Haematology

An acute leukaemia is a haematological emergency that requires immediate investigation. Patients may present with constitutional symptoms such as fatigue, unexplained weight loss, night sweats, bone pain, lymphadenopathy or splenomegaly, or unexplained bleeding such as bruises, gum hypertrophy or gum bleeding. Often, these are picked up on a blood film examination when abnormal immature circulating blood cells (blasts) are seen.

Initial workup

• FBE + blood film examination, biochemistry including renal function and liver function tests, LDH
• Extended coagulation profile including d-dimer and fibrinogen

Referral guidelines

EMERGENCY:

• All cases of acute leukaemia should be immediately discussed with the duty haematologist and considered for hospital admission either directly or via the emergency department.

Anaemia is defined as Hb < 135 g/L in an adult male and Hb < 125 g/L in an adult female. Causes of anaemia may be multifactorial including haematinic deficiencies, viral infections e.g. parvovirus infection, bleeding disorders, anaemia of chronic disease, bone marrow disorders such as myelodysplasia, aplastic anaemia, multiple myeloma etc.

Initial workup

• FBE + blood film examination
• Biochemistry including renal and liver function test, LDH
• Iron studies, B12 and folate levels
• CRP
• Reticulocyte, direct antiglobulin test (DAT), haptoglobin
• Serum protein electrophoresis
• Parvovirus serology

Referral guidelines

URGENT:

• Anaemia with other cytopenias e.g. neutropenia or thrombocytopenia, or
• Lymphadenopathy/splenomegaly
• Leucoerythroblastic blood picture on blood film examination
• Persistent anaemia Hb < 80g/L, no cause found.

NON URGENT:

• Anaemia not meeting the above criteria.

Initial workup

• FBE + blood film examination, biochemistry including renal and liver function tests, LDH
• Coagulation studies including INR, APTT, fibrinogen
• If appropriate, Von Willebrand Disease screen or coagulation assays appropriate to family history e.g. factor assays for haemophilia
• History of bleeding diathesis e.g. gum bleeding post brushing, menorrhagia, spontaneous haematomas, bleeding post-surgical intervention, haemarthrosis, GI and intracranial bleeding
• Family history of bleeding disorders
• Current medication list

Referral guidelines

NON URGENT:

• Any patient with a suspected bleeding disorder will be triaged according to their clinical urgency e.g. any planned surgical intervention. This may depend on the severity of abnormal blood test results.

Initial workup

• FBE + blood film examination
• Biochemistry including renal and liver function test
• Haptoglobin level
• Relevant investigations such as haemoglobinopathy studies or alpha thalassaemia genetic tests, or Eosin-5-maleimide binding studies
• Family history of thalassaemia or red cell membrane disorders
• Concerns regarding pregnancy or family planning

Referral guidelines

NON URGENT:

• Please supply the above information, as well as laboratory results for both partners if there are concerns regarding pregnancy or family planning. Referrals will be triaged according to clinical urgency. Patients with thalassaemia minor may not need to be seen.

Conditions that may increase the risk of venous thromboembolism (VTE) include malignancies, recent long distance travel, recent immobility e.g. injury, trauma or surgery, and pregnancies. The usual treatment duration for a provoked VTE varies between 6 weeks to 3 months, and in the outpatient setting, may include enoxaparin, warfarin and direct oral anticoagulants (DOACs) such as apixaban and rivaroxaban.

Initial workup

• FBE
• Biochemistry including renal and liver function tests, LDH
• Coagulation studies (INR, APTT, fibrinogen)
• Relevant prior imaging
• Past history of prior thrombosis, or miscarriages
• Family history of thrombosis or miscarriages or thrombotic disorders

Referral guidelines

ROUTINE:

• The first episode of provoked thrombosis which is associated with recent (<4-6 weeks) surgery, immobility or trauma is usually not reviewed in the haematology clinic. Most patients with superficial thrombophlebitis also do not usually require a clinic review. Advice regarding anticoagulation may be sought from the duty haematologist.
• For unprovoked thrombosis or recurrent thrombosis, please supply the above information for referrals. Referrals will be triaged according to clinical urgency.
• Thrombosis due to malignancy or hormone-induced usually require 1-2 clinic reviews for the development of a management plan for primary care practitioners.
• VTE in pregnancy will be reviewed in the haematology clinic. Please provide information on gestation as well as current anticoagulation treatment.

Leucocytosis is defined as white cell count >11 x 109/L. The leucocytosis (neutrophilia or eosinophilia), may be reactive for example due to an allergy or parasitic infections or may indicate a primary bone marrow disorder such as chronic myeloid leukaemia, chronic eosinophilic leukaemia etc.
 

*Acute leukaemia and lymphocytosis are covered in other areas of this document.

Initial workup

• FBE + blood film examination
• Biochemistry including renal and liver function, LDH
• CRP
• Any prior stool culture results for parasitic infections

Referral guidelines

EMERGENCY:

• New suspected chronic myeloid leukaemia with WCC >100 x 109/L or symptoms of hyperviscosity (headaches, visual changes). Please contact the duty haematologist via RAH switchboard.

URGENT:

• Suspected chronic myeloid leukaemia. Please arrange for BCR-ABL PCR via SA Pathology laboratories and contact the duty haematologist via RAH Switchboard.
• Unexplained leucocytosis WCC > 50 x 109/L (e.g. neutrophilia, eosinophilia, monocytosis) in the absence of reactive or inflammatory conditions
• Leucoerythroblastic blood film examination

NON URGENT:

• Persistent leucocytosis not meeting the above criteria

Lymphadenopathy may occur in infective or malignant conditions and may be isolated or widespread involving more than one nodal group. Concerning features associated with lymphadenopathy are progressive, persistent lymphadenopathy, constitutional symptoms (night sweats, unexplained weight loss, fevers), and hepatosplenomegaly.
 

Initial workup

• FBE +/- blood film examination
• Biochemistry including renal and liver function, calcium, LDH
• Prior imaging, preferably CT staging scans of the neck, chest, abdomen, and pelvis
• Biopsy results confirming the presence of a lymphoproliferative disorder. An FNA (fine needle aspiration) to rule out solid organ malignancies is acceptable however if lymphoma is strongly suspected, it is preferable to obtain 2 x 18G core biopsies.

Referral guidelines

URGENT:

• All suspected or proven lymphomas will be triaged by the lymphoma referral stream.

Lymphocytosis is associated with lymphocyte counts > 4 x 10 9/L. Lymphocytosis can be seen in reactive conditions such as acute viral infections, post splenectomy, smoking or lymphoproliferative conditions for e.g. MBL (monoclonal B lymphocytosis), chronic lymphocytic leukaemia.

Initial workup

• FBE + blood film examination, renal and liver function
• LDH
• Lymphocyte surface markers performed on peripheral blood
• Any prior imaging
• Prior biopsy results

Referral guidelines

URGENT:

• Lymphocytosis in association with cytopenias (anaemia, neutropenia or thrombocytopenia), constitutional symptoms such as unexplained weight loss, night sweats or fevers, splenomegaly or progressive lymphadenopathy.
• Lymphocytosis > 20 x 109/L or rapidly rising lymphocyte count (doubling time).
• Lymphocytosis with blasts/immature cells on blood film examination.

NON URGENT:

• Persistent lymphocytosis without any of the above symptoms.

Macrocytosis is defined as a Mean Cell Volume (MCV) > 90fL. Common causes of macrocytosis include B12 and folate deficiency, thyroid disorders, alcohol misuse, certain drugs such as methotrexate or hydroxyurea. Macrocytosis can also be seen in pregnancy. Less common causes include bone marrow disorders such as myelodysplasia.

Initial workup

• FBE + blood film examination
• Reticulocyte count
• Biochemistry including renal and liver function test
• B12, folate and thyroid function tests
• Alcohol and medication history
• Serum protein electrophoresis

Referral guidelines

URGENT:

• Suspected myelodysplasia.
• Macrocytosis with any accompanying cytopenia (e.g. anaemia, neutropenia).

NON URGENT:

• Persistent macrocytosis without cytopenias.

Neutropenia is defined as an absolute neutrophil count < 1.8 x 109/L. Causes of neutropenia include drugs, viral infections, autoimmune conditions, benign ethnic neutropenia, cyclical neutropenia, B12 or folate deficiency, bone marrow disorders such as myelodysplasia, aplastic anaemia or malignant infiltration of the marrow by a non-haematological malignancy.

Benign ethnic neutropenia is an inherited neutropenia mainly occurring among people of African or Middle Eastern descent. The neutrophil count in this condition is usually between 1-1.5 x 109/L however it can occasionally be less than 1.0 x 109/L. and is not usually associated with an increased risk of infections.

Initial workup

• FBE + blood film examination
• Biochemistry including renal and liver function, LDH
• Lymphocyte surface markers on peripheral blood
• Autoimmune screen
• Viral screens including HIV, hepatitis B and C serology
• History of autoimmune conditions
• Ethnic origin and any previous FBE results
• Current medication list

Referral guidelines

EMERGENCY:

• Neutrophil count < 0.5 x 109/L. Please discuss with duty haematologist via RAH switchboard.

URGENT:

• Neutropenia (>0.5 x 109/L) in association with anaemia or thrombocytopenia, lymphadenopathy or splenomegaly.

Pancytopenia or bicytopenia may be due to drugs, haematinic deficiencies, viral infections, or bone marrow disorders such as myelodysplasia, aplastic anaemia, acute leukaemia etc.

Initial workup

• FBE + blood film examination
• Lymphocyte surface markers on peripheral blood
• B12, folate and iron studies
• Medication history and current medication list

Referral guidelines

EMERGENCY:

• Bicytopenia/pancytopenia with circulating blasts on blood film examination (see section on acute leukaemia).

URGENT:

• Bicytopenia/pancytopenia (Hb < 80g/L, neutrophils <1.0 x 109/L, platelets < 50 x 109/L) and splenomegaly or leucoerythroblastic blood picture on blood film examination.
• Bicytopenia/pancytopenia (Hb < 80g/L, neutrophils <1.0 x 109/L, platelets < 50 x 109/L) with lymphocyte surface markers showing an abnormal myeloid or lymphoid cell population.

NON URGENT:

• All cytopenias not meeting the above criteria.

Monoclonal proteins, detected on serum protein electrophoresis, may be associated with plasma cell dyscrasias such as MGUS (monoclonal gammopathy of uncertain significance), multiple myeloma, amyloidosis, or lymphoproliferative disorders such as chronic lymphocytic leukaemia (CLL), Waldenstroms macroglobulinaemia etc.

Occasionally, in MGUS or multiple myeloma, there also may be abnormal clonal light chain production resulting in a clonal proliferation of either kappa or lambda light chains with an abnormal kappa/lambda ratio.

Initial workup

• FBE, biochemistry including renal function, calcium levels, liver function test, LDH
• Serum protein electrophoresis
• Serum free light chains
• Beta-2-microglobulin
• Urine Bence Jones protein
• CT skeletal survey or any other prior imaging. Please note that an IgM paraprotein is more commonly associated with a lymphoproliferative disorder. Hence please organise CT neck, chest, abdomen, pelvis.

Referral guidelines

EMERGENCY:

• Any new paraprotein with features of acute worsening renal impairment, hyperviscosity (headaches, visual changes, epistaxis), symptomatic hypercalcaemia (confusion, ECG changes), threatened spinal cord compression (back pain, urinary or bowel incontinence, lower limb sensory changes). Please discuss immediately with the duty haematologist via the RAH switchboard (08) 7074 0000.

URGENT:

Any new paraprotein, abnormal kappa or lambda light chain results with:

• Anaemia
• Unexplained renal impairment
• Asymptomatic mild hypercalcaemia
• Lytic bone lesions or pathological fracture, not at risk of cord compromise
• Unexplained cardiac failure
• Urinary proteinuria

NON URGENT:

• Any new paraprotein, abnormal kappa or lambda light chain results without any features of symptomatic myeloma, lymphoproliferative disorder or amyloidosis.

Polycythaemia refers to an increase in haemoglobin above the normal range. This can be primary polycythaemia where there is an increase in red cell mass due to a mutation in red blood progenitor cells; or secondary polycythaemia where various conditions which lead to an increased erythropoietin production (such as hypoxia) can also cause an increase in haemoglobin. Certain medications e.g. anabolic steroids or androgens may also cause polycythaemia.
 

Initial workup

• FBE (on more than 1 occasion) + blood film examination
• Iron studies
• Erythropoietin level (please note that this test cannot be rebated under Medicare). Please check with the pathology provider)
• JAK2 V617F mutation (rebated under Medicare)
• History of chronic hypoxia, smoking, renal disease (e.g. renal cysts, renal artery stenosis)
• Current medication list including supplements

Referral guidelines

EMERGENCY:

• Hb >200 g/L (Packed cell volume or haematocrit >0.60) in the absence of conditions associated with secondary polycythaemia such as chronic hypoxia. Please discuss with the duty haematologist via the Royal Adelaide Switchboard (08) 7074 0000.
• Polycythaemia with associated symptoms of ischaemia e.g. neurological symptoms, chest discomfort or vision changes. Please note that patients with any signs and symptoms of an acute myocardial event or acute neurological event should be directed to the nearest emergency department as a medical emergency.

URGENT:

• Polycythaemia in association with history of arterial or venous thrombosis.

NON URGENT:

• Polycythaemia not meeting the above criteria.

Thrombocytopenia is defined as platelet count <150 x 109/L. Most patients with platelet counts of >50 x 109/L are asymptomatic.

Differential diagnosis of thrombocytopenia include autoimmune causes such as idiopathic thrombocytopenia purpura (primary or secondary), drugs including alcohol misuse, primary marrow disorder, liver disease (with or without cirrhosis), hypersplenism, haematinic deficiency such as B12 or folate deficiency, microangiopathic haemolytic anaemia due to disseminated intravascular coagulopathy or thrombotic thrombocytopenic purpura.

Initial workup

• FBE (on more than one occasion) and blood film examination, biochemistry including renal and liver function test
• B12, Folate
• LDH
• Coagulation studies including INR, APTT, fibrinogen, d-dimer
• Autoimmune screen, including screening for antiphospholipid syndrome (lupus anticoagulant, anticardiolipin and beta-2-glycoprotein-1 antibodies)
• Viral screens including HIV, hepatitis B and C serology
• Medication history including alcohol intake and recent heparin administration.

Referral guidelines

EMERGENCY:

• Platelet count <20 x 109/L or if actively bleeding, presence of red cell fragments or blasts on blood film examination or associated with coagulation abnormalities. Please discuss with the duty haematologist via the Royal Adelaide Hospital Switchboard.
• Platelet count < 50 x 109/L, with concurrent thrombosis. Please discuss with the duty haematologist via the Royal Adelaide Switchboard.

URGENT:

• Platelets with platelet count < 50 x 109/L, or if there are other associated cytopenias e.g. neutropenia and anaemia.

NON URGENT:

• Thrombocytopenia not meeting the above criteria. Stable isolated thrombocytopenia with platelet count ≥100 and no abnormalities on coagulation testing are usually not reviewed in clinic.

Thrombocytosis is defined as platelet count >450 x 109/L. Thrombocytosis may be associated with iron deficiency, reactive or inflammatory conditions. Thrombocytosis is also commonly seen post splenectomy. Occasionally, thrombocytosis may be associated with bone marrow disorders such as a myeloproliferative neoplasm (MPN) or myelodysplasia. In myeloproliferative disorders, very high platelet counts are associated with both thrombosis and bleeding risk (due to platelet dysfunction).

Initial workup

• FBE + blood film examination
• Biochemistry including renal and liver function test
• Iron studies
• CRP
• JAK2 V617F mutation (rebated under Medicare)
• History of smoking, malignancies, recent trauma/surgery

Referral guidelines

URGENT:

• Platelet count >1000 x 109/L.
• Platelet count 600-1000 x 109/L, associated with recent arterial or venous thrombosis (e.g. DVT, PE, TIA, CVA, MI or unstable angina), or abnormal bleeding symptoms.
• High platelet count with associated cytopenias e.g. neutropenia, anaemia (unexplained).

ROUTINE:

• Thrombocytosis not meeting the above requirements.