L9 - haemostasis Flashcards
define haemostasis
A multifactoral process in which bloodflow is stopped as a result of injury to prevent haemorrhage
Haemostasis is a three step process. The first step is vasoconstriction - this reduces the blood pressure downstream of the insult, what are the following two steps
2) The primary haemostatic response - Formation of a primary haemostatic plug from activated platelets that stick to both the vessel and the underlying connective tissue - weak (second to minutes)
3) The secondary haemostatic response - Formation of the secondary haemostatic plug (Fibrin haemostatic plug, 30 mins)
There are three steps in platelet activation - adhesion, activation and aggregation. Briefly describe each
Adhesion - Platelet adheres to subendothelial layer at site of insult via von willebrand factor binding its receptor
Activation - Contact with collagen in the underlying layer activates the platelets, platelets now release ADP which amplifies the response
Aggregation - Platelets change shape and cross link to form a plug
NOTE - Von willebrand factor is in the blood, receptor is sub-endothelial and receptor ligand complex allows contact with collagen
Thrombocytopenia is a low platelet count in the blood, will the PT or APTT be raised?
No neither will be raised, it is the function of the platelets not the clotting cascade which is impaired
Give two potential causes and the symptoms of thrombocytopenia
Causes - decreased platelets due to drugs/malignancies
Increased consumption of platelets due to infection/splenomegaly/DIC
Symtpoms - Petechia in the skin due to bleeding from small peripheral vessels
How is fibrin activated, only the key components at the end of the clotting cascade need be discussed
Thrombin is the end product of the clotting cascade, it cleaves circulating fibrinogen to fibrin which then forms the secondary haemostatic plug
Which pathway requires tissue factor released from damaged cells
Extrinsic pathway
Note - the intrinsic pathway doesn’t require vessel damage to occur
Give an example of natural anticoagulants released as clotting is started
antithrombin/ protein C
What plasma protein is responsible for fibrinolysis - a process which is activated immediately alongside clot formation?
plasmin which is the cleaved and activated form of plasminogen. Plasminogen is the circulating inactive form of plasmin
which test assesses the extrinsic pathway PT or APTT?
PT - utilises tissue factor in a test tube to look at how long it takes a clot to form (tests common pathway too)
APTT looks at intrinsic and common pathway
How are coagulation factor disorders treated
With recombinant forms of the deficient factor
Give some symptoms of haemophilias A and B
Easy brusing/massive haemorrhage after surgery/joint deformities
What would the results be to the following tests in a haemophiliac:
platelet count
PT
APTT
platelet counut - normal
PT - normal
APTT - prolonged
Intrinsic pathway is compromised
Which factor is deficient in each haemophilia?
A - F VIII
B - F IX
Give some common symptoms of vWB disease
Easy bruising/ spontaneous bleeds from mucous membranes/ prolonged bleeding after trauma
What do we see clinically in vWB disease i.e. at factor level?
Reduced platelet adhesion to wall/
Reduced vWB and F VIII as vWB carries and protects this factor/
Raised bleeding time and APTT
What levels are raised in DIC?
PT, APTT and raised D dimers
What is DIC ?
A clotting activator gets into the blood from tissue damage causing bodywide microthrombi, it is a secondary complication causing excessive consumption of platelets and clotting factors as well as fibrinolysis
What are DIC patients at high risk of and what is the treatment?
Great risk of bleeding and thrombosis due to excessive clotting - bleeding becasue of using up factors
Treat - heparin and possible platelet transufsion as they are used up AND TREAT THE UNDERLYING CAUSE
Give an example of a condition that predisposes to DIC
severe trauma/ sepsis/ malignancy/ snake bite/ extensive burns
What are thrombophilias ?
A set of conditions which predispose to thrombosis
Other than ADP what else is released by platelets to amplify the activation response?
thromboxane A2
How does aspirin work?
It inactivates an enzyme responsible for the production of thromboxane A2 and thus downregulates the clotting response
How do the elements of the clotting cascade activate each other concurrently?
Proteolytic cleavage
What does plasmin degrade fibrin too? When do we clinically measure this?
Many things but mainly D dimers
Thus we measure D dimers in patients with a suspected deep vein thrombosis, raised D dimers suggest a likely DVT/PE
Therapeutically we take advantage of plasmin to break down clots, what plasminogen activator do we use clinically for this?
Streptokinase
What inheritance pattern do we see in haemophilia?
X-linked recessive (need to look at first semester again to go over inheritance patterns)
Describe the symptoms of haemophilia
Bleeding into muscles and joints/regular mucous membrane bleeds/easy bruising etc.
What would coagulation tests show in haemophilia?
Prolonged APTT/deficient in the particular factor/normal platelet count, PT and bleeding time
What is the inheritance pattern of vWB disease?
autosomal dominant
Give an example of an inherited thrombophilia
Anticoagulant e.g. antithrombin deficiency
What would you give to a patient who had overdosed on warfarin (note this is easy to do very narrow therapeutic range)?
Vitamin K - Warfarin is a vitamin K antagonist, there are many vitamin K dependent factors in the clotting cascade
How does heparin work?
Binds to antithrombin to improve its ability in inactivating thrombin
Give some symptoms of DIC
confusion/gangrene/renal failure/respiratory distress (end organ damage doe to poor blood flow from microthrombi
Calcium is an important co-factor required for clotting
T
Prothrombin requires Vitamin K for its synthesis
T
What is INR and what is it used for?
Calculated from PT, gives an indication of how well anticoagulant therapy is working
What is trousseaus syndrome?
an acquired thrombophilia due to disseminated cancer - cancer causes hypercoagulability and endothelial damage. Two important prongs of virchow’s triad for thrombosis.
Give symptoms of a DVT
- pain and tenderness in one of your legs (usually your calf)
- swelling
- a heavy ache in the affected area.
- warm skin in the area of the clot.
- red skin, particularly at the back of your leg below the knee.
How does a DVT form?
Immobility or whatever causes stasis of blood -> increased risk of thrombosis -> formation of a thrombus
What are some risk factors for DVT?
the combined contraceptive pill/surgery/pregnancy/immobility/dehydration
