The evolution of advanced nursing practice has been influenced by changes in healthcare delivery, financial constraints and consumer demand. Moore and Sweedman (2004) suggested that the advanced practice role has evolved in response to the development of more complex therapies, limited resources and nursing shortages. Core characteristics of advanced practice include that the practitioner should be clinically autonomous, have a client-centred role and be empowered to make high-level decisions. Many of these decisions become more complex due to the increasing complexity of disease, with malignancies now affecting 1 in 2 of the population and an ageing population (Ahmad et al, 2015).
With increasing access to laboratory tests, diagnostic imaging and other investigations, we should not forget the fundamental importance of history taking and evaluation of patients. In one study of an evaluation of 80 patients, history-taking alone led to the correct final diagnosis in 76% of patients (Peterson et al, 1992).
Haematological conditions may be difficult to diagnose as they make up only a small percentage of conditions seen in day-to-day practice. A full-time GP is likely to diagnose one person with leukaemia only every 3-5 years and Hodgkin's lymphoma once in their career (National Institute for Health and Care Excellence (NICE), 2021a), which may offer some explanation as to why patients are often referred to specialties with some degree of delay, so a haematological diagnosis may not be high up on the list of differentials.
With advanced nurse practitioners (ANPs) now often assessing new patients, this article explores, from a haematological perspective, the importance of history taking, clinical assessment and significant findings relevant to patient management, and to gaining insight to a patient's baseline function prior to developing symptoms.
Anatomy and organs involved within haematology
Blood is essential for many roles, including oxygen synthesis, transportation of nutrients and fighting infection. There are many diagnoses that can arise from changes within blood components, some concerning and others benign, involving over- or under-production of blood cells.
The bone marrow is essentially the factory for blood cell production. Over- or under-production of cells may provide an indication of a potential problem with the bone marrow, leading to a haematological diagnosis (Table 1).
Table 1. Haematological symptoms and potential diagnoses
| Symptom | Potential haematological diagnosis |
|---|---|
| Elevated red cells | PolycythaemiaPolycythaemia vera (a myeloproliferative neoplasm) |
| Elevated white cells | Leukaemia (acute or chronic) |
| Production of monoclonal protein | Myeloma (symptomatic or asymptomatic)Monoclonal gammopathy of undetermined significance (MGUS) |
| Elevated platelets | Essential thrombocythaemia (ET), a myeloproliferative neoplasm |
| Reduced production of one or more cell line | Myelodysplasia (MDS)Aplastic anaemiaMyelofibrosis |
| Enlarged lymph nodes | Lymphoma |
| Enlarged spleen | LymphomaMyelofibrosis |
The lymphatic system runs alongside the blood vessels with many lymph nodes throughout the body, and includes the spleen. Lymphadenopathy ‘swollen or abnormal glands’ may develop, including splenomegaly.
Haematological malignancies
The incidence of haematological malignancy is rising, with figures set to increase with ageing populations and lifestyle choices. To put this into context, the incidence of global leukaemia rose by 26% between 2006 and 2016, with 466 802 cases. Similarly, there were 461 000 new cases of non-Hodgkin's lymphoma, with figures rising by 45% over a 10-year review period (Castellino, 2018).
In day-to-day practice the ANP may meet many patients with abnormal blood parameters. But what do they mean and does succinct history taking and physical examination provide the ANP with the appropriate differentials or potentially highlight ‘red flags’ that will require urgent follow-up?
Common haematological presentations
Clinics for new haematology patients often have regular recurring themes for referrals, including deranged blood results, swollen lymph glands, easy bruising and recurrent venous thromboembolism. What do these mean for the patient and is there clinical significance?
History taking is one of the fundamental skills learnt within advanced practice, with key findings relevant to body systems. Common symptoms experienced in haematological disorders, along with the duration of onset of signs and symptoms, potentially play a key factor in diagnosis.
Presenting complaint/symptoms
Many patients report constitutional symptoms, including loss of appetite, early satiety, weight loss, fever, night sweats and fatigue. These will be explored in relation to a haematological diagnosis.
Anaemia may develop with an initial gradual onset of symptoms, including shortness of breath and fatigue, reduced exercise tolerance and light-headedness. Patients may also experience increasing frequency of angina pectoris symptoms. More rapid onset of symptoms may indicate an acute loss of blood, for example gastric bleeding.
More concerning features associated with a history of anaemia, include bone pain, pathological fractures and renal dysfunction as these may provide red flags for a diagnosis of myeloma, a haematological cancer involving plasma cells. A rapid onset of anaemia with elevated white cell count may be indicative of an acute leukaemia and warrants urgent investigation.
Many referrals are based on increasing night sweats. It is important to ask:
- Are they are frequent?
- Are they drenching in nature, requiring a change of nightwear/bedclothes?
- Is the patient pyrexial?
Mold et al (2004) suggested that 41% of adults experienced night sweats with peak prevalence between the ages of 41 to 55 years. There are many common reasons for night sweats, not related to malignancy, that should be considered:
- Menopausal symptoms
- Anxiety
- Hypoglycaemia
- Alcohol or drug use
- Medications, including some antidepressants and painkillers
- Bacterial infections, including endocarditis
- Viral infections
- Fungal infections in immunocompromised patients.
Night sweats become more concerning when accompanied with weight loss of >10% and evidence of lymphadenopathy, as these may be signs of malignancy and, from a haematological perspective, lymphoma. Night sweats related to lymphoma are almost always drenching in nature, requiring a change of nightwear and bedding, but may also be seen in myelofibrosis. It is worth noting that it is rare to see deranged blood results in lymphoma at diagnosis unless the lymphoma is extensive and has infiltrated the bone marrow.
Weight loss and early satiety are also concerning features, requiring physical examination of the patient. Early satiety may be suggestive of an enlarged spleen, which may be physically palpated or assessed with abdominal ultrasound. An enlarging spleen reduces the capacity of the stomach to expand, resulting in a feeling of fullness, which in turn may reduce appetite and result in significant weight loss.
Recurrent infections, mouth ulcers and skin infections may be secondary to neutropenia (low white cell count) and warrant further investigation. A full blood count and review of historic blood results will aid assessment of whether this is chronic or is an acute onset, which may prompt urgent referral and review to the specialist teams.
Fatigue is often more difficult for the patient to quantify but is regularly described as debilitating. This has many causes, including malignancy, anaemia and, more recently, it has been suggested that thrombocytopenia (low platelet count) induces significant fatigue in patients (Hill et al, 2015).
Relevant past medical history
The patient's past medical history may hold vital clues to their diagnosis. Many conditions may in turn affect the functioning of the bone marrow (Table 2). This may be due to an autoimmune process, resulting in cytopenia or suppression of the bone marrow. A more prevalent cause for cytopenia in today's society is associated with malabsorption and deficiency in essential vitamins and minerals including vitamin B12, iron, vitamin K and folate, seen in restrictive diets, following bariatric surgery and vegan diets. These minerals are essential for erythropoiesis within the bone marrow.
Table 2. Factors affecting the functioning of the bone marrow
| Auto-immune conditions | Treatments | Surgery | Other causes |
|---|---|---|---|
| Coeliac diseaseConnective tissue disorderSystemic lupus erythematousAntiphospholipid syndrome | Drugs (including cytotoxic agent)Heparin induced thrombocytopenia (HIT)Vaccine-induced immune thrombotic thrombocytopenia (VITT) | SurgeryOrgan transplant | Alcohol excessHIVChronic kidney diseaseThrombotic disordersVirusesBone marrow failure |
Family history
Any significant family history, including bleeding disorders, malignancy or inherited conditions such as haemophilia, thalassaemia, sickle cell disease or von Willebrand disease may be relevant to the patient's presenting complaint and should be explored during the consultation.
Familial links between haematological malignancies is unclear, with current research projects exploring this issue (). Therefore it is important to ask about family history of acute leukaemia, chronic leukaemia, myeloma or lymphoma. A recent Swedish study by Sud et al (2019) suggested that having a first-degree relative with a haematological diagnosis predisposes an individual to developing the same malignancy.
Bruising/bleeding history
Easy bruising is a common reason for referral, but is this of concern? Bruising is caused by vascular damage or injury resulting in the formation of a haematoma in the subcutaneous tissue, often as a result of trauma. Non-accidental bruising may be secondary to a bleeding disorder or a medical condition such as:
- Vascular disorders: for example senile purpura seen commonly in elderly people due to fragility of blood vessels caused by the ageing process. This results in bruising often seen on hands and forearms after minor trauma
- Platelet disorders: for example idiopathic thrombocytopenic purpura, leukaemia or liver disease
- Drug-related causes: in patients taking warfarin, direct oral anticoagulants (DOACs), aspirin, and non-steroidal anti-inflammatories (NSAIDs)
- Coagulation disorders: haemophilia, vitamin K deficiency or von Willebrand disease.
Alcohol/recreational drug usage may also lead to a reduction in vitamin K synthesis due to liver dysfunction.
If a patient presents with unexplained bruising and bleeding, history taking is of vital importance. An accurate bleeding history should include:
- History of troublesome bleeding during dental extractions
- Bleeding during operations
- History of epistaxis
- Gum bleeding
- Menorrhagia
- Previous blood transfusion requirements.
Physical examination should assess pattern and location of bruising, any evidence of petechiae (appearance of small red pinpricks that are non-blanching, especially seen on lower limbs and forearms), and hepatosplenomegaly.
It is recommended that a clotting screen, urgent full blood count, and liver and renal screens are performed. An urgent peripheral blood smear, which is examined under the microscope, should be requested to exclude a differential diagnosis of leukaemia.
The National Institute for Health and Care Excellence (NICE) (2021b) recommends referral to a haematologist if there is:
- A low platelet count
- Abnormal clotting screen
- Normal blood results, but a bleeding disorder is suspected.
Smoking history
Smoking history and lung disease may be significant if a patient has been referred with an elevated white cell count or raised haemoglobin and haematocrit. Smoking may lead to an elevation in haemoglobin as the body manages the hypoxia caused by smoking and lung damage. Hypoxia induces an increased erythropoietin level, resulting in increased red cell production to aid oxygen transportation around the body. This is known as secondary polycythaemia. Concurrently, the white cell count may also be elevated in response to inflammation caused by smoking.
If the patient has an elevated platelet count, with no haematological cause found, it is essential to exclude primary malignancy, including lung pathologies, with a chest X-ray in such cases.
Medications/recreational drug use
Many medications cause haematological side effects. Common ones to be aware of and consider during a consultation are listed in Table 3.
Table 3. Medications that may cause haematological side effects
| Haematological side effect | Medication |
|---|---|
| Bleeding | NSAIDs, antiplatelets, DOACs, SSRIs |
| Erythrocytosis | Anabolic steroids, testosterone |
| Anaemia | Many drugs, including chemotherapy |
| Thrombocytopenia | Low-molecular-weight heparin |
| Neutropenia | NSAIDs, antipsychotics, anticonvulsants, antibiotics, chemotherapy |
| Neutrophilia | Corticosteroids, adrenaline, lithium, G-CSF |
Key: DOACs=direct oral anticoagulants; G-CSF= granulocyte-colony stimulating factor; NSAIDs=non-steroidal anti-inflammatories; SSRIs=selective serotonin reuptake inhibitors
Travel history
A patient's travel history may become relevant if assessing venous thromboembolism (VTE) risk. Flights of more than 4 hours' duration are a significant contributory risk factor for VTE.
A history of travel to tropical regions including Africa or Asia may become relevant to a patient presenting with severe anaemia, because malaria may lie dormant for up to 12 months.
Occupation
The occupational relationship to haematological malignancies is often under-recognised but emerging data demonstrates that benzene and ionising radiation are carcinogenic to the haematopoietic system. Increased incidence of acute myeloid leukaemia has been recorded with professions using these substances (Snyder, 2012).
Physical examination
Physical examination of the patient should be top to toe and may reveal key signs to assist with a differential diagnosis. Some common examination findings relevant to disorders of the blood are included in Table 4.
Table 4. Common physical symptoms in haematological patients
| Examination finding | Possible haematological cause of findings |
|---|---|
| Pallor, jaundice | Anaemia, Haemolysis |
| Bruising or evidence of petechiae | Thrombocytopenia |
| Koilonychia (spoon nails) | Iron deficiency |
| Oral candidiasis, oral ulceration | Neutropenia or immunocompromised |
| Hypertrophy of gums, inflammation or gum bleeding | Thrombocytopenia, leukaemia |
| Palpable lymph glands (with or without tenderness)—cervical, occipital, axilla, femoral | Lymphoma |
| Palpable liver or spleen | LymphomaMyelofibrosis |
| Unilateral limb swelling | Venous thromboembolism (VTE) |
Following examination and review of a patient, a potential list of differential diagnoses may be formed. In many cases, if a haematological diagnosis is suspected, a referral to the local haematology team is recommended for further investigations. These may include a bone marrow biopsy and imaging with positron emission tomography (PET), computerised tomography (CT) or magnetic resonance imaging (MRI) scans. It is important to remember a diagnosis of lymphoma can be made histologically only with a biopsy, therefore, if lymphoma is suspected, biopsies should be requested by the referring team to avoid delays in the patient pathway.
Throughout the consultation it is important to consider potential red flags as these may require referral to other specialties, including the spinal, gastroenterology, gynaecology or renal teams.
Haematological red flags
The following are red flags for haematological disease:
- Recent VTE
- Unexplained sepsis
- Unexplained anaemia
- Recurrent severe infections
- Back pain, bone pain
- Metabolic emergencies in correlation with pancytopenia, hypocalcaemia, acute renal failure hyperuraemia, tumour lysis syndrome
- Cord equina syndrome.
Venous thromboembolism
VTE is not routinely managed by the haematology team. Management requires prompt diagnosis and treatment to prevent post-VTE complications including the formation of a pulmonary embolism. Only a small percentage of VTEs are unprovoked, with many VTEs provoked (having secondary causes). These include:
- Sepsis
- Postoperative complications
- Significant immobility
- Hormonal causes (use of the combined oral contraceptive pill, hormone replacement therapy) or pregnancy
- Malignancy
- Heart failure
- Significant trauma to the vein (such as from a peripherally inserted central catheter (PICC)
- Vaccination for COVID-19 (more common with the Astra-Zeneca vaccine) (Public Health England, 2021).
When no obvious cause is found, the VTE is classed as unprovoked. According to NICE guidance (2020a), anyone with an unprovoked VTE requires investigations for underlying malignancy, including:
- Physical examination, including breast examination in females
- Chest X-ray
- Blood tests, including full blood count, renal, calcium, hepatic function, prothrombin time (PT) and activated partial thromboplastin time (aPTT)
- Offering further investigations for cancer to people with unprovoked VTE is not recommended unless they have relevant clinical symptoms or signs (NICE, 2020b).
Thrombophilia testing
Testing for hereditary thrombophilia should not routinely be performed in people who are continuing anticoagulation treatment (NICE, 2020b).
Thrombophilia testing in people should not be performed in patients who have had a provoked VTE (NICE, 2020b).
Testing for antiphospholipid antibodies (an acquired form of thrombophilia), should be considered in people who have had unprovoked VTE, if planning to stop anticoagulation treatment. These tests may be affected by anticoagulants and specialist advice from the haematology team may be required (NICE, 2020b).
Hereditary thrombophilia testing should be considered in people with a history of unprovoked VTE who are planning to discontinue anticoagulation, and who have a first-degree relative who has had VTE (NICE, 2020b). These tests may be affected by anticoagulants and may require specialist input from the haematology team.
Haematological emergencies
Neutropenia refers to a low neutrophil count, which can be subcategorised further as:
- Mild: 1.0-1.5 x 109
- Moderate: 0.5-1.0 × 109
- Severe: <0.5 × 109 (Berliner, 2021).
Neutropenic sepsis is a life-threatening medical emergency. Mortality rates of between 2% and 21% have been reported in adults (NICE, 2012). Neutrophils are the first line of defence against bacterial infections and, in general, a neutrophil count of <0.5 × 109 is considered a greater risk for developing a life-threatening infection.
Neutropenic sepsis develops rapidly. Patients may compensate initially, but as the sepsis spreads a patient may develop hypotension and tachycardia, due to an inflammatory cascade. This reduces systemic vascular resistance, leading to hypotension and end-stage organ failure. As the inflammatory response progresses, myocardial depression becomes more pronounced and may result in a falling cardiac output. Capillary leakage occurs with peripheral and pulmonary oedema that may progress to acute lung injury and acute respiratory distress syndrome (Daniels and Nutbeam, 2010).
A patient awaiting further assessment for neutropenia should always be counselled about the need to seek urgent medical review if they develop a temperature of >37.50C, as a delay in review may be life threatening, if they do not receive urgent intravenous antibiotics.
Conclusion
The scope of advanced practice has extended with many ANPs now at the forefront of patient assessment within both primary and secondary care. With an increase in longevity of life and related health issues and comorbidities it is vital that professionals stay up to date with current practice and guidelines.
Haematological diagnoses rely heavily on obtaining a thorough history, arranging appropriate tests and referring to specialist services in a timely manner. It is of vital importance to recognise emergency situations and, above all, provide reassurance to patients during what is often an anxious time for them.
KEY POINTS
- Investigation of haematological abnormalities requires concise detailed history taking, involving all systems and examination
- Advanced assessment skills are required with appropriate referrals to other specialties, as required
- Haematological malignancy rates are increasing. One in two individuals will develop malignancy in their lifetime
- Neutropenic sepsis is a haematological emergency requiring prompt treatment as it may be life threatening if not treated
- Unprovoked venous thromboembolism requires full assessment for possible undiagnosed malignancy
CPD reflective questions
- How would you adapt your communication to ensure you gain the best patient history to include assessment for haematological disease?
- How does the review of historic blood results aid your differential diagnosis?
- Would you have considered assessment for malignancy when a person presents with unprovoked venous thromboembolism? If not, how will you now change practice in keeping with NICE guidelines?