Buku Haematology

High haemoglobin

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Low haemoglobin

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High MCV

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Low MCV

Quick tip; Microcytic anaemia in the UK is most commonly caused by iron deficiency

The differential for microcytic anaemia is quite limited. The most important causes are;

  • Iron deficiency anaemia (uncommonly due to dietary deficiency, more often from bleeding or malabsorption)
  • Anaemia of chronic disease (more often normocytic however)
  • Thalassaemia or thalassaemia trait
  • Hookworm very common in developing world, uncommon in UK practice
  • Lead poisoning (rare)
  • Congenital sideroblastic anaemia (very rare)

Workup;

  • Repeat full blood count with blood film (comments of microcytosis, hypochromia and pencil cells/rod poikilocytes would support iron deficiency particularly)
  • Ferritin (with soluble transferrin receptor if available and history of acute/chronic inflammation- see 'Low Haemoglobin' module)
  • Serum B12 and folate
  • Haemoglobinopathy screen in patients of family background at risk of haemoglobinopathy (these patients will have a high/normal RBC whereas iron deficient patients will have low RBC, and often a very low MCH).
    • Note; Alpha thalassaemia trait will not be detected on a haemoglobinopathy screen but is not clinically relevant unless at risk of alpha zero (aa/--)-seen in east Asian populations. This is because if a patient's partner is also a possible carrier of alpha zero any child would be at risk of Hb Barts --/-- (incompatible with life)

If no evidence of thalassaemia, referral to gastroenterology should be considered because primary haematological causes for microcytosis are uncommon. Identification of a source of malabsorption or bleeding is the priority. If associated with changes in bowel habit or an older patient particularly, consider 2 week wait referral. 

Links; NICE CKS

High platelets

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Low platelets

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High white cell count

Quick Tip; Unless significantly raised the white cell count itself does not indicate likelihood of an underlying haematological disorder, as leukaemia and lymphoma may have a normal or low white cell count therefore a thorough assessment with blood film are critical

Broadly speaking a high white cell count will be either due to increased myeloid cells (neutrophils or less commonly eosinophils, basophils, blasts) or lymphocytes

Common causes;

  • Reactive
    • Secondary to infection or inflammation
    • Smoking
  • Glucocorticoids
  • Hyposplenism (mild)
  • Haematological disorder
    • Acute/chronic myeloid leukaemia
    • Chronic lymphocytic leukaemia
    • Acute lymphoblastic leukaemia
    • Certain lymphoma subtypes

Investigations are merited if;

  • The count is significantly raised
  • The elevation is persistent
  • Other cell lines are also affected (anaemia/thrombocytopenia)
  • Blood film comments on any significant haematological pathology

Workup

  • Blood film with differential to help identify whether elevated cell counts are myeloid or lymphoid
  • If blood film shows reactive picture then could repeat at reasonable interval after improvement in inflammatory/infective problem to check findings resolved
  • If there is any concerning pathology (e.g blasts/immature cells on the film or other cell cytopenias, then a comment would be given on the blood film with advice for further management or, if not, contact the on call haematologist for advice)

If the blood film reports that a malignancy such as leukaemia is likely, see the 'Workups' submenu for next steps in investigation with urgent haematology input

High neutrophils

Quick Tip; Neutrophilia is only very rarely is caused by a malignant problem

Almost all cases of neutrophilia are due to an acute insult, and reactive counts of over 50x109/L can sometimes be seen

Common causes;

  • Bacterial infection
  • Corticosteroid use
  • Smoking
  • Chronic myelomonocytic leukaemia (associated with monocytosis and dysplastic features on blood film)
  • Chronic myeloid leukaemia
  • Chronic neutrophilic leukaemia (very rare)

Workup;

  • History and examination
  • Medication review
  • Full blood count and blood film
  • CRP

Review of trend is the most important feature in assessing neutrophilia. 

These are some features to help identify probable aetiology

  • Bacterial infection- Acute rise, will drop quickly after insult resolves. Can sometimes rise even above 50x109/ml- no specific action needed unless the neutrophilia fails to resolve after the insult has
  • Smoking can lead to a persistent neutrophilia (see reference below about blood donors- neutrophilia seen in 22% of smokers and 2% of non-smokers)
  • CMML is a slow-growing leukaemia which usually presents as an incidental finding of chronic, slowly rising neutrophilia and monocytosis in a middle aged/older person. The blood film will show dysplastic features. It would require a non-urgent referral to haematology (although officially is a malignancy so see local protocols for referral guidance). If other counts (haemoglobin and platelets) had reduced, or there were systemic symptoms e.g splenomegaly/weight loss, urgent referral is recommended.
  • Chronic myeloid leukaemia is also slow-growing and usually associated with basophilia (fairly unique to CML in this context), thrombocytosis and splenomegaly. This would also merit a non-urgent referral to haematology (although officially is a malignancy so see local protocols for referral guidance).
  • Chronic neutrophilic leukaemia is very rare and associated with an isolated, persistent and progressive neutrophilia.

Specific references

Smoking as a Cause for Mild Chronic Neutrophilia. Stemmelin G et al. Blood 2004 104:3796.

Links:   Elsevier summary

Low neutrophils

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High lymphocytes

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Low lymphocytes

Quick tip; HIV is the most significant cause of lymphopenia, and otherwise often has little clinical significance

Lymphopenia is almost always due to reversible causes and a count of over 0.5 x 109/L is rarely of clinical significance.

Common causes

  • Bacterial infection
  • Increased age
  • HIV infection
  • Autoimmune disease e.g rheumatoid arthritis
  • Drugs; chemotherapy e.g immunosuppressants, alcohol 
  • Congenital immunodeficiency syndrome
  • Bone marrow disease e.g  lymphoma, myelodysplastic syndrome (uncommon, especially in the absence of other cytopenias)

Workup

  • History for above risk factors and examination for organomegaly or lymphadenopathy
  • Repeat full blood count in 2-3 months with blood film
  • HIV screen
  • Autoimmune screen
  • Serum immunoglobulins

If lymphopenia is mild (>1 x109/L) and remains stable over a 6-12 month period with no other indicators of underlying disease then no specialty referral is needed as there would be no treatment for it and it does not confer a clinical risk. Persistent lymphopenia of <1 x109/L would merit further investigation as above and referral to the appropriate medical specialty

Lymphopenia is incredibly common in clinical practice and haematological causes for it are rare therefore referral to haematology is only recommended if there is other evidence to support underlying haematological problems like other cytopenias (e.g suspected MDS) or symptoms or signs in keeping with lymphoma (weight loss, fevers, sweats, lymphadenopathy)

Links:   BMJ (requires subscription)  

High eosinophils

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High ferritin

Quick tip. Ferritin is an acute phase protein, can often be elevated as a result of inflammation/infection and does not necessarily indicate iron overload.

Causes of raised ferritin (e.g. >300 µg/L in men and postmenopausal women; >200 µg/L in premenopausal women-check local reference ranges)

  • Acute or chronic inflammation, infection
  • Alcohol abuse, liver disease (ferritin released from damaged liver cells), renal failure, metabolic syndrome, malignancy
  • Genetic Haemochromatosis
  • Myelodysplasia
  • Thalassaemia
  • (Rarer causes include Gaucher's disease, porphyria cutanea tarda, sideroblastic anaemia, haemophagocytic lymphohistiocytosis, Friedrich's ataxia)

Workup

  • Has the patient got any inflammatory/infective conditions?
  • Any evidence of genetic haemochromatosis (family history, joint pains, liver disease, arthropathy, bronzed skin, diabetes, endocrinopathy)? If so discuss with haematology as HFE genotyping could be performed from GP to expedite specialist assessment 
  • FBC, biochemistry including Liver function tests, CRP +/or ESR, glucose & HbA1c, lipids
  • Repeat ferritin at a time later when any inflammation/infection has settled (>1000 µg/L more supportive of primary iron overload disorder)
  • Iron studies- raised tranferrin saturation (>45%) more indicative of primary iron overload disorder. 
  • Consider ultrasound abdomen if suspicion of underlying liver disease

Referral to gastroenterology/haematology (according to local practice) is recommended if primary iron overload disorder suspected (no obvious underlying cause and elevated transferrin saturations most supportive of this)

LinksBMJ (subscription required)    GP journal summary article

(High) paraprotein

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Elevated light chains

Quick tip; The most relevant part of a serum free light chain test is an abnormal ratio of kappa to lambda rather than increases in the kappa or lambda individually

Light chains are a distal fragment of the immunoglobulin protein (purple lines on the below image)

The two light chains reported on a serum free light chain screen are Kappa and Lambda. Results will be given as a ratio of Kappa:Lamba. The reference range varies between hospitals- please see you local reference range.

A proportional rise in light chain subtypes is seen in inflammation and renal impairment.

A significant change in this ratio may be in keeping with myeloma; either as part of a paraprotein or as part of a light-chain only myeloma

If a significant discrepancy is identified between the ratio, investigate as per a high paraprotein/ "Myeloma" workup section