Haemostasis - Bleeding: Disorders of Primary Haemostasis Flashcards
What is haemostasis?
the cellular and biochemical processes that enables both the specific and regulated cessation of bleeding in response to vascular injury
What is haemostasis for?
Prevention of blood loss from intact vessels
Arrest bleeding from injured vessels
enable tissue repair
Briefly outline the process of haemostasis.
vessel constriction > primary haemostasis > secondary haemostasis > fibrinolysis
What is involved in primary haemostasis?
formation of an unstable platelet plug (platelet adhesion/aggregation)
What is involved in secondary haemostasis?
stabilisation of the plug with fibrin (blood coagulation)
What is involved in fibrinolysis?
vessel repair + dissolution of clot (cell migration/proliferation)
Why do we need to understand haemostatic mechanisms?
diagnose/treat bleeding disorders, control bleeding, identify risk factors for thrombosis, treat thrombotic disorders, monitor drugs used for treatment
Normal haemostasis is a balance between?
bleeding vs thrombosis
fibrinolytic factors, anticoagulant proteins vs platelets, coagulant factors
What are two reasons why haemostatic balance is tipped towards bleeding?
lack of specific factor (production failure, increased clearance) or defective fx of specific factor (genetic or acquired)
In what two ways does platelet adhesion occur?
indirectly via VWF + GIpIb or directly to collagen via GIpIa
The release of what factors causes platelet aggregation?
release of ADP and thromboxane
What factors are involved in platelet aggregation?
Ca2+
fibrinogen
What is low numbers of platelets called?
thrombocytopenia
Causes of low platelets?
bone marrow failure e.g. leukaemia, B12 deficiency
accelerated clearance e.g. ITP, disseminated intravascular coagulation
What does ITP stand for?
immune thrombocytopenic purpura
Categorise platelet disorders.
low numbers (thrombocytopenia) or impaired function
How can platelet function be impaired?
hereditary absence of glycoproteins or storage granules, acquired from drugs (aspirin, NSAIDs, clopidogrel)
How does aspirin act as an anti-platelet therapy?
irreversibly blocks COX
How does clopidogrel act as an anti-platelet therapy?
irreversibly blocks the ADP receptor on platelets
How do you get Von Willebrand Disease?
hereditary decrease of quantity/fx or acquired due to antibody
What two functions does von willebrand factor have in haemostasis?
binding to collagen and capturing platelets
stabilising Factor VIII
What inheritance pattern does von willebrand disease have?
autosomal
What is type 1, 2, 3 von willebrand disease?
Type1/3 VWF deficiency
VWF with abnormal function
List categories of primary haemostasis disorders.
platelets
VWF
vessel wall
What are vessel wall causes of disorders of primary haemostasis?
inherited (Ehlers-Danlos, connective tissue disorders, hereditary haemorrhagic telangiectasia)
acquired (steroids, ageing, vasculitis, scurvy)
How does ITP (Idiopathic thrombocytopenic purpura) work?
antiplatelet autoantibodies bind to sensitised platelets > engulfed by macrophages
Describe typical primary haemostasis bleeding.
immediate, prolonged bleeding from cuts, prolonged nose/gum bleeds, menorrhagia, bruising, prolonged bleeding after trauma or surgery
Petechiae and purpura are caused by?
bleeding under the skin
When purpura have pressure applied what happens?
do not blanch
Clinical feature of thrombocytopenia?
petechiae
Clinical feature of severe VWD?
haemophilia like bleeding
Clinical features of disorders of primary haemostasis
ecchymosis
petechiae
purpura
increased skin elasticity in connective tissue disorders
What are tests for disorders of primary haemostasis?
platelet count/morphology, bleeding time, VWF assays, clinical observation
What are the principles of treatment of abnormal haemostasis where production/function failure is the root cause?
replace missing factor/platelets (prophylactic/therapeutic) stop drugs (e.g. aspirin, NSAIDs)
What are the principles of treatment of abnormal haemostasis where immune destruction is the root cause?
immunosuppression (e.g. prednisolone)
splenectomy for ITP
What are the principles of treatment of abnormal haemostasis where increased consumption is the root cause?
treat cause
replace as necessary
List some additional haemostatic treatments.
desmopressin
tranexamic acid
fibrin glue/spray
other (oral contraceptive pill for menorrhagia)
