Haemeostasis Flashcards
Describe Primary Haemostasis
Formation of an unstable platelet plug
platelet adhesion & aggregation
Limits blood loss +provides surface for coagulation
Describe secondary Haemostasis
Stabilization of platelet plug with fibrin
blood coagulation
stops blood loss
What happens in Fibrinolysis?
Vessel repair and dissolution of clot
Cell Migration/proliferation & Fibrinolysis
Restored vessel integrity
What are the possible reasons for a decrease in Coagulant factors?
Failure of production - Congenital/acquired
Defective function of a specific factor - Genetic/acquired
Where do platelets adhere to on collagen?
VWB Factor via GIpIp receptor
GIpIa receptor
What causes platelet aggregation?
Release of thromboxane and ADP
Name a disorder of primary Haemostasis that results in low Platelet numbers?
Thrombocytopenia
Bone marrow failure - leukaemia, B12 Deficiency
Accelerated clearance - Immune, Disseminated Intravascular Coagulation.
Pooling & destruction in an enlarged spleen
Describe what happens in Immune Thrombocytopenic Purpura (ITP)?
Antiplatelet autoantibodies stick to sensitized platelets, which are then cleared by Macrophages in the spleen.
ITP is a common cause of thrombocytopenia
Name 2 causes for impaired platelet function in primary haemostasis?
Hereditary absence of glycoproteins or storage granules.
Acquired due to drugs; Aspirin, NSAIDs, clopidogel.
Which receptor is absent in Glanzmann’s thrombasthenia?
GPIIb/GPIIIa
Which receptor is absent in Bernard Soulier syndrome?
GPIb
What is storage pool disease?
A group of disorders referring to reduction of granular content of the dense granules.
What are antiplatelet drugs commonly used to treat?
Cardiovascular and cerebrovascular disease
How does asprin work?
Inhibiting the production of thromboxane A2, by blocking the action of cyclo-oxygenase reducing platelet aggregation.
Why does cyclo-oxygenase not inhibit platelet aggregation via Prostacyclin synthase?
It can be further generated by the endothelial cell.
How does clopidogrol work?
By blocking the ADP receptor on platelets
What are the 2 functions of VWF in haemostasis?
Binding to collagen and capturing platelets
Stabilising Factor VIII
What is Von Willebrand Disease?
Disorder of primary Haemostasis
Hereditary ( autosomal inheritance) decrease of quantity/function
Acquired due to antibody (rare)
Which type of VWD is caused by a deficiency in VWF?
1&3
Which type of VWD is caused by abnormal VWF function?
2 - rare
Which disorders of primary haemostasis involve the vessel wall?
Inherited (rare) - Hereditary haemorrhagic telangeiectaisa, Ehlers-Danlos syndrome + connective tissue disorders.
Acquired ( common) - Steroid therapy, ageing, vasculitis, scurvy
What are the clinical features of disorders of primary Haemostasis?
Immediate Prolonged bleeding from cuts Prolonged nose bleeds Prolonged gum bleeding Menorrhagia Bruising - spontaneous/easy Prolonged bleeding after surgery.
What are some clinical features specific to thrombocytopenia?
Petechiae & Purpura - caused by bleeding under the skin.
Purpura do not blanch when pressure is applied
What type of bleeding takes place in severe VWD?
Severe - haemophilia like.
How do you test for disorders of Primary Haemostasis?
Platelet count/ morphology Bleeding time - PFA100 Assays of VWF Clinical observation Coagulation screen (PT, APTT) would be normal except in severe cases of VWD.
What is a normal Platelet count?
150-400 X10^9/L
What platelet count would cause spontaneous bleeding?
<40
What platelet count would cause severe spontaneous bleeding?
<10
What platelet count would cause bleeding with trauma but no spontaneous bleeding?
<100
What are some treatment options for disorders of primary haemostasis?
Depends on cause Replace missing factors/ platelets - prophylactic/therapeutic. Stop drugs - aspirin/NSAIDs Immunosuppression e.g prednisolone Tranexamic acid - Antifibrinolytic Fibrin/glue spray Contraceptive pill for mennorhaggia
Why can desmopressin be used to treat disorders of primary haemostasis?
Releases VWF from endothelial cells
What is the role of Coagulation?
Generation of thrombin IIa, which will convert fibrinogen to fibrin.
Deficiency in coagulation factors will result in a failure of this process.
What are 3 causes of coagulation factor deficiencies?
Deficiency of coagulation factor production
Dilution - Acquired e.g. blood transfusion
Increased consumption
What are the types of Coagulation factor production deficiencies?
Hereditary - Factor VIII/IX, Haemophilia A/B
Acquired - Liver disease, Anticoagulant drugs; warfarin.
What are some acquired disorders of increased consumption in regard to coagulation?
Disseminated intravascular coagulation DIC - rare
Immune, autoantibodies, rare.
Define Haemophilia:
Failure to generate fibrin to stabilize platelet plug
What are the presentations of Haemophilia?
Haemarthrosis
Chronic Haemarthrosis
Muscle wasting
What should be avoided in a patient with haemophilia?
Intramuscular injections
Which coagulation factor deficiency is lethal?
Prothrombin (Factor 2 deficiency)
Why does liver failure lead to coagulation disorders?
Most coagulation factors are synthesized in the liver.
Decreased production.
How can a blood transfusion lead to coagulation disorders?
Dilution of blood as red cell transfusions do not contain plasma, major haemorrhage requires transfusion of plasma as well as red cells and platelets.
What happens in Disseminated Intravascular coagulation?
Generalised activation of coagulation – Tissue factor
Associated with sepsis, major tissue damage, inflammation
Consumes and depletes coagulation factors
Platelets consumed - thrombocytopenia
Activation of fibrinolysis depletes fibrinogen – raised D-dimer
(a breakdown product of fibrin)
Deposition of fibrin in vessels causes organ failure
What are the clinical features of coagulation disorders?
superficial cuts do not bleed (platelets)
bruising is common, nosebleeds are rare
spontaneous bleeding is deep, into muscles and joints
bleeding after trauma may be delayed and is prolonged
Bleeding frequently restarts after stop
What is the major clinical distinction between Platelet & Coagulation defects?
Platelet - Superficial bleeding + immediate following injury.
Coagulation - Deep tissues bleeding + delayed but more severe.
BOTH CAN BE LIFE THREATENING
What are the tests for coagulation disorders?
Screening tests (‘clotting screen’) Prothrombin time (PT) - extrinsic Activated partial thromboplastin time (APTT) - intrinsic Full blood count (platelets)
Coagulation factor assays (for Factor VIII etc)
Tests for inhibitors
What would cause a normal PT but a high APTT?
Haemophilia A
Haemophilia B
Factor XI deficiency
Factor XII deficiency
What would cause a high PT but a normal APTT?
Factor VII deficiency
What would cause a High PT & APTT?
Liver disease
Anticoagulant drugs e.g. warfarin
DIC (platelets and D dimer)
Dilution following red cell transfusion
What are the treatment options for the replacement of missing Coagulation factors?
Plasma (fresh frozen plasma FFP)
Contains all coagulation factors
Cryoprecipitate
Rich in Fibrinogen, FVIII, VWF, Factor XIII
Factor concentrates
Concentrates available for all factors except factor V.
Prothrombin complex concentrates (PCCs) Factors II, VII, IX, X
Recombinant forms of FVIII and FIX are available
‘On Demand’ to treat bleeds
Prophylaxis to prevent bleeds
What are some novel haemophilia treatments?
Gene therapy (Haem A and B)
Bispecific antibodies (Haem A)
Emicizumab
Binds to FIXa and FX
Mimics procoagulant function of FVIII
RNA silencing (Haem A and B) Targets natural anticoagulant - antithrombin
Which drugs increase anticoagulation factors?
tPA
Heparin
How does Pulmonary embolism present?
Tachycardia Hypoxia Shortness of breath Chest pain Haemopysis Sudden death
How does Deep Vein thrombosis present?
Painful leg Swelling Red Warm May embolise to lungs Post thrombotic syndrome
What do we mean by thrombosis?
Intravascular coagulation Inappropriate coagulation Venous (or arterial) Obstructs flow May embolise to lungs
What are the 3 contributory factors in Virchow’s triad?
Blood: dominant in venous thrombosis
Vessel wall: dominant in arterial thrombosis
Blood flow: contributes to both arterial and venous thrombosis
What is thrombophilia?
Increased risk of venous thrombosis
What are the presentations of thrombophilia?
Thrombosis at young age
‘spontaneous thrombosis’
Multiple thromboses
Thrombosis whilst anticoagulated
What is increased in thrombosis?
Factor VIII Factor II Factor V Leiden (increase activity due to activated protein C resistance) Myeloproliferative disorders (plts )
What is decreased in thrombosis?
Antithrombin
Protein C
Protein S
What are the different risks associated with Anticoagulant deficiencies?
Antithrombin - 1-2% - 25-50
Protein C - 2-4% -
Protein S - 2-4% - 10-20
What are the different risks associated with Procoagulant excesses?
Factor V Leiden - 20% - 3.6-12
Factor VIII (>1.5 iu/ml, NR 0.5 -1.5) - 24% - 2.3-10
Prothrombin (factor II) - 6% - 1.4-5.6
What is the relationship between thrombosis free survival and age?
decreases with age
How would you describe the causes of venous thrombosis?
Multicausal - arising from interacting genetic and Acquired risk fators
What is the treatment for venous thrombosis?
Prevention Assess and prevent risks Prophylactic anticoagulant therapy Reduce risk of recurrence/extension lower procoagulant factors e.g.: warfarin, DOACs increase anticoagulant activity e.g: heparin
