Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BRS Flashcards (Y2) > Haemostasis > Flashcards

Haemostasis Flashcards

1
Q

What is haemostasis?

A

The cellular and biochemical processes that enables both specific and regulated cessation of bleeding in response to vascular insult

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is haemostasis for?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Outline the mechanisms of haemostasis

A

Response to injury to endothelial lining:
Vessel constriction
- Vascular smooth muscle cells contract locally, limiting blood flow to injured vessel
Formation of an unstable platelet plug (primary haemostasis)
- platelet adhesion and aggregation (aided by vWF)
- limits blood loss and provides surface for coagulation
Stabilisation of plug with fibrin
- blood coagulation
- stops blood loss
Vessel repair and dissolution of plug (fibrinolysis)
- cell migration/proliferation & fibrinolysis, restoring vessel integrity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Why do we need to understand haemostatic mechanisms?

A
  • Can diagnose and treat bleeding disorders
  • Control bleeding in those that doesn’t have underlying bleeding disorders
  • Identify risk factors for thrombosis
  • Treat thrombotic disorders
  • Monitor drugs used to treat bleeding and thrombotic disorders
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How is normal haemostasis maintained?

A

Balance between thrombosis (coagulant factors, platelets) and bleeding (fibrinolytic factors, anticoagulant proteins)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the steps of platelet adhesion

A
  • Damage to endothelium results in exposure of collagen in vessel wall
  • Platelets adhere to vessel wall directly via Glp1a receptor or indirectly using Von Willibrand Factor via the Glp1b receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the steps of platelet aggregation

A
  • Platelets release their granular contents and ADP and thromboxane are generated causing activation of platelets
  • Leads to flip-flopping and activation of GlpIIb/IIIa receptor on platelets - causes aggregation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What disorders can cause thrombocytopenia?

A

Bone marrow failure - e.g. leukaemia, B12 deficiency
Accelerated clearance - immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC)
Pooling and destruction in an enlarged spleen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What happens in immune thrombocytopenia purpura (ITP)?

A
  • Anti-platelet autoantibodies generated and stick to sensitised platelet
  • Platelet cleared by macrophages of the reticulo-endothelial system in the spleen
  • Common cause of thrombocytopenia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What disorders can cause impaired function of platelets?

A

Hereditary absence of glycoproteins or storage granules (rare):
- Glanzmann’s thrombasthenia - absence of GpIIb/IIIa receptor
- Bernard Soulier syndrome - absence of GpIb receptor
- Storage Pool disease - group of disorders referring to reduction in granular (dense) contents of platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are acquired causes of impaired platelet function?

A

Drugs: aspirin, NSAIDs, clopidogrel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How does aspirin work?

A

Irreversibly blocks Cyclo-Oxygenase (COX) resulting in a reduction in platelet aggregation
Prevents production of thromboxane A2 from arachidonic acid in platelets
(Also inhibits prostacyclin synthesis but this can be produced by endothelial cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How long does a single dose of aspirin last?

A

7 days
Until most of the platelets present at the time of ingestion have been replaced by new ones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How does clopidogrel work?

A

Irreversibly blocks ADP receptor P2Y12 on platelet cell membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Von Willebrand Factor can be reduced or defective in which condition?

A

Von Willebrand Disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What causes Von Willebrand disease?

A

Hereditary - decrease of quantity and/or function (common)
Acquired due to antibody (rare)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the functions of VWF in haemostasis?

A

Binding to collagen and capturing platelets
Stabilising factor VIII - if VWF is very low, factor VIII may be low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the different types of Von Willebrand Disease?

A

Usually hereditary - autosomal inheritance pattern
- Deficiency of VWF -> Type 1/3
- VWF with abnormal function -> Type 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Give examples of disorders of the vessel wall affecting primary haemostasis

A

Inherited (rare): Hereditary haemorrhagic telangiectasia Ehlers-Danlos syndrome and other connective tissue disorders
Acquired (common): steroid therapy, ageing (‘senile’ purpura), vasculitis, scurvy (vitamin C deficiency)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the typical clinical features of primary haemostasis bleeding?

A

Immediate
Prolonged bleeding from cuts
Nose bleeds (epistaxis): prolonged >20 mins
Prolonged gum bleeding
Heavy menstrual bleeding (menorrhagia)
Easy/spontaneous brushing (ecchymosis)
Prolonged bleeding after trauma or surgery
Petechiae
Purpura

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What clinical feature of primary haemostasis bleeding is more stable commonly seen in thrombocytopenia?

A

Petechiae

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How can you distinguish between petechiae, purpura and ecchymosis?

A

Petechiae - <3mm
Purpura - 3-10mm
Ecchymosis - >10mm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

When is purpura typically observed?

A

Platelets disorders - e.g. thrombocytopenic purpura
Vascular disorders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Is purpura blanching?

A

Nope, does not blanch when pressure is applied
Caused by bleeding under skin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Haemophilia-like bleeding may be present in the severe form of which disorder?

A

Von Willebrand Disease - due to low FVIII

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

List tests for disorders of primary haemostasis

A

Platelet count, platelet morphology
Bleeding time (now replaced by Platelet Function Analyser (PFA100) in lab)
Assays of VWF
Clinical observation - e.g. stretchy skin, hyper-elasticity - connective tissue disorders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What would you observe in a coagulation screen if someone with a disorder of primary haemostasis?

A

Tend to be normal except in more severe VWD cases where FVIII is low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Describe the relationship between platelet count and thrombocytopenia (using figures)

A

150-400 x 10^9/l - typical range
<100 x 10^9/l - no spontaneous bleeding but bleeding with trauma
<40 x 10^9/l - common spontaneous bleeding
<10 x 10^9/l - severe spontaneous bleeding

29
Q

How do you treat primary haemostasis disorders caused by failure of production/function?

A

Replace missing factors/platelets (e.g. VWF containing concentrates) as a prophylactic or therapeutic measure
Stop drugs, e.g. aspirin/NSAIDs

30
Q

How do you treat primary haemostasis disorders caused by immune destruction?

A

Immunosuppression, e.g. prednisolone
Splenectomy (for ITP)

31
Q

How do you treat primary haemostasis disorders caused by increased consumption of platelets, e.g. DIC)

A

Treat underlying cause
Replace as necessary

32
Q

Outline some addition haemostatic treatments for abnormal haemostasis

A

Desmopressin (DDAVP)
- 2-5 fold increase in VWF (and FVIII)
- releases endogenous stores so only useful in mild disorders
Tranexamic acid - antifibrinolytic
Fibrin glue/spray
Hormonal - oral contraceptive pill for menorrhagia

33
Q

What is the role of coagulation and what would deficiency of any coagulation factor result in?

A

Role of coagulation is to generate thrombin (IIa) - converts fibrinogen to fibrin
Deficiency of any coagulation factor would cause a failure of thrombin generate and hence fibrin formation

34
Q

Give examples of disorders of coagulation with their causes

A

Deficiency of coagulation factor production
- Hereditary: factor VIII/IX - Haemophilia A/B
- Acquired: liver disease, anticoagulants (warfarin, direct oral anticoagulants)
Dilution
- Acquired: blood transfusion
Increased consumption
- Acquired: DIC (common)
- Immune - antibodies (rare)

35
Q

Describe the inheritance pattern of hereditary coagulation disorders

A

Haemophilia:
- Sex-linked
- 1 in 10,000 births
Others are rare - autosomal recessive inheritance

36
Q

What happens in normal secondary haemostasis vs haemophilia?

A

Haemostasis: fibrin clot stabilises platelet plug
Haemophilia: failure to generate fibrin results in platelet plug being unstable and falling apart - bleeding

37
Q

What is the hallmark of haemophilia?

A

Haemoarthrosis - spontaneous joint bleeding due to FVIII/FIX deficiency
However access to prophylactic/factor replacement therapy in developed countries results in better joint function outcome when started earlier in life (e.g. when babies start to crawl)

38
Q

What can chronic haemoarthrosis lead to?

A

Joint deformity - target joints
Muscle wasting

39
Q

Should intramuscular injections be given to patients with haemophilia?

A

No, can cause a haematoma

40
Q

How do deficiencies of coagulation factors differ in effect?

A

Factor VIII/IX
- Severe but compatible with life
- Spontaneous joint and muscle bleeding
Prothrombin (FII)
- Lethal
Factor XI
- Bleed after trauma but not spontaneously
Factor XII
- No bleeding at all

41
Q

Why can liver failure lead to coagulation disorders?

A

Most coagulation factors are synthesised in the liver
Liver failure -> decreased production of coagulation factors

42
Q

What factors are not produced in the liver?

A

VWF - produced in endothelial cells lining blood vessels
FV - produced in platelets

43
Q

What are some causes of acquired coagulation disorders?

A

Liver failure - decreased production
Anticoagulant drugs
Dilution - red cell transfusions don’t contain plasma - major haemorrhage requires transfusions of plasma, red cells and platelets
Increased consumption - disseminated intravascular coagulation

44
Q

Outline the pathophysiology of DIC

A

Generalised (unregulated), rather than localised, activation of coagulation associated with sepsis, major tissue damage or inflammation causing tissue factor to come into contact with FVIIa
Consumes and depletes coagulation factors
Platelet consumption - thrombocytopenia
Activation of fibrinolysis depletes fibrin - raised D-dimmer (breakdown product of fibrin)
Deposition of fibrin in vessels causes organ failure and shearing of RBCs (leading to RBC fragmentation)
Characterised by clotting and bleeding

45
Q

What are the clinical features of (secondary haemostatic) coagulation disorders?

A

Superficial cuts do not bleed (platelets are working fine and platelet plug is sufficient)
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 stopping

46
Q

What are some basic differences between primary and secondary haemostatic disorders?

A

Platelet/vascular (primary):
Superficial bleeding into skin, mucosal memebranes
Bleeding immediately after injury

Coagulation (secondary):
Bleeding into deep tissues, muscles, joints
Delayed but severe bleeding after injury - bleeding often prolonged

Both can be life threatening

47
Q

Label the classical coagulation cascade model with the intrinsic and extrinsic components

A
48
Q

What tests can be used for coagulation disorders?

A

Screening tests:
- Prothrombin time
- Activated partial thromboplastin time (APTT)
- Full blood count (platelets)
Coagulation factor assays (e.g. for FVIII)
Tests for inhibitors

49
Q

What conditions could cause a normal PT and prolonged APTT?

A

Haemophilia A
Haemophilia B
Factor XI deficiency
Factor XII deficiency

50
Q

What conditions could cause a prolonged PT and normal APTT?

A

Factor VII deficiency (extrinsic pathway)

51
Q

What conditions could cause a prolonged PT and APTT?

A

Liver disease
Anticoagulants, e.g. warfarin
DIC (platelets and D-dimer)
Dilution following red cell transfusion

52
Q

What are the different treatment options for replacement of missing coagulation factors?

A

FFP - contains all coagulation factors
Cryoprecipitate - rich in fibrinogen, FVIII, VWF, FXIII
Factor concentrates - available for all factors, except FV; prothrombin complex concentrates (PCCs) contain FII, VII, IX, X
Recombinant forms of FVIII and FIX - available on demand to treat bleeds or as a prophylaxis

53
Q

Describe the evolution of haemophilia treatment

A
54
Q

What are some novel treatments of Haemophilia?

A

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

55
Q

Bleeding due to increased fibrinolytic factors and anticoagulant proteins is rare except when induced by which drugs?

A

tPA (stroke)
Heparin

56
Q

What are the symptoms of a pulmonary embolism?

A

Tachycardia
Hypoxia
Shortness of breath
Chest pain
Haemoptysis
Sudden death

57
Q

What are the symptoms of deep vein thrombosis?

A

Painful leg
Swelling
Red
Warm
May embolism to lungs
Post thrombotic syndrome (vessel incompetency following DVT)

58
Q

What are the characteristics of thrombosis?

A

Intravascular coagulation
Inappropriate coagulation
Venous (or arterial)
Obstructs flow
May embolise to lungs

59
Q

Outline the three contributory factors to thrombosis in Virchow’s triad

A

Blood - dominant in venous thrombosis
Vessel wall - dominant in arterial thrombosis
Blood flow - contributes to both arterial and venous thrombosis

60
Q

What is thrombophilia and how may it present?

A

Increased risk of venous thrombosis:
- Thrombosis at a young age
- ‘Spontaneous’ thrombosis
- Multiple thromboses
- Thrombosis whilst anticoagulated

61
Q

A deficiency in which anticoagulant proteins may predispose to DVT?

A

Antithrombin
Protein C
Protein S
E.g. in nephrotic syndrome where they leak through the kidney

62
Q

Increases in which coagulation factors may predispose to DVT?

A

Mainly genetic but may have other causes
Factor VIII (genetic, cancer, post surgery, pregnancy)
Factor II
Factor V Leiden (resistance to protein C inactivation)
Myeloproliferative disorders (increased platelets)

63
Q

How do Protein C/S and antithrombin work?

A
64
Q

Which inherited thrombophilic trait has the highest odds ratio of developing thrombosis?

A

Antithrombin deficiency - however, lowest frequency

65
Q

Explain the role of the vessel wall in venous thrombosis

A

Not much known
However, many proteins active in coagulation are expressed on the surface of endothelial cells and their expression is altered in inflammation (link between inflammation and thrombosis)
E.g. thrombomodulin receptor, endothelial protein C receptor (EPCR)

66
Q

How do blood flow contribute to VT?

A

Reduced blood flow (stasis) increases risk of thrombosis
E.g. long haul flights, surgery, pregnancy

67
Q

Is age a risk factor for DVT?

A

Yes

68
Q

Describe the interplay between genetic and acquired risk factors for VT

A
69
Q

How is VT treated?

A

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

BRS Flashcards (Y2) (79 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions