Special heme disorders

Question 1

What is characterized by thrombosis of mesenteric, hepatic, portal veins, with erythromelalgia (redness, warmth, burning pain in lower extermities), night sweats/hot flashes, mucosal bleeding, bruising, hemorrhage, fatigue, splenomegaly?

Answer 1

essential thrombocytopenia “thrombocytosis”

Question 2

What makes someone at risk for essential thrombocytopenia “thrombocytosis”?

Answer 2

JAK2 mutation, 64-73 women

Question 3

What causes essential thrombocytopenia “thrombocytosis”?

Answer 3

megakaryocyte proliferation –> high and abnormal platelet counts that do not adhere –> bleeding disorder

Question 4

What do you need to rule out with essential thrombocytopenia “thrombocytosis”?

Answer 4

reactive thrombocytosis with CRP, ESR, and an iron panel

Question 5

What are tests to start diagnosing essential thrombocytopenia “thrombocytosis”?

Answer 5

elevated platelet count
smear = large platelets
WBC mildly elevated
HCT and RBC normal

bone marrow biopsy = high numbers of enlarged, matured megakaryocytes w/ morphology abnormality

genetic testing (JAK2, MPL, CALR mutations, CML philadelphia chromosome)

Question 6

What is the diagnosis criteria for essential thrombocytopenia “thrombocytosis”?

Answer 6

all 4 major, or first 3 major + minor:
1) platelet count >450
2) BM biopsy = enlarged, matured megakarytocytes w/ hyperlobulated nuclei
3) presence of mutation
4) not meeting criteria for other myeloid neoplasms
minor: presence of a clonal marker or absence of evidence for reactive thrombocytosis

Question 7

How do you treat essential thrombocytopenia “thrombocytosis”?

Answer 7

PO hydroxyurea to maintain platelet count <500
add anagrelide if anemia develops!

aspirin for erythromelalgia and for reduction of thrombosis risk

Platletphresis for severe bleeding

consider progression to myelofibrosis, or conversion to acute leukemia, massive splenomegaly

Question 8

What disorder is characterized by asymptomatic when high HCT is noted otherwise HA, dizziness, tinnitus, blurred vision, fatigue, epistaxis, vasomotor symptoms, early satiety and GI discomfort, pruritus following warm water/bath (basophilia), bone pain?

Answer 8

polycythemia vera

Question 9

What puts someone at risk for polycythemia vera?

Answer 9

JAK2 mutation, ~60years, associated with peptic ulcer disease

Question 10

What causes polycythemia vera?

Answer 10

overproduction of all 3 cell lines (WBC, platelets) with RBC PREDOMINATION

hyperactive bone marrow!

Question 11

What would you see on PE of polycythemia vera?

Answer 11

venous engorgement (retinal), palpable spleen, thrombosis, bleeding, PUD

Question 12

What would you see on CBC of polycythemia vera?

Answer 12

HCT over 49% males, 48% females at sea level, with elevated cell counts, WBCS: basophilia and eosinophilia predominant

Question 13

How can you confirm diagnosis of polycythemia vera?

Answer 13

JAK2 mutation screening

bone marrow = hypercellular, elevated B12, hyperuricemia

Question 14

What’s the diagnostic criteria for polycythemia vera?

Answer 14

all 3 major, or first 2 major + minor:

1) evidence of increased red cell volume, Hg >16.5m, 16f or Hct >49%m or 48%f

2) bone marrow biopsy w/ hypercellularity for age w/ panmyelosis w/ prominent erythroid, granulocytic and megakaryocytic proliferation
3) presence of mutation

minor: serum EPO level below normal range

Question 15

How can you treat polycythemia vera?

Answer 15

phlebotomy weekly until Hct <45%

hydroxyurea if phlebotomy is prohibitive or more aggressive treatment is needed

avoid iron supplementation! aspirin for thrombosis risk, consider: allopurinol and antihistamines

Question 16

What’s the risk with polycythemia vera?

Answer 16

arterial thrombosis – #1 cause of mortality

Question 17

What is characterized by high iron levels w/ no symptoms or fatigue or arthralgia (early), joint disease - symmetric arthropathy, hepatomegaly, skin pigmentation (grey/brown), cardiac enlargement, DM (late Type 1), erectile/gonadal dysfunction (late)?

Answer 17

hemochromatosis

Question 18

What is the triad of hemochromatosis?

Answer 18

cirrhosis, bronze skin, DM1

Question 19

What puts someone at risk for hemochromatosis?

Answer 19

autosomal recessive gene, >50 men, worse w/ ETOH use, obesity, DM

Question 20

What causes hemochromatosis?

Answer 20

iron overload and deposition disorder, hemosiderosis (accumulation in tissue - liver, pancreas, heart, adrenals, testes, pituitary, kidneys)

high incidence of hepatocellular carcinoma + intrahepatic cholangiocarcinoma

Question 21

How can you diagnose hemochromatosis?

Answer 21

elevated plasma iron w/ transferrin sat >45%
low unsaturated iron binding capacity (UIBC)
mildly elevated AST and alk phosphatase

MRI/CT - show iron overload in liver, liver biopsy

Question 22

In who should you check for iron overload?

Answer 22

• chronic liver disease
• ED
• chondrocalcinosis
• DM1, late onset

consider genetic testing, liver biopsy, MRI if screening tests are high

Question 23

How can you treat hemochromatosis?

Answer 23

avoid intake - red meat, supplemental iron, etc (also EtOH, vitamin C, raw shellfish)

depletion of iron stores by phlebotomy weekly for 2-3y Symptomatic patients OR men-serum ferritin OR high fasting iron sat

Consider PPIs to lower maintenance phlebotomy need, chelation w/ deferoxamine if patient has anemia w/ iron overload from thalassemia and is intolerant of phlebotomy