HAEMATOLOGY GP Pathway

Guides
V.4 11 February 2021
Contents

1. Lymphadenopathy
2. Splenomegaly
3. Lymphocytosis
4. Lymphopenia
5. Neutropenia
6. Neutrophilia
7. Eosinophilia
8. Polycythaemia
9. Thrombocytosis
10. Thrombocytopenia
11. Paraprotein
12. Microcytic anaemia
13. Normocytic Anaemia
14. Macrocytosis
15. Pancytopenia
16. Hyperferrintinaemia
Please note there is also a Manchester Anaemia Guide-
Please click the link below to see the Manchester Anaemia
Guide in full
https://mft.nhs.uk/app/uploads/2018/09/anaemia-v3.pdf
 Lymphadenopathy

B Symptoms
• Weight loss >10% over 6 months Lymphadenopathy
• Drenching sweats,
• Unexplained fever >38°C

Lymphadenopathy- look for causes

Lymphadenopathy associated Localised unexplained

with: adenopathy
• B symptoms OR
• Liver and spleen Concerns of metastatic node
enlargement
• Rapidly increasing in size
• Generalised
lymphadenopathy
Appropriate referral to
• Cytopenias
surgical team or ENT for
biopsy/ radiological biopsy (US
or CT guidance)

Refer to Haematology on urgent

(suspected cancer) pathway

Causes:
• Acute and chronic bacterial infections
• Syphilis
• Auto immune conditions
• Malignancy (haematological/ metastatic)
• Viral infections (including HIV, EBV, CMV)

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Pathway Guide Lymphadenopathy | Clinical Lead: Dr Rachel Brown| V.3 | Created: 16/04/2020
 Splenomegaly

B symptoms Splenomegaly NB: Spleen increases with height.

• weight loss >10% over 6 On average increases in length by
months 0.2 cm for every inch > 6ft
• drenching sweats,
• unexplained fever >38°C
Spleen >13cm

• B symptoms
• Cytopenias If Criteria not met for urgent
• Increased LDH referral look for causes
• Paraprotein
• Lymphadenopathy
• high haemoglobin or
increased platelet count
• Evidence of haemolysis
• High WBC
If no obvious cause refer to
• Leuco-erythroblastic
Haematology
blood film

Refer to Haematology on
urgent (suspected cancer)
pathway

Causes
• Infections – Viral (HIV, EBV, CMV) and parasitic
• Alcohol
• Liver disease
• Cardiac failure
• Autoimmune
• Lymphoproliferative disorders
• Myeloproliferative disorders (such as CML or myeloproliferative disorders)
• Haemolysis

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Pathway Guide Splenomegaly | Clinical Lead: Dr Rachel Brown| V.3 | Created: 16/04/2020
 Lymphocytosis

B Symptoms
• Weight loss >10% over 6 months Lymphocytosis
• Drenching sweats,
• Unexplained fever >38°C

Lymphocytosis >5x109/L

Lymphocytosis 5-20x109/L
• Lymphocytosis >20x109 /L
• Other cytopenias
• B symptoms
• Lymphadenopathy
• Splenomegaly Repeat FBC in 6 weeks and
look for causes

Refer urgently (suspected If persistent

cancer) to haematology If <10x 109/L
>10x 109/L refer
monitor 6
routinely to
monthly
Haematology

Causes:
• Smoking
• Viral infections especially Glandular fever
• Lymphoproliferative disorders (such as CLL)
• Bacterial infections
• Post-splenectomy
• Rheumatoid arthritis

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Pathway Guide Lymphocytosis | Clinical Lead: Dr Rachel Brown| V.3 | Created: 16/04/2020
 Lymphopenia

Red Flag signs

• Weight loss Lymphopenia
• Fevers
• Drenching night sweats
• Recurrent infections
Lymphocytes<1.0x109/L

If >0.5x109/L and >70 years of If no red flag symptoms repeat

Lymphocytes <1 and red flag
age no need for further FBC in 6 weeks and look for
symptoms
investigations causes

If no obvious cause and

Lymphocytes <1 and red flag
persistent over 6 months refer
symptoms
routinely to Haematology

Causes:

• Elderly patients
• Infections including HIV, hepatitis B and C
• Excess alcohol
• Malnutrition
• Medications-steroids, chemotherapy
• Systemic immune conditions
• Systemic illness(renal, cardiac, liver failure, malignancy)
• Lymphoma

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Pathway Guide Lymphopenia | Clinical Lead: Dr Rachel Brown| V.3 | Created: 16/04/2020
 Neutropenia

Causes To Consider
• Drugs Neutropenia
• Myeloma
• B12/folate deficiency
• Autoimmune
• Any viral infection
including HIV/Hepatitis Neutrophil Count <1.8 x 109 /L
B/C

Neutrophil Count <0.5 x 109 /L Neutrophil Count 0.5 - 1 x 109/L Neutrophil Count >1 x 109/L

Repeat FBC in 1 week and look for Repeat FBC in 6 weeks and look
Patient well with Evidence of causes for causes
no fever sepsis

If persistently <1.0 x 109/L and no

If no obvious If between 1.0-1.8x 109/L then
obvious cause found, refer to
cause (see box Admit to monitor annually.
Haematology
above) refer hospital for
urgently management
(suspected of Neutropenic
cancer) to sepsis
Haematology

Note:
• A neutrophil count of between 1-5 - 2.0 x 109/l whilst below the normal range is unlikely to be of any clinical
significance.
• People of Afro-Caribbean or Middle Eastern ethnicity have a lower normal range for the neutrophil count
(constitutional or ethnic neutropenia) 1 - 1.8 x 109/l. This is of no clinical consequence. Only refer if their
neutrophils are <1.0 x 109/l on repeat testing.

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Pathway Guide Neutropenia | Clinical Lead: Dr Rachel Brown| V.3 | Created: 16/04/2020
 Neutrophilia

Neutrophilia

Neutrophil count elevated

If chronic myeloid leukaemia is

suspected you will be
contacted by a haematologist
to organise urgent admission
or outpatient review and
further investigations as
indicated

Assess if there is a clear cause

for this:
• Infection
• Inflammation
• Steroids
• Pregnancy
• Smoking
• Underlying neoplasia

If cause unclear check:

• Blood Film
• ESR
• CRP
• U&E
• LFT
• ANA & Rheumatoid Factor
• PSA etc. led by history

Neutrophil count >15 X 109/L,

persistent at 3 months &
unexplained:
Refer to Haematology

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Pathway Guide – Neutrophilia | Clinical Lead: Dr Rachel Brown | v0.1 | Created: 13/04/2020
 Eosinophilia

Red Flag Signs

• If Eosinophil count>2.5 look Eosinophilia
for signs of organ damage and
consider urgent admission:
• Venous Thromboembolism
• Congestive Heart Failure
• Gastrointestinal Eosinophils >0.5x109/L
• Neurological
• Pulmonary

Repeat FBC in 2 weeks and look for causes if > 1.5 (such as IgE
level, Autoimmune Screen, Stool Cultures)

If secondary cause found, treat as

No cause found
appropriate

If <5.0 x 109/L and

If >5.0 x 109/L
persistent for 3 months

Refer routinely to Refer urgently to

Haematology Haematology

Causes
• Asthma / atopic dermatitis / acute urticarial
• Infections: especially those due to parasites (most commonly helminthes - hookworm, schistosomiasis - but
also giardiasis or other protozoal infections and strongyloides)
• Drugs (penicillins, carbamazepine, sulphonamides are common but any drug is a possible cause)
• Connective tissue disease (rheumatoid arthritis, polyarteritis nodosa, Wegener's granulomatosis)
• Solid malignancy (breast, renal and lung cancer)
• Respiratory disease (Churg-Strauss syndrome, bronchiectasis, cystic fibrosis)
• Myeloproliferative disorders

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Pathway Guide Eosinophilia | Clinical Lead: Dr Rachel Brown| V.3 | Created: 16/04/2020
 Polycythaemia

Polycythaemia

High haematocrit (Hct) >0.51 in men,

>0.48 in women

• Hct Male > 0.600, Female Does not meet criteria for
> 0.560 in the absence of urgent referral- repeat in 2
congenital cyanotic heart months and consider causes
disease (see below)
• Recent arterial or venous
thromboembolism
• Neurological symptoms
• Visual Loss
• Abnormal bleeding If no obvious secondary cause
and persistent, refer to
Haematology routinely.

Refer to Haematology on
urgent (suspected cancer)
pathway

Causes
• Drugs – diuretics, testosterone, anabolic steroids
• Lifestyle choices -smoking, alcohol
• Hypoxia

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Pathway Guide Polycythaemia | Clinical Lead: Dr Rachel Brown| V.3 | Created: 16/04/2020
 Thrombocytosis

Thrombocytosis

Platelets >450x109/L

• Platelets >1000 x 109/L Platelets >450 x 109/L

• Recent arterial or venous
thromboembolism
• Neurological symptoms
• Abnormal bleeding

Repeat FBC in 6 weeks and look

for causes

Refer urgently (suspected

cancer) to aematology
If persistent >450 x 109/L and no
obvious cause refer routinely to
Haematology

Causes
• Iron Deficiency Anaemia
• Malignancies especially the LEGO cancers (lung, endometrium, gastric and oesophageal)
• Inflammation
• Infection
• Post-Splenectony and Hyposplenism (e.g. Coeliac Disease)
• Myeloproliferative Disorders
• Post-Operatively

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Pathway Guide Thrombocytosis | Clinical Lead: Dr Rachel Brown | V.3 | Created: 16/04/2020
 Thrombocytopenia

If platelets are less than

50x109/L please stop all Thrombocytopenia
antiplatelet agents and
anticoagulation as unsafe to
continue.
Please refer urgently to
Haematology Platelets<150x109/L

Platelets <20 Platelets <50x𝟏𝟎𝟗 /OR

• Active Bleeding • Associated with Cytopenias,
• Blasts In Film • Splenomegaly
Platelets >50x 𝟏𝟎𝟗 /L
• Fragments In Film • Lymphadenopathy
• Altered Conscious Level Or • Pregnancy
Confusion • Upcoming surgery

D/W on call Haematology to

Repeat FBC in 6 weeks and look
arrange urgent direct Repeat FBC in 1 week
for causes
assessment

If persistent refer urgently to If persistent and unexplained

Haematology refer to Haematology routinely

Causes
• Spurious result from clumping – please look at blood film report and repeat using citrated sample
• Immune thrombocytopenic purpura (ITP)
• Alcohol
• Liver dysfunction
• Medications
• B12/folate deficiency
• HIV/Hepatitis B/C
• Bone marrow failure/infiltration

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Pathway Guide Thrombocytopenia | Clinical Lead: Dr Rachel Brown| V.3 | Created: 16/04/2020
 Paraprotein

End Organ Damage:

• Hypercalcaemia
• Unexplained renal
impairment
• Anaemia or other
cytopenias
• Bone pain or pathological Paraprotein on Serum Protein
fracture Electrophoresis

• Paraprotein <30
Any of following:
• SFLC ratio <8 or >0.1
• No Immunoparesis • Paraprotein >30
• No End Organ Damage • SFLC ratio >8 or < 0.1
• Immunoparesis (low IgM/G/A)
• End Organ Damage
• Lymphadenopathy
• Splenomegaly
Low Risk MGUS
High Risk MGUS
• IgG <15
• IgM and IgA <10 • IgG>15
• SFLC ratio <8 or >0.1 • IgM and Ig A>10
Urgent (suspected cancer) referral
• No Organ Damage
to Haematology

Note:
Non-urgent referral to Urgent referral to
Haematology Haematology If there are concerns regarding
the interpretation of paraprotein
or Serum Free Light Chain results
please discuss with the
Haematology team.

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Pathway Guide Paraprotein| Clinical Lead: Dr Rachel Brown | V.3 | Created: 16/04/2020
 Microcytic Anaemia

Microcytic Anaemia

Hb <120g/L Woman
Hb<130g/L Man
AND
MCV <80

Ferritin <30mcg/L
Is a Or <50mcg/L with Iron sats
thalassaemia / <20%
Rpt FBC,
Hb variant ?h/o menorrhagia, bowel
ferritin
likely? symptoms, bleeding

Yes
Commence oral
Ferritin >50mcg/L
iron replacement

Haemoglobinopathy
testing advised
Possible Anaemia
of chronic disease
/ inflammation
Hb No Hb If cause If cause
abnormality abnormality unknown known
found found
Refer to
Haematology or
A referral to the Possible alpha through advice Treat underlying
sickle cell and thalassaemia. If and guidance if Check patient diet, cause
thalassaemia additional no evidence of TTG antibody,
centre will be concern, discuss chronic disease / consider referral to
automatically through advice inflammation gastroenterology for
generated and guidance GI investigation /
gynaecology.
Patients with IDA DO
NOT need to be
referred to
haematology

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Pathway Guide – Microcytic Anaemia | Clinical Lead: Dr Rachel Brown | v0.1 | Created: 13/04/2020
 Normocytic or Macrocytic Anaemia

Hb <120g/L Woman
Hb<130g/L Man
AND
MCV >80

Check:
• FBC
• Blood Film
• UE/LFT
• TFT
• Vit B12
• Folate
• Ferritin
• Iron Saturations
• Reticulocyte count
• Serum
Immunoglobulins
• Serum Free Light
Chains

All tests normal Ferritin

Elevated
or reticulocytes Paraprotein Deranged renal Thyroid function <50mcg/L, low
reticulocyte
low or picture detected function abnormal Vit B12 or
count
unclear Folate

Check calcium
and suggest Look for
Consider advice referral to evidence of Suggest replace
Treat thyroid
and guidance if Haematology bleeding or deficiency and
Suggest referral dysfunction and
not anaemia of for paraprotein haemolysis and assess for
to renal team repeat testing
chronic investigation refer to underlying
4-6 weeks
inflammation Exclude other appropriate cause
causes of department
anaemia

Note: Markers of haemolysis include a raised

reticulocyte count and high bilirubin and LDH.

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Pathway Guide – Normocytic or Macrocytic Anaemia | Clinical Lead: Dr Rachel Brown v0.1 | Created: 13/04/2020
 Macrocytosis

Macrocytosis
With/without
anaemia
Check
• Alcohol history Notes
• Medication (e.g.methotrexate, High Mean Cell Volume *A high MCV can be a normal
metformin, some (MCV)* physiological finding in
anticonvulsants, pregnancy
hydroxycarbamide, antiretroviral
drugs etc.) Repeat FBC to ensure not
• Blood Film spurious (e.g. delayed
• Vit B12 and folate transport/ overheating
• Reticulocyte count/LDH etc.)
• LFT
• TFT
• Serum immunoglobulins MCV remains
• Serum Free Light Chains raised
• Family history

If Vit B12/folate
deficient and Hb Consider referral to Haematology
<80g/L or other if:
cytopenias • No secondary cause and
MCV>105fL if other cytopenias
or>110fL in the absence of
other cytopenias
• No history of liver disease
• Dysplasia on blood film
Repeat FBC with reticulocyte • Paraprotein detected
count 5-7 days after starting
replacement therapy

More information on treating B12/folate can be found

In the Manchester Anaemia Guide:
https://mft.nhs.uk/app/uploads/2018/09/anaemia-v3.pdf

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Pathway Guide – Macrocytosis | Clinical Lead: Dr Rachel Brown| v0.1 | Created: 13/04/2020
 Pancytopenia

Pancytopenia
Clinical assessment and
assessment of severity

Severe if any of:

• Hb <80 g/L
• Neutrophils <0.5 x 109/L
• Platelets < 30 x 109/L

Consider reversible causes:

• Drugs e.g.methotrexate
• Haematinic deficiency
• Enlarged spleen
Check:
• Vit B12/folate
• Reticulocyte count
• U&E/LFT
• Bone profile
• Request blood film if not already available
• Immunoglobulins and serum free light chains

Severe features
Blood film shows Unwell/ febrile/
Non-severe present
concerning features Clear cause other clinical
No clear cause but clinically
E.g. evidence of: concerns
stable
• DIC
• Blasts
• Leucoerythroblastic
Routine referral
?possible features Discuss with on-
to general Treat underlying
reversible cause call Haematologist
Haematology cause and monitor
Consider
clinic to ensure resolves
admission

Follow advice from

No blood film report
or discuss with on
call Haematologists
2WW referral with Yes
close interim
monitoring
Treat and discuss with
Haematology team

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Pathway Guide – Pancytopenia | Clinical Lead: Dr Rachel Brown | v0.1 | Created: 13/04/2020
 Hyperferritinaemia

Hyperferrinitinaemia

*Note: it is recommended to screen ADULT

first degree relatives (siblings) of known
C282Y HOMOZYGOTES ONLY for genetic Raised ferritin
haemochromatosis due to their increased risk > 400 μg/L male
for C282Y homozygosity. Screening should be >200 μg/L female
performed by iron studies and ferritin, with
genetic testing reserved for those with
abnormal results. HFE testing can be
performed in primary care and does not
require referral to haematology or clinical
genetics (see text).
HFE testing in children is inappropriate as
this is an adult onset condition . Check
Repeat serum ferritin
Full Blood Count,
Liver Function Test,
Transferrin Saturation

If Ferritin
ONLY if FBC is >1000mcg/L
If FBC abnormal &
NORMAL & If Tsat is NORMAL and normal iron
Tsat raised
Tsat is RAISED consider: sats
(>50% male, 40%
(>50% male,
female)
40% female) Alcohol excess
Consider iron Inflammatory
Proceed to HFE disorders
loading anaemia Refer to
genotyping* Metabolic syndrome
Malignancy hepatology

Yes No

Treat underlying
cause and monitor If Ferritin
to ensure resolves <100mcg/L repeat
in 6 monhts

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TBC TBC TBC TBC

Pathway Guide – Hyperferrintaemia| Clinical Lead: Dr Rachel Brown | v0.1 | Created: 13/04/2020