Buku

High haemoglobin

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Low haemoglobin

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High MCV

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Low MCV

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High B12

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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 monocytes

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High ferritin

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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)

In myeloma and other plasma cell disorders, the clonal plasma cell makes the same protein over and over again. 75% of myeloma cases secrete a clonal heavy and light chain, and 20% secrete light chains only. 5% are non-secretory. The light chain element can only be kappa or lambda, and therefore if one is produced clonally, it will increase significantly in proportion to the other.

A standard serum free light chain screen will report Kappa and Lambda light chain levels and 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 e.g kappa and lambda levels of around 150mg/L, but with a retained ratio, or one that is only just outside the reference range.

A significant imbalance in this ratio however 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 the Myeloma workup section