Polisitemia

dr Putra Hendra SpPD UNIBA

Erythrocytosis
Definition: An increase in the number of circulating RBCs per volume of blood. Synonym = polycythemia. Reflected as an elevated hemoglobin and hematocrit. Causes are classified as:
Secondary (Polyclonal) Primary (clonal)

Secondary Causes of Increased Red Cell Mass (Erythrocytosis)

Chronic pulmonary or cardiac disease Decreased 2,3-diphosphoglycerate High oxygen affinity hemoglobinopathy Increased carboxyhemoglobin (in smokers) and methemoglobin Residence at high altitude Adrenal cortical hypersecretion Hydronephrosis Tumors producing erythropoietin or anabolic steroids Relative (stress) Disorders associated with decreased plasma volume (e.g., diarrhea, emesis, renal diseases)

Diagnosis:
More Common Hematocrit level >52 percent (0.52) in white men, >47 percent (0.47) in blacks and women Hemoglobin level >18 g per dL (180 g per L) in white men, >16 g per dL (160 g per L) in blacks and women) Plethora Pruritus after bathing Splenomegaly Weight loss Weakness Sweating

Other Signs and

Less Common Bruising/epistaxis Budd-Chiari syndrome Erythromelalgia Gout Hemorrhagic events Hepatomegaly Ischemic digits Thrombotic events Transient neurologic complaints (headache, tinnitus, dizziness, blurred vision, paresthesias) Atypical chest pain

Symptoms of Polycythemia Vera

Diagnosis
PV should be suspected when hemoglobin and/or hematocrit levels are elevated
(> than 18 g per dL [180 g per L] in white men and > than 16 g per dL [160 g per L] in blacks and women)

hematocrit level greater than 52 percent (0.52) in white men and 47 percent (0.47) in blacks and women

A diagnosis of polycythemia vera is made when a patent fulfills all three of the major criteria Or any two major and any two minor criteria Major Criteria total RBC vol Men > or = to 36 mL/kg Women > or = to 32 mL/kg arterial 02 saturation > or = to 92% Splenomegaly Minor Criteria Thrombocytosis with platelet count > 400,000/mL Leukocytosis with WBC > 12,000/mL Increased leukocyte alkaline phosphatase LAP > 100U/L (no infection) Serum B12 > 900 pg/mL or binding capacity UB12 BC > 2200 pg/mL

P vera - symptoms
Sx common to all erythrocytosis
Headache, mental acuity, weakness

Sx more specific to P vera

Pruritis after bathing Erythromelalgia Hypermetabolic symptoms Thrombosis (arterial or venous) Hemorrhage

P vera - PEx Findings

Facial plethora Splenomegaly
found in 70% of pts

Hepatomegaly
40% of pts

Distension of retinal veins

P vera - Lab Findings

CBC
Hgb/Hct WBC in 45% Plts in 65% Basophilia (seen in all MPDs)

Uric acid (can lead to gout) and B12 Leukocyte alkaline phosphatase score Low epo levels Positive JAK2 V617F

Labs
Bone marrow studies are not necessary to establish the diagnosis but the findings of:
hypercellularity hyperplasia of the erythroid, granulocytic and megakaryocytic cell lines myelofibrosis

support the diagnosis of a myeloproliferative process.

Komplikasi
Examples of thrombotic events include arterial and venous thrombosis, cerebrovascular accident, deep venous thrombosis, myocardial infarction, peripheral arterial occlusion, and pulmonary infarct

P vera - Treatment
Phlebotomy Myelosuppressive agents
Hydroxyurea Alkylating agents such as busulfan 32P

Interferon alpha

P vera - phlebotomy
Generally, the best initial treatment for P vera
No increase in progression to AML Rapid onset No BM suppression

Remove 500 cc blood 1-2x/wk to target Hct 45%, then maintain

P vera - Myelosuppression
Hydroxyurea
can be used in conjunction with phlebotomy May increase the risk of leukemic transformation from 1-2% to 4-5%

32P

increase the risk of leukemic transformation from 1-2% to 11% May be appropriate for pts intolerant of medications or for elderly patients Single injection may control hemoglobin and platelet count for a year or more.

 Benefits
No No No OK

P vera - interferon alpha

myelosuppression increase in progression to AML increase in thrombosis risk in pregnancy

Drawbacks

Must be given by injection Side effects may be intolerable in many pts, include flu-like symptoms, fatigue, fever, myalgias, malaise

Treatment
Occasionally, chemotherapy may be given to suppress the bone marrow. The use of anti-platelet therapy (such as aspirin) is controversial because it may cause gastric bleeding. Allopurinol is given for hyperuricemia (gout).

Risk stratification in PCV

Risk category Age > 65 or h/o thrombosis Cardiovascular risk factors ? (high cholesterol, DM, smoking, HTN, CHF) No Recommended treatment

Low

No

Phlebotomy and low dose ASA

Intermediate

No

Yes

Hydrea, phlebotomy and ASA

High

Yes

Hydrea, phlebotomy and ASA

Consider IFNa in pregnant women and busulfan or 32P in elderly

Treatment
splenectomy in patients with painful splenomegaly or repeated episodes of thrombosis causing splenic infarction

Prognosis
The major causes of morbidity and mortality are as follows:
Thrombosis Hemorrhagic complications Peptic ulcer disease Myelofibrosis and pancytopenia Acute leukemia or a myelodysplastic syndrome