1b Haemostasis Flashcards by Isabella Dhoot

What is haemostasis?

the cellular and biological processes that enable both the specific and regulated cessation of bleeding in response to vascular insult

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What is haemostasis for?

Prevention of blood loss from intact vessels
Arrest bleeding from injured vessels
Enable tissue repair

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What is the response to injury to endothelial cell lining?

Vessel constriction - vascular smooth muscle cells contract locally which limits blood flow to the injured vessel

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What does primary haemostasis involve?

Formation of an unstable platelet plug - platelet adhesion and platelet aggregation

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What is the purpose of primary haemostasis?

Limits blood loss and provides a surface for coagulation

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How do platelets bind directly to the exposed collagen?

The platelets bind to the GpIa receptor = binds directly to the exposed collage

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How do platelets bind to Von Willebrand Factor?

Using the GpIb receptor

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What happens to the platelets after they bind and adhere to the endothelial lining?

Release of their granular contents = ADP anf thromboxane

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How do platelets aggregate with each other in primary haemostasis?

Using the GpIIb / IIIa receptor

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What term is used to describe low platelet numbers?

Thrombocytopenia

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What are some causes of thrombocytopenia?

Bone marrow failure like leukaemia, or B12 deficiency

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What conditions might cause accelerated clearance of platelets?

immune ITP, Disseminated Intravascular Coagulation

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What is ITP?

Immune Thrombocytopenic Purpura

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Describe how ITP occurs?

Antiplatelet autoantibodies bind to the sensitized platelet
The sensitized platelets are then cleared by macrophages in the spleen

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What is a very common cause of thrombocytopenia?

ITP

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Describe how the function of platelets might be impaired?

Hereditary absence of glycoproteins or storage granules

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What causes of Glanzmann’s syndrome?

Absence of GPIIb / IIIa

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What causes Bernard Soulier Syndrome

Absence of GPIb

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What causes storage pool disease?

reduction in the dense granules of platelets

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Which drugs might cause an acquired impairment to the function of platelets?

Aspirin, NSAID’s, Clopidogrel

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What are the two common antiplatelet drugs?

Aspirin and Clopidogrel

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How does aspirin work?

irreversibly blocks cyclo-oxygenase meaning Thromboxane A2 cannot be produced

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Why does aspirin not affect prostacyclin synthetase?

Because it can be further generated by the endothelial cells

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How does clopidogrel work?

Ireversibly blocks the ADP receptor on platelets - P2Y12 on cell membrane

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What are the two functions of Von Willebrand Factor in primary haemostasis?

Binding to collagen and capturing platelets Stabilising factor VIII (8)

What is the usual inheritance pattern of VWD?

Hereditary = autosomal inheritance pattern - Deficiency of VWF - VWF with abnormal function

What are the inherited conditions of primary haemostasis related to the vessel wall?

Connective tissue disorders

What are the acquire disorders of primary haemostasis related to the vessel wall?

Steroid therapy causes atrophy of the collage fibres which support the blood vessels Ageing = senile purpure Vasculitis Scurvy

What is VWD a failure of?

Failure of primary haemostasis

What is a key sign of thrombocytopenia?

Petechiae - small red dots on the skin which are less than 3mm in size

What causes petechiae and purpura?

Bleeding underneath the skin

What is the difference between petechiae and purpura

Petechiae = < 3mm and Blanch when pressure is applied Purpura = 3-10mm and do not blanch when pressure is applied

What conditions result in purpura on the skin?

Platelet (thrombocytopenic purpura) or vascular disorders

What are the typical bleeding features of primary haemostasis?

Immediate bleeding Prolonged bleeding from cuts Nose / gum / Heavy menstrual bleeding Prolonged bleeding after trauma / surgery Bruising

What is the medical term for nose bleeds?

Epistaxis

What is the medical term for heavy menstrual bleeding?

Menorrhagia

What type of bleeding is seen in Severe VWD?

Haemophillia like bleeding - around joints

What are the visible clinical features of primary haemostasis?

Petechiae Purpura Ecchymosis Senile Purpura Increased Skin Elasticity

What would a coagulation screen (APPT and PT) show in a disorder of primary haemostasis?

Would be normal

What tests are done for disorders of primary haemostasis?

Platelet count Bleeding time VWF assays Clinical Observations

What range of platelet count would result in no spontaneous bleeding but bleeding with trauma?

40-100 x 10^9 / L

What range of platelet count would result in spontaneous bleeding?

10-40 x 10^9 / L

What range of platelet count would result in severe spontaneous bleeding?

<10 x 10^9 / L

What is the treatment principle for abnormal haemostasis due to immune destruction?

Immunosuppression Splenectomy for ITP

What is the treatment principle for abnormal haemostasis due to failure of production / function?

Replace the missing platelets / factors Stop drugs like Aspirin

What is the treatment principle for abnormal haemostasis due to Increased Consumption?

Treat the cause Replace as necessary

What is desmopressin and how can it help in disorders of primary haemostasis?

2-5 fold increase in VWF and Factor 8 - releases endogenous stores so only useful in mild disorders

What is secondary haemostasis?

Coagulation

What is the role of coagulation?

To generate THROMBIN (IIA) = converts fibrinogen into fibrin

What are the three stages of secondary haemostasis?

Initiation Amplification Propagation

What factor is deficient in patients with Haemophillia A?

Factor 8 deficiency

What factor is deficient in patients with Haemophillia B?

Factor 9

What are some caused of acquired deficiency of coagulation factor production?

Liver disease Anti-coagulant drugs - Warfarin and direct oral anti-coagulants

What is dilution and how does it cause a coagulation disorder?

Inadequate plasma replacement following blood transfusion, as only RBC's are given, not plasma therefore more dilute

What is the inheritance pattern of Haemophillia?

Sex (X) Linked

What is haemophillia?

Lack of clotting factors results in a failure to generate fibrin to stabilise a platelet plug, therefore it becomes unstable, falls apart and bleeds

What is the hallmark of haemophillia?

Haemarthrosis - spontaneous joint bleeding

What specific method of treatment should be avoided in patients with haemophillia?

Intramuscular injections

Which clotting factor deficiencies are compatible with life?

Haemophillia

Which clotting factor deficiencies are not compatible with life?

prothrombin deficiency

What does a factor 12 deficiency result in?

NO bleeding at all

What does a factor 11 deficiency result in?

Bleeding after trauma but not spontaenouslt

Why might liver failure case an acquired coagulation disorder?

Most of the clotting factors are synthesised in the liver - except VWF which is made in the endothelial cells of blood vessels

What is disseminated intravascular coagulation?

Generalised activation of coagulation due to tissue factor which therefore consumes and depletes coagulation factors, resulting in thrombocytopenia

What dimer is raised in DIC?

D dimer - breakdown product of fibrin due to increased fibrinolysis

Why do superficial cuts not bleed in coagulation disorders?

The unstable platelet plug is sufficient to stop small vessel bleeds

What are the clinical features of coagulation disorders?

Bruising is common, nose bleeds are rare Spontaneous bleeding into the muscles and joints Delaye bleeding after trauma, and prolonged

What are the two main clinical distinctions between bleeding due to platelet and coagulation defects?

Platelet = Bleeding is subcutaenous, mucosal membranes, and immediate after injury Coagulation = bleeding is deeper (in muscle and joints) and is delayed after injury, but prolonged

What does APTT measure?

The intrinsic pathway (12 11 9 8)

What does PT measure?

The extrinsic pathway (3+7 - 10 5 2)

What found conditions could cause a normal PT time but elevated APTT time?

Haemophillia A / B factor 8 / 9 deficiency

What condition could cause a normal APTT time but abnormal (elevated) PT time?

Factor 7 defiency

What conditions could cause both APTT and PT to be raised?

Liver disease Anticoagulant drugs DIC Dilution following RBC transfer

What is used to replace all the coagulation factors?

Fresh Frozen Plasma

What does cyroprecipitate contain?

Fibrinogen, Factor 8, VWF and factor 13

What are recombinant forms of Factor 8 used for?

Used on demand to treat bleeds

What are some of the novel treatments for haemophillia?

Gene therapy Bispecific antibodies RNA silencing

Which drugs are increase fibrinolytic factors?

tPA and Heparin

What are the signs of pulmonary embolism?

Tachycardia - palpitations hypoxia Shortness of breath Chest Pain

What are the signs of Deep vein Thrombosis/

Painful leg Swelling Redness Warmth May embolise to the lungs

What do most people with disorders of thrombosis die of?

haemostatic end point

What is a thrombosis?

It is an intravascular coagulation, can be venous or arterial (more commonly venous) which obstructs flow

What are the three contributory factors to Virchow's triad?

Blood Vessel Wall Blood Flow

Which factor in Virchow's triad is dominant in venous thrombosis?

Blood

Which factor in Virchow's triad is dominant in arterial thrombosis?

Vessel wall

Which factor in Virchow's triad contributes to both arterial and venous thrombosis?

Blood flow

What is thrombophillia?

Increased risk of venous thrombosis

What are anti-coagulant proteins?

Anti-thrombin Protein C and Protein S

What change to anti-coagulant proteins might lead to venous thrombosis?

Decreased anticoagulant proteins

What might increase in order for a thrombosis to occur?

Coagulant factors Platelets - in myeloproliferative disorders

How does the risk of venous thrombosis change with age?

Increases with age

How does inflammation relate to arterial thrombosis?

Many proteins active in coagulation are expressed on the surface of the endothelial cels and their expression is altered in inflammation

What is stasis and what can cause it?

reduced blood flow Surgery, long haul flights, surgery, pregnancy

What is the cause of venous thrombosis?

Multi-causal = arises from interacting genetic and acquired risk factors, results in a cumulative risk which is over the thrombotic threshold

What is the treatment of venous thrombosis?

Assess and prevent risks Prophylactic anti-coagulation therapy Reduce risk of recurrance - lower procoagulant factors, or increase anti-coagulant activity