MRCP revision battle 18.1: Warfarin

Today is another 'octopus' day with 8 battles to embrace (three of which are mercifully brief)

So the topics are:

MRCP revision battle 18.1: Warfarin
MRCP revision battle 18.2: Psoriasis
MRCP revision battle 18.3: Beau's lines
MRCP revision battle 18.4: Elliptocytosis
MRCP revision battle 18.5: Aortic stenosis
MRCP revision battle 18.6: Polymyalgia rheumatica
MRCP revision battle 18.7: Threadworm
MRCP revision battle 18.8: Pseudohypoparathyroidism






MRCP revision battle 18.1: Warfarin


Ah, warfarin... everyone's favourite out-of-hours bleep as a houseofficer.  Originally made as a rat poison, it quickly became a favourite in the UK for the treatment of DVTs, PEs and prevention of clots associated with mechanical heart valves.


Warfarin works by inhibiting vitamin K epoxide reductase, which prevents vitamin K being recycled.  Since vitamin K is a cofactor for factors II, VII, IX and X it decreases coagulation.


Note however that vitamin K is also a cofactor for protein C and protein S, which help inhibit the clotting cascade.  As protein C is initially affected more than the clotting factors by lack of vitamin K warfarin is initially a procoagulant and when started therefore increases the risk of thrombosis.


Warfarin is monitored by INR.  The targets are:

• PE/DVT: INR 2-3
• metallic valve: INR 3-4

The duration of anticoagulation depends on the cause of the clot:

• below knee DVT after surgery: 6 weeks
• above knee DVT/PE after surgery: 3 months
• DVT/PE without precipitating factor identified: 6 months

1-2% of patients on warfarin have a haemorrhage per year.

Other complications of warfarin treatment include:

• increased risk of osteoporosis
• purple toe syndrome - toes turn purple ?secondary to cholesterol deposits 3 to 8 weeks after starting warfarin

Warfarin levels are notoriously difficult to regulate.

Things which increase the effect of warfarin include:

• erythromycine/clarithromycin
• metronidazole
• hyperthyroidism
• cranberry juice
• alcohol
• amiodarone
• propranolol
• fluconazole
• isoniazod
• cimetidine
• omeprazole

Things which decrease the effect of warfarin include:

• rifampacin
• carbamazepine
• chlordiazepoxide
• avocado in excess!

Management of INR outside the desired range depends both on the level and if there is bleeding:

• major bleed
• stop warfarin
• give vit K 5-10mg IV
• give prothrombin complex (II, VII, IX, X) or FFP if this is not available
• INR>8 but no/minimal bleeding
• stop warfarin
• give vit K 2.5-5mg PO/0.5-1mg IV
• restart warfarin when INR<5
• INR 5-8, no bleeding
• stop warfarin
• restart when INR<5
• INR 5-8 minor bleeding
• stop warfarin
• give 1-2.5mg vitamin K PO
• restart when INR<5

As an aside, with an eye on the future, a new drug called dabigatran is looking to usurp warfarin as king of the anticoagulants.  Trials such as RELY and RECOVER have shown dabigatran to be non-inferior to warfarin in preventing thrombosis, to cause fewer bleeding adverse effects and even better not require regular blood tests to check levels.  Of course its expensive and so not yet approved...



On to the second battle of the day, psoriasis...

MRCP revision battle 18.2: Psoriasis

Psoriasis is an autoimmune disease that classically causes a silver-scale topped rash on the skin.

It affects 1-2% of the population.

The cause is believed to be abnormal activity of the type 1 T helper cells.
It is associated wtih HLA CW6, B13, B17 and B27.


Females tend to be affected at a younger age than males.


The main 'types' of psoriasis are:

1. chronic plaque
2. generalised pustular
3. palmo-plantar pustulosis
• strong association with smoking
• tends to affect middle-aged females
4. guttate
• usually young adults/teenagers
• is often preceded by a strep infection 2-4 weeks before
• resolves spontaneously in 2-3 weeks
5. nail
6. flexural

Athropathy is a feature in 8% and may be in the form of :

• symmetric arthritis - appears rheumatoid-like; 50%
• asymmetric arthrtitis - 35% - dactylitis
• arthritis mutilans - <5%
• spondylitis
• distal interphalangeal predominant

Psoriasis can be worsened by multiple factors, including:

• trauma
• infection
• post-partum
• beta blockers
• lithium
• stress
• alcohol
• NSAIDs

Management for skin psoriasis is by a host of lotions and potions - coal tar, dithranol, topical vitamin D.... if these haven't already been drummed into you a brief visit to the BAD website (british association of dermatologists, trying to sound cool) to recap might be a good idea.



Now for a brief skirmish with Beau's lines

MRCP revision battle 18.3: Beau's lines

Beau's lines are transverse depressions in nails due to temporary arrest in their growth.

They are associated with:

• psoriasis
• diabetes
• metabolic disturbances

Now onwards to another very brief battle, elliptocytosis

MRCP revision battle 18.4: Elliptocytosis

Elliptocytosis is an autosomal dominant condition which results in cigar-shaped elliptocytes:

In severe cases they can cause haemolytic anaemia; happily the majority of people with elliptocytosis have no ill effects from it at all.


Now on to a more substantial battle again: aortic stenosis

MRCP revision battle 18.5: Aortic stenosis

Aortic stenosis may be detected incidentally (keen houseofficer noticing the classical ejection systolic murmur radiating to the carotids) or may present with its classical triad of symptoms that can be remembered as 'DAD':

• exertional dyspnoea
• etertional angina
• exertional dizziness

Signs of aortic stenosis include:

• ejection systolic murmur radiating to carotids
• slow rising pulse
• narrow pulse pressure
• heaving apex beat

Things which suggest severe aortic stenosis include:

• LVF
• soft S2
• paradoxically split A2
• S4

 The formal divisions of severity are as follows:

• mild: area >1.5cm, gradient <25
• moderate: area 1-1.5cm, gradient 25-50
• severe: area <1cm, gradient >50
• critical: area <0.7cm, gradient >80

The main causes of aortic stenosis are:

• calcification of the valve
• bicuspid aortic valve

ECG changes which may be associated with aortic stenosis include:

• p mitrale
• LVH
• LAD
• poor R wave progression
• complete heart block if calcification involves the conduction tissue.

Treatment is surgical.  The operative mortality is around 20-25% if there is LVF, 2-8% if not.



So from the very factual aortic stenosis on to the slightly touchy-feeling PMR...

MRCP revision battle 18.6: Polymyalgia rheumatica

Polymyalgia rheumatica (PMR) is a slightly nebulous condition which the Oxford handbook defines as 'symmetrical aching, tenderness and morning stiffness in shoulders and proximal limb muscles, +/- systemic features'.  These systemic features can include anything from fatigue to anorexia...


It generally affects over 70s and is rare in under 60s.


Bloods tend to show a raised ESR


Treatment is with prednisolone (15mg PO OD) which tends to produce a dramatic improvement in days.  This should be decreased by 1mg per month, and of course anti-OP treatment should be given concurrently.

If symptoms recur on decreasing the dose and you have a lovely little old lady stuck on >10mg OD for over a year, it is worth considering methotrexate or azothioprine to try and allow you to decrease the steroid.


As a random aside, 10% of patients with PMR will suffer from carpal tunnel syndrome.



Now get ready to itch as we move on to the penultimate battle of the day, threadworm....

MRCP revision battle 18.7: threadworm

Threadworm, AKA enterobius vernicularis, appears frequently in MRCP questions, usually in relation to patients in institutions.

They tend to present with perianal itching.

Treatment is mebendazole 100mg (or piperazine if the patient happens to be under 2 yrs of age)



On that pleasant note, on to the last battle of the day, pseudohypoparathyroidism

MRCP revision battle 18.8: Pseudohypoparathyroidism

Pseudohypoparathyroidism is an autosomal dominant condition that occurs when a person is insensitive to PTH.


Features include:

• short metacarpals (esp 4th and 5th)
• short stature
• round face
• obese
• low IQ
• dental hypoplasia

It can be diagnosed by a failure of cAMP to increase after injection of parathyroid hormone.  More traditionally, the clinical picture of low calcium, high PTH and normal/raised alk phos is enough.


Treatment is with alfacalcidol.

It is worth noting it is associated with slipped femoral epiphysis.



To end today's battles on an almost comic note (and the fact I find this comic is a reflection that I really should get out more) there also exists a pseudopseudohypoparathyroidism, which is essentially the morphological features of pseudohypoparathyroidism but with normal biochemistry.  Hopefully that'll make you smile if it comes up!


A few questions on yesterday's battles are now online here, otherwise see you tomorrow!

MRCP questions: War 17

As with previous 'wars' after 'battles' these are just a few quick questions to see if your brain cells have retained the information provided in battles 11.1 to 11.4.

Grab a piece of paper, jot down your answers then compare them to my answers here


Question 1:
What haematological picture do you get in DIC?


Question 2:
What symptoms are associated with jugular foramen syndrome?


Question 3:
Name the commonest form of thyroid cancer.



Question 4:
List 3 causes of unilateral pleural calcification



Question 5:
What condition is associated with a 'plucked chicken skin' appearence?



Question 6:
Legionella is a gram positive bacteria.  True or false?




Question 7:
Which biochemical disturbance is classically associated with legionella?


The answers are here

MRCP revision battle 17.1: DIC

Lots of short battles from a variety of specialities today so buckle up for a ride through some haematology, neurology, endocrinology, respiratory and dermatology.  Yeee-hhaaaa!

MRCP revision battle 17.1: DIC
MRCP revision battle 17.2: Jugular foramen syndrome
MRCP revision battle 17.3: Thyroid cancer
MRCP revision battle 17.4: Legionella infection
MRCP revision battle 17.5: Pleural calcification
MRCP revision battle 17.6: Pseudoxathoma elasticum






MRCP revision battle 17.1: DIC


Disseminated intravascular coagulation (=DIC) is the pathalogical widespread activation of coagulation.


Blood tests will show:

• prolonged PT
• prolonged aPTT
• massively raised d-dimer levels
• low platelets
• low fibrinogen
• schistocytes

Of these, it is the level of fibrinogen which best correlates to the severity.


Causes of DIC include:

• obstetric
• crush injury
• septicaemia
• malignancy
• transfusion reaction

The treatment is:

• treat the cause
• give platelets if platelets <50
• cryoprecipitate
• FFP
• activated protein C if septic.

Now lets canter onwards to jugular foramen syndrome....

MRCP revision battle 17.2: Jugular foramen syndrome

Jugular foramen syndrome, also known as Vermet's Syndrome, is a condition arising from the compression of the cranial nerves that run through the jugular foramen.


Now just in case they aren't quite on the tip of your tongue, the nerves that run through the jugular foramen are IX, X and XI.


The syndrome is therefore characterised by:

• loss of taste to posterior 1/3 of tongue (CN IX)
• dysphagia (CN X)
• sternocleidomastoid and trapezius paralysis (CN XI)

Anything that compresses the jugular foramen can cause this syndrome.  The commonest cause is a paraganglioma.



Now we've acquired a bit more esoteric MRCP knowledge, lets gallop on to discover some details about thyroid cancer...

MRCP revision battle 17.3: Thyroid cancer

Under 5% of thyroid lumps are malignant, and in general those with a malignant mass will be euthyroid.


There are 4 main types of thyroid cancer:

1. papillary - 70% - mainly affects young females, excellent prognosis
2. follicular - 20% 
3. medullary - 5% - associated with MEN-2 (more on MEN tomorrow)
4. anaplastic - 1% - very poor prognosis and resistant to treatment.

Rarely a patient can have lymphoma of the thyroid - this usually follows hashimotos disease.


The mainstay of treatment for thyroid cancer is surgery.



Lets break into a canter as we head on to legionella...

MRCP revision battle 17.4: Legionella

Legionella is a gram negative bacteria which causes legionella disease/pneumonia and in MRCP questions is most likely found living in a cruise ship/hotel's water tank or airconditioning system.



The symptoms of legionella disease are:

• flu-like
• dry cough
• dypnoea
• GI upset

Complications of legionella which may show up in the blood results include:

• SIADH - low sodium
• hepatitis - deranged LFTs

Legionella is killed above 60c, cannot multiply between 50 and 60c and are happiest between roughly 35 to 45 c


Males are more affected than females, 3:1


CXR may show bibasal consolidation.


Treatment is with antibiotics which achieve a high intracellular concentration, such as clarithromycin, rifampicin or fluroquinolone.


Legionella has a 10% mortality.



Lets now trot on to pleural calcification...

MRCP revision battle 17.5: Pleural calcification

Pleural calcification pops up both in real life and in MRCP questions intermittently.


The commonest cause is asbestosis. 
This tends to be bilateral and spare the costophrenic angles


So, if the pleural calcification is unilateral consider:

• previous haemothorax
• previous TB pleuritis
• previous empyema

Other differentials to consider are:

• previous radiotherapy/radiation exposure
• post talc pleurodesis, which will mimic calcification.

Lets return to a full-speed gallop to our last battle of the day, pseudoxanthoma elasticum

MRCP revision battle 17.6: Pseudoxanthoma elasticum

Pseudoxanthoma elasticum is fragmentation and calcification of elastic fibres.


It is an autosomal recessive condition, found on chromosome 16.


Its various associations are:

• a characteristic 'plucked chicken' skin (google it, memorise it, get ready to spot it in part 2)
• angioid streaks in retina/vision problems
• rarely GI bleeds
• claudication/cardiovascular problems.

There is no treatment so management is symptomatic only.


Thats all for today, proceed to the war if you are up to.

MRCP questions: War 16

As with previous 'wars' after 'battles' these are just a few quick questions to see if your brain cells have retained the information provided in battles 16.1 to 16.7.

Grab a piece of paper, jot down your answers then compare them to my answers here


Question 1:
List 8 symptoms/signs of pagets disease


Question 2:
Which oral medication would you give to treat pagets disease?


Question 3:
Which medication would you use to treat PCP?


Question 4:
A patient has muscle weakness that gets worse on exercise.  What medication would you give them?


Question 5:
A patient tells you they have weak muscles which get better on exercising.  They state they believe its due to their lung cancer.  What condition do they have?


Question 6:
]What is the commonest cause of hemiballismus?



Question 7:
What is the medical treatment for hyperprolactinoma?


Question 8:
'Waiters tip' is associated with which palsy?




The answers are here

MRCP revision battle 16.1: Pagets disease of bone

In between catching up on seemingly endless loads of washing (do socks breed when left alone in a wash basket?) a few hours of MRCP revision has been done and 7 new battles have been written...

MRCP revision battle 16.1: Pagets disease of bone
MRCP revision battle 16.2: Pneumocystis carinii
MRCP revision battle 16.3: Myasthenia gravis
MRCP revision battle 16.4: Lambert-Eaton syndrome
MRCP revision battle 16.5: Hemiballismus
MRCP revision battle 16.6: Prolactin
MRCP revision battle 16.7: Erbs palsy





MRCP revision battle 16.1: Pagets disease of bone


Pagets disease of bone is accelerated, disorganised bone turnover due to increased number and activity of osteoclasts and osteoblasts.


It is rare in under 40s.


Predisposing factors include:

• increasing age
• northern latitude
• family history
• being male

Features of Pagets include:

• bone pain
• bowing of tibia
• bossing of skull
• secondary arthritis
• deafness/other cranial nerve compression
• high output heart failure
• pathological fractures
• bone sarcomas (occur in 1% over 10 yrs)

My way of remembering the features of pagets is this slightly random rhyming story:
"Bowing to the Boss, oh what a pain,
I'm deaf and arthritic and since the fracture I'm lame
my heart's now a failure, and oh what a shame
I've got bone sarcoma - thats the end of the game"



Bloods in Pagets show:

• raised ALP
• normal calcium (unless a long period of immobility)
• normal phosphate

Treatment is alendronic acid



That wasn't too bad... onwards to battle 16.2...

MRCP revision battle 16.2: Pneumocystis carinii

Pneumocystis carinii, AKA pneumocystis jiroveci, is a unicellular eukaryote.

It can cause pneumonia in patients with HIV and accounts for 40% of all AIDS-defining illness.
If CD 4 count is less than 200 PCP prophylaxis (=co-trimexazole) should be started.



Features of PCP:

•  dyspnoea
• dry cough
• fever
• few chest signs on examination
• desaturation on exercise

CXR typically shows mid-lower bilateral interstitial infiltrates, but it may look normal.

Sputum cultures are often negative so BAL may be needed.



Treatment is:

• co-trimexazole
• IV pentamidine if severe
• steroids if hypoxia
• use of steroids decreases respiratory failure by 50% and death by 1/3)

On to battle 3 of the day and a classic condition - myasthenia gravis.

MRCP revision battle 16.3: Myasthenia Gravis

Myasthenia gravis is an autoimmune condition in which muscles become easily tired and weak.  It affects 1 in 20 000.


90% of patients have autoantibodies to nicotinic acetylcholine receptors.
If these are negative consider looking for MUSK antibodies (= muscle specific kinase)


The key feature of MG is repetitive stimulation leading to decreased evoked response.


The order in which muscle groups are affected in MG is:

• extraoccular (--> diplopia)
• bulbar
• face
• neck
• lumb
• trunk

Reflexes are normal in MG.


Test of choice: tensilon test = edrophonium


Treatment of MG is:

• cholinesterase inhibitors eg pyridostigmine
• prednisolone if pyridostigmine unsuccessful (but be aware that paradoxically steroids can worsen MG)
• plasmaphoresis/IV IG if respiratory muscle involvement.

If there is hyperplasia of thymus/thyroma, up to 60% of cases will remit after surgery.


Up to 10% of patients with MG will have hyperthyroidism.


Drugs which exacerbate MG include:

• penicillamine
• quinidine
• beta blockers
• lithium
• phenytoin
• gentamycin

Now on to the 'similar but different' Lambert-Eaton syndrome...

MRCP revision battle 16.4: Lambert Eaton Syndrome

Lambert-Eaton syndrome is a rare condition affecting voltage-gated calcium channels which results in:

• muscular weakness that improves with activity
• autonomic symptoms (dry mouth, constipation, impotence)
• hyporeflexia

 

It is most commonly a paraneoplastic phenomenon, usually due to small cell lung cancer (very rarely due to breast or ovarian cancer).  It can also be autoimmune.


Treatment is 3,4 diaminopyridine.

Regular CXR should be performed as Lambert-Eaton may preceed the development of small cell lung cancer by up to 4 years.



Notice how although both MG and Lambert-Eaton are characterised by muscle weakness there are lots of differences - weakness gets worse on repetition in MG but better in LE, reflexes are normal in MG but reduced in LE and there may be autonomic symptoms in LE but not MG.  Also not involvement of occular muscles is far more common in MG.



Lets now diversify to something completely different - hemiballismus...