Part 6



Fibrin degradation product 

Small present in blood after a clot is degraded by fibrinolysis 

Contains two D fragments of the fibrin cross linked 

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0.8-1.2 = normal 

2-3  = desired target for warfarin user 

3.5 if a more intense strategy is required 

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Leads to irreversible inhibition of COX1 

TXA2 comes from platelets and is a potent platelet agonist, vasoconstrictor and mitogen and its a major product of platelet COX-1 

This drug does not affect the synthesis of PG12 as the endothelium can continue to produce COX 2 (and with the inhibition of COX-1 more COX2 is made to compensate) 

PG12 is anti-thrombolytic 

Ratio of TAX2:PG12 is reduced and PG12 dominates 

High risk patients vascular death is reduced by 15% 

Not fatal vascular events reduced by 30% 

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Clopidogrel and Prasugrel

Irreverisble P2Y12 antagonists 

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Superior to aspirin in preventioin of vascular ischaemic events and death 

There is a decreased pharmacological response in 20-30% of patients 

Broken down in a two step process by the liver and only the active metabolite has an anti-platelet effect however some of the populatio has genetic polymorphisms in CYP450 and CYP2C19 

Defective enzymes leads to defective metabolism 

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Improved efficacy on clopidogrel (10x) 

not affected in genetic variation by CYP450 and has a more rapid onset due to increased converstion to active metabolite (one step) 

However comes with an increased risk of bleeding event 

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P2Y12 antagonist 

Decreased death of vascular events 

Decreased MI 

similar risk of major bleeding events 

Does not require metabolism as a thienopyridine derivative 

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P2Y12 antagonist 

IV function returns to normal after 20mins 

Acute and therefore given prior PCI 

Near complete inhibition of aggregation 

Does not require metabolism as a thienopyridine derivative 

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FXa inhibitors








Better efficacy as well as being safer than heparin 

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Licensed oral anticoagulants in the UK







(prescribed over warfarin for people with non valvular AF) 

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Option for prophylaxis of atherothrombotic events 

With aspirin alone or with aspirin and clopidogrel

after an acute coronary syndrome in people with elevated cardiac biomarkers 

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Direct thrombin inhibitors

Block the active site of thrombin 

IV - as effective as LMWH, short acting 






Dabigatran (licensed for AF and DVT)

As effective as warfarin, less risk of haemorrhage 

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Only DOAC with an antidote ...

(But management and pharmacokinetics of DOACs as easier compared to other anticoagulants / platelets) 

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Robertsonian translocations

Only the acrocentric chromosomes - 13,14,15,21,22 

All p arms are short and identical - code for rRNA 

Occur when there is a break at the centrome and the two long arms join together - therefore balanced carriers have 45 chromosomes 

Prevelance of 1 in 1000 

Balanced carriers are phenotypically normal but have reproductive risks 

Recurrent miscarriage 

Patau and Down syndrome 

Male infertility 

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Alternate = balanced, adjacent = unbalanced

Which out of alternate and adjacent segregation leads to balanced and which to unbalanced 

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Exchange of material from two non-homologous chromosomes 

Prevelance of 1 in 500 

Balanced carriers are phenotypically normal 

50% of conceptions will have normal chromosomes or be balanced 

Unbalanced results in - miscarriage or dysmorphic delayed child (if the segment translocated it small) 

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Deletions and duplications

Result from aberrant recombination 

Typically due to repeat sequences 

De novo or inherited 

Examples included prader-willi, Angelman and diGeorge 

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Monogenic disorders

Examples include 

Spinal muscular atrophy 

Cystic Fibrosis 

Duchene Muscular Dystrophy 

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Cystic fibrosis

US of a fetus showing an echogenic bowel 

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Aneuploidy screening and sexing 

Microsatellite markers used to identify and count chromosomes 


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Detects genomic imbalance 

Compares two complete genomes (sample and control) and detects the differences in copy number across the whole genome 

Control = green - Si-3 

Test = red - Si-5 

Sensitivity of ~120kB (very sensitive) 

Report time in 10 days 

Prenatals report all imbalances >400kB and all within a known syndrome region 

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G banding

Confirmation of aCGH and follow up 

5-10mB resolution 

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Di George

22q11.21 (deletion from 22) 


Broad nasal bridge 

Hypo-plastic left branch pulmonary branch 

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US - 1st trimester

Routie scan - 12wks from LMP 

Used to date the pregnancy

Check for single fetus or multiple 

Measurement - in terms of dating: 

Crown-rump length; 45-84mm = 11+2-14+2 weeks 

If CRL >84mm date by head circumference 

Also offer screening for trisomies 

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US - second trimester

Routine anomaly scan at 18-20wks 

Assess fetal growth and anomalies 

Placental site - low and covering the cervix or high up 

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HC, Bi-parietal diameter, abdo circumference, femu

Four things we measure to assess fetal growth / biometry 

All combined to estimate the fetal weight 

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Head circumference

You know you are in the right place when you see:

The midline 

Cavum septum pellucidum at the anterior 

At the posterior there is the post. horn of the ventricle 

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Bi-parietal diammeter

Measurement between the two parietal bones 

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Small for gestational age

<10th centile but stays on the same curve 

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Aetiology of SGA

Growth restricted 40%

Insufficient nutrient delivery 

Mother - HTN, PET, DM, SCA (decreased O2 capacity) 

Placental damage (smoking) 

Intrinsically small 20%

chromosomal abnormality (Trisomy) 

Infections - CMV 

Environmental - fetal alcohol syndrome 

Healthy small 40%

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Low levels are associated with poor placentation 

Leading to an increased risk of SGA and PET 

Give aspirin 60mg OD, will help with placentation if given before 16 weeks 

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Stimulate pancreatic beta cells to secrete insulin 

Side effects = Hypoglycaemia, weight gain and hyponatraemia 



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Direct replacement 

Main side effects = 

Hypoglycaemia, weight gain, lipodystrophy 

All patients with T1DM and poorly controlled T2DM 

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Increases insulin sensitivity 

Decreases hepatic gluconeogenesis 

Side effects =

GI upset 

Lactic acidosis 

First line medication to treat T2DM 

Cannot be given to patients with GFR <30 

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Activate PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid up take

Can cause weight gain and fluid retention 

e.g. pioglitazone 

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DPP-4 inhibitors (-gliptins)

Increases incretin levels whichi inhibits glucagon secretion 

Generally well tolerated but can cause pancreatitis 

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SGLT-2 inhibitors (-gliflozins)

Inhibits reabsorption of glucose in the kidney 

Side effects = UTI 

Typically result in weight loss 

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GLP-1 agonists (-tides)

Incretin mimetic which inhibits glucagon secretion 

Given sc

Side effects = nausea, vomitting and pancreatitis 

Typically results in weight loss 

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Weight loss 



May present with DKA:

Abdo pain 


Reduced consciousness 

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Often picked up incidently on routine blood tests 



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Diagnostic criteria for diabetes

Fasting glucose greater than or equal to 7mmoml/l 

random glucose greater than or equal to 11.1mmoml/l (or after 75g oral glucose tolerance test) 

HbA1c greater than or equal to 6.5% (if less does not exclude the disease) 

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Left ventricular free wall rupture

Sudden heart failure 

Raised JVP 

Pulsus parodoxus 

Recent MI 

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Verapamil, adenosine

Drugs that can cause heart block

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