Easy Bruising: History Taking and Differential Diagnoses

History of Presenting Complaint

Overview

With each symptom, always (if relevant) ask about:

When did it start?
Did it come on suddenly or gradually?
Is it continuous or intermittent?
Has this ever happened before?

Bruising and bleeding

Site:
- Where are the bruises?
- Bruising in areas that are not typical for bruises (such as the knees or elbows) suggests an underlying disorder or abuse
Onset:
- When did the bleeding and bruising start?
  - Lifelong symptoms suggest congenital or genetic disorders
  - Recent symptoms suggest acquired conditions
- What causes the bruising?
  - Was there any trauma?
Associated symptoms:
- Do they have any bleeding?
- Do they have nosebleeds?
- Do they have bleeding gums when brushing their teeth?
- If applicable, do they have heavy periods?
Timeline:
- How long do their bleeding and bruising last?
Severity – ask about number and size:
- How big are the bruises?
- How many bruises are there?

Review of systems

Ask about red flags for malignancy:
- Fevers, weight loss, night sweats
- Swollen glands (lymphadenopathy)
Ask about red flags for gastrointestinal bleeds:
- Have they vomited up any blood?
- Have they vomited up ‘coffee-ground’ material?
- Have they passed any blood in their stool?
- Have they passed dark, black stools?
Ask about and consider red flags for non-accidental injury (NAI):
- Bruising on a non-mobile child
- Characteristics of bruises due to NAI are:
  - Disproportionately to the explanation of the injury, unusually large, present at multiple sites/in clusters, similar in shape and size, patterned in the shape of a hand print/stick/teeth/belts or have fingertip gaps
  - Associated petechiae are present
- Some places are strongly suggestive of NAI:
  - Sites not typical for a child such as non-bony parts of the body or face (e.g. eyes, ears, cheeks, back, abdomen, buttocks, arms, genitalia)
  - On the neck – this suggests strangulation
  - On the ankles and wrists
- The explanation of the bruising is inconsistent, does not add up, or is inadequate:
  - The story may vary between parents/carers or change over time
- There may be a delay in presentation

Past Medical History

Questions include:

Have they ever had bleeding or bruising in the past?
Do they have any other medical conditions?
Have they ever had any previous surgery?
Do they take any regular medications?
Do they take any over-the-counter medications, herbal remedies, or supplements?

Family History

Is there any family history of anything similar?

Allergy History

Are they allergic to anything?
- What happens during the allergic reaction?

Social History

Do they smoke?
- If so, how much and how long?
Do they drink alcohol?
- If so, how much and how long?
Do they use any illicit drugs?
- If so, how much and how long?
What is their occupation?
Who’s at home?
- What support do they have?
How has this impacted their activities of daily living?
Has anyone around them been ill?

Physical Examinations

Overview

An examination of the mucosa and skin is performed to identify and characterise bruises. Petechiae and/or purpura may be present. In general, petechiae are generally seen in thrombocytopenias and purpuras may be seen in vasculitides.

Investigations

Overview

When suggesting investigations in an OSCE, the BOXES (Blood tests, orifice tests, x-rays, ECGs, special tests) mnemonic is useful for deciding the order of investigations:

Blood tests:
- Full blood count (FBC) and white cell differential:
  - May show thrombocytopenia
  - May show other blood dyscrasias (e.g. anaemia)
- Coagulation studies:
  - Identifies coagulation pathway defects
- International normalised ratio (INR):
  - In patients taking warfarin
- Anti-factor xA levels:
  - Monitoring is not routinely done but can be in patients taking low molecular weight heparin who are at increased risk of bleeding – anti-factor Xa activity is monitored in these situations
- Fibrinogen:
  - For disseminated intravascular coagulation
- Blood film:
  - May show abnormal cell morphology associated with an underlying diagnosis
- Liver function tests (LFTs):
  - Liver disease can cause coagulation problems
- Urea and electrolytes (U&Es):
  - Chronic kidney disease can impair the clearance of anticoagulants
Special tests:
- Immunophenotyping:
  - To identify cells by cell marker
- Bone marrow biopsy:
  - Diagnostic in many haematological malignancies

Differential Diagnoses

Anticoagulant use

A history may reveal:
- The use of warfarin, direct oral anticoagulants (DOACs, such as apixaban, rivaroxaban, edoxaban, and dabigatran), or low molecular weight heparin
- Other drugs include corticosteroids and NSAIDs
- Gastrointestinal bleeding
Investigations may reveal:
- International normalised ratio (INR):
  - Raised if the patient is using warfarin
- Activated partial thromboplastin time (APTT):
  - Raised if the patient is using heparin
- Anti-Xa level:
  - Raised if the patient is taking low molecular weight heparin

Liver disease

A history may reveal:
- Patients may have jaundice
- There may be a history of variceal bleeding (e.g. haematemesis and/or melaena)
- There may be a history of chronic excessive alcohol consumption
A physical exam may reveal:
- Jaundice, ascites, spider naevi, palmar erythema, hepatosplenomegaly, asterixis, caput medusae
Investigations may reveal:
- Liver function tests (LFTs):
  - Deranged
- Prothrombin time (PT):
  - Prolonged
- Activated partial thromboplastin time (APTT):
  - Prolonged
- Liver ultrasound and transient elastography (FibroScan):
  - May show nodularity/evidence of fibrosis

Vitamin C deficiency

A history may reveal:
- Malnutrition, poverty, a diet of ‘tea and toast’ in older people
- Bleeding gums, poor wound healing
- Associated malaise, anorexia, low mood
Investigations may reveal:
- Vitamin C:
  - Low

von Willebrand disease

A history may reveal:
- Lifelong easy bleeding and bruising
- Patients may have a history of heavy periods, prolonged bleeding after dental procedures, prolonged nosebleeds etc.
- A family history may be present
Investigations may reveal:
- Coagulation screen:
  - Prothrombin time (PT): normal
  - Activated partial thromboplastin time (APTT): may be prolonged
  - Bleeding time: prolonged
  - Factor VIII activity may be decreased
- vWF antigen and factor function assay:
  - Reduced

Haemophilia

A history may reveal:
- Generally younger, male patients
- There may be a positive family history
- Haemarthrosis and muscular pain due to easy bleeding are common
A physical exam may reveal:
- Erythematous, swollen, and tender joints with a limited range of movement due to haemarthrosis
- Bruises and bleeding
Investigations may reveal:
- Coagulation screen:
  - Prothrombin time (PT): normal
  - Activated partial thromboplastin time (APTT): prolonged
  - Bleeding time: normal – Thrombin time: normal
- Factor VIII and IX assay:
  - Factor VIII reduced in haemophilia A
  - Factor IX reduced in haemophilia B

Abuse

A history and examination may reveal:
- Bruising in non-mobile people
- Bruising that is disproportionate/inconsistent with the history, unusually large, present at multiple sites/in clusters, similar in shape and size, patterned (e.g. a handprint, finger gaps, teeth marks, or belt-shaped)
- Bruising found on unusual sites (e.g. non-bony parts of the body or face such as the ears, eyes, cheeks, abdomen, back, arms, or genitalia)
- There may be a delay in presentation
- The history may change between parents/carers and over time
- There may be an unstable home environment
- There may be a history of social services input

Vasculitides

A history may reveal:
- Joint pain, fever, night sweats, and unexplained weight loss
- There may be haematuria, haemoptysis, wheezing, or sinusitis
A physical exam may reveal:
- Palpable purpura
Investigations may reveal:
- Urinalysis:
  - May show haematuria and proteinuria
- Urea and electrolytes (U&Es)
  - May show derangements
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP):
  - May be elevated
- Anti-neutrophil cytoplasmic antibodies (ANCA):
  - May be positive

Cushing’s syndrome

A history and examination may reveal:
- Facial plethora, facial fullness (‘moon face’), truncal obesity, purple striae, acne, depression, proximal muscle weakness, hirsutism
- Bitemporal hemianopia may be present in Cushing’s disease
Investigations may reveal:
- 24-hour urinary free cortisol:
  - Elevated
- Overnight dexamethasone suppression tests:
  - Helps with localising underlying cause

Haemolytic uraemic syndrome (HUS)

A history may reveal:
- Usually seen in children
- Diarrhoea that turns bloody after up to 3 days
- Features of haemolytic anaemia – pallor, fatigue, shortness of breath, and jaundice may be present
Investigations may reveal:
- Full blood count (FBC):
  - Haemoglobin – reduced
  - Platelets – reduced
  - Reticulocyte count – increased
- Blood film:
  - Schistocytes
- Urea and electrolytes (U&Es):
  - Urea and creatinine increased – AKI
  - Metabolic acidosis may be seen – diarrhoea
- Coagulation assay:
  - Prothrombin time (PT) and activated partial thromboplastin time (APTT) are normal
- Markers of haemolysis:
  - Bilirubin – elevated
  - Lactate dehydrogenase (LDH) – increased
  - Haptoglobins – low
- Direct Coomb’s test:
  - Negative – rules out autoimmune haemolytic anaemia
- Stool culture:
  - May detect Shiga toxin-producing E. coli
- Polymerase chain reaction (PCR):
  - May detect Shiga toxin

Thrombotic thrombocytopenic purpura (TTP)

A history may reveal:
- Fever, neurological symptoms (e.g. headaches, confusion, drowsiness, seizures, weakness, altered sensation), gastrointestinal symptoms (abdominal pain, nausea, vomiting, and diarrhoea)
A physical exam may reveal:
- Neurological abnormalities (e.g. weakness, altered sensation, altered mental status)
Investigations may reveal:
- Full blood count (FBC):
  - Haemoglobin – reduced
  - Platelets – reduced
  - Reticulocytes – increased
- Blood film:
  - Schistocytes
- Urea and electrolytes:
  - Urea and creatinine increased – AKI
  - Metabolic acidosis may be seen – diarrhoea
  - May show proteinuria and decreased eGFR – chronic kidney disease
- General markers of haemolysis:
  - Bilirubin – elevated
  - Lactate dehydrogenase (LDH) – increased
  - Haptoglobins – low
- Direct Coomb’s test:
  - Negative – rules out autoimmune haemolytic anaemia
- ADAMTS-13 activity assay:
  - Decreased activity

Disseminated intravascular coagulation (DIC)

A history may reveal:
- The presence of an underlying serious disorder such as sepsis, organ failure (e.g. hepatitis or pancreatitis), or obstetric complications (e.g. eclampsia, amniotic fluid embolism)
A physical exam may reveal:
- Excessive bleeding or oozing blood from sites with intravenous access
- Ischaemic digits
Investigations may reveal:
- Full blood count (FBC):
  - Shows thrombocytopenia
- Blood film:
  - May show schistocytes
    - Clots form in blood vessels which can shred red blood cells (microangiopathic haemolytic anaemia)
    - This is not specific to DIC as they can occur in other microangiopathic haemolytic anaemias such as haemolytic uraemic syndrome
- Coagulation testing:
  - Increased prothrombin time (PT):
    - Measures extrinsic and common pathways
  - Increased activated partial thromboplastin time (APTT):
    - Measures intrinsic and common pathways
  - Increased D-dimer/fibrinogen degradation products
    - These rise after any thrombotic event when fibrin and fibrinogen break down
    - D-dimer is the most notable fibrin degradation product
    - Fibrin is responsible for clot retraction
  - Decreased fibrinogen – but may be normal/elevated
    - Fibrinogen is converted into fibrin to make clots and is broken down into fibrin degradation products, however, it is a positive acute-phase reactant, which may give a normal/high result

Immune thrombocytopenia (ITP)

A history may reveal:
- Usually seen in children
- Bruising following a viral illness or immunisation
A physical exam may reveal:
- Bleeding and bruising but no other abnormalities (e.g. constitutional symptoms, lymphadenopathy, or hepatosplenomegaly)
Investigations may reveal:
- Full blood count (FBC):
  - Thrombocytopenia is seen
- Blood film:
  - No evidence of cell abnormalities (e.g. schistocytes, myelodysplasia etc.)

Acute lymphoblastic leukaemia (ALL)

A history may reveal:
- Usually seen in young children (generally <5 years)
- Fatigue, bruising, and frequent/severe infections may be present
A physical exam may reveal:
- Pallor, fever, splenomegaly with/without hepatomegaly, and lymphadenopathy may be present
Investigations may reveal:
- Full blood count (FBC) and white cell differential:
  - Normocytic normochromic anaemia
  - Leukocytosis
  - Neutropaenia
  - Thrombocytopenia may be present
- Blood film:
  - Lymphoblasts seen – not sufficient enough to diagnose ALL
- Coagulation profile:
  - This is generally done in patients with bleeding and petechiae to screen for coagulopathy
- Urea and electrolytes (U&Es):
  - Hypercalcaemia may be seen – due to bone infiltration/PTH-like hormone release
  - Hyperphosphataemia may be seen – due to leukaemia itself or tumour lysis
  - Hyperkalaemia – due to leukaemia cell lysis
  - Hyperuricaemia – due to tumour lysis
- Liver function tests (LFTs):
  - May be deranged if there is liver infiltration
- Lactate dehydrogenase (LDH):
  - May be elevated due to increased cell turnover
- Immunophenotyping:
  - Involves using flow cytometry on blood and/or bone marrow blood samples
  - Identifies specific protein markers on cells which correlate their lineage (e.g. CD20 is a protein found on B-cells)
- Bone marrow aspiration + trephine biopsy:
  - ≥20% lymphoblasts in the bone marrow is diagnostic for ALL

Acute myeloid leukaemia (AML)

A history may reveal:
- May present with anaemia, bruising, and frequent/severe infections
- More common in older adults
A physical exam may reveal:
- Pallor, fever, splenomegaly with/without hepatomegaly, and lymphadenopathy may be present
Investigations may reveal:
- Full blood count (FBC) and white cell differential:
  - Haemoglobin: low
  - MCV: may be raised
  - White cell count: raised
  - Neutrophils: low
  - Platelets: low
- Blood film:
  - Auer rods or Phi bodies seen
  - ≥20% of cells are blasts on the film
  - Hypergranular promyelocytes with bilobed nuclei with Auer rods may be seen
- Urea and electrolytes (U&Es):
  - May show hyperkalaemia and hyperuricaemia due to cell turnover
- Lactate dehydrogenase (LDH):
  - May be increased due to cell turnover
- Bone marrow biopsy and trephine biopsy – diagnostic:
  - Shows ≥20% blasts and Auer rods
- Flow cytometry:
  - Can detect myeloid antigens to aid diagnosis with the biopsy

Multiple myeloma

A history and physical examination may reveal:
- CRAB IT features:
  - Calcium raised – (‘bones’, stones’ abdominal groans, psychiatric moans’):
    - Bones – bone pain, fractures
    - Stones – renal stones, polyuria, polydipsia
    - Abdominal groans – nausea, anorexia, constipation
    - Psychiatric moans – depression, insomnia, impaired memory, lethargy
  - Renal problems
  - Anaemia
  - Bone pain
  - Infection – frequent and severe
  - Thrombocytopenia
Investigations may reveal:
- Full blood count (FBC):
  - May show normocytic and normochromic anaemia
- Urea and electrolytes (U&Es):
  - Urea and creatinine are usually increased
- Serum calcium:
  - Hypercalcaemia may be present
- Serum free light-chain assay:
  - May show increased concentration of free light chains in serum
- Serum albumin:
  - Usually raised
- Serum and urine protein electrophoresis:
  - Diagnostic test
  - Shows paraprotein spike e.g. raised IgG or raised IgA paraprotein spike
  - Shows hypogammaglobulinaemia except for the singular raised paraprotein
- Whole-body imaging:
  - To identify osteolytic lesions
  - May be done with a CT, however, MRI whole-body MRI is being increasingly used
  - Essential in all patients with MM, shows osteolytic lesions and pathological fractures
- Bone marrow aspiration and biopsy:
  - Diagnostic test
  - Shows monoclonal plasma cell infiltration

Lymphoma

A history may reveal:
- Non-tender supraclavicular/rubbery lymphadenopathy
  - Rarely, this can be painful when drinking alcohol in Hodgkin’s lymphoma (HL)
- B-symptoms – fevers, night sweats, weight loss
- Pruritus
A physical exam may reveal:
- Lymphadenopathy
- Splenomegaly/hepatomegaly
Investigations may reveal:
- Full blood count (FBC) and white cell differential:
  - Haemoglobin: may be low due to bone marrow involvement
  - White cell count: high or low – depending on bone marrow involvement
  - Platelets: low – due to bone marrow involvement
- Erythrocyte sedimentation rate (ESR):
  - May be elevated
- Chest x-ray:
  - May show mediastinal mass
- Immunophenotyping:
  - Can differentiate HL and NHL using flow cytometry– HL is usually CD30 positive and CD15 positive
- Lymph node biopsy:
  - Shows Reed-Sternberg cells in Hodgkin’s lymphoma – these are cells that are either nucleated or have a bilobed nucleus with eosinophilic inclusion-like nucleoli. They have an ‘owl’s eye’ appearance

Myelofibrosis

A history and physical exam may reveal:
- Anaemia, constitutional symptoms
- Massive splenomegaly with/without hepatomegaly – this may cause abdominal discomfort and early satiety
Investigations may reveal:
- Full blood count (FBC) and white cell differential:
  - Anaemia may be present
  - White cell counts may be low, normal, or high
  - Thrombocytosis is often seen, but thrombocytopenia can be present
- Blood film:
  - Tear-drop poikilocytes are seen
- Uric acid:
  - Increased due to increased cell turnover
- Lactate dehydrogenase (LDH):
  - Increased due to increased cell turnover
- Bone marrow aspiration and biopsy:
  - Bone marrow aspiration would not be possible due to fibrosis – known as a ‘dry tap’
    - If this occurs, a trephine biopsy is performed
  - Bone marrow biopsy shows fibrosis and is diagnostic
- Gene mutation analysis:
  - JAK2 mutation may be positive

Myelodysplastic syndrome

A history and physical examination may reveal:
- More common in older patients (>65 years)
- Features depending on cell lineages affected (e.g. anaemia, recurrent and severe infections, bruising)
Investigations may reveal:
- Full blood count (FBC) and white cell differential:
  - Shows one or more cytopenias
- Reticulocyte count:
  - Inappropriately normal or low for the severity of anaemia
  - Due to the inability to generate new red blood cells
- Haematinics:
  - To screen for other causes of anaemia
  - B12 and folate are normal
  - Iron studies are normal
- Bone marrow aspiration and biopsy:
  - Shows dysplastic cells

Aplastic anaemia

A history may reveal:
- Idiopathic in many cases
- May be secondary to NSAIDs, chloramphenicol, carbamazepine, phenytoin
- There may be a history of infection with parvovirus B19, Epstein-Barr virus (EBV), HIV, or hepatitis
A physical exam may reveal:
- Features of anaemia (pallor, shortness of breath etc.)
Investigations may reveal:
- FBC and differential:
  - There must be two of the following:
    - Haemoglobin <100 g/L
    - Platelet count <50 x 10⁹/L
    - Neutrophil count <1.5 x 10⁹/L
- Reticulocyte count:
  - Usually low due to the bone marrow being unable to generate new cells
- Bone marrow biopsy:
  - Definitive diagnostic test, shows hypocellular marrow with no abnormal cells

Ehlers-Danlos syndrome

A history and physical examination may reveal:
- Joint hypermobility with stretchy skin, poor wound healing
- There may be a history of joint subluxations or dislocations
- There is often a positive family history
Investigations may reveal:
- Clinical diagnosis

Marfan syndrome

A history and examination may reveal:
- Tall stature, arachnodactyly, wide arm span
- Pectus excavatum
- Mitral and/or aortic valve murmurs
- Pes planus
- Upwards lens dislocation
- A positive family history
Investigations may reveal:
- Genetic testing:
  - Positive

Author

Ishraq Choudhury
FY1 doctor working in North West England.
MB ChB with Honours (2024, University of Manchester).
MSc Clinical Immunology with Merit (2023, University of Manchester).<br
Also an A-Level Biology, Chemistry, Physics, and Maths tutor.
Interests in Medical Education, Neurology, and Rheumatology.
Also a musician (Spotify artist page).
The A-Level Cookbook
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