Coagulation Disorders Flashcards
What are the different stages of haemostasis?
- constriction of blood vessels
- Temp platelet plug =primary haemostasis
- Activation og coagulation cascade
- Formation of ‘fibrin plug’ =secondary haemostasis
- Clot resolution - tertiary haemostasis.
What is the process of vasoconstriction in coagulation?
Within 30 minutes of trauma to bv
ECM/collagen exposed to blood components
Release of clotting factors and platelets
Altered substances released by endo cells - dec NO, increase endothelin and thromboxane
What happens during formation of a primary platelet plug?
Cytokines and inflammatory markers lead to adhesion of platelets and aggregation
vWF helps platelets adhere to site on injury
Activates platelets release granules - positive feedback for process
What is the role of the coagulation cascade in blood clots?
Extrinsic and intrisncie pathway
Occr spontaneous and result in activation of factor X.
Continues as the common pathway.
Each step involves various coagulation factors
End goal - fibrinogen-> fibrin to form a stable clot and mesh formation (secondary haemostasis)
What coagulation factors are Vitamin K dependent?
1972
10, 9, 7, 2
How does clot resolution occur?
Tertiary haemostasis - activated platelets contract, leading to shrinkage of the clot volume.
Plasminogen is activates to plasmin = lysis of the fibrin clot
Restores blood flow in the damaged vessels.
What are the different indications for a coagulation screen?
- Confirm a suspected coagulopathy
- Acute blood loss
- Monitor a patient on anti-coagulant drugs
- Assess coagulation status prior to surgery
- Assess the synthetic function of the liver
What investigations are commonly ordered alongside a coagulation screen?
FBC for platelets
LFTs for general liver function
Albumin - liver synthetic function/malnutrition
D-dimer (if clinically indicated)
Cross match and group and save - if requiring blood transfusion.
How should a prothrombin time (PT) be interpreted?
Extrinsic pathway
It can be standardised as the INR for monitoring warfarin
Mainly focuses on factor 7
Higher time indicates higher bleeding risk.
What can cause a deranged PT test result?
Overall clotting factor synthesis - liver disease, DIC, Vitamin K deficiency and warfarin.
How should an activated partial thromboplastin time (aPTT) be interpreted?
Intrinsic pathway
Normally focus on VIII, IX, XI
High time = increased risk of bleeding.
What can cause an abnormal aPTT?
Overall cloting factor synthesis/consumption - DIC, liver failure, VitK defieicny
Von Willebrands disease
Haemophilias
Note anti-phospholipid syndrome can cause a high aPTT despite being a clotting disorder as it inactivates phospholipid in test.
What is the genetics of Haemophilia?
X-linked recessive condition (primarily affects males)
Haemophilia A - factor 8 deficiency - more common
Haemophilia B - factor 9 deficiency - Christmas disease
How does Haemophilia tend to present?
Severe bleeding disorders with a risk of excessive bleeding in response to minor trauma or even spontaneously.
Neonates - IC haemorrhage, haematoma, cord bleeding
Spontaneous haemarthrosis (ankle, knee, elbow).
May bleed from oral mucosa, epistaxis, GIT, UT.
What is the common management of Haemophilia?
IV infusion of affected clotting factors.
(beware of formation of inhibitor antibodies against these)
What is the most common inherited bleeding disorder?
Von Willebrand’s disease
What is the genetics behind Von Willebrands disease?
Autosomal dominant
Deficient, absence of malfunctioning of vWF - reduces platelet adhesion, aggregation.
What are the three different types of von Willebrand disease?
type 1 - partial deficiency of vWF (most common
type 2 - reduced function of vWF
type 3 - complete deficiency of vWF (rare and severe)
What is the common presentation of von Willebrands disease?
Unusually easy, prolonged/heavy bleeding - gums, nosebleeds, menorrhagia, surgical operation sites
FH very important.
How is von Willebrands disease often diagnosed?
History - inc FH
Bleeding scores
Lab investigation - coag screen
Genetic testing
Common have a low F8 as vWF transports this.
What is the management for von Willebrands disease?
Only in response to significant bleeding/trauma:
1. Desmopressin (mimics ADH) - stimulates vWF release from endothelial cells
2. Tranexamic acid (anti-fibrinolytic)/mefenamic acid (NSAID)
3. vWF infusion +/- factor 8
4. Mirena coli, norehisterone, hysterctomy
What is disseminated intravascular coagulation?
Rare but lifethreatening - abnormal blood clotting throughout the body.
Two stages:
1. Overactive clotting -> blood clotes throughout vessels = organ damage
2. Platelets and clotting factors run out -> uncontrolled bleeding
What commonly causes DIC?
Inflammation - sepsis or malignancy
What is the common treatment for DIC?
Manage underlying cause +/- blood products.
What makes up Virchow’s triad?
Hemodynamic changes/stasis
Endothelial injury/dysfunction
Hypercoagulability
What are some specific hyper-coagulable conditions?
Antiphospholipid antibody syndrome
Factor 5 Leiden mutation
Protein C deficiency
Protein S deficiency
Prothrombin gene mutation
What is the typical question stem for antiphospholipid syndrome?
Young female - recurrent miscarriages and personal/family history of VTE
What is the relevant risk of a DVT when a patient has a septal defect in their heart?
Thrombus can pass into left side heart and into systemic circulation
Travels to brain and may cause a stroke.
What inpatient prophylaxis may be offered for a VTE?
LMWH - enoxaparin injections
Anti-embolic stokcings - not in PAD
What is the PERC rule?
Used when physician concern over a DVT/PE is low - may justify not performing a D-dimer
When might thrombolysis be indicated for a PE?
If PE confirmed and haemodynamically unstable.
What is the first line anti-coagulant for DVT/PE in pregnancy?
LMWH
What is Budd-Chiari syndrome?
An obstruction to the outflow of blood from the liver due to thrombosis in the hepatic veins or inferior vena cava
Associated with hyper-coagulable states
Present: abdominal pain, hepatomegaly, ascites.
What is the common treatment for Budd-Chiari syndrome?
Confirm with doppler ultrasonography
Anticoagulation (LMWH)
Endovascular procedure (thrombolysis or angioplasty)
Trans-jugular intrahepatic portosystemic shunt.
Liver transplant.
What are the most common anti-platelets?
Aspirin = COX inhibitor
Clopidogrel and Aspirin = platelet aggregation inhibitors
What are some common indications of anti-platelet medications?
ACS
post-PCI/CABG
Mechanical heart valves
Acute ischemic stroke
Essential thrombocytosis
Primary prevention of VTE
What are some adverse effects of anti-platelets?
Upper GI bleed
Easy bruising
Haematuria
Epistaxis
Thrombocytopaenia
What are some contraindications for anti-platelets?
Oesophageal varices
Recent stroke (<2yrs)
History of ICH/sig bleed
Major surgery - clopidogrel/tricagerlor stopped 5days prior to major surgery
What are the key indications of anti-coagulants?
Atrial fibrillation
VTE
Heart valve replacements
VTE prevention in high-risk patients
What are the common contraindications for anti-coagulants?
Active bleeding
Coagulopathy
Recent major surgery
History of ICH
GI bleed
Aortic dissection
Geriatrics (patient case be case)
How does kidney disease affect anti-coagulation choice?
Stage 1-3 DOACs are preferred
Stage 4 - DOAC or warfarin
End-stage renal disease - warfarin.
Compare the use of unfractionated and LMW heparin?
Unfractionated - prevention and treatment of VTE, rapid onset, short half life
LMW - longer duration of action, longer half life
Both are complex with AT-3 to inhibit various clotting factors.
Monitored with anti-factor Xa assay.
What is the key clinical knowledge of warfarin?
Inhibits VitK (affects clotting factors 10,9,7,2)
Narrow therapeutic window - requires frequent monitoring with INR
Affect altered by diet, other drugs, genetic mutations
What is the main mechanism of action of direct thrombin inhibitors?
Dabigatran
Inhibit the cleavage of fibrinogen to fibrin by thrombin (factor 2a)
What is the key clinical knowledge of a DOAC?
Inhibit 2a or Xa
Less suspectible to interaction and rarely require monitoring
Apixaban - oral only, non-valvular AF, prevent/treat VTE.
How can anti-coagulants be reversed?
Activated charcoal if within 2hrs of last ingestion
Haemodialysis
Blood transfusion for anaemia
Platelet transfusion for thrombocytopenia
Surgical or endoscopic intervention
Warfarin = Vit K
What is meant by bridging with anti-coagulants?
When should it be used?
Used for patients with consideral risk of thrombotic events
DOACs - takes 2-3hrs
Warfari - 4 to 5 days
The use of a short acting anti-coag (LMWH?UFH) when a normal anti-coagulat must be stopped for a short period of time.
