual clots, or the presence of splenomegaly on examination. Jump right to evaluation of a MPN (discussed below) if these are present.
If none of these are present, check a ferritin. If low, replete the patient's iron deficiency and recheck the platelet count in 1-2 months. If still elevated, hematology should be involved. If normal or high, look for a family history (if present, send to hematology) or evidence of infection, inflammation, or a splenectomy. If the latter are present, you can try treating. If unsure, send to hematology.
What do I do if I suspect a myeloproliferative neoplasm (MPN), specifically ET?
Molecular diagnostics are the first test of choice. Screen with JAK2 testing first, as 50% of cases of ET have a positive mutation.
Next, get a BCR-ABL, MPL + CAL-R if JAK2 negative. (Remember that CML can present with isolated thrombocytosis). After this, additional testing including FISH and bone marrow biopsy may be needed.
There are specific diagnostic criteria for ET. Of the following, you need to have numbers 1-3 OR 1,3, 4 & 5.
Sustained platelet count >450,000
Presence of an acquired pathogenic mutation (eg JAK2, CALR, or MPL)
No other myeloid malignancy, especially PV, PMF, CML, or MDS
No reactive cause for thrombocytosis and normal iron stores
Marrow studies showing increase megakaryocytes displaying a sprectrum of morphology with prominent large hyperlobulated forms.
What is the treatment of ET like?
The treatment of ET is based on the revised International Prognostic Score for Essential Thrombocytosis (revised IPSET).
This score looks at the patient's age (more or less than 60), specific mutations, and history of clot. Patients who are low risk can be observed with low-dose aspirin, but higher risk patients generally need cytoreduction or targeted therapies.
References:
2. MKSAP 17: Chapter 01: Hematopoietic Stem Cells and Their Disorders.
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