Haemostasis and Bleeding Flashcards
What are the 3 necessary qualities required for normal haemostasis?
- Speed and efficiency
- localised damage / repair
- careful regulation
What is haemostasis?
The process that causes bleeding to stop (clot formation at the site of injury)
What does epistaxis mean?
Nose bleed
If a patient comes in complaining of nose bleeds that take ages to stop (which her sister and father also suffer with) is known to be iron deficient and has lesions on lips and tongue with dilated bloods vessels in those regions too what is the likely diagnosis?
Hereditary Haemorrhagic Talengectasia
What type of genetic disorder is Hereditary Haemorrhagic Talengectasia? (Note the girls father and sister suffer from it)
Autosomal Dominant
Want is thrombocytopenia?
Low platelet count
What is the most common form of thrombocytopenia?
Immune Thrombocytopenia (autoimmune condition)
How should you treat thrombocytopenia?
Autoimmune: With steroids as giving platelet infusion would only result in the immune system attacking the new platelets
Bone marrow failure: platelet transfusion
If a baby presents with a hot swollen knee which he cannot bend, with no history of trauma and a low Factor VIII test result what is he likely to have?
Haemophilia A
What type if genetic inheritance are Haemophilia A and B?
X-linked recessive (therefore far more men than women suffer with them)
What clotting factor is deficient in Haemophilia B?
Factor IX
If a 74 year old lady presents with dark tarry stools, a BP of 90/60, looking pale, with a pulse if 124bpm and a PMH of atrial fibrillation for which she is taking Warfarin what should you check?
Her INR (coagulation speed) If it is slow it is likely she has a GI bleed due to warfarin
What processes does Primary Haemostasis involve?
1) Vasoconstriction
2) Platelet aggregation (plug)
What processes does Secondary Haemostasis involve?
Clot forming with fibrin mesh
What converts fibrinogen (FI) to fibrin (FIa)?
Thrombin (FIIa = activated factor II)
What is the precursor for thrombin?
Prothrombin (FII)
What is the final common pathway in the coagulation cascade?
Prothrombin (FII) to thrombin (FIIa) which initiates Fibrinogen (I) to convert into Fibrin (FIa)
When would secondary haemostasis not be necessary?
With a very small injury e.g. Paper cut or pin prick (platelet plug enough)
What is fibrinolysis and how does it occur?
It is the breakdown process of a clot (necessary in normal haemostasis )
It occurs by plasmin lysing fibrin into it’s degradation products
What is D-Dimer test and what is it used to help diagnose?
It tests the level of fibrin degradation products
Helps diagnose: Thrombosis e.g. DVT
What is Haemophilia B also known as?
Christmas disease
What clotting factors do not exist?
FIII, FIV and FVI
What part of the coagulation cascade is known as the “extrinsic pathway”?
Tissue Factor and FVIIa activating FXa with the aid of FVa
What is special about FXa in the coagulation cascade?
It is the link between the extrinsic and intrinsic pathways to the final common pathway. It is the factor that goes on to convert prothrombin (FII) into thrombin (FIIa)
What occurs in the “Intrinsic Pathway” of the coagulation cascade?
FXII > FXIIa which converts FXI > FXIa which converts FIX > FIXa
FIXa with the aid of FVIIIa converts FX to FXa (where it overlaps with the “extrinsic” cascade
How does initial platelet adhesion occur after injury to a blood vessel?
The endothelial layer is damaged exposing the subendothelium. The subendothelium contains collagen and von Willebrand factor (vWF) (expressed on exposed collagen) to which the inactivated platelets adhere
How does platelet adhesion progress to platelet aggregation?
Once platelets have adhered to vWF on the collagen they release ADP and calcium (which triggers the coagulation cascade). The ADP activates platelets helping them to stick to endothelium and allow GPIIb and GPIIIa to be expressed on platelet surface to which Fibrin (FIa) binds allowing linkage of platelets
What are clotting factors, where are they produced and in what form?
Proteins / enzymes
Produced in the liver in inactive form ‘zymogens’
What is the most abundant clotting factor?
Fibrinogen (factor I / FI)
If you are treating a haemorrhage in an emergency situation what single clotting factor are you most likely to administer to stop the bleeding quickly?
FVIIa - as it gets activated as soon as it contacts tissue factor
What are urokinase and tissue plasminogen activator (tPA)?
They are both thrombolytics used to convert plasminogen into plasmin which in turn breaks down fibrin into its degradation products
When testing TT (thrombin time) what part of the coagulation cascade are you assessing?
The final step - time it takes thrombin to convert fibrinogen to fibrin
What blood sample tube would you use to perform the TT test and why?
The light blue top - it contains K+ citrate which doesn’t inhibit or contribute to clotting therefore does not affect clotting time
How do you perform the TT test?
1) You put the plasma (which includes the individual’s natural clotting factors) in the blue top tube which contains K+ citrate
2) Add thrombin
3) Add Ca++ and immediately start the timer
4) move in and out of 37.5 degree water bath and stop timer when clots (should take around 18secs or 1/3 of a min)
What are differential diagnoses for a prolonged clotting (TT) time?
Either low fibrinogen / poor quality fibrinogen (RARE)
Or
That the patient is on an antithrombin medication e.g. Heparin
(Cannot be problem with thrombin as that is being added in the test)
When testing PT (prothrombin time) what part of the coagulation cascade are you assessing?
The extrinsic pathway
What do you require for the PT (prothrombin time)?
Plasma and Tissue factor (from brain??)
What are you testing with all: TT, PT and APTT tests
Plasma clotting time
Which part of the clotting cascade are you assessing with the Activated Partial Thromboplastin Time (APTT) test?
The intrinsic pathway
What clotting factors specifically are you assessing with the PT?
FVII, FV and FII (all activated)
What clotting factors specifically are you assessing with the APTT?
FXI, FIX and FVIII (arguably FXII - though note suggest that this would not cause a bleeding disorder…)
How long should TT, PT and APTT take to achieve clot formation?
TT: 18secs (1/3 min)
PT: 12secs (1/5 min)
APTT: 32secs (1/2 min)
Name two major disorders of a primary haemostasis
1) von Willebrand disease (low vWF > platelet plug failure)
2) Thrombocytopenia (low platelet count)
Name two major disorders of a secondary haemostasis (coagulation)
1) Haemophilia - A = reduced FVIII / B (Christmas disease) = FIX (congenital deficiency)
2) Liver Disease (acquired deficiency) - cannot synthesise zymogens affectively
What term is used for a clotting disorder which combines both primary and secondary haemostatic insufficiencies?
Disseminated Intravascular Coagulation
DIC is evidenced by what?
Activation of both Thrombin and Plasmin
Thrombosis can occur, but more often haemorrhage does as clotting factors become exhausted
What are the 3 typical bleeding symptoms of primary haemostatic failure?
1) immediate bleeding after trauma
2) mucocutaneous bleeding e.g. Mouth & Gut
3) purpura (petichial rash)
What are the 3 typical bleeding symptoms of secondary haemostatic (coagulation) failure?
1) delayed bleeding after trauma
2) muscle and joint bleeding
3) bruising
(NEVER see petichial rash with coagulation failure)
How do you treat Haemophilia prophylactically?
Coagulation factor replacement (FVIII or IX)
DDAVP (des oppression) subcut injection (increases factor 5-fold)
Tranexamic Acid (inhibits activity of plasmin therefore stabilising fibrin)
Name 3 disorders in which DDAVP is used for treatment
Haemophilia (antihaemorrhagic)
Diabetes insipidus (anitdiuretic)
von Willebrand Disease (antihaemorrhagic)
Name some of the causes of DIC
- Sepsis
- Extensive burns
- Obstetric causes: preeclampsia, antepartum haemorrhage, amniotic fluid embolism, intrauterine foetal death
- Malignancies
What is INR?
Stands to International Normalised Ratio
Created to standardise PT (prothrombin time)
List types of pharmacological treatments that can be used in bleeding disorders caused by reduced coagulation ability
Coagulation factors: plasma derived and recombinant (haemophilia)
Vitamin K (reverse oral anticoagulant, Vit K deficiency, newborn Haemorrhagic disease)
Anti-fibrinolytic drugs e.g. Tranexamic acid
What will the effects of a Vit K deficiency be?
Malabsorption (no fat soluble foods will be absorbed)
Obstructive Jaundice
What is the action of Tranexamic Acid?
It prevents the conversion of plasminogen to plasmin (which would ordinarily breakdown fibrin) it therefore stabilises the clot
What is Tranexamic Acid useful for treating?
Bleeding from mucous membranes: Epistaxis Dental/Mouth bleeds GI bleeds Menorrhagia
What is Tranexamic Acid contraindicated in?
Haematuria
Name the 4 main categories of pharmacological treatments used in patients with thrombosis / risk of
1) anti-coagulants (e.g. Heparin - LMWH usually used)
2) anti-platelets (e.g. Aspirin or Dipyridamole)
3) fibrinolytic therapy (e.g. Alteplase recombinant plasminogen activator)
4) vitamin K antagonists (e.g. Warfarin - also anticoagulant)
