Dr Nnenna Osuji Dr Stella Appiah-Cubi Dr Stella Kotsiopoulou
21/05/2014 Slide 2 Focus on primary/secondary care interface
Discuss cases encountered and practical lessons Highlight
diagnostic clues Encourage confidence around community care of
chronic stable haematological malignancies Information gathering
Sickle vaccinations USC referrals Slide 3 Name the current
consultants. How do you contact haematology for advice? Blood film
suggests CLL. How are you going to refer this patient? Indications
for 2WR Haematology Referrals Slide 4 Monoclonal Protein MGUS Vs
Multiple Myeloma Case Discussions CLL Case Discussion Slide 5 It is
a monoclonal immunoglobulin secreted by an abnormally expanded
clone of plasma cells that can be detected by immunofixation of
serum and/or urine. Slide 6 Slide 7 Varies greatly with age. 1 - 2%
of people in their 6th decade 2-4% in their 7th decade 4-5% in
their eighth decade 14% over the age of 90 Racial variation Twice
as common in black people as white people Slide 8 Haematological
malignancies Multiple myeloma Solitary plasmacytoma (skeletal or
extra- medullary) Waldenstrom's macroglobulinaemia Low grade
non-Hodgkins lymphoma Monoclonal gammopathy of undetermined
significance ( MGUS) AL amyloidosis Slide 9 Slide 10 There were
only 2 statistically significant risk factors for progression The
concentration of monoclonal protein The type of monoclonal protein
IgA and IgM gammopathy more likely than IgG to progress IgM rarely
becoming myeloma Slide 11 Low risk defined as IgG M-proteinSlide 12
Slide 13 New International Staging System: ISS Stage CriteriaMedian
survival IBeta2 microglobulin3.5 g/dl 62 mo. IINeither I or III45
IIIBeta2 microglobulin >5.5 mg/L29 Slide 14 Symptoms of bone
disease, persistent unexplained backache Impaired renal function
Anaemia Hypercalcaemia Recurrent or persistent bacterial infection
Hyperviscosity Spinal cord/nerve root compression Symptoms
suggestive of amyloidosis (nephrotic syndrome, cardiac failure)
High ESR (incidental finding) Slide 15 Slide 16 Slide 17 Slide 18
67-year old Afro-Caribbean Right hypochondrial pain Fatigue
Recently treated for epistaxis Slide 19 FBC: Hb 6.6, WBC 5.0, plts
85 Urea 10.2, creatinine 128 Adj. Ca 4.38, albumin 28 ESR 138 mm/h
Slide 20 Admit Anaemia due to ? Malignancy ? Epistaxis 3 units of
blood transfusion i.v. fluids + Pamidronate Slide 21 IgA
paraprotein 75 g/l (t.prot 127 g/l) 2 microglobulin 5.6mg/l BM
plasma cells 40% INR 1.32, APTTr 1.34, fibrinogen 1.67 g Slide 22
Drowsy Transfer to ITU Bleeding from mouth HD Methylprednisolone
Subsequent C-VAD, Z-Dex chemotherapy Slide 23 EMERGENCY !!!
Hyperviscosity Treatment plasmapheresis, HD steroids, iv hydration
Slide 24 49-year old Afro-Caribbean Back pain - 9 mo. (6 mo. off
work) Not able to mobilize from bed without help Slide 25 FBC
clotted Urea 6.5, creatinine 150 Adj. Ca 2.68, albumin 19 Total
protein 174 g/L Paraprotein 141 g/L IgG Slide 26 Hb 3.4 (citrate
blood) INR 1.5, APTTr 1.25, fibrinogen 1.41 Slide 27 3 sessions of
plasmapheresis at RMH Blood transfusion after plasmapheresis Z-Dex
chemotherapy Abnormal ECHO CThal Dex chemotherapy Slide 28 48-year
old Afro-Caribbean Sudden lower-back pain on sneezing 3 mo. prior
to admission 5/7 history back pain and reduced power in left leg
Slide 29 FBC: Hb 10.5, WBC 6.8, plts 278 Urea, creatinine, adj. Ca
- N T. protein 99 paraprotein 45 g/L IgG Slide 30 05/08/2005 Left
leg no movement Right leg reduced power Slide 31 Spinal cord
compression Treatment radiotherapy, Dexamethasone Slide 32 1 st
August Lumbar spine X ray 2 nd August MRI 2 nd August CT- guided
biopsy 4 th August - diagnosis ?MM, ?NHL 4/5 th August referral to
haematology 5 th August - referral for radiotherapy 6 th August -
radiotherapy Slide 33 20 Gy 5 doses 1 course Z-Dex, 3 courses C-VAD
!! Able to take few steps with crutches Right leg back to normal
Left leg much improvement Slide 34 71-year old Caucasian 3/12 back
pain Spine X-ray lytic lesion lumbar Slide 35 FBC: Hb 15.6, N 5.7,
plts 237 Us&Es, Ca, t. protein normal Small IgG paraprotein BM
3% plasma cells CT-guided biopsy plasma cells Slide 36 PLASMACYTOMA
Treatment 40 Gy in 20 fractions Slide 37 SURGERY Contraindicated in
the absence of structural instability Management of persistent pain
Vertebroplasty bone strengthening and pain relief but does not
restore height (polymethacrylate) Kyphoplasty vertebral height can
be restored (small inflatable balloon) Slide 38 Slide 39 Slide 40
Slide 41 Clonal B cell malignancy. Progressive accumulation of long
lived mature lymphocytes Most common leukemia of Western world.
Male to female ratio is 2:1. Median age at diagnosis is 65-70
years. Small proportion are familial Aetiology unknown Slide 42
Mostly disease of elderly with Often asymptomatic. Classic B
symptoms recurrent infections Lymphadenopathy, hepatosplenomegaly.
Marrow failure Autoimmune haemolytic anaemia/thrombocytopenia Slide
43 Persistent lymphocytosis > 5 x 10 9 /l. Morphology Mature
looking lymphocytes -clumped chromatin Immunophenotyping BM not
required for diagnosis. Slide 44 Majority score 4/5 Score < 3
not CLL Slide 45 Slide 46 Complications Infection Bacterial
hypogammaglobulinaemi a Viral T-cell dysfunction (H. Zoster)
Autoimmune ITP/Haemolytic anaemia Other malignancies Transformation
Richters, Hodgkins Slide 47 Many watch and wait stage A
Chemotherapy Bone marrow failure=stage progression B symptoms
weight loss, sweats, fevers (unexplained) Symptoms from enlarged
lymph nodes/spleen Transformation Not for high WBC alone Median
survival 10 years Slide 48 When to refer back B symptoms
Lymphadenopathy Hepatosplenomegaly Falling haemoglobin, platelets,
rapidly rising lymphocyte count Recurrent infections Autoimmune
complications How often? Every 3 months Then reduce frequency if
stable Slide 49 2004 Aged 80, Routine FBC- lymphs 8. Normal
Hb/neutrophils/plats Well, no B symptoms, lymphadenopathy or
hepatosplenomegaly Diagnosis CLL Watch and wait policy Discharged
2011 GP to monitor Slide 50 Anaemias B12 Deficiency Case Discussion
Iron Deficiency Vs Thalassaemia Trait Elevated Ferritin Slide 51
Definition Categorized according to Red Cell indices MCV and MCH:
Hypochromic and Microcytic (low indices) Normochromic and
Normocytic (normal indices) Macrocytic (high MCV) Can you name one
cause for each category? Slide 52 How do we investigate? 1 st line
tests: B12, Folate, TSH, reticulocyte count, LDH, LFTs, blood film:
? Any dysplastic features. ? History of alcohol consumption 2 nd
line tests: SPE, UPE, DAT/haemolysis screen 3 rd Line: Bone Marrow
investigations Slide 53 Slide 54 Sources of dietary vitamin B12
Vitamin B12 absorption Causes of B12 deficiency Indications for
measuring B12 level Clinical presentation of B12 deficiency
Investigations to help define the cause of B12 deficiency. A guide
to management Slide 55 Foods of animal origin- meat, fish, eggs,
milk, cheese but not in plants. Recommended daily requirement is 1-
2g/day Total body stores of 2000-5000g Mainly stored in the liver(
up to 2yrs stores) Slide 56 Slide 57 Slide 58 Inadequate vitamin
B12 in diet strict vegans Vitamin B12 malabsorption Pernicious
anaemia-loss of GPIF( increased of CA stomach ~ 2-3%) Long term use
of PPI or H2-antagonist Chronic alcoholism Coeliac disease Small
bowel( esp. terminal ileal) surgery Generalised malabsorption e.g.
Tropical sprue, IBD Blind loop syndrome +/- small bowel bacterial
overgrowth Fish tapeworm Drugs Biguanides e.g.. Metformin Oral
contraceptive pill Slow K, Cholestyramine Slide 59 Haematological
Isolated red cell macrocytosis Macrocytic anaemia ( esp. if MCV>
110fl) Pancytopenia ( esp. if MCV> 110fl) Neurological or
psychiatric Peripheral neuropathy Cognitive change e.g. dementia
Optic neuritis Gastrointestinal Investigation of possible
malabsorption process Other (rare) Angular stomatitis, glossitis
(sore beefy red tongue) Slide 60 Slow onset symptoms of mild
anaemia Pallor and mild Jaundice( ineffective erythropoesis)
Glossitis & angular stomatitis Neurological changes( B12<
60ng/L)( SCDC) Glove and stocking parasthesia Early loss of
vibration sense Progressive weakness and ataxia Dementia Slide 61
FBC-Megaloblastic anaemia with hypersegmented neutrophils Serum B12
level- low Serum folate may be normal or high Anti-intrinsic factor
( anti-IF)- highly specific but +ve in 50-60% of PA. Parietal cell
antibodies- +ve in 90%( PA) but less specific TSH &
anti-thyroid Ab Test for coeliac disease Test for generalised
malabsorption Endoscopy Schilling test- obsolete Slide 62 B12
deficiency without neurological involvement: 1mg Hydroxocobalamin 3
times a week for 2 weeks then every 3 months B12 deficiency with
neurological involvement: 1mg Hydroxocobalamin every other day
until no further improvement then every 2 months Folic acid 5mg
daily for 4 weeks Slide 63 Serum B12> 150ng/l- Confirm test
Significant proportion of these patients will go on to become
symptomatic. Treat with oral vitamin B12 supplements + monitor
level every 2-3months If no response then consideration given to
parenteral B12 replacement Slide 64 53y old legal secretary
Previously fit & well A&E with RIF 3/12 general lethargy
& inability to concentrate Slide 65 PMHx- Nil relevant
SHx-Single, good diet with mixture of animal & diary products
No alcohol or smoking Slide 66 Pale, mildly jaundiced, sore and
smooth tongue. No pedal oedema, no hepatosplenomegally BP- 95/50,
Pulse -110/min RIF tenderness with guarding? appendicitis Slide 67
FBC- Hb- 6.8g/dl, WBC- 2.5 Plt- 58, MCV- 130fl, U&E- NAD,
LFT-Normal except Bili=26( 21- ), LDH- 8498, TSH- Normal,
Hepatitis, HIV ve. Slide 68 Slide 69 Slide 70 Slide 71 Folate- 9
B12- 72 GP & IF ab- Positive Coeliac Screen Negative Slide 72
Vitamin B12 replacement- 1mg X 3 for 2 weeks. Then 3 monthly Folic
acid 5mg daily for 4 weeks Slide 73 South East Asian origin Saw GP
with tiredness, SOB O PMHz- II DM on metformin SHx- Banker, strict
vegetarian, Alcohol o, smoking o O/E- Unremarkable Slide 74 Hb-
10.6 WBC- 3.2 Plt- 223, MCV- 120, LFT-NAD, LDH-640, U&E-NAD,
TSH- Normal Blood film- macrocytosis with occasional hypersegmented
neutrophils seen Serum B12- 140, Folate- 12, Ferritin 45 GP &
IF ab, Coeliac screen- Negative Slide 75 Oral supplementation
Cyanocobalamin 50-100g PO daily Recheck serum B12 in 2-3 months.
Continue if replete If not, consider parenteral B12 injections.
Slide 76 48y old Female Long H/O bloatedness Good diet. SHx-
Research nurse, no smoking or alcohol Slide 77 O/E- Unremarkable
Bloods- Hb-9.8 WBC- 7.8 Plt-350 MCV-86fl Blood film unremarkable
U&E, LFT, TSH- NAD Slide 78 Ferritin- 6/dl, serum B12 160,
Folate- 8 Tissue transglutaminase (tTG) Slide 79 Referred to
gastroenterologist Given oral B12 and FeSO4 Recheck 3 monthly Slide
80 What tests would you consider in the following cases: (Fer Vs
Fer+HbEP) 25 y.o. lady, Norwegian, fatigued, Hb:100 g/l, RBC: 3000,
MCV: 74fl, MCH: 26pg 50 y.o. lady, Cypriot, routine check, Hb:100
g/l, RBC 5000, MCV 70fl, MCH 24 pg Slide 81 Slide 82 Slide 83 Slide
84 Low Ferritin = Iron Deficiency Raised Ferritin = Too much iron??
Slide 85 Iron overload( Primary & Secondary) High Ferritin
Without Iron Overload Slide 86 Primary Hereditary haemochromatosis
Hereditary aceruloplasmin( Wilsons disease) Secondary Transfusion
overload Ineffective erythropoiesis( thalassemia, sideroblastic
anaemia) Excess dietary iron Slide 87 Liver disease Alcohol excess
Chronic inflammatory conditions( RA, IBD, bacterial infection)
Malignancy Slide 88 FBC LFT Ferritin Transferrin saturation Slide
89 59yr old female Severe RA On immunosuppressive drugs Slide 90
Hb- 99 WBC- 13.5 Plt-420 ESR- 43 CRP- 35, Ferritin 400g/l U&E,
LFT- NAD Blood film Normochromic normocytic anaemia Serum
electrophoresis- polyclonal increase in immunoglobulin Slide 91
Cause of raised ferritin- acute phase response No specific
therapy/investigations required for this Treat the RA Slide 92 38yr
old German ancestry Fit & well City Banker Alcohol- 10u/week
Well man clinic Slide 93 Hb- 154 WBC- 8.7 Plt- 210 Ferritin- 200g/l
B12/Folate- within normal range U&E, LFT-NAD O/E- Nicely tanned
but unremarkable otherwise Transferrin saturation ( serum Fe &
TIBC)- 89% Slide 94 Test for HFE mutation Homozygous for
C282Y/C282Y Diagnosis: Hereditary Haemochromatosis Slide 95
Elevated Fe with no obvious cause Family history TS > 55% for
men & post menopausal women TS > 50% in premenopausal woman
Test for HFE mutation Refer patient to gastro-enterologist in CUH
Venesection will be done by haematologist Slide 96 Sickle cell
vaccination Community follow up for long term haematological
conditions Any others? Slide 97 Pneumococcal Vaccine every 5 years
Hib immunisation (once in lifetime) Tetravalent Meningococcal
vaccine ACWY (once in lifetime) Hepatitis B vaccination Seasonal
Flu Vaccination (annually) WHY???? Slide 98 Can you name 2
(previously presented in this talk)? Can you suggest others? Slide
99 Slide 100 Thank you! Dr Stella Kotsiopoulou Haematology
Specialty Doctor Croydon University Hospital
