Polycythemia vera (PV) merupakan gangguan myeloproliferatif dengan bcr/abl-
negative,
Gangguan myeloproliperatif klasik termasuk trombositopenia esensial dan mielifibrosis primer. Masing masing penyakit ini menunjukkan myeloproliferatif klonal stem sel. Yang mana PV ditandai dengan ekspansi dengab morfologi sel darah merag normaltiga lini Each of these MPDs represents a stem-cell–
derived clonal myeloproliferation, with PV being characterized by
a trilineage expansion of morphologically normal red cells, white
cells, and platelets without significant bone marrow fibrosis.
WHO 2016 criteria untuk PV:
Hb> 16.5 gr/dl/HCT 49 laki laki
Hb> 16 gr/dl/HCT 48 perempuan
Dengan mutasi pada JAK 2
BMP: PV dengan trombositosis esensial causa mutasi JAK 2
JAK2.
Kriteria diagnostik polisitemia vera study goup
Category A
1. Total red blood cell mass – In males, greater than or equal to 36 mL/kg; in females, greater than or equal to 32 mL/kg
2. Arterial oxygen saturation greater than or equal to 92%
3. Splenomegaly
Category B
- Thrombocytosis with platelet count greater than 400,000/μL
- Leukocytosis with a white blood cell count greater than 12,000/μL
- Increased leukocyte alkaline phosphatase (ALP) greater than 100 U/L
- Serum vitamin B-12 concentration greater than 900 pg/mL or binding capacity greater than 2200 pg/mL
The diagnosis is established with A1 plus A2 plus A3 or A1 plus A2 plus any 2 criteria from category B.
PatofisiologiBeberapa studi menunjukkan bahwa mutasi pada Janus kinase-2 gene (JAK2) merupakan gene yang terlibat dalam patogenesis PV karena JAK2 secara langsung terlibat dalam signaling intraseluler mengikuti paparan terhadap cytokine yang mana progenitor sel PV menunjukkan keadaan hipersensitivitas.
Trombosis dan bleeding merupakan komplikasi yang paling sering muncuk pada pasien dengan PV, dan muncul sebagai akibat dari gangguan hemostatik karena peningkatan kadar sel darah merah dan trombosit. Tissue faktor juga dihasilkan oleh sel darah putih. Dan juga berkontribusi terhadap thrombosis.
Acquired von Willebrand syndrome merupakan penyebab utama perdarahan pada PV, sekitar 12-15% pada pasuen. Von Willebrand syndrome berkaitan dengan absorpsi von Willebrand factor ke dalam platelet : menurunkan platelet.
Researchers believe that PV begins with one or more mutations in the DNA of a single hematopoitic stem cell, although it remains unclear exactly what initiates the disorder. Mutation in the JAK2 gene seems to be particularly important for the development of PV, as nearly all affected individuals have a mutation in this gene. Mutations in the JAK2 and TET2 genes are associated with polycythemia vera. The function of the TET2 gene is unknown. JAK2 gene mutations result in the production of a JAK2 protein that is constantly turned on (constitutively activated), which improves the cell’s ability to survive and increases production of blood cells. With so many extra cells in the bloodstream, abnormal blood clots are more likely to form. Thicker blood also flows more slowly throughout the body, which prevents organs from receiving enough oxygen. Many of the signs and symptoms of PV are related to a lack of oxygen in body tissues.
Mild-moderate splenomegali
, mild-to-moderate
Gejala konstitusional seperti fatigue dan pruritus
Gejala hyperviskositas, leukocytosis,
thrombocytosis, microvascular(e.g., sakit kepal, gangguam visual, nyeri dada, erythromelalgia, paresthesia),
Tatalaksana
1.konservatif pada low-risk PV (phlebotomy kombinasi dengan aspirin dosis 1 hingga 2 kali sehari)
2. Cytoreduktif therapy pada“high-risk” patients;
Lini 1, hydroxiurea
Lini 2: peg interferon
Lini 3: busulfan
Pertimbangkan JAK2 inhibitor therapy bila ada gatal yang terus menerus dan pembesaran limpa. Oleh karna bila ada gejala tersebut, umumnya refrakter dengan pengobatan cytoreduktif.
