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CP reviewer 1 > Acquired Bleeding Disorders > Flashcards

Acquired Bleeding Disorders Flashcards

1
Q

Why are anticoagulants used in patients with atrial fibrillation?

A

To prevent stroke; if ventricles and atria are not contracting in time, blood can pool in atria and form clots

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2
Q

What are the 4 major classes of anticoagulants?

A
  1. Heparin
  2. Vitamin K antagonists
  3. DOACs
  4. Fondaparinux
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3
Q

What is heparin derived from?

A

Pigs (porcine)

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4
Q

Mechanism of action of unfractionated heparin vs LMWH?

A

UH form a complex with antithrombin;

  • Inhibition of factors: thrombin (factor IIa), factor IXa, Xa, XIa and XIIa.
  • This prevents fibrin formation and inhibits thrombin-induced activation of platelets and factors V, VIII, and XI.

LMWH are too short to bind to antithrombin and thrombin simultaneously but bind to antithrombin alone;
- Inactivates factor Xa
- Only reduced inhibitory activity against thrombin (factor IIa) relative to
factor Xa.

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5
Q

Which factors does unfractionated heparin inhibit?

A
  • Thrombin (factor IIa)
  • Xa
  • IXa (lesser extent)
  • XIa (lesser extent)

Inhibits Xa and IIa in 1:1 ratio

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6
Q

Which factor does LMWH predominantly inhibit?

A

Factor Xa

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7
Q

Does LMWH heparin inhibit platelet function? Does UH?

A

LMWH - no

UH - yes

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8
Q

Half life of;

a) UH
b) LMWH?

A

a) 1 hour IV, 2 hours SC

b) 4 hours SC

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9
Q

Frequency of administration of;

a) UH
b) LMWH?

A

a) continuous infusion

b) daily

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10
Q

Bioavailability of;

a) UH
b) LMWH?

A

a) 50%

b) 100%

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11
Q

Elimination route of;

a) UH
b) LMWH?

A

a) renal and hepatic

b) renal

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12
Q

Frequency of HIT in;

a) UH
b) LMWH?

A

a) high

b) low

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13
Q

What is HIT?

A

Heparin Induced Thrombocytopenia

A clinicopathological syndrome that occurs when heparin dependent IgG antibodies bind to heparin/platelet factor 4 complexes to activate platelets and produce a hypercoagulable state.

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14
Q

How is UH monitored? LMWH?

A

UH - monitor with APTT ratio

LMWH - anti-Xa levels (assay)

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15
Q

One complication of heparin can be osteoporosis. How does this occur?

A

a) Heparin causes increased bone resorption by stimulating osteoclasts and suppressing osteoblast function, leading to decreased bone mass.
b) Causes depletion of mast cells in bone marrow and enhancement of parathyroid hormone function, an important regulator of calcium in the body.

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16
Q

What drop in platelets defines HIT?

A

o drop in platelet count >50% from baseline

o usually 5-10 days after starting heparin

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17
Q

What is the 4Ts Score?

A

The 4Ts Score is a clinical scoring system to differentiate patients with HIT from those with other causes of thrombocytopenia.

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18
Q

What does the 4Ts Score include?

A

Thrombocytopenia (extent of fall in platelet count)

Timing (onset of fall in platelet count or thrombosis in relation to initiation of heparin)

Thrombosis (or other sequelae)

Other causes of Thrombocytopenia

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19
Q

How should bleeding on UH be treated? (2 main steps)

A
  1. Stop IV heparin

2. Start protamine sulphate

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20
Q

What medicine is used to reverse the effects of unfractionated heparin?

A

protamine sulphate

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21
Q

What is the maximum protamine sulphate that can be given?

A

50mg - can cause severe allergic reactions

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22
Q

Why should be checked when giving protamine sulphate?

A

derived from fish sperm; check patient not got fish allergy

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23
Q

Effectiveness of protamine sulphate in reversal of;

a) UH
b) LMWH

A

a) very effective

b) only 60% effective

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24
Q

How should bleeding on LMWH be treated? (2 main steps)

A
  1. Stop LMWH
  2. Start protamine sulphate

(if still bleeding despite protamine, consider rFVIIa)

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25
Q

What is Fondaparinux? Mechanism?

A

• Synthetic pentasaccharide;
o Substitute for patient’s not wanting to receive pig-derived heparin / allergies
• Given subcutaneously

Mechanism: Binds to antithrombin and inhibits Xa activity

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26
Q

What are the 2 major vitamin K antagonists anticoagulants?

A
  1. Warfarin

2. Sinthrome (Acenocoumoral)

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27
Q

Where are clotting factors synthesised?

A

Liver

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28
Q

Where is protein C and S synthesised?

A

Liver

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29
Q

What coagulation factors is vitamin K required to synthesise in the liver?

A 
o	Factor II
o	Factor VII
o	Factor IX
o	Factor X 
o	Protein C
o	Protein S
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30
Q

Why is the starting of warfarin overlapped with heparin?

A

Warfarin works by slowing down the process in the liver that uses vitamin K to make clotting factors. Because it may take several days before warfarin becomes completely effective, heparin or LMWH is given until the warfarin is working.

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31
Q

What is an INR test used to monitor?

A

Used to monitor patient response to warfarin

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32
Q

How long should a patient on warfarin be kept on heparin for?

A

Keep on heparin until INR >2 on two separate occasions

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33
Q

If heparin isn’t overlapped with warfarin, what disease can this lead to?

A

Can lead to warfarin induced skin necrosis

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34
Q

What is warfarin induced skin necrosis caused by?

A

If heparin isn’t overlapped with warfarin, protein C and S will fall quicker than other clotting factors. Can lead to warfarin induced skin necrosis due to deficiency of these proteins.

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35
Q

What does INR measure?

A
  • INR = (prothrombin ratio)^ISI
  • Prothrombin ratio = patient’s prothrombin time/ mean normal prothrombin time
  • ISI = Correction factor to account for sensitivity of thromboplastin compared with the international reference preparation (IRP).

Prothrombin time = II, V, VII, X and fibrinogen

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36
Q

Which factors involved in prothrombin time are affected by vitamin K?

A

II, VII and X

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37
Q

Which foods can interact with effects of warfarin?

A

Food interactions; Vitamin K containing foods can lower INR

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38
Q

How is major bleeding/excess anticoagulation on warfarin treated? (3 main steps)

A
  1. Stop warfarin
  2. Give prothrombin complex concentrate (PCC)
  3. Give IV vitamin K simultaneously
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39
Q

What is prothrombin complex concentrate (PCC)?

A

A medication made up of blood clotting factors II, VII, IX, and X –> will raise these clotting factors and hopefully stop bleeding

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40
Q

Why is IV vitamin K required simultaneously during treatment of bleeding/excess anticoagulation on warfarin?

A

due to short half-life of clotting factors

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41
Q

When should INR be measured during treatment of bleeding/excess anticoagulation on warfarin?

A

Measure INR 15 mins and 12 hours after PCC

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42
Q

What are the 2 types of DOACs?

direct oral anticoagulants

A

a) Drugs that inhibit factor Xa

b) Drugs that inhibit thrombin (factor IIa)

43
Q

What are 3 examples of DOACs that inhibit factor Xa?

A

a. Rivaroxaban
b. Apixaban
c. Edoxaban

44
Q

What is an example of a DOAC that inhibits factor IIa (thrombin)?

A

Dabigatran

45
Q

Function of factor Xa?

A

converts prothrombin to thrombin

46
Q

Function of factor IIa (thrombin)?

A

converts fibrinogen to fibrin

47
Q

Predictable dose response of warfarin vs DOACs?

A
  • Dose of warfarin varies 40-fold –> requires monitoring

* For the DOACs, the dose is uniform for most patients –> no need for routine monitoring

48
Q

Why is Dabigatran contraindicated in patients with renal impairment?

What should be given instead?

A

Mainly excreted by the kidneys

a. Rivaroxaban
b. Apixaban
c. Edoxaban

49
Q

What are 3 specific contraindications/cautions for DOACs?

A

o Renal impairment
o Women of childbearing age
o Extremes of body weight > 120Kg

50
Q

What 2 special populations need to be managed on warfarin and not DOACs?

A
  1. mechanical valves,

2. antiphospholipid syndrome

51
Q

Why are routine coagulation tests unsuitable for quantitative assessment of drug level of DOACs?

A
  • DOACs variably affect PT and APTT

* Abnormalities picked up in the lab may not be recognised as due to DOAC

52
Q

Possible indications for need to measure anticoagulant drug levels?

A
  • Bleeding
  • Need for emergency surgery/procedure
  • Question of adherence
  • Recurrent thrombosis?
  • Renal impairment
  • Potential drug interactions
  • Extremes of weight
53
Q

Which drug is used as an emergency antidote for Dabigatran?

A

Idarucizumab

54
Q

Function of Idarucizumab?

A

Idarucizumab is a specific reversal agent for Dabigatran and is indicated when rapid reversal of its anticoagulant effects is required for emergency surgery or in life-threatening/uncontrolled bleeding.

55
Q

What is response to minor bleeding on DOACs?

A
  • Local measures

- Consider drug withdrawal

56
Q

There are 2 classes of antithrombotic drugs. What are these?

A
  1. Anticoagulants

2. Antiplatelets

57
Q

Antiplatelets vs anticoagulants mechanism?

A

Antiplatelets: prevent platelets from clumping and also prevent clots from forming and growing.

Anticoagulants: slow down clotting, thereby reducing fibrin formation and preventing clots from forming and growing

58
Q

What is the medical name for Aspirin?

A

Acetylsalicylic acid (ASA)

59
Q

Is Aspirin an antiplatelet or an anticoagulant?

A

Antiplatelet

60
Q

How does aspirin function as an antiplatelet?

A

Inhibits cyclooxygenase-1 in platelets which blocks formation of thromboxane A2 (a potent vasoconstrictor and platelet aggregant)

61
Q

Are there any reversal agents for Aspirin?

A
  • Irreversible effect, lasts 4-5 days

* No reversal agents

62
Q

Do P2Y12 antagonists function as antiplatelets or an anticoagulants?

A

Antiplatelets

63
Q

What are 3 examples of P2Y12 antagonists?

A
  1. Clopidogrel
  2. Prasugrel
  3. Ticagrelor
64
Q

What is treatment for critical bleeding of patients on Aspirin?

A

Give 2-3 adult doses of platelets in critical bleeding

65
Q

What is treatment for critical bleeding of patients on P2Y12 antagonists?

A

No reversal agents –> platelet transfusions.

66
Q

How do P2Y12 antagonists function as antiplatelets?

A

They antagonise the platelet P2Y12 receptor which prevents the binding of ADP.

This inhibits platelet activation and aggregation and the reaction of platelets to stimuli of thrombus aggregation such as thrombin.

67
Q

What are 5 examples of acquired bleeding disorders?

A
  1. Vitamin K deficiency
  2. Liver disease
  3. Renal disease
  4. Major haemorrhage
  5. DIC
68
Q

What clotting factors are vitamin K dependent? What factor is the most sensitive?

I.e. which factors will be deficient in a vitamin K deficiency?

A

Factors II, VII, IX, X

Factor VII is the most sensitive of the vitamin K dependent clotting factors

69
Q

A vitamin K deficiency prolongs which part of the coagulation assay?

A

Prolongs PT +/- APTT

70
Q

4 potential causes of a vitamin K deficiency?

A
  1. Obstructive jaundice
  2. Prolonged nutritional deficiency
  3. Broad spectrum antibiotics
  4. Neonates (classical 1-7 days)
71
Q

How can obstructive jaundice lead to a vitamin K deficiency?

A

The flow of bile to the bowel is interrupted—bile being necessary for the intestinal absorption of vitamin K

72
Q

How can broad spectrum antibiotics lead to a vitamin K deficiency?

A

Antibiotics, particularly a class known as cephalosporins, reduce the absorption of vitamin K in the body as these drugs may kill beneficial, vitamin K-activating bacteria.

73
Q

Treatment of vitamin K deficiency?

A

Treat with IV/Oral Vitamin K 10mg for 3-5 days

74
Q

where are clotting factors made?

A

liver

75
Q

How can cirrhosis lead to coagulopathy?

A

The liver plays a central role in haemostasis, as it is the site of synthesis of clotting factors, coagulation inhibitors, and fibrinolytic proteins.

76
Q

What are the 2 most common coagulation disturbances occurring in liver disease?

A
  1. thrombocytopenia

2. impaired humoral coagulation.

77
Q

Describe Factor VIII and vWf levels in liver disease?

A

Factor VIII and vWf levels will increase in acute phase but all other clotting factors will drop –> risk of severe bleeding

Recent studies document raised plasma VWF levels as a prognostic marker of outcome in patients with acute and chronic liver disease

78
Q

Do patients with liver disease commonly experience spontaneous bleeding?

A

No - risk of severe bleeding in invasive procedures or surgery e.g. dental extractions, liver biopsies

79
Q

What are the 2 potential causes of thrombocytopenia in liver disease?

A
  1. Problem with production of platelets

2. Problem with spleen

80
Q

How does liver disease lead to spleen problems?

A

Splenomegaly/hypersplenism due to portal congestion

81
Q

How does liver disease lead to problem with production of platelets?

A

Thrombopoietin (TPO) is made by liver that regulates production of platelets –> stimulates the production and differentiation of megakaryocytes, the bone marrow cells that bud off large numbers of platelets

82
Q

There is reduced plasma concentration of all coagulation factors (due to reduced synthesis) in liver disease except which factor?

A

FVIII

83
Q

Describe plasmin activity in liver disease?

A
  • Excessive plasmin activity

* Platelet dysfunction (plasmin induced cleavage of surface glycoproteins)

84
Q

Symptoms of bleeding are seen in what % of chronic renal failure patients?

A

30-50%

85
Q

What type of bleeding is typically seen in chronic renal failure patients?

A

Tends to be more mucocutaneous;

o Easy bruising, petechia, gum bleeding, nosebleeds, excessive bleeding from venepuncture/lines

86
Q

What are 2 risk factors for bleeding in chronic renal failure patients?

A
  1. Haemodialysis

2. Uncontrolled high BP

87
Q

Why is anaemia a common side effect of renal disease?

A

Lack of EPO

88
Q

How can anaemia lead to bleeding?

A
  1. A healthy amount of RBCs normally push platelets to vascular lining. In anaemia, there is decreased platelet interaction with vascular lining.
  2. Red cells release ADP and thromboxane which enhance platelet function; anaemia reduce this.
89
Q

Why can Penicillin lead to bleeding in renal disease?

A

Drugs accumulating in renal failure (penicillins) can bind to platelets and block their receptors

90
Q

Renal disease can lead to uraemia.

How can uraemia lead to bleeding?

A

As urea increases it can;
o disrupt platelet-platelet and platelet-vessel wall interactions
o Alter arachidonic acid metabolism
o Deficient ADP and serotonin stores in platelets
o Impair binding of fibrinogen and vWF

91
Q

Prevention of bleeding in renal disease?

A
  • Correction of anaemia; EPO and transfusions
  • Avoidance of antiplatelet drugs for at least 7 days prior to procedures
  • Dialysis
  • DDAVP pre procedures
  • Tranexamic acid pre procedures
92
Q

What is Tranexamic acid?

A

Tranexamic acid (sometimes shortened to txa) is a medicine that controls bleeding by acting as an antifibrinolytic. It helps your blood to clot and is used for nosebleeds and heavy periods.

93
Q

When is Tranexamic acid contraindicated?

A

Contraindicated if involving urinary tract due to risk of haematuria

94
Q

What 2 drugs are used in the treatment of bleeding in renal disease?

A
  1. DDAVP/Desmopressin

2. Tranexamic acid

95
Q

How does DDAVP function to stop bleeding in renal disease?

A

o Desmopressin; causes the release of von Willebrand’s antigen from the platelets and the cells that line the blood vessels where it is stored.

o Von Willebrand’s antigen is the protein that carries factor VIII –> This increase in von Willebrand’s antigen and factor VIII helps to stop bleeding.

96
Q

When would cryoprecipitate be used to stop bleeding in renal disease?

A

Cryoprecipitate used in cases not responsive to DDAVP (rich in FVIII, VWF, fibrinogen, FXIII)

97
Q

During major haemorrhage, what should be given in cases of;

a) falling Hb
b) APTT and/or PT ratio >1.5
c) fibrinogen <1.5 g/l
d) platelet count <50x19^9/l

A

a) red cells
b) FFP
c) cryoprecipitate 2 packs
d) platelets 1 adult dose

98
Q

What is Dilutional Coagulopathy?

A

Dilutional Coagulopathy refers to the coagulopathy seen during massive transfusion for major trauma and/or hemorrhaging:
• Thrombocytopenia
• Coagulation factor depletion - mainly factors V & VIII and fibrinogen
• DIC common
• Citrate toxicity: uncommon - hypothermia and neonates - increased susceptibility

99
Q

What is DIC?

A

DISSEMINATED INTRAVASCULAR COAGULATION

A clinicopathological syndrome which complicates a range of illnesses. It is characterised by systemic activation of pathways leading to and regulating coagulation, which can result in the generation of fibrin clots that may cause organ failure with concomitant consumption of platelets and coagulation factors that may result in clinical bleeding.

100
Q

Pathophysiology behind DIC?

A
  • Generalised disruption in the physiological balance of procoagulant and anticoagulant mechanisms.
  • Consumption of clotting factors and platelets.
  • Microvascular thrombosis: tissue ischaemia and organ damage
  • Activation of fibrinolysis
  • Microangiopathic haemolysis

Basically:

1) Excess thrombin generation
2) Reduced natural anticoagulant activity
3) Decreased fibrinolysis

101
Q

Causes of acute DIC?

A

o Sepsis (any organism)
o Obstetric complications- amniotic fluid embolism, abruption
o Trauma/Tissue necrosis/Fat embolism
o Acute intravascular haemolysis e.g. ABO incompatible blood transfusion
o Fulminant liver disease
o Organ destruction (e.g. severe pancreatitis)
o Massive blood loss
o Severe toxic or immunological reactions (e.g. recreational drugs, transfusion reactions, transplant rejection, snake bites

102
Q

Causes of chronic DIC?

A

o Malignancy
o End stage liver disease
o Vascular abnormalities (e.g. Kassbach-Merrit syndrome)

103
Q

Clinical features of DIC?

A
  • Mucosal oozing, bleeding from surgical wounds or indwelling canulae
  • Multi organ failure secondary to microthrombi (and hypovolaemia)
  • Skin necrosis
  • Thrombus

CP reviewer 1 (59 decks)

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