Haemostasis + Anti-coagulation Flashcards
What does endothelium that lines blood vessels produce to stop clots and encourage flow
Heparins TFPI - natural anti-coagulant Thrombomodulin NO Prostacylin - prevent aggregation
What flows in the blood and has potential to form clots
Platelet
Red cell
Coagulation factors
What is the process of primary haemastasis when there is vessel damage
Vasconstriction
vWF released from damaged endothelium and binds to collagen
Platelets aggregate as exposed to sub endothelial collagen
Platelet activation by ADP receptor
GIIB/11A receptors now exposed and can bind fibrinogen
Primary platelet plug = weak
Tissue factor produced from tissue e.g. damaged vessel (physiological activator of coagulation) - extrinsic
or
Activated by sub endothelial collagen (intrinsic)
Activates coagulation proteins
Work to produce a fibrin clot - secondary haemostasis
What is on surface of platelets to help binding
GPIIb/IIa receptor
What do platelets bind to
Fibrinogen
Collagen
VWf
What are platelets activated by
P2y12 / ADP pathway
COX pathway
What does COX pathway produce
Converts arachidonic acid ->Thromboxane A2 which aids aggregation of platelets + provides surface for coagulation proteins to be activated
What forms stable fibrin clot (secondary haemostasis)
Coagulation cascade
Coagulation proteins - factor XI / IV / VII activated
Intrinsic pathway
Extrinsic pathway
Activate pro-thrombin which activates thrombin
Thrombin converts fibrinogen to fibrin to form clot
What happens if coagulation proteins are deficient
Fibrin clot won’t form
Anti-coagulants inhibit these proteins as well
What are natural anti-coagulants in the blood that tell clot to stop forming
Anti-thrombin - most important
TFPI
Protein C and S
What coagulation factors does anti-thrombin act on
Factor 10
Thrombin
What is fibrinolysis
Removal of clot
What endothelial cells activate plasminogen
t-PA
u-PA
What does activated plasminogen do
Converts to plasmin to break down clots
What is left after clots broken down
Fibrin degradation product
e.g. D-dimer
What are anti-thrombotic / coagulant durgs and when are they indicated
Warfarin
Heparin
DOAC’s - Rivaroxaban / Edozaban / Dalbigatran
AF VTE Post surgery Immobilisation Valvular heart disease
What are anti-platelets
Clopidogrel / Prasugrel / Ticagrelor
Aspirin
Abciximab
What does aspirin do
Inhibits COX so stops production of thromboxane A2
What does abciximab do
Prevents GP IIB/ IIA from binding fibrinogen
Used less often
What does clopidogrel etc do
Prevents ADP pathway
Use in combination with aspirin
Who is put on antiplatelet
Angina MI Stroke Obesity DM FH SMoking Risk of abnormal clot
What is warfarin and what factors affected
Vitamin K antagonist so stops coagulation factors being produced
Hepatic metabolism by p450
1972 - 10, 9,7,2
How do you reverse warfarin and when
Vitamin K
Prothrombin complex to activate coagulation proteins if major bleed = rapid
What is indication for warfarin and what is the target INR and when is it used over DOAC
Artificial heart valves
- Aortic 2-3
- Mitral 2.5-3.5
VTE
- 2.5-3.5 (higher if recurrent)
AF
- 2-3
Artificial valve / Mitral stenosis / obesity and renal failure <30
What does warfarin require and what do you do if too low
Weekly INR check as narrow therapeutic range with dose adjustment
If INR <2
Cover with LMWH and increase dose
When is warfarin CI and SE
Unreliable to get INR check Peptic ulcer Bleeding disorder Severe hypertension Liver disease Pregnancy as teratogenic but CAN breastfeed
SE
Haemorrhage
Teratogenic so CI in pregnancy
Necrosis / purple toes
What do you do if INR 5-8, no bleed
Withhold dose
Start at lower dose
What do you do if INR 5-8, minor bleed
Stop warfarin
Admit for IV vit K 1-3mg
Restart when INR <5
What do you do if INR >8, no bleed
Stop warfarin + haematology
Don’t give IV K
Oral vit K
Restart when INR <5
What do you do if INR >8, minor bleed
Stop warfarin
Admit urgently for IV vit K 1-3mg
Restart when <5
What do you do if major bleed on warfarin regardless of INR
Stop warfarin Fluid and blood transfusion Treat cause Prothrombin complex = rapid IV Vit K 5mg Can give FFP if prothrombin not available Consider platelet replacement
What are benefits of DOAC and how do you treat bleed
Do not require monitoring
Annual blood test
DOAC
- Add charcoal to slow absorption if recent dose
- Consider specific antitode
- Can give prothrombin or FFP if severe and no antitode to reverse
When are DOAC indicated
Prevention of VTE / stroke
Preferred except in mechanical heart valves or severe MS or severe obesity
Work instantly so don’t require with LMWH like warfarin
How does rivoraxaban / abixaban work and how is it excreted
Direct factor Xa (10) inhibitor
Liver
No reversal agent
How does dapigatran work and how is it excreted
Direct thrombin inhibitor
Renal
Monoclonal Ab to reverse
When are DOAC contraindicated
Severe renal / liver
Bleeding
PT / APTT insensitive but gives a rough idea
What are options for heparin
LMWH
Unfractioned heparin
All activate anti-thrombin
What is treatment of choice for VTE
LMWH - dalteparin / anaxoparin
Also used if post op or immobile as high risk of VTE as prophylaxis as quick onset and to cover till INR target
How does LMWH work and how can it be given
SC
Inhibits factor XA only by activating anti-thrombin
Monitor factor XA but not required
Long action
How does unfractioned heparin work and how is it given
Inhibits thrombin and factor XII by activating anti-thrombin III
SC or IV
Rapid onset and short duration
Used if high risk of bleed as can be terminated rapidly
How do you monitor unfractioned heparin and reverse
APTT
Protamine sulphate
What are SE of heparin
Bleeding
Thrombocytopenia - don’t give if platelets low e.g. <50
Osteoprosis
Hyperkalaemia
What are CI to heparin
Bleeding disorder Low platelet - <50 Peptic ulcer Haemorrhage Severe hypertension Renal failure
What is used instead of heparin If CI due to renal and how does it work
Fondaparinux - inhibits factor XA
What does transexamic acid do
Binds to plasminogen and prevents conversion to plasmin
What blood tests are used to monitor coagulation
FBC - for platlet
LFT - for liver function and albumin for synthetic
D-dimer
Coag PT APTT Bleeding time Fibrinogen
What does PT look at
- Put onto paper for OSCE
Tests factors involved in extrinsic pathway (play tennis outside)
- Fibrinogen
- Thrombin
- 2,7,9, 10, (vit K dependent)
How is PT reported as and what should values be
INR - 0.8-1.2
PT - 12-13s
Use to measure clotting on a regular basis as good measure of overall clotting (as factors rarely in deficiency)
When is INR prolonged / affected
Warfarin as more strongly affects extrinsic pathway
Vit K deficiency
Liver disease
DIC
What does APTT look at
Tests factors involved in intrinsic pathway
- Fibrinogen
- Thrombin
- 5,8, 10, 11, 12
What is normal APTT
30-40s
When is APTT increased / affected
Will be affected by overall clotting so anything that affects PT can affect APTT
Also indicates issues with certain factors
Factor defieincy
Haemophilia A and B / acquired
vWF
Anti-phospholipid
DIC
When is bleeding time prolonged
- Should be 1-6 minutes
Platelet issues will increase the time Thrombocytopenia Uraemia Aspirin use VWF deficiency as can't make plug TTP / ITP / HUS / DIC
What factors affect coagulation
pH
Temp - hypothermia
Calcium
How much platelets do you need for major surgery
100 - required for plug
When would you get purpura
<30
When would you get spontaneous bleeding
<10
Coag values warfarin / vit K deficiency
PT - prolonged
APTT - normal (increased in vit K deficiency)
Bleeding - Normal
Platelet - normal
Coag values aspirin
PT - normal
APTT - normal
Bleeding - prolonged as stops platelet aggregating but does not affect coag so everything else normal
Platelet - normal
Coag values heparin / NOAC
PT - normal / prolonged
APTT - Prolonged as factors in extrinsic pathway
Bleeding - Normal
Platelet - normal
Coag values DIC
PT - prolonged
APTT - prolnged
Bleeding - prolonged
Platelet - low
Require platelet and clotting factors
Coag values Haemophilia
PT - normal
APTT - prolonged as factors
Bleeding - normal
Platelet - normal
Coag values vWF
PT normal as to do with platelet not able to adhese
APTT - prolonged as to do with VIII in intrinsic pathway
Bleed - prolonged
Platelets - normal
Coag values HUS / TTP / ITP
PT -normal
APTT - normal
Bleeding - prolonged
Platelet - low
Normal PT / APTT good differentiator form DIC
NEVER give platelets
What do you do if any bleeding on anti-coagulant
Compress Assess haemodynaic status - BP - Basic coag bloods - FBC / U+E Get Hx of when got last dose
Surgery on warfarin
Stop 5 days before and when INR <1.5
If emergency reverse with prothrombin
Restart as soon as you can
What drugs may increase warfarin
p450 inhibitor as can't break down Liver disease Anti-fungal Macrolide Ciprofloxacin Amiadarone SSRI Acute alcohol Sodium valrpoate NSAID - platelet function Sulphonamide
What drugs may decrease
p450 inducer Vit K Barbiturates Phenytoin Carbamazepine Cholestrolamine Rifampicin St Jon's wort Chronic alcohol Smoking
