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 

0.8-1.2 = normal 

2-3  = desired target for warfarin user 

3.5 if a more intense strategy is required 

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% 

Irreverisble P2Y12 antagonists 

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 

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 

P2Y12 antagonist 

Decreased death of vascular events 

Decreased MI 

similar risk of major bleeding events 

Does not require metabolism as a thienopyridine derivative 

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 

Oral

Rivaroxaban 

apixaban

edoxaban 

IV

Fondaparinux 

Idraparinux 

Better efficacy as well as being safer than heparin 

Warfarin 

DOACs 

Apixaban 

Dabigatran 

edoxaban 

rivaroxaban 

(prescribed over warfarin for people with non valvular AF) 

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 

Block the active site of thrombin 

IV - as effective as LMWH, short acting 

Hirudin

Lepirudin 

Desirudin 

Bivalirudin 

Oral

Dabigatran (licensed for AF and DVT)

As effective as warfarin, less risk of haemorrhage 

Only DOAC with an antidote ...

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

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 

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

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) 

Result from aberrant recombination 

Typically due to repeat sequences 

De novo or inherited 

Examples included prader-willi, Angelman and diGeorge 

Examples include 

Spinal muscular atrophy 

Cystic Fibrosis 

Duchene Muscular Dystrophy 

US of a fetus showing an echogenic bowel 

Aneuploidy screening and sexing 

Microsatellite markers used to identify and count chromosomes 

13,18,21,X,Y 

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 

Confirmation of aCGH and follow up 

5-10mB resolution 

22q11.21 (deletion from 22) 

ASD 

Broad nasal bridge 

Hypo-plastic left branch pulmonary branch 

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 

Routine anomaly scan at 18-20wks 

Assess fetal growth and anomalies 

Placental site - low and covering the cervix or high up 

Four things we measure to assess fetal growth / biometry 

All combined to estimate the fetal weight 

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 

Measurement between the two parietal bones 

<10th centile but stays on the same curve 

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%

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 

Stimulate pancreatic beta cells to secrete insulin 

Side effects = Hypoglycaemia, weight gain and hyponatraemia 

Gliclazide 

Glimpiride 

Direct replacement 

Main side effects = 

Hypoglycaemia, weight gain, lipodystrophy 

All patients with T1DM and poorly controlled T2DM 

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 

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

Can cause weight gain and fluid retention 

e.g. pioglitazone 

Increases incretin levels whichi inhibits glucagon secretion 

Generally well tolerated but can cause pancreatitis 

Inhibits reabsorption of glucose in the kidney 

Side effects = UTI 

Typically result in weight loss 

Incretin mimetic which inhibits glucagon secretion 

Given sc

Side effects = nausea, vomitting and pancreatitis 

Typically results in weight loss 

Weight loss 

Polydipsia 

Polyuria 

May present with DKA:

Abdo pain 

Vomitting 

Reduced consciousness 

Often picked up incidently on routine blood tests 

Polydipsia 

Polyuria 

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) 

Sudden heart failure 

Raised JVP 

Pulsus parodoxus 

Recent MI 

Drugs that can cause heart block