Polycythemia

Question 1

Causes of neonatal polycythemia

Answer 1

1. Intrauterine hypoxia - SGA, previa, maternal HTN, smoking, maternal heart disease
2. Hypertransfusion - TTTS, materno-fetal, delayed cord clamping
3. Endocrinopathy
4. Chromosomal - T13, 18, 21. BWS
5. Altitude
6. High-affinity Hb

Question 2

Neonatal polycythemia - when to treat?

Answer 2

HCT 65% with symptoms
70% when asymptomatic

Exchange transfusion to target HCT 50-55%
Ex vol (ml)=((observed HCT-desiredHCT)x bloodvolume) /observed HCT

Question 3

Childhood polycythemia Classification/Differential

Answer 3

1. Relative Polycythemia (hemoconcentration, dehydration)
2. Primary Polycythemia: Congenital-Primary Familial Congenital Polycythemia (PFCP) (EPOR mutation d/t germline mutation), Acquired-polycythemia vera (due to somatic mutation)
3. Secondary Polycythemia :
   (A) Insufficiency oxygen delivery
   Physiologic: Fetal life, low environmental oxygen
   Resp or Cardiac disease, AV shunts
   Abnormal Hb: methemoglobinemia, carboxyhemoglobinemia, 2,3-BPG deficiency
   (B) Increase in EPO (inappropriate polycythemia)
   i. Endogenous: Renal, Endocrine,Liver, cerebellum, uterus, ovaries
   Ii. Exogenous: testosterone and growth hormone
   (C)Polycythemia with characteristics of both primary and secondary polycythemias
   Chuvash, other VHL mutations, HIF2alpha gene and PHD2 gene mutations

Question 4

Treatment of PV

Answer 4

Phlebotomy to keep HCT<45%
Low-dose ASA
Cytoreductive chemotherapy
- HU 20-30mg/kg
- INFalpha
- Anagrelide

Question 5

High-affinity hemoglobins

• inheritance
• testing

Answer 5

• Auto dominant
• typically B globin defects
• P50 (partial pressure at which 50% of hemoglobin carries oxygen). Should be decreased (also for 2,3BPG deficiency). Beta globin sequencing is gold standard.

Question 6

What should all polycythemic neonates be monitored for?

Answer 6

hypoglycemia
hypocalcemia
hyperbilirubinemia

Question 7

what complications can occur as a result of neonatal polycythemia?

Answer 7

tachypnea and resp distress-TTN
seizures
CHF

Question 8

what is the cause of primary polycythemia

Answer 8

results from somatic or germline mutations of erythroid progenitor cells that make them very sensitive to EPO or other cytokines

Question 9

What is the definition of childhood polycythemia?

Answer 9

Hb >170 or hematocrit >50%

or Hb >99%ile for age

Question 10

what is the most common mutation leading to PV?

Answer 10

JAK2 V617F
(a gain of function kinase at codon 617)

Other type of mutation is JAK2 exon 12 mutation

Question 11

For the treatment of PV when should cytoreductive therapy be used?

Answer 11

prior hx of thrombosis or TIA OR

platelet count >1.5million

Question 12

What is Chuvash polycythemia?

Answer 12

AR disorder, caused by loss of function mutation in VHL gene
Can be grouped as a primary polycythemia because erythroid progenitors are sensitive to EPO
Can also be called a secondary polycythemia because EPO itself can be upregulated
Clinical symptoms are varicose veins, vascular anomalies, plethora, symptoms of polycythemia

Question 13

what is 2,3-DPG?

Answer 13

promotes hemoglobin transition from high oxygen affinity state to a low oxygen affinity state. It binds to the central portion of the hemoglobin tetramer, changing its conformation and shifting the 02 dissociation curve to the right

Question 14

What initial testing should be done in a patient with polycythemia

Answer 14

family hx!
CBC
EPO level
P50 
measure 02 saturation (arterial)
imaging-renal, look for masses

Question 15

what is methemoglobin

Answer 15

generated when oxygen carrying ferrous iron (Fe2+) has been oxidized to ferric iron (Fe3+) which can’t bind O2
the acquired form happens due to oxidizing substances like nitrates and sulf containing antibiotics
Patient presents with cyanosis and low oxygen saturation by pulse oximetry but has normal PaO2 level