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year 2 - brs > 5.11 - Haemostasis > Flashcards

5.11 - Haemostasis Flashcards

1
Q

What is haemostasis?

A

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

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2
Q

What is haemostasis for? (3)

A
  • prevention of blood loss from intact vessels
  • arrest bleeding from injured vessels
  • enable tissue repair
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3
Q

What is the overall mechanism of haemostasis?

A
  1. injury to endothelial lining
  2. vessel constriction, VSMCs contract locally to limit blood flow to injured vessel
  3. primary haemostasis - formation of an unstable platelet plug - platelet adhesion (to vessel wall via VWF) and aggregation (to each other) = limits blood loss + provides surface for coagulation
  4. secondary haemostasis - stabilisation of the plug with fibrin - causes blood coagulation to stop blood loss
  5. fibrinolysis - vessel repair and dissolution of clot - cell migration/proliferation and fibrinolysis to restore vessel integrity
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4
Q

Why do we need to understand haemostatic mechanisms? (5)

A
  • diagnose and treat bleeding disorders
  • control bleeding in individuals who do not have underlying bleeding disorder
  • identify risk factors for thrombosis
  • treat thrombotic disorders
  • monitor the drugs that are used to treat bleeding and thrombotic disorders
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5
Q

What is haemostasis a balance between?

A

Bleeding (fibrinolytic factors, anticoagulant proteins) and thrombosis (coagulant factors, platelets)

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6
Q

When can the haemostatic balance be tipped towards bleeding?

A
  • too many fibrinolytic factors / anticoagulant proteins
  • not enough coagulant factors / platelets
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7
Q

What are the causes of reduced coagulant factors / platelets?

A

Lack of a specific factor:

  • failure of production - congenital and acquired
  • increased consumption/clearance

Defective function of a specific factor:

  • genetic
  • acquired - drugs, synthesis defect, inhibition
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8
Q

What is happening during platelet adhesion and aggregation?

A
  • damage to endothelium wall
  • platelets bind to exposed collagen - either directly to vessel wall through GPIa receptor, or indirectly via VWF to GPIb receptor
  • platelets release granular contents (ADP which binds P2Y12 on other platelets to activate them, VWF) and become activated along with thromboxane A2 release which activates other platelets (also release Ca2+)
  • leads to flip flopping and activation of GPIIb/IIIa receptors on platelets (allows fibrinogen to bind)
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9
Q

What about platelets can cause a problem in primary haemostasis? (2)

A
  • low numbers - thrombocytopenia
  • impaired function
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10
Q

What can cause a low number of platelets (thrombocytopenia)? (3)

A
  • bone marrow failure e.g. leukaemia, B12 deficiency
  • accelerated clearance e.g. immune (ITP), disseminated intravascular coagulation (DIC)
  • pooling and destruction in an enlarged spleen (splenomegaly)
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11
Q

What is auto-ITP (autoimmune thrombocytopenic purpura)?

A
  • antiplatelet antibodies bind to sensitised platelets
  • macrophages of reticular endothelial system in spleen clear these platelets
  • ITP is a very common cause of thrombocytopenia

(Treatment: splenectomy)

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12
Q

What can impaired function of platelets be due to? (2)

A
  • hereditary absence of glycoproteins or storage granules (rare) - e.g. Glanzmann’s thrombasthenia, Bernard-Soulier syndrome, storage pool disease
  • acquired due to drugs: aspirin, NSAIDs, clopidogrel (common)
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13
Q

What are some examples of hereditary platelet defects causing impaired function? (3)

A
  • Glanzmann’s thrombasthenia - absence of GPIIb/IIIa
  • Bernard Soulier syndrome - absence of GPIb
  • storage pool disease - reduction in contents of dense granules of platelets (ADP, ATP, serotonin, Ca2+)
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14
Q

What is antiplatelet therapy used for?

A

Prevention and treatment of cardiovascular and cerebrovascular disease

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15
Q

How does aspirin work (antiplatelet)?

A
  • irreversibly binds to COX
  • reduction in thromboxane A2 production therefore reduction in platelet aggregation (platelets)
  • even though prostacyclin production is inhibited too (prostacyclin inhibits platelet aggregation), the endothelial cells can produce more unlike the non-nucleated platelets
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16
Q

How does clopidogrel work (antiplatelet)?

A

Blocks ADP receptor P2Y12 on platelets (reduce platelet recruitment + aggregation etc)

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17
Q

What about Von Willebrand Factor can cause a problem in primary haemostasis?

A

Von Willebrand disease

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18
Q

What are the causes of Von Willebrand disease? (2)

A
  • hereditary disease of quantity and/or function (common)
  • acquired due to antibody (rare)
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19
Q

What are the two functions of VWF in haemostasis?

A
  • binding to collagen and capturing platelets
  • stabilising factor VIII (factor VIII may be low if VWF is very low)
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20
Q

Describe the inheritance of hereditary VWD?

A
  • autosomal inheritance pattern
  • deficiency of VWF is type 1 or 3
  • VWF with abnormal function is type 2
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21
Q

What about the vessel wall can cause a problem in primary haemostasis? (2)

A
  • inherited (rare) - e.g. hereditary haemorrhagic telangiectasia, Ehlers-Danlos syndrome and other connective tissue disorders
  • acquired (common) - e.g. steroid therapy, ageing (‘senile’ purpura), vasculitis, scurvy (vitamin C deficiency)
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22
Q

What happens in VWD?

A

Failure of primary haemostasis - platelet plug cannot form

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23
Q

What are the clinical features of bleeding in primary haemostasis? (7)

A
  • immediate bleeding
  • prolonged bleeding from cuts
  • nosebleeds (epistaxis): prolonged >20min
  • gum bleeding: prolonged
  • heavy menstrual bleeding (menorrhagia)
  • bruising (ecchymosis), may be spontaneous/easy
  • prolonged bleeding after trauma/surgery
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24
Q

What is a particular feature of thrombocytopenia?

A

Petechiae - small spots under skin caused by bleeding under skin

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25
Q

In what types of disorders do we see purpura?

A
  • platelet (thrombocytopenic purpura)
  • vascular disorders (wet purpura if over mucosal surfaces like gums)
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26
Q

How can we tell the difference between petechiae and purpura?

A
  • both are caused by bleeding under the skin
  • purpura do not blanch when pressure is applied
  • petechia <3mm, purpura 3-10mm, bruise >10mm
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27
Q

What is the bleeding pattern like in severe VWD?

A

Haemophilia-like bleeding (due to low FVIII too)

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28
Q

What are the tests for disorders of primary haemostasis? (4)

A
  • platelet count, platelet morphology
  • bleeding time (PFA100 in lab - platelet function analysis)
  • assays of VWF
  • clinical observation
  • note - coagulation screen (PT, APTT) is normal, except more severe VWD where FVIII is low
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29
Q

What are the platelet count ranges for normal and thrombocytopenia?

A
  • normal range: 150-400 x10^9/l
  • no spontaneous bleeding, but bleeding with trauma: 40-100 x10^9/l
  • spontaneous bleeding common: 10-40 x10^9/l
  • severe spontaneous bleeding: <10 x10^9/l
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30
Q

How do we treat failure of production/function in primary haemostasis?

A
  • replace missing factors/platelets e.g. VWF containing concentrates
  • can be prophylactic (e.g. before surgery) or therapeutic (e.g. after bleeding)
  • stop drugs e.g. aspirin/NSAIDs
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31
Q

How do we treat immune destruction in primary haemostasis?

A
  • immunosuppression e.g. prednisolone
  • splenectomy for ITP
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32
Q

How do we treat increased consumption (e.g. in DIC) in primary haemostasis?

A
  • treat underlying cause
  • replacement therapy as necessary
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33
Q

What additional haemostatic treatments are there for primary haemostasis disorders? (4)

A
  • desmopressin (ddAVP) - vasopressin analogue that causes 2-5x increase in VWF (and FVIII) - releases endogenous stores so only useful in mild disorders
  • tranexamic acid - antifibrinolytic
  • fibrin glue/spray
  • other approaches e.g. hormonal (oral contraceptive pill for menorrhagia)
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34
Q

What is the role of coagulation?

A

To generate thrombin (IIa), which will convert fibrinogen to fibrin

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35
Q

What would a deficiency of any coagulation factor cause?

A

A failure of thrombin generation and hence fibrin formation

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36
Q

What are the main causes of disorders of coagulation? (3)

A
  • deficiency of coagulation factor production
  • dilution
  • increased consumption
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37
Q

What are the two types of deficiency of coagulation factor production and what makes these up?

A
  • hereditary - factor VIII/IX (haemophilia A/B)
  • acquired - liver disease, anticoagulant drugs (warfarin, DOACs)
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38
Q

What can dilution be caused by?

A
  • acquired - through red blood cell transfusions that do not have plasma
  • a major haemorrhage requires a transfusion of plasma as well as red cells and platelets to avoid dilutional effect with reduction in coagulation factors
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39
Q

What are the common and rare causes of increased consumption?

A
  • acquired
  • disseminated intravascular coagulation (DIC) - common
  • immune - antibodies - rare
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40
Q

What is haemophilia A?

A

Factor VIII deficiency, sex-linked

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41
Q

What is haemophilia B?

A

Factor IX deficiency, sex-linked

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42
Q

What do both haemophilias A&B do mainly?

A
  • cause a failure to generate fibrin to stabilise platelet plug
  • unstable platelet plug breaks away leading to bleeding
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43
Q

What is the hallmark of haemophilia?

A
  • haemarthrosis - spontaneous bleeding of joints when factors are low
  • usually seen in more developing countries because factor replacement therapy is more accessible in developed countries
  • long term - chronic haemoarthritis with target joints having recurrent bleeds and damaging the synovial lining leading to joint deformity and muscle wasting
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44
Q

What happens if an intramuscular injection is given to a haemophilia patient?

A

There is extensive haematoma that occurs - avoid!!

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45
Q

Is haemophilia (A/B) compatible with life?

A

Yes - severe but compatible with life, spontaneous joint and muscle bleeding

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46
Q

Is prothrombin (factor II) deficiency compatible with life?

A

No - lethal

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47
Q

What does factor XI deficiency lead to?

A

Bleed after trauma but not spontaneously (so less severe than haemophilia)

48
Q

What does factor XII deficiency lead to?

A

No bleeding at all

49
Q

How can liver failure cause decreased production of coagulation factors?

A

Liver synthesises most coagulation factors (apart from VWF made by endothelial cells and factor V made by platelets) so liver failure reduces production

50
Q

What happens in disseminated intravascular coagulation (DIC)?

A
  • generalised activation of coagulation due to tissue factor (normally does not contact factor VIIa)
  • consumes and depletes coagulation factors and platelets (thrombocytopenia)
  • activation of fibrinolysis depletes fibrinogen –> raised D-dimer (breakdown product of fibrin)
  • deposition of fibrin in vessels causes organ failure and shearing of RBCs causing RBC fragmentation
51
Q

What does activation of fibrinolysis raise (DIC)?

A

D-dimer (breakdown product of fibrin)

52
Q

What does deposition of fibrin in vessels cause (DIC)?

A
  • organ failure
  • shearing of RBCs causing red cell fragmentation
53
Q

What can DIC be triggered by? (4)

A
  • sepsis
  • major tissue damage
  • inflammation
  • pre-eclampsia
54
Q

How do we treat DIC? (2)

A
  • treat underlying cause
  • meanwhile give supportive treatment with replacement of missing coagulation factors e.g. give FFP and platelets
55
Q

What are the clinical features of coagulation disorders? (5)

A
  • superficial cuts do not bleed (platelets functioning and platelet plug enough for small cuts)
  • 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
56
Q

How do you clinically distinguish between platelet/vascular deficiencies and coagulation deficiencies? (platelet/vascular vs coagulation)

A
  • superficial bleeding into skin, mucosal membranes VS bleeding into deep tissues, muscles, joints
  • bleeding immediate after injury VS delayed, but severe bleeding after injury, often prolonged
57
Q

What tests are there for coagulation disorders? (3)

A
  • screening tests (‘clotting screen’) - prothrombin time (PT), activated partial thromboplastin time (APTT), full blood count (platelets)
  • coagulation factor assays (for FVIII etc)
  • tests for inhibitors
58
Q

Describe the extrinsic pathway (tests for coagulation disorders, recap phase 1a)

A
  • trauma exposes the cells below the endothelial layer e.g. smooth muscle cells
  • these cells have tissue factor (factor III) in their membrane
  • factor VII is floating in the blood - some is already active (VIIa) so is set to proteolytically cleave other proteins
  • factor VIIa binds to a TF and Ca2+ –> VIIa-TF complex on surface of smooth muscle cells
  • [TF and Ca2+ (released by nearby activated platelets) are cofactors - must bind to VIIa for it to function]
  • VIIa-TF complex cleaves factor X –> factor Xa
  • factor Xa cleaves factor V –> factor Va
  • factor Xa uses factor Va and Ca2+ as cofactors to form the prothrombinase complex (one can activate thousands of thrombins = enormous amplification)
  • activates prothrombin (factor II) –> thrombin (factor IIa)
59
Q

Describe the intrinsic pathway (tests for coagulation disorders, recap phase 1a)

A
  • circulating factor XII comes into contact with negatively charged phosphates on membranes of activated platelets or subendothelial collagen exposed by trauma
  • undergoes conformational change –> activated into factor XIIa
  • factor XIIa proteolytically cleaves factor XI –> factor XIa
  • factor XIa combines with Ca2+ –> proteolytically cleaves factor IX –> IXa
  • factor IXa forms a complex with Ca2+ and factor VIIIa –> proteolytically cleaves factor X –> factor Xa
  • (factor VIII degrades rapidly in blood unless bound to VWF)
  • Xa –> Va –> Xa + Va + Ca2+ –> IIa
60
Q

What is the role of thrombin? (recap phase 1a)

A
  • thrombin uses Ca2+ as a cofactor and has many procoagulative effects:
    1. thrombin binds to receptors on platelets and activates them
    2. activates three cofactors: factor V (common pathway), factor VIII, fabin - cleaves soluble fibrinogen (I) –> insoluble fibrin (Ia) - fibrin precipitates out of plasma and forms long rope-like protein chains
    3. proteolytically cleaves stabilising factor (XIII) –> XIIIa - combines with Ca2+ cofactor to form cross links between fibrin chains –> further reinforcing the fibrin mesh
61
Q

What is the currently accepted model for coagulation (recap phase 1a)?

A
  • initiation: TF combines with FVIIa (and Ca2+), IX–>IXa, X–>Xa, II–>IIa (small amount of thrombin)
  • amplification: thrombin causes cofactor V–>Va, VIII–>VIIIa, IX–>IXa (increased by XIa), platelet activation, IXa with VIIIa and Ca2+ amplifies X–>Xa
  • propagation: amplified X–>Xa causes rapid burst in thrombin production which cleaves fibrinogen (I)–> fibrin (Ia)
62
Q

What does prothrombin time (PT) measure?

A

Extrinsic pathway

63
Q

What does activated partial thromboplastin time (APTT) measure?

A

Intrinsic pathway

64
Q

What could cause an increased APTT but normal PT?

A
  • deficiencies in intrinsic pathway factors
  • haemophilia A (factor VIII)
  • haemophilia B (factor IX)
  • factor XI deficiency
  • factor XII deficiency (does not cause bleeding)
65
Q

What could cause an increased PT but normal APTT?

A
  • deficiencies in extrinsic pathway factors
  • factor VII deficiency
66
Q

What could cause an increased APTT and PT? (5)

A
  • liver disease
  • anticoagulants like warfarin
  • DIC (platelets and D-dimer)
  • dilution following red cell transfusion
  • deficiency of factors II, V, X (common factors in both pathways)
67
Q

What are the treatments for coagulation disorders? (3)

A

Factor replacement therapy:

  • plasma (fresh frozen plasma FFP)
  • cryoprecipitate
  • factor concentrates
68
Q

What does FFP/plasma contain?

A

All coagulation factors

69
Q

What does cryoprecipitate contain?

A

Rich in fibrinogen, FVIII, VWF, FXIII

70
Q

What do factor concentrates include?

A
  • concentrates available for all factors except factor V (FFP/platelets needed)
  • prothrombin complex concentrates (PCCs) - factors II, VII, IX, X
71
Q

What are recombinant forms of FVIII and FIX used to treat?

A
  • ‘on demand’ to treat bleeds
  • prophylaxis to prevent bleeds
72
Q

What has the evolution of haemophilia treatment been like?

A
  • plasma-derived clotting factors (1969) –> widespread viral contamination
  • currently improved recombinant clotting factors VIII, IX, VIIa (1990s) - improved safety, eliminated potential for transmission of blood borne pathogens
  • investigational therapies (2008+) - prolonged half-life (VIII/IX), gene therapy, novel agents
73
Q

What novel treatments are emerging for haemophilia? (3)

A
  • gene therapy (for both A and B)
  • bispecific antibodies (for haemophilia A e.g. Emicizumab) - binds FIXa and FX, mimics procoagulant function of FVIII
  • RNA silencing (for both A and B) - targets antithrombin (natural anticoagulant)
74
Q

What other treatments can be used alongside factor replacement for coagulation disorders? (2)

A
  • desmopressin (ddAVP)
  • tranexamic acid - antifibrinolytic
75
Q

When can fibrinolytic factors and anticoagulant proteins be increased?

A
  • extremely rare except when induced by drugs:
    • tPA (stroke)
    • heparin
76
Q

What are two examples of venous thrombosis?

A
  • pulmonary embolism (PE)
  • deep vein thrombosis (DVT)
77
Q

What are the symptoms of pulmonary embolism (PE)? (6)

A
  • tachycardia
  • hypoxia
  • shortness of breath
  • chest pain
  • haemoptysis
  • sudden death
78
Q

What are the symptoms of deep vein thrombosis (DVT)? (6)

A
  • painful leg
  • swelling
  • red
  • warm
  • may embolise to lungs –> PE
  • post thrombotic syndrome - damage to valves causing long term damage
79
Q

When do most patients with thrombosis die?

A

At the haemostatic endpoint

80
Q

What is thrombosis? (4)

A
  • intravascular and inappropriate coagulation
  • venous (or arterial)
  • obstructs flow
  • may embolise to lungs
81
Q

What is Virchow’s triad?

A

The three contributory factors to thrombosis:

  • blood - dominant in venous thrombosis
  • vessel wall - dominant in arterial thrombosis
  • blood flow - contributes to both venous and arterial thrombosis
82
Q

What is thrombophilia?

A

Increased risk of venous thrombosis

83
Q

How might thrombophilia present? (4)

A
  • thrombosis at young age
  • ‘spontaneous’ thrombosis (unprovoked)
  • multiple thromboses
  • thrombosis whilst anticoagulated
84
Q

What does the balance of haemostasis look like in venous thrombosis?

A
  • reduced fibrinolytic factors + anticoagulant proteins
  • increased coagulant factors + platelets
85
Q

What anticoagulant proteins would decrease to cause thrombosis? (3)

A
  • antithrombin (most powerful)
  • protein C
  • protein S
86
Q

What coagulant factors would increase to cause thrombosis? (3)

A
  • factor VIII
  • factor II
  • factor V Leiden (increase activity due to activated protein C resistance)
87
Q

What would cause an increase of platelets (leading to thrombosis)?

A

Myeloproliferative disorders

88
Q

What is the role of the vessel wall in venous thrombosis?

A
  • many proteins active in coagulation are expressed on the surface of endothelial cells and their expression altered in inflammation:
    • thrombomodulin receptor
    • endothelial protein C receptor
    • tissue factor
89
Q

What are examples of situations where reduced blood flow (stasis) increase the risk of thrombosis? (3)

A
  • surgery
  • long haul flight
  • pregnancy (compression from foetus)
90
Q

How do we treat venous thrombosis? (2 areas)

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
91
Q

How can we prevent venous thrombosis?

A
  • assess and prevent risks
  • prophylactic anticoagulant therapy
92
Q

How can we reduce risk of recurrence/extension of venous thrombosis?

A
  • lower procoagulant factors e.g. anticoagulants like warfarin, DOACs
  • increase anticoagulant activity e.g. heparin
93
Q

What coagulopathies are involved in SARS-CoV-2? (5)

A
  • DIC - disseminated intravascular coagulation
  • SIC - sepsis-induced coagulopathy
  • HPS - haemophagocytic syndrome
  • APS - antiphospholipid syndrome
  • TMA - thrombotic microangiopathy
94
Q

What are some therapeutic indications for anticoagulation?

A
  • venous thrombosis - initial treatment to minimise clot extension/embolisation (<3 months), long term treatment to reduce risk of recurrence
  • atrial fibrillation - 800/100k potentially eligible in one year, to reduce risk of embolic stroke
  • mechanical prosthetic heart valve (increased stroke risk)
95
Q

What are some preventative (thromboprophylaxis) indications for anticoagulation?

A

E.g. following surgery, during hospital admission, during pregnancy

96
Q

What is heparin?

A
  • naturally occurring glycosaminoglycan
  • produced by mast cells of most species
  • porcine products used in UK
  • varying number of saccharides in chains - differing lengths
97
Q

What are the two chain lengths of heparin?

A
  • long chains - unfractionated (UFH) - intravenous administration, short half -life
  • low molecular weight heparin (LMWH) - subcutaneous administration
98
Q

What are the actions of unfractionated heparin? (4)

A
  • enhancement of antithrombin
  • inactivation of thrombin (hep binds AT and thrombin)
  • inactivation of FXa (hep binds AT only)
  • (inactivation of FIXa, FXIa, FXIIa)
99
Q

What are the actions of low molecular weight heparin (LMWH)? (2)

A
  • contain pentasaccharide sequence for binding antithrombin
  • predictable dose response in most cases so does not require monitoring (compared to UFH) - if required, measure anti-Xa
100
Q

How were coumarins (vitamin K antagonists) discovered?

A
  • 1920s - fatal haemorrhagic disease in cattle fed mouldy sweet clover
  • 1930s - haemorrhagic cattle ‘deficient in prothrombin’, sterol (vitamin K) cures similar disease in chickens, dicoumarol isolated from spoilt sweet clover in 1939
  • 1940s - dicoumarol effective in VTE and MI, warfarin marketed as rat poison in 1948
  • 1950s - warfarin more effective anticoagulant than dicoumarol
101
Q

How does warfarin work?

A
  • warfarin blocks recycling of vitamin K
  • inactivates factors II, VII, IX, X, protein C and protein S
  • competes with vitamin K - complicated metabolism (many dietary, physiological and drug interactions, narrow therapeutic index and needs monitoring)
  • reduces production of functional coagulation factors
  • induces an anticoagulated state slowly
  • reversible
102
Q

How is warfarin reversible?

A
  • reversed slowly by vitamin K administration - takes several hours to work
  • reversed rapidly by infusion of coagulation factors:
    • PCC - contains factors II, VII, IX, X
    • FFP
103
Q

What are the side effects of warfarin? (4)

A
  • bleeding - minor 5%, major 0.9-3%, fatal 0.25%
  • skin necrosis (mitigate by starting heparin)
  • purple toe syndrome
  • embryopathy - chondrodysplasia punctata - avoid in first trimester of pregnancy
104
Q

What happens in skin necrosis (warfarin side effect)?

Reduce with heparin

A
  • severe protein C deficiency
  • 2-3 days after starting warfarin
  • thrombosis predominantly in adipose tissues
105
Q

What happens in purple toe syndrome (side effect of warfarin)?

A
  • disrupted atheromatous plaques bleed
  • cholesterol emboli lodge in extremities
106
Q

What happens in chondrodysplasia punctata (warfarin side effects)?

A
  • early fusion of epiphyses
  • warfarin teratogenic in 1st trimester
107
Q

How do we monitor warfarin?

A

INR = (PT / PTc)^ISI

  • INR = international normalised ratio
  • ISI = international sensitivity index
108
Q

What are the ranges for unanticoagulated normal INR and target INR?

A
  • unanticoagulated normal INR = 1.0
  • target INR usually 2-3
109
Q

What can cause resistance to warfarin? (4)

A
  • lack of patient compliance (measure warfarin levels, proteins induced by vitamin K absence PIVKA)
  • diet, increased vitamin K intake
  • increased metabolism Cyt P450 (CYP2C9)
  • reduced binding (VKORC1)
110
Q

What are some examples of DOACs and what factors they inhibit?

A
  • rivaroxaban, apixaban, edoxaban - Xa
  • dabigatran - IIa
111
Q

What are the differences between warfarin VS DOACs?

A
  • onset/offset - slow vs rapid
  • dosing - variable vs fixed
  • food effect - yes vs no
  • interactions - many vs few
  • monitoring required - yes vs no
  • renal dependence - no vs some
  • reversibility - vitamin K/PCCs vs specific antibodies available for dabigatran and in development for FXa inhibitors
112
Q

What anticoagulants should be used for therapeutic management of venous thrombosis?

A
  • initial treatment to minimise clot/embolisation - DOAC/LMWH for first few days followed by DOAC/warfarin
  • long term to reduce risk of recurrence - DOAC/warfarin
113
Q

What anticoagulants should be used for therapeutic management of atrial fibrillation?

A

DOAC/warfarin to reduce risk of embolic stroke

114
Q

What anticoagulants should be used for therapeutic management of mechanical prosthetic heart valves?

A

Warfarin (DOACs not effective and should be avoided)

115
Q

What anticoagulants should be used for preventative (thromboprophylaxis) measures? (note lower doses used)

A
  • following surgery - LMWH/DOAC
  • during hospital admission (DOACs not effective for use as medical thromboprophylaxis, heparin used)
  • during pregnancy - LMWH (DOACs not safe)

year 2 - brs (84 decks)

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