1. Common Queries (and hopefully some answers)
Simon Watt
Consultant Haematologist
UHSM

2. B12 deficiency What is normal? Large intrapatient variation
Investigations:
Consider malabsorption eg. Coeliac
Intrinsic factor Antibodies
Schillings test not available

3. Treatment
B12 injections if less than 100 or definite signs or symptoms
Consider oral if greater than 100 and asymptomatic and repeat in 3-6 months

4. High ferritin Acute phase marker Also increased by liver disease
Suspect haemochromatosis when above absent
Check iron levels
TIBC saturation will be raised in haemochromatosis

5. Hereditary Haemochromatosis5

6. Genetics and prevalence
Odds ratio of developing clinical iron overload by genotype
Prevalence of genotype amongst patients with clinical iron overload because of hereditary haemochromatosis (%)
C282Y/C282Y
2300
60-90
C282Y/H63D 49
0-10
C282/WT
3.1
Rare
H63D/H63D
6.3
0-4
H63D/WT
1.6
WT/WT 1
15-30 6

7. Frequency of C282Y mutation in the population

8. Thrombophila
Who to test?
Nobody?

9. Thrombophilia screening
Factor V Leiden (V resistant to cleavage by Protein C)
Prothrombin gene G20210A variant (high II)
Protein C
Protein S
Low Antithrombin

10. Thrombophilia screening
Antiphospholipid antibodies
Anticardiolipin antibodies
Lupus anticoagulant
Anti-Beta2 glycoprotein I antibodies
High homocysteine

11. Thrombophilia?

12. Recurrence

13. Testing of relatives Should only ever test 1st degree relatives
May make a difference to management eg OCP or pregnancy (rarely for men)
Only really useful if the affected relative has a known thrombophilia
May provide false reassurance if unknown/undetectable thrombophilia in family

14. Neutropenia Common Rarely a serious cause found Multiple causes
Note ethnic group

15. Referral? If neutrophils less than 1 Progressive
Associated with other FBC abnormalities
Recurrent infection requiring antibiotics

16. Some common causes Auto-immune Myelodysplasia Liver disease/alcohol
Portal hypertension
Drugs
B12/folate deficiency
Infection and antibiotics

17. Paraproteins More common than you think Probably 10-15% of over 80s

18. What could it be? MGUS-most common
Approximately 1% per year progress to
Asymptomatic myeloma
Active myeloma
Plasmacytoma
Waldenstroms- IgM

19. Assessment Level and type of paraprotein IgA higher risk
IgG less than 15g/l lower risk
Normal SFLC lower risk
IgM associated with Waldenstroms and not myeloma

20. Assessment-doesn’t need HSC if
FBC- normal or unchanged
Calcium-normal
No new pains eg back pain
Renal function normal or stable

21. Major Symptoms at MM Diagnosis
Bone pain: 58%
Fatigue: 32%
Weight loss: 24%
Paresthesias: 5%
11% are asymptomatic or have only mild symptoms at diagnosis
At diagnosis, approximately 60% of patients present with bone pain localized to the ribs, back, or other location. Approximately one third of the patients complain of fatigue, approximately one quarter have weight loss, and 5% complain of paresthesias, which frequently present as numbness or tingling in the hands and feet. Only approximately 11% of patients are asymptomatic or have very mild symptoms at diagnosis. Most patients are symptomatic.
Kyle RA, et al. Mayo Clin Proc. 2003;78:21-33. 21