Myeloproliferative Disorders Flashcards
Pathyphysiology of Myeloproliverative Disorders?
overproduction of cells in the bone marrow
What are the four main types of myeloproliferative disorders?
- chronic myelogenous leukemia (CML)
- polycythemia vera
- myelofibrosis
- Essential thrombocytosis
Polycythemia is mainly characterized by what?
elevated red cell mass, Hgb, & HCT
What are the 3 main causes of polycythemia?
- appropriateely elevated erythropoietin: hypoxemia
- Inappropriately elevated EPO: renal cell carcinoma, hepatocellular carcinoma
- germline and somatic mutation: polycythemia vera
Polycythemia vera is most commmon among who?
most frequently found in men over age 60
Polycythemia vera sx
very non-specific
- HA
- Weakness
- Dizziness
- Excessive Sweating
- pruritus **hallmark is itching post bathing
- erythromelalgia: burning pain in feet and/or hands often with pallor, erythema, or cyanosis
- may have palpable pulses
-sx may also be related to thrombosis; aterial and venous thrombosis, transient visual disturbances (amaurosis fugax, scintillating scotomata)
- GI sx:
- -epigastric discomfort
- -hx of peptic ulcer disease
- gastroduodenal erosions
Lab abnormalities in polycythemia
polycythemia, thrombocytosis, leukocytosis and others.
Hgb/HCT > 18.5/56 men
Hgb/HCT > 16.5/50 women
WBC >10.5
Platelets >450K
elevated serum lactate dehydrogenase in 50%
JAK2 mutation in 98%
abnormal low serum EPO in 81%
Hypercellular bone marrow
iron storage in bone marrow is absent (b/c its being consumed in making RBC)
low EPO
Polycythemia aka?
erythrocytosis
Physical exam findings in polycythemia vera?
- splenomegaly
- facial plethora (ruddy cyanosis; reddish complexion)
- hepatomegaly
- injection of conjunctival small vessels &/or engorged veins of the optic fundus
- excoriation of skin (from pruritus)
- gouty arthritis
Polycythemia Vera Tx
-targeted at lowering HCT and decreasing thrombosis
- phlebotomy to keep HCT 60 or prior thrombotic episode)
- -Interferon alpha: use instead of hydroxyurea in women of childbearing age or if hydroxyurea is ineffective.
- pruritus: Antihistamines, H2 blockers, myelosuppression, interferon alpha, antidepressants (paxil, fluoxetine), photo chemotherapy
- hyperuricemia(gout): allopurinol for prevention
- erythromelagia: aspirin 75-100mg
Polycythemia vera can progress into much more serious disorders of bone marrow metabolism such as:
myelofibrosis
acute leukemia
Myelofibrosis, what is this?
where bone marrow is replaced by connective tissue.
unknown etiology,
**hematopoiesis will occur extramedullary to compensate
Myelofibrosis occurs among who most commonly?
- primarily middle aged and elderly patients (67)
- more often in men than women
Major causes of morbidity and mortality of myelofibrosis
- progression to acute leukemia
- infection
- bleeding
- portal HTN
- vascular complications
Clinical Manifestations of Myelofibrosis
most commonly severe fatigue and LUQ
- splenomegaly(90%): LUQ pain(w/ or w/o radiation to left shoulder) and early satiety
- hepatomegaly(40-70%): RUQ pain, early satiety, ascites, esophagearl and gastric varices, GI bleeding, hepatic encephalopathy, portal vein thrombosis, portal HTN
- weight loss
- low grade fever, nigh sweats
- asymptomatic (15-30%)
How might extramedullary hematopoiesis present and why?
- may present as splenomegaly, hepatomegaly, lymphadenopathy, pleural effusions, pericardial effusions, abdominal effusion, GI, GU, or respiratory (dyspnea)
- production of RBC occurs outside the bone marrow in these areas.
What does peripheral blood smear of Primary Myelofibrosis look like?
- marked poikilocytosis
- tear drop poikilocytes
- anisocytosis (RBC of unequal size)
- myelocyte (bone marrow cell)
Bone marrow biopsy and blood results of Myelofibrosis
blood and bone marrow at the early stage: high white count w/ a left shift, and a hypercellular marrow.
as disease progresses, the marrow becomes replaced with fibrous tissue.
Myelofibrosis Lab abnormalities
depends upon stage of disease
- WBC can be low or high
- Platelets can be low or high
- Elevated alkaline phosphatase (d/t liver or bone diseases)
- elevated lactate dehydrogenasee (d/t ineffective hematopoiesis)
- elevated uric acid (d/t enhanced turn over of hematopoietic tissue)
- Vit B12 (d/t increased neutrophil mass)
- may have JAK2 mutation (for regulation of the production of cells in be bone marrow)
Diagnosis of Myelofibrosis
- bone marrow fibrosis
- absence of philadelphia chromosome
- splenomegaly
- Tear drop erythrocytes
- circulating myeloid cells
- circulating erythroblasts
- clusters of megakaryoblasts
Tx for Myelofibrosis
- stem cell transplant
- hydroxyurea
- chemotherapeutic agents
- JAKK2 inhibitors: urxolitinib
- splenectomy but may cause worsening hepatomegaly
- radiation therapy
What is thrombocytosis?
overproduction of platelets, these platelets may be abnormal and nonfunction therefore it may lead to thrombosis or bleeding.
*elevated platelet count without other blood cell abnormalities
Who does thrombocytosis most commonly occur in?
Women over the age of 50
Thrombocytosis:
- are platelets affected?
- are WBC affected?
- what does a peripheral blood smear look like?
- what does bone marrow biopsy reveal?
- are there any JAK2 mutations?
- platelet counts markedly elevated
- WBC may be slightly elevated
- peripheral smear shows normal RBC morphology
- Bone marrow biopsy reveals increased numbers of megakaryocytes but otherwise normal
- high frequecy of JAK2 mutaitons
Thrombocytosis Sx
- HA
- lightheadedness
- visual changes
- numbness, tingling or burning in the feet
- splenomegaly
- hx of thrombosis
WHere is thrombosis most likely to occur?
hands feet, brain, but may occur anywhere
venous thrombosis: mesenteric, hepatic, and portal vein, as well as deep vein thrombosis
Tx of Thrombocytosis
- low dose aspirin
- hydroxyurea (keep platelet count below 500,000)
Thrombocytosis may progress to what other diseases?
- fibrotic bone marrow
- massive splenomegaly
- myelofibrosis
- 1-2% risk of acute myelogenous leukemia over 20years
