mcmullin blood dyscrasias

8/12/2019 McMullin Blood Dyscrasias

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Mary Frances McMullin

[email protected]

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Conflict of interest

Speakers fees: Novartis and Bristol-

Myers Squibb

Advisory boards : Novartis, Bristol-

Myers Squibb and Takeda

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Definition: Blood Dyscrasia

A pathological condition in which any of

the constituents of the blood are

abnormal in structure, function or quality

as in leukaemia or haemophilia

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Outline

Myelodysplastic syndromes

Autoimmune Haemolytic anaemia

Multiple myeloma

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MDS: Typically a disease of the

elderly

80% of patients

diagnosed with

MDS are over

60 years

Elderly patients

are not usually

eligible for

bone marrow

transplantation1

Adapted from Williamson PJ, et

al.2

MDS

2 1 2 2 4

9

16

26

52

59 61

89

0

10

20

30

40

50

60

70

80

90

30- 35- 40- 45- 50- 55- 60- 65- 70- 75- 80- 80+

Age-specific incidence rates

(per 100,000)

Less than 50: 0.5

5059: 5.36069: 15

7079: 49

80 and over: 89

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Clinical features

Anaemia often macrocytic

Bleeding and bruising

Infections

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Threshold for cytopenia HB < 100g/L

Absolute neutrophil count < 1.8 x 109/L

Platelets< 100 x 109/L

Values above threshold do not exclude a

diagnosis of MDS

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Subtype Blood Bone marrow

Refractory anaemia (RA)

Refractory neutropenia (RN)Refractory thrombocytopenia (RT)

Anaemia; no or rare blasts

NeutropeniaThrombocytopenia

Erythroid dysplasia only;


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Survival by WHO classification

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Diagnosis

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Laboratory Features

Pancytopenia

Anaemia: macrocytic or diamorphic

Neutropenia

Thrombocytopenia

Blasts in peripheral blood

Trilineage dysplasia in bone marrow

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Diamorphic red cells

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http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=7qwQFKCTwXaeXM&tbnid=Wg7kuyvkWNrMiM:&ved=0CAUQjRw&url=http://www.pathologyoutlines.com/topic/myeloproliferativeRCMD.html&ei=1QRvUb3aIoPP0QXW9IDQDQ&bvm=bv.45368065,d.d2k&psig=AFQjCNGRmBnK2iRSoVcCV6vhBcYDz2baDA&ust=1366316533525496


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Treatment options for MDS

.

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Clinical vignette (1)

Female: DOB 2/11/1924

2011: referred with anaemia and easybruising

Previous aortic and mitral valvereplacement on warfarin

Hb 97g/L, WCC 3.7 x 109/L, neuts 1.9 x109/L and platelets 36 x 109/L

Bone marrow: hypercellular with trilineage

dysplasia Myelodysplasia: WHO refractory cytopenia

with multilineage dysplasia

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Treatment

Darbopoeitin 100ug SC once every 2

weeks

4 weeks later Hb 113g/L

Over next 2 years Hb maintained

between 105 and 120g/L on

darbopoietin

Died March 2013 following a fall andfractured femur

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Autoimmune haemolytic anaemia

Antibody production by the body against

its own red cells

warm antibodies reacting at 370C

or cold antibodies reacting at 40C

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Clinical features

Symptoms and signs of anaemia

Jaundice

Splenomegaly

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Laboratory Features

Anaemia

Increased reticulocytes

Spherocytes on blood film

Increased bilirubin

Increased LDH

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http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=OIry2chUZhZlEM&tbnid=ZwIoBRa1XQYFtM:&ved=0CAUQjRw&url=http://studydroid.com/index.php?page=viewPack&packId=205124&ei=ksFtUfLnIu-k0AXos4AY&bvm=bv.45218183,d.d2k&psig=AFQjCNE3h4PraCWQyyxhgRmgMKkVCV838A&ust=1366233816036249


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http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=FrxjpwHKxmeztM&tbnid=FL0cAwG1TdlF0M:&ved=0CAUQjRw&url=http://www.merckmanuals.com/professional/hematology_and_oncology/anemias_caused_by_hemolysis/autoimmune_hemolytic_anemia.html&ei=5r9tUevCIIbC0QWZ2IG4Dg&bvm=bv.45218183,d.d2k&psig=AFQjCNEHvRmpaxrdWit9Tvsgh2WD0P-XyQ&ust=1366233342509803


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Treatment

Corticosteroids

Splenectomy

Immunosuppression

Folic acid

Blood transfusion

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Female DOB: 13/8/1928

2009: Admitted on medical take withanaemia

Hb76g/L, MCV 100fl, 42.3 pg (27-32),MCHC 412g/L (320-360), WCC 4.5 x109/L, platelets 194 x 109/L, retics 3.5%.

Total bilirubin 59umol/L, LDH 694U/L

Direct Coombs test positive

Antibody screen: Non Specific Cold

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Follow up

No underlying cause identified

Prednisolone: minor transient response

Transfused

Refused further immune suppression

Transfusion: 2 units every 2-3 months

Continuing fully functioning with

infrequent transfusions to maintain her

Hb >100g/L

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Multiple Myeloma

Neoplastic clonal plasma cell

accumulation in the bone marrow

98% of cases over 40 years with peak

incidence in 7thdecade

Develops from a monoclonal

gammopathy of undetermined

significance

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Symptomatic myeloma

Monoclonal protein in serum and/or

urine

Increased clonal plasma cells in bone

marrow

Related organ or tissue impairment

Tissue damage:

CRAB ( hypercalcaemia, renalimpairment, anaemia, bone disease).

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Clinical features

Bone pain, vertebral collapse,

pathological fractures

Features of anaemia

Recurrent infections

Renal failure and/or hypercalcaemia

Bleeding and bruising

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Laboratory features

Paraprotein Elevated serum free light chains

Immune paresis: reduced normal serumimmunoglobin levels

Normochromic normocytic or macrocyticanaemia

High ESR

Raised serum calcium Raised serum creatinine

Low serum albumin

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Plasma protein electrophoresis showing monoclonal IgG kappa bandMFMcM

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Treatment options

Suitable for intensivechemotherapy

Courses of

chemotherapy (CDT)

followed by ASCT Plateau

Relapse

Bortezomib

Lenalidomide, etc

Not suitable forintensive therapy

Melphalan, prednisolone

and thalidomide

Plateau

Relapse

Bortezomib

Lenalidomide etc

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Supportive/emergency care

Renal failure: rehydrate and dialysis

Hypercalcaemia: rehydration and

corticosteroids and bisphosphonates

Compression paraplegia:

decompression or irradiation

Anaemia: transfusion or erythropoietin

Infections: rapid antibiotics

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Female: DOB 21.11.1937

In 2005 referred with IgA kappaparaprotein 3g/L

SOB with respiratory disease (smoker) Hb 110g/L, with normal WCC and pts

Normal biochemistry and no immuneparesis

Normal skelatal survey and normal bonemarrow aspirate

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Follow-up

Seen every 6mths with stable

paraprotein

2013:IgA kappa paraprotein 5g/L

Swelling over right scapula

Lytic lesion and skeletal survey small

number of further lytic lesions

Bone marrow 10% plasma cells

Due to start on MPT

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Survival in myeloma

Non-intensive 3-4 years

Autologous transplant increases by

1- 2 years

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Monoclonal gammopathy of

undetermined significance

1% of population over 50years

3% of those over 70 years

Rate of development of myeloma 1%

per year

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