Quick tip: A high Hb is often not due to a primary haematological problem.
An elevated Hb can be due to either a primary myeloproliferative neoplasm (e.g polycythaemia vera), or may be secondary to other conditions. Secondary causes are either due to hypoxia, or less commonly excess erythropoietin or endocrine disorders. It will often be identified as an incidental finding on a full blood count, but may present with thrombosis, more often arterial than venous, or constitutional symptoms of hyperviscosity such as headaches, itching, blurred vision parasthesiae or chest pain. Haematocrit is probably a more reliable measure of polycythaemia.
Referral to haematology should be considered in patients with a persistently elevated haemoglobin in the absence of a respiratory cause (or if the Haematocrit is over 0.48 (48%) in females or 0.52 (52%) in males, discussion should be had with haematology).
If contacting a haematology on-call service before referring the patient consider asking if testing for JAK2 V617F mutation would be appropriate as this may improve efficiency of haematology outpatient review.
An urgent referral should be sent in those presenting with thrombosis or symptoms of hyperviscosity for urgent venesection. Aspirin is recommended in primary polycythaemia but not secondary polycythaemia, after the appropriate risk assessment for risks and benefits of aspirin use.
Secondary polycythaemia can be managed by venesection in certain cases although evidence is often weak (see BSH guideline).
Quick Tip; Mean corpuscular volume is a mean reading therefore a 'normal' MCV could be a combination of a micro- and macrocytic process
Anaemia investigations involve determining whether it is an intrinsic problem with the bone marrow or due to an extrinsic cause. This process can be made easier by separating the anaemia by red cell size;
Refer to haematology if concerned about underlying haematological or bone marrow problem such as a raised paraprotein which may indicate myeloma (see Paraprotein and Light chains sections), or myelodysplasia (macrocytosis in the absence of other obvious causes, especially if other cell lines affected e.g low platelets/ white blood cells)
B12/folate replacement strategies (Adapted from NICE CKS B12 deficiency guidance);
*Iron studies interpretation;
Tests for a patient's iron status can be confusing. Those most commonly used are;
Quick Tip; If a patient is B12 and folate deficient, B12 must be replaced before folate as the surge in red cell production if folate is given first can causes a dramatic consumption of remaining and B12 and risk of subacute combined degeneration of the cord
An increased mean corpuscular volume is seen due to abnormal DNA production, conditions which increase the proportion of immature cells in the circulation, or when red cells are exposed to toxic substances.
Referral to haematology is recommended if haemolysis, dysplasia or myeloma are identified on the bloods and blood film, or if other cytopenias are present (thrombocytopenia/ leukopenia).
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;
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
Quick Tip; An acutely raised high platelet count is most commonly reactive due to infection or bleeding and often needs only observation
Thrombocytosis is a common finding in hospital inpatients as a reactive feature to acute illness. Persistent or significantly raised platelet counts (>450 x 109/L), especially in the absence of an inflammatory trigger, should be referred for investigation for a possible underlying myeloproliferative disorder (essential thrombocythaemia, polycythaemia vera or myelofibrosis).
Essential thrombocythemia/myeloproliferative disorder
Workup of chronic thrombocytosis
If on repeat an elevated count is persistent and no other trigger is obvious, refer to haematology.
If significantly elevated (>600 x 109/L) or the patient has an increased risk of thrombosis (history of acute coronary syndrome, venous thromboembolism or cerebrovascular disease) or is aged over 60, consider referring more urgently to haematology services/ seek on-call haematology advice as these features all increase the thrombosis risk
Quick Tip; Bleeding from mucosal surfaces such as the gums or GI tract in the context of thrombocytopenia are associated with increased risk of serious bleeds such as intracranial bleeds therefore merit urgent assessment
Thrombocytopenia is a common referral to haematology, both acute and through outpatient clinics. The common causes listed below are broadly divided into more acute or chronic causes.
Chronic/gradual thrombocytopenia (<150x109/L)
* Some of the medications most frequently associated with thrombocytopenia include; Heparin, quinine, penicillins, cephalosporins, rifampicin, NSAIDS, anticonvulsants, disease-modifying anti-rheumatic drugs, gold salts, tirofiban, amiodarone, furosemide (See refs)
ITP does not have any specific diagnostic tests therefore referral to haematology should be performed in the case of a prolonged or severe thrombocytopenia, and when non-haematological causes seem unlikely.
See "Transfusion Threshold" module for advice on safe platelet levels peri-operatively and pre-procedures
Visentin G, Liu C. Drug-Induced Thrombocytopenia. Hematology/Oncology Clinics of North America. Volume 21, Issue 4, Pages 685-696
Aster R, et al. Drug-induced immune thrombocytopenia: pathogenesis, diagnosis, and management. Journal of Thrombosis and Haemostasis. Volume 7, Issue 6, June 2009, Pages 911–918
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
Investigations are merited if;
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
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
Review of trend is the most important feature in assessing neutrophilia.
These are some features to help identify probable aetiology
Smoking as a Cause for Mild Chronic Neutrophilia. Stemmelin G et al. Blood 2004 104:3796.
Links: Elsevier summary
Quick Tip; A count of 1 x 109/L or more is unlikely to be associated with a significant risk of infection
Most cases of incidental neutropenia will resolve on a repeat after a reasonable period as they will be due to transient infection. For those that do not resolve, around a third will be chronic idiopathic (see ref Lima et al.-note small study population), with other causes listed as below.
Neutropenia is defined as mild: 1-1.5 x109/L, moderate: 0.5-1 x109/L or severe: <0.5 x109/L.
If neutrophil count >1 x109/L, chronic and the patient has no clinical features of neutropenia (frequent infections, mouth ulcers) and initial investigations for an underlying disorder are negative then it is likely that no further action is needed apart from a repeat count in a few months to measure the trend in neutrophil count. If any clinical concern, especially in the context of other low cell counts or evidence of infection/organomegaly/mouth ulcers/fever then discuss with haematology.
In the case of fever and neutropenia prompt treatment with antibiotics is critical, especially in those patients with a neutrophil count of less than 1 x109/L.
Quick tip: A normal lymphocyte count does not rule out lymphoma
Lymphocytosis will often be identified as an incidental finding on routine bloods. Many cases will be benign, some may indicate chronic haematological malignancy, and rarely they will indicate acute leukaemia but this will be identified by the laboratory performing the test and the patient will often be very unwell.
Referral to haematology is recommended in the case of persistent lymphocytosis, especially when associated with B symptoms or lymphadenopathy.
A persistent lymphocytosis under 10 in an otherwise well patient may be reported as 'Monoclonal B cell lymphocytosis' on the blood film. This condition is thought to be a CLL precursor which needs monitoring alone, as without any clinical features it needs no treatment. Once the lymphocyte count is over 10 it is more likely to have a blood film comment of 'suspected CLL' possibly with advice for referral.
Caring for known CLL in the community
The CLL disease course is most often slowly progressive and a slow increase in the lymphocyte count is expected. Features that would require a more urgent referral to haematology or more prompt follow up than planned would be a rapidly rising white cell count (doubling time less than 6 months), any new cytopenias, progressive lymphadenopathy, and progressive constitutional symptoms such as fevers or sweats.
Links: BMJ (needs subscription)
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.
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)
Quick Tip; Persistent eosinophilia over 1 x 109/L will always merit investigation
Eosinophilia is a relatively uncommon finding but elevated counts should be investigated if persistent or there is associated clinical concern. Eosinophils are involved in fighting multicellular parasites and in atopy and allergy.
A history should concentrate on;
According to BSH guidance if there is a count of 0.5-1 x 109 and no end organ damage or probable cause from the history then no further investigations may be required. If however, there is a probable cause that merits investigation, end organ damage or eosinophilia over 1 x 109 then further investigation is merited. This would traditionally be with haematology unless there is a recent history of foreign travel and suspicion of helminthic infection in which case an infectious disease referral may be more appropriate.
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)
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)
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