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West Herts GP Consultant Forum (08/09/2010)

Haematological IrritationsDr Anna Wood

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Topics for discussion

Polycythaemic indices Neutropaenia Lymphocytosis Platelet clumping Immunoglobulins Thrombophilia

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Normal indices

Female Hb 12-

15g/dl Hct 0.36-

0.44 Rbc 3.86-4.9 x

Male Hb 13-

16g/dl Hct 0.38-

0.49 Rbc 4.15-5.15 x

Polycythaemic indices

HCT > 0.48 HCT > 0.52

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Polycythaemic indices

When does it matter? What are the consequences? When to investigate and how far? When to refer?

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1) When does it matter?Clinical Context

Age Persistence or

progression of abnormality

VTE Arterial disease Abdominal mass Family history

Drugs Smoker Alcohol Cyanotic heart

disease Chronic respiratory

disease Hypertension

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Definition and Classification of Polycythaemia

Hct > 0.52 men and > 0.48 women

True Polycythaemia

Primary (MPD)SecondaryCongenital eg high o2 affinity Hb Erythropoetin- driven Drugs eg androgens Post renal transplant

Relative PolycythaemiaRelative Polycythaemia

Reduction in plasmaReduction in plasmavolume but no increase in volume but no increase in red cell massred cell mass

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2) What are the consequences?A Primary High risk VTE and

stroke

Pseudo/Apparent Unknown risk of VTE

Secondary Less risk VTE

B Underlying pathology

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3) When to investigate and how far? History and Examination If no obvious cause repeat (uncuffed) Age if young (?) do renal / abdominal

ultrasound Urate levels (a) well hydrated 87 year old man, non smoker (b) 37 year old female, non smoker, asthmatic

on ventolin, normal renal USS

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4) When to refer?

No obvious cause (pseudo) and persistence of abnormality

If white cells and platelets elevated as well

If obvious cause AND VTE/ Arterial history

If there is obvious cause but concern re necessity for venesection

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Case 1

82 year old lady 3 episodes VTE and stroke/ now on

indefinite warfarin GP referral with Hb 17.8 g/dl HCT 0.549

WCC 7.1 x109/L Platelets 268 x 109/L

JAK 2 V617 mutation positivePrimary proliferative polycythaemia

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Case 2 59 year old male/ heavy smoker Went to GP as tired Progressively abnormal Hb and HCT 2007Hb 16.2 g/dl HCT 0.47 2009Hb 18.3 g/dl HCT 0.53 Haematology referral Epo levels 40iu/l (5-25)

Renal cancer

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Mild NeutropaeniaFacts

Normal Neutrophil count 1.9 – 7.0 x109/L Ethnic variant 0.8 x 109/L

When does it matter? Clinical context ? Recent acute/ severe viral infection Drugs Other abnormal haematological indices History of recurrent bacterial infections Disease associations eg SLE Degree of neutropaenia Blood film appearance

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Importance of blood film

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Neutropaenia

What are the consequences? Of neutropaenia < 0.5 x 109/L Of underlying condition

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Case provided

68 year old man of Asian origin, negative viral screen, on no medication, well.

Neutrophils 1.16 x 109/L How often should this be

monitored? Request blood film and if normal

recheck in 3-4 months

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Lymphocytosis

Normal 1.2 - 3.5x109/L Age Causes Clinical context

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Causes isolated lymphocytosis in elderly

CLL Low grade lymphoma Monoclonal B-cell Lymphocytosis

(MBL) Splenectomised Smoking Endocrine

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CLL Diagnosis of lymphocytes > 5 x109/L Median age 72 Stage A accounts for 80% cases Outcome for stage A

50% stable and never require treatment50% progress and require treatment

Median survival 9 years 20% Stage B and C require treatment

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Case provided (CLL)

76 year old lady, IHD on various medications

Lymphocytes 6 x 109/L How often to monitor? When to refer?

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How often to monitor?

First must request blood film.

If no lymphadenopathy, organomegaly, B symptoms and otherwise normal blood count 6 monthly and there is an ‘assumption’of CLL

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CLL blood film

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Other lymphoproliferative disorder

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When to refer If rapid rise in lymphocytes (LDT < 6 months)

If at diagnosis presence of ‘B’ symptoms, hepatosplenomegaly or additional abnormality in blood count

Patient choice ie would like a substantive diagnosis

Blood film suggestive of other low grade lymphoproliferative disorder.

Initial Lymphocytes > 30 x 109/L

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Importance of Red blood cell countRaised RBC with Microcytosis

Thalassaemia traitHb 9 g/dl MCV 62 RBC

6.0 x 109/L

Iron deficient primary polycythaemia

Hb 16 g/dl MCV 77 RBC 5 x 109/L

Compare Primary

polycythaemiaHb 20 g/dl MCV 90 x

109/l RBC 6 x 109/L

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Platelet clumping

In vitro phenomenon Of no clinical consequence Lab should delete platelet count Citrated sample sometimes helps

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Platelet clumping

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Polyclonal increase immunoglobulins

Connective tissue disease Chronic infections (HIV TB) Non haematological malignancies

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Thrombophilia

Young girl with family history VTE Prior to COCP Should we test for thrombophilia?

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Why do thrombophilia tests?

Predict the rate of recurrence in a patient with VTE

Predict the risk of 1st VTE in family member

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1) Predicting rate of recurrence VTE

Recurrence rate 15-20% First 2 years

Post op Other provoked SpontaneousMinimal 10% 20%

No additional risk factor for recurrence if thrombophilia

Single biggest risk factor for recurrence VTE is VTE

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2) Prediction VTE in unselected cases

Background incidence VTE women childbearing age 1 per 10,000 per year

COCP 3x risk COCP + Factor V Leiden 30x risk Screening all women not

economically viable

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3) Selective screening of asymptomatic relatives

Thrombotic family Defect identified Risk VTE

asymptomatic family member is UNCERTAIN unless

HIGH RISK antithrombin deficiencyProtein C /S deficiency

Thrombotic family Defect not identified Risk VTE

asymptomatic family member is UNCERTAIN

False reassurance

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Testing females prior COCP with family history

BSCH guidelines 2010First degree relative VTE

Tested positive Tested negative Not tested

Consider an alternative contraception or transdermal HRT

Thrombophilia testing not recommended

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Thank youAny Questions