38 - Acquired bleeding disorders Flashcards
What does APTT stand for?
Activated partial thromboplastin time
Heparin examples
UFH (unfractionated heparin)
Enoxaparin
Vit K antagonist e.g.s
Warfarin
Direct thrombin inhibitors
Hirudins
Problems with antithrombotics
High incidence of serious adverse effects (mainly bleeding-related)
Routine monitoring needed
Narrow therapeutic margin
Limited effectiveness in preventing VTE (venousthrombo embolism)
Vitamin K deficiency affects which factors
II, VII, IX, X
Causes of vit K deficiency
Obstructive jaundice
Prolonged nutritional deficiency
Broad spectrum antibiotics
Neonates (classical 1-7 days)
Liver disease - in relation to blood
Cirrhotic coagulopathy
Problems with cirrhotic coagulopathy
Increased risk of severe bleeding from invasive procedures or surgery
Conventional treatments don’t work
What is liver essential for in relation to blood
Making normal coagulation factors
Components of fibrinolytic system
Naturally occurring anticoagulants
Impaired haemostasis in liver disease leads to
Thrombocytopenia Platelet dysfunction Reduced [plasma coagulation factors] except FVIII Delayed fibrin polymerisation Excessive plasmin activity
Massive transfusion definition
Volume equal patient’s blood volume in less than 24 hours
50% blood volume loss within 3 hours
Haemostatic abnormalities due to massive transfusion
Dilutional depletion of platelets and coagulation factors
Due to DIC - risk factors: trauma, head injury, prolonged hypotension
Underlying disease: liver or renal disease, drug treatment, surgery
When do effects of dilution set in and cause problems in haemostasis after how many litres?
> 7-8 litres
Dilution problems in haemostasis
Thrombocytopenia
Coagulation factor depletion, namely, Factor V and VIII and fibrinogen
DIC common
Citrate toxicity - uncommon
Hypocalcaemia - no clinically significant effect on coagulation
Citrate toxicity which groups are vulnerable
Hypothermic patients
Neonates
Pathophysiology of DIC
- General disruption of physiological balance of procoagulant and anticoagulant mechanisms
- Consumption of clotting factors + platelets
- Microvascular thrombosis
- Activation of thrombolysis
- Microangiopathic haemolysis
DIC - generally what is it?
Over active clotting proteins causing microclots
Acute DIC - causes
Acute DIC Sepsis Obstetric complications Trauma/tissue necrosis Acute intravascular haemolysis e.g. incompatible blood transfusion Fulminant liver disease
Chronic DIC - causes
Malignancy
End stage liver disease
Severe localised intravascular coagulation
Obstetric: retained dead foetus
DIC - lab tests
FBC and Blood Film
Coagulation screen:
PT (70% prolonged)
APTT (50% prolonged)
TCT (usually prolonged)
[Fibrinogen]
FDP or D-dimer (elevated in 85%)
Not single diagnostic test - scoring systems used
Management of DIC - underlying cause
Antibiotics
Obstetric intervention
Chemo/ATRA (all trans retinoic acid) /tumour resection
ATRA
All trans retinoic acid
For acute myeloid leukaemia
Management of DIC - supportive treatment
Maintain tissue perfusion
Co-ordinate invasive procedures
Folic acid and vitK supplements to support recovery period
Oral anticoagulants
Control of dosing by INR
What is INR?
Prothrombin ratio
Patient’s PT time / mean normal PT time
Drugs which increase warfarin effect
Cimetidine Amiodarone Sulphinpyrazone Cotrimoxazole Erythromycin Cephlosporins Ampicillin NSAID's Chlorpromazine Sulphonylureas Corticosteroids
Drugs which antagonise warfarin effect
Cholestyramine Spironolactone Rifampicin Carbamazepine VitK
When to reverse oral anticoagulant treatment
Life threatening haemorrhage
Non-major bleeding
INR>8.0 w/o haemorrhage
INR>5
Life threatening haemorrhage
5-10mg vit K via IV
Four factor concentrate
Non-major bleeding
Withhold warfarin
Give vitK 1-3mg IV
INR of >8.0 w/o haemorrhage
Withhold warfarin
Give vitK 1-5mg orally
INR >5.0
Withhold warfarin.
Consider oral vitK if high risk for bleeding
Unexpected bleeding at therapeutic levels
Reverse warfarin
Workout underlying cause
What is tested for to monitor heparin?
Full anticoagulation assay
APTT most commonly used assay
Alternative monitoring of heparin
Protamine titration
Anti-Xa assay
Calcium thrombin time
Anti-Xa (LMWH)
Properties of LMWH vs UFH
LMWH: higher ratio of anti-Xa to anti-IIa activity
Higher bioavailability
Longer half-life allowing once daily administration
More predictable response not needing monitoring
