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Haematology > Bleeding disorders > Flashcards

Bleeding disorders Flashcards

1
Q

What two categories of bleeding disorder are there

A

Bleeding

Thrombosis

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2
Q

What categories of bleeding are there?

A

Primary haemostasis failure

Secondary haemostasis failure

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3
Q

What components of primary haemostasis can be defective?

A

Collagen (vessels)
Platelets
von WIllebrand Factor

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4
Q

What general symptoms can collagen defects cause?

A

East bruising and bleeding into the skin

Rarely bleed from mucous membranes

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5
Q

What are some hereditary collagen defects?

A

Marfans

Hereditary haemorrhagic telangiectasia (HHT)

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6
Q

How is hereditary haemorrhagic telangictasia (HHT) inehrited?

A

Autosomally

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7
Q

Describe HHT

A

Capillary dilation gives small red dots that blanch- mainly in nose and GI tract

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8
Q

What are some symptoms of HHT?

A

Epistaxis

GI bleeds- lead to iron deficient anaemia

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9
Q

What are some acquired causes of collagen defects?

A 
Vasculitis
Scurvy
Senile purpura
Steroid induced
Infection- Meningococcal septicaemia 
Henoch–Schönlein purpura
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10
Q

Describe Henoch-Schonlein purpura

A

Type III hypersensitivity (immune complex) caused but acute URTI.
Ab against cell wall

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11
Q

What are some symptoms of Henoch–Schönlein purpura?

A

Mainly in children

Purpura in legs and buttocks, abdo pain, arthritis, hematuria, glomerulonephritis

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12
Q

What infection classically gives purpura due to damage to cell walls?

A

Meningococcal septicaemia

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13
Q

What symptoms characterize platelet defective/deficient primary haemostatic failure?

A

Purpura and mucosal bleeding.

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14
Q

How may platelets cause uncontrolled bleeding?

A 
Reduced number (thrombocytopenia) 
Reduced platelet function
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15
Q

What does the platelet count look like in patients with reduced platelet function?

A

Normal or increased

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16
Q

How does the bleed time change in patients with reduced platelet function?

A

Prolonges

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17
Q

What are some hereditary causes of reduced platelet function?

A

Glanzmann’s thrombasthenia
Bernard–Soulier syndrome
Storage pool disease

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18
Q

Describe Glanzmann’s thrombasthenia

A

Lack GPIIb-IIIa on platelets therefore fibrinogen cannot bind and cause aggregation.

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19
Q

Describe Bernard–Soulier syndrome

A

Lack GPIb therefore cannot bind to vWF.

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20
Q

What are some acquired causes of reduced platelet function?

A

Drugs- Aspirin, NSAIDs

Renal failure- Urea can interfere with platelet function

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21
Q

What is a reduced platelet number called?

A

Thrombocytopenia

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22
Q

What is the commonest cause of primary haemostatic failure?

A

Thrombocytopenia

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23
Q

Is thrombocytopenia usually hereditary or acquired?

A

Acquired

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24
Q

How do you investigate thrombocytopenia?

A

Bone marrow biopsy

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25
Q

What can cause thrombocytopenia?

A

Reduced platelet production
Increased platelet destruction
Hypersplenism

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26
Q

How can hypersplenism cause thrombocytopenia?

A

Sequester platelets there

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27
Q

What can cause decreased platelet production?

A

Bone marrow failure

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28
Q

What can increase platelet destruction?

A

Coagulopathy

Immune destruction

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29
Q

What coagulopathies can cause increased platelet destruction?

A

Disseminated intravascular coagulation (DIC)

Thrombotic thrombocytopenic purpura (TTP)

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30
Q

Describe thrombotic thrombocytopenic purpura

A

Platelet consumption leads to profound thrombocytopenia.

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31
Q

What causes thrombotic thrombocytopenic purpura?

A

Endothelial damage and microvascular thrombosis (due to inability to degrade vWF).

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32
Q

What are some risk factors for thrombotic thrombocytopenic purpura?

A 
Pregnancy
Oral contraceptive
SLE
Infection
Clopidogrel
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33
Q

What are some symptoms of TTP?

A 
Purpura
Fever
Fluctuating cerebral dysfunction
Haemolytic anaemia with red cell fragmentation/Haemolytic Urea Syndrome (HUS)
Renal Failure
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34
Q

How do you diagnose TTP?

A

Normal coag screen

Raised lactic dehydrogenase (LDH)- Due to haemolysis

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35
Q

How do you treat TTP?

A

Plasma exchange
Cryoprecipitate and FFP
Pulsed intravenous methylprednisolone

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36
Q

What immune conditions can cause a thrombocytopenia?

A

Immune thrombocytopenic purpura (ITP)

Post-transfusion purpura (PTP)

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37
Q

Describe post-transfusion purpura (PTP)

A

Alloantibodies against platelets
2-12 days after transfusion
Mainly in women immunised by pregnancy

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38
Q

Describe immune thrombocytopenic purpura (ITP)

A

Immune destruction of platelets by macrophages

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39
Q

What are the types of immune thrombocytopenic purpura (ITP)?

A

Child

Adult

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40
Q

Describe ITP in children

A

Onset 2-6YO
Acute onset with mucosal bleeding- sometimes following viral infection.
Severe but rarely life threatening.

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41
Q

Describe ITP in adults

A

More chronic than in children.
More common in women and associated with other autoimmune disease (SLE, thyroid and autoimmune haemolytic anaemia), malignancy and infection.

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42
Q

How do you treat ITP in children?

A

Only treat in very symptomatic
Short course high-dose prednisolone
i.v. IgG

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43
Q

How do you treat IPT in adults?

A

Oral prednisolone 1mg/kg body weight body weight
Splenectomy
i.v. IgG
Platelet transfusion- only in extreme cases

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44
Q

What are the symptoms of ITP?

A

Easy bruising, purpura, epistaxis and menorrhagia are common
Major haemorrhage is rare
Splenomegaly is rare

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45
Q

How do you diagnose ITP?

A

Blood count normal bar for thrombocytopenia
Normal or increased numbers of megakaryocytes
Platelet antibodies

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46
Q

In what two ways can vWF be affected to cause a thrombocytopenia?

A

Decreased volume

Decreased function

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47
Q

Describe hereditary vWF defects causing thrombocytopenia

A

Autosomal dominant
Common
Variable severity
Form Ab against vWF

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48
Q

What is a secondary haemostasis failure also known as?

A

Coagulopathy

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49
Q

What are the two categories of coagulopathy?

A

Multiple clotting factor deficiency

SIngle clotting factor deficiency

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50
Q

Are multiple clotting factor deficiencies normally inherited or acquired?

A

Acquired

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51
Q

How do you test for multiple clotting factor deficiencies?

A

Prolonged PT and APTT

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52
Q

What are some causes of multiple clotting factor deficiencies?

A

Disseminated intravascular coagulation (DIC)
Liver failure
VK deficiency
Warfarin therapy

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53
Q

How can warfarin therapy cause multiple clotting factor deficiencies?

A

Antagonised VK

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54
Q

Which coag factors are needed for VK to make?

A

II, VII, IX, X, Protein C and Protein S

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55
Q

Where do we get VK from and how is it absorbed?

A

Diet (green leafy veg)
Bowel bacteria
Absorbed in upper intestine and needs bile salts

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56
Q

What can cause VK deficiency?

A

Poor dietary intake
Malabsorption- Antibiotic therapy and obstructive jaundice
Vitamin K antagonists (warfarin)

57
Q

What are some symptoms of VK deficiency?

A

Bruising
Haematurea
GI bleed
Cerebral bleed

58
Q

How do you treat a VK deficiency?

A

Phytomenadione (vitamin K1) 10mg IV for minor bleed

59
Q

What is VK deficiency called in newborns?

A

Haemorrhagic disease of the newborn

60
Q

What is Haemorrhagic disease of the newborn?

A

VK deficiency of newborn

Treat with VK shot

61
Q

Describe Disseminated intravascular coagulation (DIC)

A

Excessive and inappropriate activation of the haemostatic system- primary, secondary and fibrinolysis- that then leads to bleeds.

62
Q

What can cause DIC?

A
  • Malignant disease
  • Septicaemia (e.g. Gram-negative and meningococcal)
  • Haemolytic transfusion reactions
  • Obstetric causes (e.g. abruptio placentae, amniotic fluid embolism)
  • Trauma, burns, surgery
  • Other infections (e.g. falciparum malaria)
63
Q

What organs are most commonly affected in DIC?

A

Brain, skin and kidneys

64
Q

What are some symptoms of DIC?

A

Acutely ill and shocked
No bleeding at all to profound haemostatic failure with widespread haemorrhage
Bleeding may occur from the mouth, nose and venepuncture sites and there may be widespread ecchymoses
Thrombotic events

65
Q

How do you diagnose DIC?

A 
Clinical
Prolonged PT, APTT and TT
Reduced fibrinogen
High levels of D-Dimer
Severe thrombocytopenia
Fragmented RBC
66
Q

How do you treat DIC?

A

Treat underlying condition
Maintain blood volume and tissue perfusion
Transfusions of platelet concentrates, FFP, cryoprecipitate and red cell concentrates is indicated in patients who are bleeding
Do NOT use tranexamic acid!!!

67
Q

What things in the history suggests a generalised haemostatic defect?

A

Bleeding from multiple sites
Spontaneous bleeding
Excessive bleeding after injury

68
Q

What things suggest a platelet bleeding disorder?

A

Easy bruising
Spontaneous bleeding from small vessels
Bleed into skin- purpura (petechiae and ecchymoses (bruise))
Bleeding often occurs from mucous membrains

69
Q

What things suggest a coagulopathy disorder?

A

Bleeding after surgery or injury

Haemoarthrosis and haemotomas

70
Q

What lab tests can be used to investigate a bleeding disorder?

A

Blood count/film
Bleed time
Coagulation tests

71
Q

What are some coagulation tests?

A 
Prothrombin time (PT)
Activated partial thromboplastin time (APTT) 
Thrombin time (TT)
72
Q

How is blood stored for a coagulation test?

A

Blood collected in citrate (neutralizes Ca ions to prevent clotting)

73
Q

Describe thrombin time test

A

Add thrombin to plasma
Normal 12-14s
Prolonged in fibrinogen deficiency, heparin etc

74
Q

Describe Activated partial thromboplastin time test

A

Add surface activator, phospholipids and Ca to plasma.
Normal 30-50s
Measures V, VIII, IX, X, XI, XII, prothrombin and fibrinogen. Not dependent on VII.
Intrinsic coagulation

75
Q

Describe Prothrombin time test

A

Add tissue factor (thromboplastin) and Ca to plasma.
Normal 12-16s
INR
Measure of extrinsic coagulation pathway (V, VII, X, prothrombin and fibrinogen)
Prolonged if problems with coag factors, liver disease or warfarin
Most sensitive.

76
Q

What are thrombotic disorders?

A

Excessive coagulation

77
Q

What two categories of thrombotic disorder are there?

A

Arterial/platelet

Venous/coagulation

78
Q

What are some risk factors for developing an arterial thrombotic disorder?

A

Hypertension
Smoking
High cholesterol
Diabetes

79
Q

What is the underlying condition precipitating an arterial thrombotic disorder?

A

Atherosclerosis

80
Q

Describe atherosclerosis

A

Damage to endothelium and foamy macrophages. Forms plaques rich in cholesterol.

81
Q

Where does atherosclerosis normally form?

A

Areas of turbulence- bifurcations

82
Q

What are some forms of stable atherosclerosis?

A

Stable angina

Intermittent claudications

83
Q

What are some forms of unstable atheroclerosis?

A

Plaque ruptures and platelets are recruited causing acute thrombosis.
Unstable angina, MI and stroke.

84
Q

How do you treat an arterial thrombotic disorder?

A

Treat underlying cause
Antiplatelets
Thrombolysis

85
Q

Name four antiplatelets

A

Aspirin
Clopidogrel
Dipyridamole
Abciximab

86
Q

How does aspirin work?

A

Inhibits COX which is needed to produce Thromboxane A2 (platelet agonist)

87
Q

What are some side effects of aspirin?

A

Bleeds
Gastric ulcers
Bronchospasm

88
Q

How does clopidogrel work?

A

ADP receptor antagonist

89
Q

How does Dipyridamole work?

A

Phosphodiesterase inhibitor- reduces cAMP production which is second messenger in platelet activation.

90
Q

How does Abciximab work?

A

Inhibits GPIIb/IIIa preventing aggregation.

91
Q

How can you treat bleeding associated with antiplatelets?

A

PLatelet transfusion

92
Q

What enhances thrombolytic therapy?

A

Aspirin

93
Q

Give some examples of thrombolytic drugs

A

Streptokinase
Alteplase
Reteplase

94
Q

Describe streptokinase

A

Helps to convert plasminogen to plasmin.
Can develop antibodies against it.
Can lead to haemorrhage.

95
Q

What are alterplase and reteplase?

A

Plasminogen activators

96
Q

What are some risk factors for a venous thrombosis?

A

Virchow’s triad:
Stasis
Vessel wall damage (blood clot damages valves leading to stasis and more damage)
Hypercoagubility (increased tissue factor, vWF and VIII)

97
Q

What can increase hypercoagubility?

A

Age, pregnancy, malignancy, genetics, oestrogen therapy and trauma

98
Q

What are some venous thrombosis embolic conditions?

A

Deep venous thromboses

Pulmonary Embolism

99
Q

What are some risk factors for developing a venous thrombotic event?

A 
Age
Obesity
Pregnancy
Oestrogen therapy
Previous event
Trauma/surgery
Malignancy
Paralysis
Infection
Thrombophilia
100
Q

What are the symptoms of a DVT?

A

Hot swollen and tender limb with pitting oedema.

Can lead to ulceration

101
Q

What are the symptoms of a PE?

A

Pleuritic chest pain
CV collapse and death
Hypoxia
Right heart strain

102
Q

What are thrombophilias?

A

Defects of haemostasis leading to predisposition to arterial or venous thrombosis.

103
Q

Give an example of an acquired thrombophilia

A

Antiphospholipid syndrome

104
Q

Describe antiphospholipid syndrome

A

Ab activate primary and secondary haemostasis.

Ab specific for anionic phospholipids and prolong coag time (Lupus anticoagulants).

105
Q

What are the symptoms of antiphospholipid syndrome?

A

Recurrent thromboses- arterial and venous
Recurrent foetal loss
Mild thrombocytopenia

106
Q

How do you treat antiphospholipid syndrome?

A

Aspirin

Warfarin

107
Q

When should you screen for a hereditary thrombophilia?

A

Vt<45
Recurrent VT events
Family history of Vt or thrombophilia

108
Q

Give some examples of hereditary thrombophilia

A 
Factor V Leiden
Prothrombin 20210 mutation
Antithrombin deficiency
Protein C deficiency
Protein S deficiency
109
Q

Describe Factor V Leiden

A

Mutant form of FV resulting in impaired inactivation by PC.

110
Q

Describe prothrombin 20210 mutation

A

Results in excessive prothrombin.

Interaction with FV Leiden and contraceptive pill.

111
Q

Describe antithrombin deficiecy

A

Autosomal dominant
Many mutations
Acquired from: surgery/trauma and contraceptive pill.
Get recurrent thrombotic episodes starting from a young age.

112
Q

Describe protein C and S deficiency

A

Autosomal dominant

Venous thrombosis before age 40

113
Q

Are single clotting factor defects acquired or hereditary?

A

Hereditary and rare

114
Q

Give two examples of single clotting factor defect conditions?

A

Haemophilia

von WIllebrand Disease

115
Q

How is haemophilia inherited?

A

X-linked

116
Q

Describe haemophilia

A

Repeated prolonged bleed from medium to large vessels

No primary abnormality

117
Q

How do clotting tests present in haemophilia?

A

Normal PT, prolonged APTT

118
Q

What two forms of haemophilia are there?

A

Haemophilia A

Haemophilia B

119
Q

What causes haemophilia A?

A

Factor VIII deficiency

120
Q

What causes haemophilia B?

A

Factor IX deficiency

121
Q

What are some symptoms of severe haemophilia?

A

Frequent spontaneous bleeding from early life.
Haemarthrosis are common
Bleed into muscle common

122
Q

What can recurrent hemarthrosis cause?

A

Deformities

123
Q

Give some symptoms of moderate haemophilia

A

Severe bleeding following injury

Occasional spontaneous bleeds

124
Q

Give some examples of mild haemophilia

A

Bleeding only after injury or surgery

125
Q

How do you treat haemophilia A?

A 
IM administration of factor VIII concentrate 
Synthetic vasopressin (desmopressin )
126
Q

How do you treat haemophilia B?

A

Factor IX concentrates
Prophylactic doses are given twice a week
Desmopressin is ineffective

127
Q

What is a complication of haemophilia A?

A

VIII Ab

128
Q

What are haemophiliacs vaccinated against?

A

Hep A and B

129
Q

What do haemophiliacs not get if they have HIV?

A

Kaposi sarcoma

130
Q

Which is more common: haemophilia A or B?

A

A

131
Q

Describe von Willebrand disease

A

Platelet and VIII dysfunction due to loss or abnormal vWF.

132
Q

What are the three forms of vWD?

A

Type 1
Type 2
Type 3

133
Q

Describe Type 1 vWD

A

Partial quantitative deficit in vWF.

Autosomal dominant

134
Q

Give some symptoms of Type 1 vWD

A

Bleeding follows minor trauma or surgery

Epistaxis and menorrhagia

135
Q

Describe Type 2 vWD

A

Qualitative abnormality in vWF

Autosomal dominant

136
Q

Give some symptoms of Type 2 vWD

A

Bleeding follows minor trauma or surgery

Epistaxis and menorrhagia

137
Q

Describe Type 3 vWD

A

Complete vWF deficit

Autosomal recessive

138
Q

Give some symptoms of Type 3 vWD

A

Severe bleeding

Haemoarthrosis rare

139
Q

How do you treat vWD

A

Desmopressin

vWF- only for symptom treatment

Haematology (12 decks)

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