Case presentation and review of PV and PMF

1. CASE PRESENTATION
Presenter: M5 Clerk 楊 憶

2. CASE 1 PROFILE
• Name: 何O貴
• Chart No: 890451
• Age: 66 y/o
• Gender: Male

3. PAST HISTORY
Past Medical History
1. Type 2 DM
2. Dyslipidemia
3. PAOD
4. CAD
5. Gallstones
6. PV

4. PAST HISTORY
Social and Personal History
1. Smoking: ??, quitted
2. Alcohol: ??
3. Betel nuts: ??
Family History: HTN, DM, CVA(father)

5. CHIEF COMPLAINT
• 2020/2/26 Referred from GI for
splenomegaly(7.7x7.5cm), favoring PV

6. PRESENT ILLNESS
• Referred from GI for hematology survey
• Check lab data, JAK2 mut
• Phlebotomy 250cc
• Phlebotomy 250cc
• Complained about numbness of his hands
2020/
2/26
• f/u data
• JAK2 mut(+)
3/18
5/27
• Regular f/u and phlebotomy at hema OPD for PV
• Slight headache, body burning sensation, muscle pain
• Loss f/u since 2014/8
Since
2011

7. 2/19
2/26

8. POLYCYTHEMIA VERA
• Definition: RBC mass ↑ ± granulocytes and Plt ↑
(without physiologic stimulus)
• Etiologies of erythrocytosis
1. Relative(plasma↓): dehydration, stress
2. Absolute:
- Primary: PV, other MPN
- Secondary: hypoxia, carboxyhemoglobinemia,
inappropiate EPO↑
(HCC, RCC, cerebellar tumor, PKD)

9. POLYCYTHEMIA VERA
• Pathophysiology
95% of primary PV patients have a mutation in the
JAK2 gene (gain of function)
→ ↑ tyrosine kinase activity
→ erythropoietin-independent proliferation of the
myeloid cell lines
→ ↑ blood cell mass (erythrocytosis,
thrombocytosis, and granulocytosis)
→ hyperviscosity + slow blood flow
→ ↑ risk of thrombosis and poor oxygenation

10. POLYCYTHEMIA VERA
Clinical features
• Often asymptomatic (incidental finding)
• Hyperviscosity(dizziness, headache, visual disturbances,
tinnitus)
• Thrombosis(Budd-Chiari syndrome, DVT, MI, stroke)
• Bleeding(easy bruising, epistaxis, GI bleeding)
• ↑histamine:
1. Pruritus: worsens when the skin comes into contact
with warm water (aquagenic pruritus)
2. Peptic ulcer
• ↑uric acid: gout

11. POLYCYTHEMIA VERA
• Plethora: facial flushing, cyanotic lips
• Splenomegaly : associated with early satiety and
abdominal discomfort; less commonly hepatomegaly
• Hypertension

12. POLYCYTHEMIA VERA
Lab findings:
1. ↑ Hb/Hct, ↑ RBCs
2. ↑ Platelets
3. ↑ Leukocytes (without physiologic stimulus)
4. ↑ Uric acid, ↑ LDH
5. ↑ Leukocyte alkaline phosphatase
6. ↓ Serum iron levels
7. ↑Vit B12
8. ↓ EPO
9. Arterial O2 saturation: normal

13. A diagnosis of polycythemia vera requires:
All three major criteria
OR
The first two major criteria AND the minor criterion

15. TREATMENT
• Phlebotomy: 250–500 mL in intervals of 2–3 days
until Hct ≤ 45%
• Low dose aspirin in all patients
• Cytoreductive therapy:
1. Hydroxyurea: high risk(>60y, prior thrombosis),
symptomatic thrombocytosis(Plt>1.5x106),
inadequate Hct by phlebotomy alone
2. Interferon alpha: young pts and pregnancy
3. JAK2 inhibitor: Ruxolitinib, if refractory or
intolerant of hydroxyurea

16. PROGNOSIS
• Median survival with treatment: 13.5y
• Increased age, ↑WBC, additional genetic mutations
→ worse prognosis
• Post-PV myelofibrosis: 10-20% cases (after 10y)
• Risk of transition to acute leukemia(<2-5%)

17. CASE 2 PROFILE
• Name: 郭O祥
• Chart No: 834980
• Age: 73 y/o
• Gender: Male
• Date of admission: 2020/06/04

18. PAST HISTORY
Past Medical History
1. Hypertension
2. CAD s/p PCI years ago at CMH
3. Dyslipidemia
4. Recurrent gastric ulcer
5. Gastric tumor, unknown type s/p resection,
10+ years ago

19. PAST HISTORY
Social and Personal History
1. Smoking: denied
2. Alcohol: denied
3. Betel nuts: denied
Family History: denied

20. CHIEF COMPLAINT
• Chest tightness off and on for months,
tarry stool 4 days ago

21. PRESENT ILLNESS
• Tarry stool
• Panendoscopy
• Chest and epigastric pain
• Lower limbs edema and dyspnea
• IM ward
→ Colonoscopy, cardiac US, abdominal US
→ Liver cirrhosis with severe splenomegaly and ascites
1month
ago
• ER: Anemia + bilirubin↑
• CXR: cardiomegaly, no pulmonary edema
• Lasix, NTG → symptoms persisted
6/3
6/4-9

23. CLINICAL COURSE
• Consult for pancytopenia and abnormal young blood
cell formation
• Bone marrow aspiration and biopsy
• Suspect myelofibrosis
• Check JAK2 mut
• f/u lab data
• Unsuitable to perform PCI
• Pending pathology report
6/9
6/10

24. 6/8

25. 6/10

26. TENTATIVE DIAGNOSIS
1. Anemia, suspect GI bleeding or myelofibrosis
2. Chest tightness, angina or myelofibrosis related
3. Pancytopenia, suspect myelofibrosis
4. Cirrhosis with severe splenomegaly, Child B
5. Congestive heart failure, CAD, s/p PCI years ago
6. Hypertension
7. Dyslipidemia
8. Gastric tumor, unknown type s/p resection, 10+ years ago

27. PRIMARY MYELOFIBROSIS
• Pre-PMF
• Overt PMF

28. PRIMARY MYELOFIBROSIS
• Etiologies of myelofibrosis:
1. MPN: primary or post-PV/ET myelofibrosis
2. Other hematologic cancers(CML,AML,ALL, MDS)
or solid cancers(breast, prostate)
3. Autoimmune: SLE
4. Toxin(benzene), radiation, granuloma(TB, fungal,
sarcoid), Gaucher disease

30. PRIMARY MYELOFIBROSIS
Diagnostic evaluation
• Anemia with variable WBC and Plt counts
• Peripheral smear: teardrop RBCs, nucleated RBCs,
immature WBCs, large abnormal platelets
• BM aspiration: dry tap
• BM biopsy: severe fibrosis(reticulin and collagen)
• JAK2 mut(60-65%), CALR mut(20-25%),
MPL mut(5%), triple negative(8-10%)
• No BCR-ABL translocation, and does not meet criteria
for CML, PV, ET, or MDS