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METABOLIC > HAEMATOLOGY - BLEEDING DISORDERS > Flashcards

HAEMATOLOGY - BLEEDING DISORDERS Flashcards

1
Q

Outline the pattern of bleeding in coagulation and platelet disorders?

A

Platelet disorders cause prolonged bleeding from cuts, bleeding into the skin e.g. purpura, and bleeding from mucous membranes
Coagulation disorders cause bleeding into joints and muscles which is more likely to be delayed.

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2
Q

What are some vascular bleeding defects?

A

Osler-Weber-Rendu syndrome
Connective tissue disease e.g. Ehlers Danlos syndrome or Marfan syndrome
Acquired: Senile purpura, Infection, Steroids, Scurvy, Henoch-Schonlein purpura

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3
Q

What is Osler-Weber-Rendu syndrome also known as?

A

Hereditary haemorrhagic telangiectasia

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4
Q

What is hereditary haemorrhagic telangiectasia?

A

A rare autosomal dominant disorder caused by mutations in genes that regulate angiogenesis, leading to the formation of fragile, dilated blood vessels called telangiectasias and arteriovenous malformations that can cause various clinical manifestations.

If they have 3 or more of the following its a diagnosis:
- epistaxis
- telangiectasia
- visceral lesions e.g. Arteriovenous malformations or GI telangiectasia
- FHx first degree relative

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5
Q

What mucous membranes does Osler-Weber-Rendu syndrome usually affect?

A

Nose and GIT

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6
Q

What are the main complications of Osler-Weber-Rendu syndrome?

A

Iron deficiency anaemia from epistaxis and chronic GI bleeding
Recurrent epistaxis
GI bleeds
Arteriovenous malformations in various organs e.g. brain, liver, lungs - can cause stroke, brain abscess, HF, respiratory distress

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7
Q

What is senile purpura?

A

Benign easy bruising that affects older adults
This is because the skin and blood vessels become more fragile

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8
Q

What is Henoch-Schonlein purpura?

A

A type 3 hypersensitivity reaction that is often preceded by an acute respiratory tract infection
It’s a type of small vessel vasculitis

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9
Q

Where is the rash characteristically in Henoch-Schonlein purpura?

A

Purpura on legs and buttocks
It’s raised

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10
Q

Whats the pathophysiology of Henoch Schonlein purpura?

A

IgA mediated small vessel vasculitis - IgA-antibody immune complexes caused by antigenic exposure from an infection or medication deposit in the small vessels of the skin, joints, kidneys, and gastrointestinal tract.

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11
Q

What are the 3 broad categories for causes of thrombocytopenia?

A

Reduced platelet production in bone marrow
Excessive peripheral destruction of platelets
Sequestration in an enlarged spleen

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12
Q

What can cause impaired production of platelets?

A

Aplastic anaemia
bone marrow failure due to drugs/disease e.g. chemo or leukaemia
Tumour infiltration into bone marrow
MDS
Myeloma
Myelofibrosis
HIV infection

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13
Q

What can cause excessive destruction of platelets?

A

ITP
Drug induced destruction
Secondary immune e.g SLE, CLL
Alloimmune neonatal thrombocytopenia
Post-transfusion purpura
DIC
TTP
HUS

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14
Q

What is ITP?

A

Thrombocytopenia due to immune destruction of platelets spleen produces IgG antibodies against GP2b/3a

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15
Q

What is acute ITP?

A

Usually affects children
Happens 2-3 weeks after a viral infection
Resolves spontaneously within 2 months

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16
Q

What is chronic ITP/

A

Seen in females of reproductive age
Lasts >6 months
Can be primary or secondary (triggered by another condition e.g. SLE, HIV)
Usually affects adults

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17
Q

How does ITP present?

A

Usually asymptomatic
In some cases it can cause purpura
In severe cases it can cause epistaxis

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18
Q

How is ITP investigated?

A

Isolated Thrombocytopenia
(In cases with significant bleeding it can cause anaemia)
Diagnosis is based on exclusion of other causes of thrombocytopenia
Normal or increased megakaryocytes - not necessary for confirming diagnoses
Platelet autoantibodies - not necessary for confirming diagnoses
Hep C and HIV testing to rule out secondary ITP

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19
Q

How is ITP managed?

A

Children and adults with platelet counts of more than 30 x 109/L generally require no treatment
Treat underlying condition in secondary ITP

When treatment is needed…
Oral corticosteroids
IV immunoglobulin

Second line:
Splenectomy (removes macrophages that destroy platelet)
TPO receptor agonists
Platelet transfusions (when platelets <10,000)

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20
Q

What is neonatal alloimmune thrombocytopenia?

A

Fetomaternal incompatibility for platelet-specific antigens, usually for human platelet alloantigen 1a, and is the platelet equivalent of HDN. The mother is HPA-1a-negative and produces antibodies that destroy the HPA-1a-positive fetal platelets.

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21
Q

What is post-transfusion purpura?

A

Rare and occurs 7-10 days after a transfusion of platelet-containing blood components
Associated with a platelet specific alloantibody, usually anti-HPA-1a
It always occurs in people who have been previously immunised by blood transfusion or pregnancy

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22
Q

What is thrombotic thrombocytopenic purpura?

A

A rare but serious blood disease that causes many small blood clots throughout the body
Caused by a severe deficiency of enzyme ADAMTS13 which usually breaks down vWF when no longer needed

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23
Q

What are the signs and sympotms of TTP?

A

Fever, neuro signs, thrombocytopenia, haemolytic anaemia and renal disease

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24
Q

What are the 2 types of TTP and which is more common?

A

Immune mediated TTP - more common
Congenital TTP

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25
Q

What is immune mediated TTP?

A

Acquired TTP which is an autoimmune disorder that usually develops in late childhood or adulthood
The immune system attacks ADAMTS13 enzyme

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26
Q

What is congenital TTP?

A

Present from birth and inherited in an autosomal recessive pattern
Low levels of ADAMTS13 enzyme

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27
Q

How is TTP diagnosed?

A

Blood tests to show deficiency of <10% ADAMTS13 activity
Present of anti-ADAMTS13 antibodies in iTTP

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28
Q

How is TTP treated?

A

Plasmapheresis
Steroids
Rituximab

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29
Q

How does plasmapheresis work for TTP management?

A

It provides a source of ADAMTS13 and removes associated autoantibodies in iTTP

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30
Q

What is haemolytic uraemic syndrome?

A

Characterised by the triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury.

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31
Q

What are the types of HUS?

A

Diarrhoea + HUS (typical HUS)
Diarrhoea - HUS (atypical HUS)

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32
Q

What is typical HUS?

A

When HUS is triggered by bloody diarrhoea
Usually affects children

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33
Q

What causes typical HUS?

A

Most common cause is enterohemorrhagic E.coli (0157;H7)

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34
Q

Outline the pathology of HUS?

A

HUS can be triggered by an infection with certain strains of E. coli bacteria (such as E. coli O157:H7), or exposure to other toxins that damage the lining of blood vessels.
damage to the endothelial cells lining the blood vessels = inflammation and release of substances that promote blood clotting.
The damaged endothelial cells also cause the activation and aggregation of platelets, which contribute to the formation of blood clots.
The combination of activated platelets and clotting factors leads to the formation of microthrombi in the small blood vessels, particularly in the kidneys.
The microthrombi damage the red blood cells as they pass through the blood vessels, leading to hemolysis and a decreased number of platelets in circulation. They can also block blood flow to the kidneys, leading to kidney damage and dysfunction.

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35
Q

What is atypical HUS?

A

No preceding diarrhoea
Damage to endothelial cells; this can be caused by infections, medications, autoimmune causes, genetic mutations
Glomerular endothelium is damaged and in response blood clots form in the kidneys

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36
Q

Whats the classic findings in HUS?

A

Microangiopathic haemolytic anaemia - schistocytes, anaemia symptoms, jaundice
Thrombocytopenia - easy bruising and purpura
Acute renal failure - uraemia

If they have TTP too then they will have neurological findings and fever

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37
Q

How is HUS diagnosed?

A

Signs of kidney damage - proteinuria and haematuria, elevated cr and urea in blood
Blood smear - schistocytes or helmet cells
Bacteria culture in diarrhoea +
In TTP-HUS - ADAMTS13 can be measured

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38
Q

How is HUS treated?

A

Supportive as shiga-like toxin clears in days to weeks
(Using antibiotics can actually worsen the problem)
In TTP-HUS give plasmapheresis

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39
Q

What is disseminated intravascular coagulation?

A

a condition in which small blood clots develop throughout the bloodstream, blocking small blood vessels. The increased clotting depletes the platelets and clotting factors needed to control bleeding, causing excessive bleeding.

40
Q

Whats the pathophysiology of DIC?

A

During serious medical conditions, procagulants are released which increase formation of new clots
This causes widespread clot formation which can block small and medium vessel s= ischaemia, necrosis and organ damage (mostly kidneys, liver, lungs and brain)
consumption of clotting factors and platelets = life-threatening hemorrhage
fibrin degradation products are also released which reduces clot formation further

41
Q

What lab findings are present in DIC?

A

Low platelets and low fibrinogen
Prolonged PT and PTT
Elevated D-dimer

42
Q

When may lab results in DIC look normal and why?

A

In chronic DIC e.g. those with solid tumours or large aortic aneurysms
There may be physiological compensation

43
Q

How is DIC treated?

A

Treat underlying cause
Support various organs e.g. ventilation, transfusions

44
Q

What are some examples of inherited platelet function disorder?

A

Glanzmanns thrombasthenia
Bernard-soulier syndrome
Storage pool disease

45
Q

What are some examples of acquired platelet function disorder?

A

Myeloproliferative disorders
Renal and liver disease
Paraproteineaemias
Drug induced

46
Q

What causes decreased production of platelets?

A

Aplastic anaemia
Marrow infiltration e.g. leukaemia
Marrow suppression e.g. chemo

47
Q

Why does renal disease cause platelet dysfunction?

A

High levels of urea - uraemic thrombocytopenia

48
Q

Why does liver disease cause platelet dysfunction?

A

TPO is predominantly produced in liver so damage to this lowers TPO levels = reduced thrombopoeitin in bone marrow

49
Q

Why do paraproetinemias cause platelet dysfunction?

A

Paraporteins interact with platelet surface glycoproteins and impair platelet adherence, activation or aggregation

50
Q

What drugs can cause platelet dysfunction?

A

Aspirin and other NSAIDs
Glycoprotein 2b/3a inhibitors
Platelet P2Y12 adenosine diphosphate receptor inhibitors

51
Q

Why do aspirin and NSAIDS cause drug-induced platelet dysfunction?

A

They prevent COX mediated production of thromboaxane A2 = increases bleeding

52
Q

What is Glanzmanns thrombasthenia?

A

a bleeding disorder that is characterized by prolonged or spontaneous bleeding starting from birth

Lack of platelet membrane glycoprotein 2b/3a complex = defective fibrinogen binding and failure of platelet aggregation

53
Q

What is Bernard-Soulier syndrome?

A

A rare inherited disorder of coagulation
lack of platelet membrane glycoprotein Ib/IX/V complex (the binding site for von Willebrand factor), causing failure of platelet adhesion and moderate thrombocytopenia

54
Q

What is storage pool disease?

A

A group of conditions caused by defects in platelet granules.

55
Q

What are some inherited coagulation disorders?

A

Haemophilia
Von Willebrand disease

56
Q

What are some acquired coagulation disorders?

A

Vitamin K deficiency
Liver disease
DIC
Fibrinogenolysis
Use of anticoagulants

57
Q

What is haemophilia?

A

an inherited bleeding disorder in which the blood does not clot properly. This can lead to spontaneous bleeding as well as bleeding following injuries or surgery.

58
Q

Deficiencies in which factors can cause haemophilia?

A

All factors except for factor 12 which is asymptomatic

59
Q

What is haemophilia A?

A

Factor 8 deficiency

60
Q

What is haemophilia B?

A

Deficiency in Factor 9

61
Q

What is the inheritance pattern of haemophilia A and B?

A

X-linked recessive

62
Q

What are the blood investigations found in haemophilia A and B?

A

Isolated prolongation of APTT
Reduced level of factor 8 or 9 depending on the haemophilia
(PT, bleeding time, platelet count and vWf normal)

63
Q

How is haemophilia managed?

A

Bleeding is treated by administration of missing clotting factor concentrated IV
Regular missing factors infusions 3+ times per week to prevent recurrent bleeding into joints and subsequent joint damage
If mild haemophilia A then it can be treated with synthetic vasopressin to increase factor 8 levels

64
Q

What are the symptoms and signs of haemophilia A and B?

A

Ecchymosis
Hepatomas
Prolonged bleeding after cuts/surgery
Oozing after tooth extractions
GI bleeds
Haematuria
Epistaxis
Hemarthrosis

65
Q

What are some complications of haemophilia A and B?

A

Joint damage from hemiarthrosis
Stroke or increased ICP due to bleeds in brain
Development of antibodies to factor VIII that inhibit its action (aka Inhibitors)

66
Q

Why is the prothrombin time normal but partial thromboplastin time raised in haemophilia A and B?

A

As factors 8 and 9 are both in the intrinsic pathway which is tested for using the partial thromboplastin time.

67
Q

Whats the problem with development of inhibitors in haemophilia?

A

Inhibitors diminish the effectiveness of treatment overt times and may cause anaphylaxis
Very difficult to treat

68
Q

What should people with haemophilia avoid?

A

Contact sports and medicines that cause bleeding e.g. aspirin.

69
Q

What is Von willebrand disease?

A

A bleeding disorder where there is a decreased quality or quantity in vWF
As VWF has a critical role as an adhesive protein in the platelet vessel wall interaction, the absence of VWF leads to impaired platelet adhesion to the subendothelium. Reduced VWF levels also lead to factor VIII deficiency

70
Q

Where is vWF synthesised ans stored?

A

In megakaryocytes

71
Q

Why does defects in vWf leads to fcator 8 deficiency?

A

as factor VIII is not protected from premature degradation. (Factor 8 is usually bound to vWF which protects it from degradation by protein C and S)

72
Q

How is vWF categorised?

A

Type 1,2 3

73
Q

What is the difference between

A

Type 1 - 75% of all cases, partial quantitiative deficiency of vWF autosomal dominant
Type 2 - qualitative abnormality of vWF, autosomal dominant
Type 3 - nearly a complete deficiency of vWF, recessive

74
Q

How is vWF diagnosed?

A

Normal platelet count
Prothrombin time normal
Activated partial thromboplastin time increased
Increased bleeding time
VWF antigen levels are low.
Measure vWF activity using ristocetin

75
Q

Why is APTT raised in vWD?

A

Factor 8 is low so intrinsic pathway is affected

76
Q

How is vWF disease treated?

A

Vasopressin analogue
Anti fibrinolytic drugs can be used to help sustain clots and prevent bleeding

77
Q

What is vitamin K needed for in coagulation?

A

For the carboxylation of glutamic acid residues on coagulation factors 2, 7, 9 and 10 and proteins C and S
Without it, these factors cannot bind calcium

78
Q

What can cause vitamin K deficiency?

A

Inadequate stores e.g. severe malnutrition
Malabsorption of vitamin K e.g. cholestatic jaundice
Oral anticoagulant drugs which antagonise vitamin K

79
Q

What lab findings will be present in vitamin K deficiency?

A

Pt and APTT prolonged as intrinsic, extrinsic and common pathways are affected

80
Q

How is vitamin K deficiency treated?

A

Minor bleeding treated with phytomenadione
Oral vitamin K

81
Q

Why can liver disease cause defects in haemostasis?

A

Cholestasis can cause vit K deficiency
Reduced synthesis of coagulation factors if severe hepatoceullular damage
Hypersplenism because of portal hypertension can cause thrombocytopenia
Functional abnormalities of platelets and fibrinogen in liver failure
DIC in acute hepatic failure

82
Q

Whats the moa of warfarin?

A

block the function of the vitamin K epoxide reductase complex in the liver, leading to depletion of the reduced form of vitamin K that serves as a cofactor for gamma carboxylation of vitamin K-dependent coagulation factors (2, 7, 9 10, proteins C and S)

83
Q

Whats the difference between unfractionated and fractionated heparin?

A

Unfractionated is heparin that’s derived physiologically. It’s a mixture of high and low molecular weight heparins.

Fractionated is created when unfractionated heparin undergoes a process where high molecular weight heparin gets depolymerised so it only contains low molecular weight heparins

84
Q

How does standard heparin work?

A

Activates antithrombin III which binds to and inactivates clotting factors such as thrombin and factor Xa

85
Q

Whats the difference between high and low molecular weight heparins?

A

High MWH has a longer glycosaminoglycans tail than LMWH
HMWH and LMWH can both binds to antithrombin 3 to increase its activity and inhibitor factor 10a
However only HMWH can bind to thrombin and inhibits it activity

86
Q

What is heparin used for?

A

Acute problems e.g. DVT, preventing DVT and PE etc
Also used in pregnancy as not teratogenic

This is because it has a rapid onset

87
Q

What is used for chronic management of coagulation and why?

A

Warfarin or DOACs
It can be taken orally and be taken at home

88
Q

What are the indications for DOACs?

A

Prevention of stroke, VTE
Treatment of DVT and PE

89
Q

Which DOAC is a direct thrombin inhibitor?

A

Dabigatran

90
Q

Whats the moa of rivaroxaban, apixaban and edoxaban?

A

Direct factor 10a inhibitor

91
Q

Whats the DOAC of choice for pt with renal impairment?

A

Apixaban

92
Q

What should you think if you see deranged coagulation in sepsis?

A

DIC

93
Q

What is heparin-induced thrombocytopenia?

A

A complication caused by heparin which results in decreased platelets in the blood

94
Q

What causes heparin-induced thrombotpenia?

A

Heparin binds to platelet factor 4 on inactivated platelets. This forms the heparin-PF-4 complex. This complex is immunogenic in some individuals; some people have IgG antibodies that recognise it as foreign

95
Q

How soon after starting heparin is heparin-induce thrombocytopenia likely?

A

1-2 weeks
Unless previously treated with heparin, in which case they may already have the antibodies and HIT can begin within a day

96
Q

What are risk factors for haemophilia?

A

Men
Fhx
elderly, pregnancy, malignancy, MS and autoimmune conditions are associate with it

METABOLIC (43 decks)

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