Cause:A clonal myeloproliferative disease, most due to a dominant "gain-of-function" mutation of JAK2 gene on short arm of chromosome 9, which may manifest as P. vera, thrombocythemia, or myelofibrosis (Nejm 2006;355:2452; 2005;352:1779)
Pathophys:Excess clonal production of defective platelets
Prevalence = 5/10 000, while that of benign thrombocytosis = 8% in high-prevalence populations (Ann IM 2003;139:470)
Sx:Bruises, melena, hematemesis, etc.
Si:Purpura, bleeding; splenomegally (40%)
CVA and seizures (Ann IM 1984;100:513); ERYTHROMELALGIA= attacks of redness and burning of extremities relieved for days by one aspirin, a platelet microvascular disorder (Ann IM 1985;102:466)
r/o: Vast majority of elevations are transient or benign thrombocythemias (Ann IM 2003;139:470); reactive causes of elevated platelets, all w no effect on clotting: stress, acute blood loss, acute infection, exercise, malignancy, Fe deficiency, s/p splenectomy, hemolytic anemia, chronic infection, drugs like vincristine
Lab:
Chem:Pseudohyperkalemia, acid phosphatase, and LDH elevated; plasma levels normal but increased in test tube due to platelet contraction
Hem:Platelets, some giant, increased usually >1 million but function may be diminished, eg, by thromboplastin generation test or response to epinephrine (Ann IM 1975;82:506); levels between 400 000 and 1 million are usually reactive in etiology.
Basophils increased >40/mm3. Marrow shows increased megakaryocyte size, inappropriately large for platelet count, unlike CML and reactive causes of elevated platelets
JAK2 gene mutation; if present, rules out benign reactive thrombocytosis
Rx:
ASA 100 mg po qd
of sx like recurrent thrombosis or abnormal clotting studies and planned surgery:
- Hydroxyurea, though leukemia risk present (Nejm 1995;332:1132); w ASA 75 mg po qd (Nejm 2005;353:33) is more effective than other options
- Anagrelide 0.5 mg q 6 h or 1 mg bid × 5-12 d until platelets decrease to normal, then 1.5-4 mg po qd, titrate to lowest effective dosage, not increasing more than 0.5 mg/d each week, monitor platelet counts qod while on medication (Nejm 1988;318:1292)
- Alkylating agents (busulfan, melphalan) rarely, but leukemia risk
- Interferon-
rarely