Physical exam findings are non-specific, but may include enlarged liver or spleen, plethora, or gouty nodules. The diagnosis is often suspected on the basis of laboratory tests. Common findings include an elevated hemoglobin level and hematocrit, reflecting the increased number of red blood cells; the platelet count or white blood cell count may also be increased. The erythrocyte sedimentation rate (ESR) is decreased due to an increase in zeta potential. Because<unk>  results from an essential increase in erythrocyte production, patients have normal blood oxygenation and a low erythropoietin (EPO) level. In primary<unk> , there may be 8 to 9 million and occasionally 11 million erythrocytes per cubic millimeter of blood (a normal range for adults is 4-6), and the hematocrit may be as high as 70 to 80%. In addition, the total blood volume sometimes increases to as much as twice normal. The entire vascular system can become markedly engorged with blood, and circulation times for blood throughout the body can increase up to twice the normal value. The increased numbers of erythrocytes can cause the viscosity of the blood to increase as much as five times normal. Capillaries can become plugged by the very viscous blood, and the flow of blood through the vessels tends to be extremely sluggish. As a consequence of the above, people with untreated<unk>  are at a risk of various thrombotic events (deep venous thrombosis, pulmonary embolism), heart attack and stroke, and have a substantial risk of Budd-Chiari syndrome (hepatic vein thrombosis), or myelofibrosis. The condition is considered chronic; no cure exists. Symptomatic treatment (see below) can normalize the blood count and most patients can live a normal life for years. The disease appears more common in Jews of European extraction than in most non-Jewish populations. Some familial forms of<unk>  are noted, but the mode of inheritance is not clear. A mutation in the JAK2 kinase (V617F) is strongly associated with<unk> . JAK2 is a member of the Janus kinase family and makes the erythroid precursors hypersensitive to erythropoietin (EPO). This mutation may be helpful in making a diagnosis or as a target for future therapy. Following history and examination, the British Committee for Standards in Haematology (BCSH) recommend the following tests are performed: * full blood count/film (raised hematocrit; neutrophils, basophils, platelets raised in half of patients) * JAK2 mutation * serum ferritin * renal and liver function tests If the JAK2 mutation is negative and there is no obvious secondary causes the BCSH suggest the following tests: * red cell mass * arterial oxygen saturation * abdominal ultrasound * serum erythropoietin level * bone marrow aspirate and trephine * cytogenetic analysis * erythroid burst-forming unit (BFU-E) culture Other features that may be seen in<unk>  include a low ESR and a raised leukocyte alkaline phosphatase. The diagnostic criteria for<unk>  have recently been updated by the BCSH. This replaces the previous<unk>  Study Group criteria. JAK2-positive<unk>  - diagnosis requires both criteria to be present: Criteria Notes A1 High erythrocyte volume fraction (EVF or hematocrit) (>0.52 in men, >0.48 in women) OR raised red cell mass (>25% above predicted) A2 Mutation in JAK2 JAK2-negative<unk>  - diagnosis requires A1 + A2 + A3 + either another A or two B criteria: Criteria Notes A1 Raised red cell mass (>25% above predicted) OR hematocrit >0.60 in men, >0.56 in women A2 Absence of mutation in JAK2 A3 No cause of secondary erythrocytosis A4 Palpable splenomegaly A5 Presence of an acquired genetic abnormality (excluding BCR-ABL) in the hematopoietic cells B1 Thrombocytosis (platelet count >450 * 109/l) B2 Neutrophil leucocytosis (neutrophil count > 10 * 109/l in non-smokers; > 12.5*109/l in smokers) B3 Radiological evidence of splenomegaly B4 Endogenous erythroid colonies or low serum erythropoietin
Polycythemia vera
Capillary leak syndrome
Essential thrombocythemia
Aplastic anemia
Primary myelofibrosis
Myomatous erythrocytosis syndrome
Immune thrombocytopenic purpura
Chronic myelogenous leukemia