Haematology multiple choice questions

The ESR is the rate in mm at which red blood cells precipitate out of a pre-filled tube (e.g. citrated blood sample).

The rate at which they flal out of circulation is dertermined by 2 main factors:
the pro sedimentation factors in the bloodstream that cause the RBC’s to stick together and precipitate out (like fibrinogen) and the negative charges on RBC’s resisting this.

During inflammatory states where lots of plasma proteins are produced (e.g. sepsis) and other conditions (like myeloma/ TB etc) the ESR will rise very high.

ESR >100 Causes:

Tuberculosis

Myeloma

Giance Cell Arteritis

Cancer

Other vasculitis

Rheumatoid Arhtritis/Lupus

Lymphoma

In immunodeficient states like Common variable immunodeficiency (CVID) the ESR may be “low”.

Sickle cell’s in sickle cell anaemia generally take longer to precipitate out, and therefore the patients have a “higher” ESR.

Ciclosporin is nor particularly toxic to the bone marrow but carries significant nephrotoxicity. 1st line renal transplant rejection agent but unfortunately is nephrotoxic.

In clinical exams remember S/E include hypertension (check BP), Acne, gum hypertrophy, peripheral neuropathy etc. If you see a renal transplant case you can then hypothesise:

“I wonder if the gum hypertrophy is related to teh use of ciclosporin, a calcineurin inhibitor that…. ” etc etc etc

TNF is a pro inflammatory cytokine important in immune upregulation and the inflammatory response.

Anti TNF drugs are generally monoclonal antibodies that either bind TNF or block its receptors.

Indication: rheumatoid arthritis/ psoriatic arthritis/ ankylosing spondylitis (not all drugs are NICE approved or licensed for all conditions)

Epoetin is recombinant human erythropoietin which is used to treat the erythropoietin deficiency that occurs in chronic renal failure. Target Hb> 10 in CRF.

Hydroxycobaliamin is an IM preparation of vitamin B12 that needs to be given every 2 months or so as part of maintenece therapy for B12 deficiency of any cause (in this case pernicious anaemia)

GCSF can be used to treat patients with significant neutropaenia. Should only be given under expert advice.

Its unlikely to be related to the infection

This is an exam. He’s a doctor. This means his ethanol intake is likely to be high(!). Fact. The MCV is therefore likely to be incidental.

Irrespective of this infections do not characteristically change the MCV.

Although mycoplasma pneumonia can cause an autoimmune haemolytic anaemia, subsequent jaundice and a reticulocytosis causing a rise in the MCV (red blood cell precursors in the form of reticulocytes are large cells) this is less likely than the finding to be incidental.

Clinical Pearl Occam’s Razor: “All other things being equal, the simplest solution is the best.”

i.e. the simplist explaination is likely to be the correct one. If a simple exlaination can account for a number of symptoms or signs then it it likely to be the cause.

e.g. fatigue, jaundice, pruritis and excessive ethanol intake point towards Liver Cirrhosis secondary to alcohol rather than to Hepatitis C & Hypothyroidism, Tinea infection

Acquired Cause

In an exam when approaching bleeding disorders be wary of clues about previous problems (e.g. von Willebrand disease: bleeding post dental surgery).

This clearly is an acute problem and therefore is likely to be an aquired condition.

This may seem blindingly obvious but its important not to get confused in the exam. Its highly unlikely to be a hereditary cause in the abscence of any other symptoms for the past 74 years!

Leukaemia

Blast cells are precursor cells from marrow that are not usually seen on the blood film. Their presence suggests a leukaemic process.

Myeloid precursor cells differentiate into: Neutrophils / eosinophils and basophils.

Lymphoid precursor cells differentiate into: lymphocytes (agranulocytes).

Arrange urgent (out of hours) full blood count

Carbimazole can cause neutropaenia. One of the only symptoms in the early phase can be a sore throat. It is essential that the FBC is checked urgently

This goes for the cytotoxic drugs in general including:

azathioprine

methotrexate

chemotherapy etc

It has a high sensitivity for DVT

D Dimers have a high sensitivity but low specificity for DVT and PE.

That makes them useful as a risk stratification score in assessment of patients with suspected DVT and PE.

Having said that a positive D –dimer is not specific to DVT or PE. Its commonly elevated in infection/immobility/ malignancy/ sepsis/ chronic inflammatory disease/ connective tissue disease/ pregnancy.

Therefore it has a lower specificity.

Ultrasound Doppler right calf

An ultrasound scan will confirm clot in the venous system. It is the simplest and least invasive of the tests available.

Always be wary when offered unusual sounding investigations like MRI calf. Although it may well show up the DVT, it wouldn’t be the investigation of choice in a routine patient.

Iron deficiency anaemia

IDA is the most likely. Don’t be put off by the ferritin being normal:

Ferritin is an acute phase protein and will go up. IN this sense it is identical to CRP. Therefore in patients with active inflammation (CRP120) this is the most likely explaination. ACOD is possible, but the low MCV makes this less likely (its usually normocytic).

Acute GI blood loss generally has a normal MCV.

None of the listed diagnoses

None of the diagnoses here: Poikilocytes are irregularly shaped red blood cells. They are seen most commonly in iron deficiency anaemia.

Hypochromia simply refers to RBC’s that stain less as a result of a reduction in iron content.

Its seen in Iron deficiency anaemia.

Overall the most likely diagnosis is therefore iron deficiency anaemia.

There are no blast cells that would suggest an acute leucaemia or early precursor cells seen in the bloodstream.

Also there is no lymphadenopthy or other clinical findings.

Beware questions about routine insurance medicals!

Palpable spleen

ITP is associated with an onset over weeks of purpura and an isolate low platelet count.

Its caused by autoantibodies that tag platelets and then they’re phagocytosed by the spleen.

Treatment: Steoroids / immunosupression / IV immunoglobulin / splenectomy / rituximab.

Rituximab is a new andi CD20 antibody which can now be used to treat some cases of ITP.

Clinical pearl: Although a splenectomy can be used to treat ITP there IS NOT a palpable spleen in ITP alone.

A viral infection can commonly raise the total WCC

Diagnosis here = viral infection.

Viral infections often cause elevated lymphocyte counts, but are less likely to raise your neutrophil count. Patients should not be treated on the basis of blood results and therefore that answer is “less correct”.

Lymphadenophthy elsewhere

The presence of lymph nodes elsewhere strongly suggests wither lymphocytic leukaemia or a lymphoma.

Inflammatory markers and non specific markers like LDH can be raised in either condition.

Immunoglobulins and protein electorophoresis

Red flags regarding back pain are waving all over the place.

He has an ESR of >100. Weight loss. Renal impairment. Low Albumin.

Only a few things do this.

Look at what’s pathological:
Back pain, renal impariment, high total protein, low albumin: this sounds like myeloma.

It is likely that he has infiltration of his spine and possible a subsequent pathological fracture. The imaging may help but will not give a diagnosis.

Although the Xrays/ MRI may reveal a lesion it will not tell you what that is.

Myeloma is a malignancy of plasma cells causing monoclonal production of antibody.

As the antibody is all the same (monoclonal) rather than all different (polycloncal) when you perform an electophoritic stip you see a single abnormal “band”.

Ig’s and electrophoresis are commonly used as screening tools for immunoglobulin production and myeloma.

Immunoglobulin production

Immonoglobulins are proteins:

When measuring total protien: you’re essentially measuring albumin and all the other plasma proteins, a large proportion of which are immunoglobulins (along with fibrinogen, CRP etc).

So in an exam where you see a high total protein and a low albumin, then think of myeloma.

Remember myeloma can cause nephrotic syndrome: however that would not explain the high total protein so its not the “best” answer.

Lytyic

The bone lesions in myeloma are lytic. This leads to the characteristic description of the “pepper pot” skull with numerous lytic lesions giving the appearance of a skull with lots of holes in it.

Classically sclerotic lesions are breast cancer and prostate cancer.

The common cancers that metastasise to bone are:
Breast
Bronchus
Kidney
Prostate
Thyroid

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The test rules out neutropaenia AND None of the listed answers are correct

To look for neutropaenia you need to look at the WCC breakdown. For example in this case if it was

Lymphocytes 4.1 x109

Neutrophills 0.3 x109 (NR 2-6 x 109)

Eosinophils 0.6×109

Then the patient is neutropaenic despite having a normal WCC.

A normal Hb rules out homozygous (“full blown” sickle cell anaemia. These patients will often run HB’s of 7-8g/dl.

A normal WCC or Lympohcyte count does not rule out HIV/AIDS.

Urgently get details of previous attendances / prior history from notes and the patient

Sickle cell anaemia is caused by malproductino on the beta chains of Hb.

“HbA” is produced in place of “HbS”.

A homozygous sickle cell patient will have 2 genes cosing for the amino acid and therefore will be HbS HbS : called HbSS.

Heterozygous patients are HbAS: this is sickle cell trait.

There are a number of other genetic deficiencies that can produce anaemia etc etc.

However the patient tells you he is “homozygous” sickle cell disease. Homozygous sickle cell patients generally will have an Hb of 6-8. An HB of 15 is not compatible with homozygous sickle cell disease. Therefore you need to speak to the patient urgently: there is always a potential for abusers of diamorphine to present requesting analgesics spuriously.

It carries a small risk of sickle cell crisis

HBAS is thought to offer some protection against malaria. Patients are susceptible to crises and sickling of the RBC’s in clood vessels under certain conditions e.g. hypoxia (remember: think post op / plane flight etc).

Palpble notch on its lateral aspect

The splenic notch can be palpated on the medial side of the spleen. Its very difficult to feel. The spleen has a dull percussion note. This differs from the kidney in the fact that a renal mass is often resonant to percussion (overlying bowel as the kidneys are retroperitoneal.

Thalassaemia

In exams “overseas” think of links to any of the conditions listed associated with country of origin or which may be of higher prevalence from communities outside of the UK: here its TB, HIV and Thalassaemia (Mediterranean).

Again: a question where a finding is “incidental”. In exams this often means the patient has a condition which may not be of great harm but can produce abnormal blood results. E.g. Gilberts Syndrome (high bilirubin). This makes HIV and TB unlikely as a cause. (Irrespective of this neither has a penchant for causing anaemia).

A low grade anaemia in a male with a disproportionately low MCV (<70) is highly suggestive of thalassaemia (minor).

Virchow

Virchow’s triad describes
-vessel wall damage
-venous stasis
-blood hypercoagulability

These three factors are key in the predisposition to thrombus formation in a vessel.

Hebberden – famous for describing (amongst other things) DIPJ nodes of OA.

Osler – the famous Osler Weber Rendu syndrome: hereditary haemorrhagic telangectasia.

Weber – see above.

Murphy – Murphy sign of RUQ pain in Cholecystitis.

True: if you use it in patients who have no clinical evidence of DVT (for example everyone presenting to primary care with leg pain) then the sensitivity and specificity with regards to detecting DVT and PE will change. This goes for almost any test.

For example:

Check D-Dimer on 100 people with a swollen leg with pitting oedema.

Vs Checking D-Dimer on 100 people in primary care (including sprained ankles etc).