Brainscape's Knowledge GenomeTM

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


See full index

Yr 2 MCD - Haem > 8 - Disorders of Haemostasis > Flashcards

8 - Disorders of Haemostasis Flashcards

1
Q

Name examples of minor bleeding symptoms

A
  • Easy bruising
  • Gum bleeding
  • Frequent nosebleeds
  • Bleeding after tooth extraction
  • Post-operative bleeding
  • Family history

In just women

  • Menorrhagia
  • Post-partum bleeding

THESE ARE QUITE COMMON

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

What is menorrhagia?

A

Abnormally heavy bleeding during menstruation

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

What makes bleeding symptoms difficult to categorise?

A

They are quite subjective

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

How can you adapt a history to help differentiate between normal bleeding and bleeding disorders?

A

Ask more specific questions

  • e.g. more than one site of bleeding, large bruises, haematoma then it can help differentiate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What symptoms could be considered signficant bleeding symptoms?

A
  • Epistaxis not stopped by 10 mins compression or requiring medical attention/transfusion
  • Cutaneous haemorrhage or bruising without apparent trauma (esp. multiple/large)
  • Prolonged (>15 mins) bleeding from trivial wounds, or in oral cavity or recurring spontaneously in 7 days after wound.
  • Spontaneous GI bleeding leading to anaemia
  • Menorrhagia requiring treatment or leading to anaemia, not due to structural lesions of the uterus.
  • Heavy, prolonged or recurrent bleeding after surgery or dental extractions.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What can cause abnormal haemostasis?

A

Lack of a specific factor

  • Failure of production
    • Congenital or acquired
  • Increased consumption/clearance

Defective function of a specific factor

  • Genetic defect
  • Acquired defect
    • more common
    • e.g. drugs, synthetic defect, inhibition
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is primary haemostasis?

A

The formation of a the unstable platelet plug

Platelet adhesion and aggregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is secondary haemostasis?

A

Stabilisation of the plug with fibrin

Blood coagulation

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

What are the components of primary haemostasis?

A

The platelets with their receptors

  • (GlpIa/GlpIb)

Von Willebrand Factor

  • acting as a bridge between the platelet and the damaged endothelial surface

The vessel wall

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How can primary haemostasis occur?

A

Direct binding of the platelets by GlpIa to collagen

OR

Indirect binding via vWF by GlpIb.

THEN..

Platelets become activated, and aggregate via GlpIIb/IIIa to form the platelet plug.

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

Overall, what are the main catgeories of disorders of primary haemostasis?

A

Problems with Platelets

Problems with Von Willebrand Factor

Problems with the Vessel Wall

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

Explain how Problems with Platelets can cause a disorder of primary haemostasis

A

LOW NUMBERS

  • Bone marrow failure
    • malignancy (leukaemia)
    • megaloblastic anaemia (B12 deficiency)
  • Accelerated clearance of platelets
    • immune (ITP)
    • DIC
  • Pooling and destruction in a large spleen

IMPAIRED FUNCTION

  • Hereditary absence of glycoproteins or storage granules
    • relatively rare
  • Acquired due to drugs
    • much more common
    • aspirin
    • NSAIDs
    • clopidogrel
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Outline Auto-Immune Trhombocytopenic Purpura (auto-ITP)

A

Auto-ITP - Disorder of Primary Haemostasis

Platelet autoantibodies are coating the platelet, sensitising it.

These complexes are cleared by the reticulo-endothelial system.

Autoimmune thrombocytopenia purpura is a common cause of thrombocytopenia.

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

What are the mechanisms and causes of thrombocytopenia?

A
  1. Failure of platelet production by megakaryocytes
  2. Shortened half life of platelets
  3. Increased pooling of platelets in an enlarged spleen (hypersplenism) + shortened half life
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is Glanzmann’s Thrombasthenia?

A

Autosomal recessive disorder

GpIIb/IIIa is lacking

Rare

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

What is Bernard Soulier Syndrome?

A

Autosomal Recessive

Lack of Gp1b.

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

What is Storage Pool Disease?

A

Broad term referring to issues with granular storage and release.

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

What is Von Willebrand Disease and how does it cause disorder of primary haemostasis?

A

Hereditary decrease of quantity+/function (common)

  • most common bleeding disorder

Can be acquired due to antibody

  • acquired von Willebrand Syndrome (rare)

VWD is usually hereditary

  • Deficiency of VWF
    • Type 1 most common – you make some VWF
    • Type 3 – you make no VWF
  • VWF with abnormal function (Type 2)
    • qualitative defects
    • what you’re making doesn’t work

VWF has two functions in haemostasis

  • Binding to collagen and capturing platelets
  • Stabilising Factor VIII (NOTE: Factor VIII may be low if VWF is very low)

MECHANISM

  • Vessel wall damaged and therefore, collagen is exposed
  • If you have no VWF then there is no primary haemostasis
  • The platelets fly past the damaged endothelium and they can’t form a primary plug
  • VWF captures platelets when they travel at high shear – without it, you don’t form the primary plug
  • You can’t even begin to stop bleeding
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What problems with vessel walls cause disorder of primary haemostasis?

A

INHERITED (RARE)

  • Hereditary haemorrhagic telangiectasia
  • Ehlers-Danlos syndrome
  • Other connective tissue disorders

ACQUIRED DEFECTS OF THE VESSEL WALL

  • Scurvy
  • Steroid therapy
  • Ageing (senile purpura)
  • Vasculitis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What paterns of bleeding are found in people with defects of primary haemostasis?

A
  • Immediate, prolonged bleeding
  • Easy bruising
  • Nosebleeds (prolonged: >20 mins)
  • Gum bleeding (prolonged)
  • Menorrhagia (anaemia)
  • Bleeding after trauma/surgery
  • Petechiae (specific for thrombocytopenia)
21
Q

What is menorrhagia?

A

Abnormally heavy bleeding at menstruation

22
Q

What are petechiae?

A
  • Small blood spots which occur in people who are thrombocytopenic
  • Appear spontaneously
  • Characteristic of thromobocytopenia
  • Pathognomonic sign of low platelet count – characteristic of low platelet count
  • Platelets are constantly busy plugging small holes in vessels – continuous process of repair going on
23
Q

What tests can be conducted if primary haemostasis is suspected?

A
  • Platelet count, platelet morphology (using microscopy)
  • Bleeding time (PFA100 in lab) – very crude test, not done much anymore – not specific or sensitive
  • Assays of von Willebrand Factor
  • Clinical observation
24
Q

Outline the process of secondary haemostasis

A
25
Q

What is the pattern of thrombin generation?

A

Picture is a thrombogram

  • Shows thrombin generation

The role of the coagulation cascade is to generate a burst of thrombin

  • Thrombin converts fibrinogen to fibrin

Deficiency of any coagulation factor results in failure of thrombin generation, and hence fibrin formation

Someone with haemophilia produces very little thrombin

26
Q

Why is fibrin needed for vessel injury plugging?

A
  • The primary platelet plug is sufficient for small vessel injury
  • In larger vessels it will fall apart
  • Fibrin formation stabilises the platelet plug
27
Q

Does primary haemostasis occur in people with haemophilia?

A

Someone with haemophilia has a very feeble thrombin burst (not very big)

They have collagen, VWF and platelets

  • so the primary platelet plug has formed

They need to generate fibrin mesh

  • not enough thrombin
  • plug will fall apart
  • DELAYED bleeding

This is why people with secondary haemostasis disorders have DELAYED BLEEDING

28
Q

What part of haemostasis is secondary?

A

Secondary haemostasis = fibrin mesh formation

29
Q

What is deficient or defective in disorders of secondary haemostasis?

A

Deficiency or defect of coagulation factor 1-13

30
Q

Outline what specifically can cause disorders of secondary haemostasis

A

GENETIC

Haemophilia A/B

  • Factor 8 or Factor 9
  • Hereditary due to genetic defect
  • Rare

ACQUIRED

Liver Disease

  • Most coagulation factors are made in the liver
  • However, anticoagulants are also made by the liver – so this tends to balance out

Drugs

  • Warfarin
  • Inhibits synthesis of coagulation factors

Dilution

  • Results from volume replacement
  • You need to give RBC + PLASMA
  • Red cell transfusions no longer contain plasma
  • Major transfusions require plasma, as well as RBC and platelets

Consumption

  • Disseminated intravascular coagulation
31
Q

What kind of bleeding/other effects differ between the causes of secondary haemostasis?

A

Factor VIII and IX deficiency (Haemophilia)

  • Severe but compatible with life
  • Spontaneous Joint and Muscle Bleeding

Prothrombin deficiency (Factor II)

  • Lethal

Factor XI deficiency

  • Bleed after trauma but not spontaneously

Factor XII deficiency

  • No excess bleeding at all
32
Q

Outline what Disseminated Intravascular Coagulation is

A

DISORDER OF SECONDARY HAEMOSTASIS

Disseminated Intravascular Coagulation (also called consumptive coagulopathy)

Results from abnormal activation of coagulation:

  • generalised activation of coagulation Tissue Factor is triggered
  • leads to uncontrolled coagulation
  • not regulated

Associated with sepsis, some obstetrics causes, major tissue damage, inflammation

Consumes and depletes coagulation factors and platelets, so platelets consumed

Activation of fibrinolysis depletes fibrinogen – increased FDPs

Deposition of fibrin in vessels causes organ failure

33
Q

What are the consequences of Disseminated Intravascular Coagulation?

A

Consequences:

  • Widespread bleeding, from IV lines, bruising, internal
  • Deposition of fibrin in vessels causes organ failure
34
Q

What are the patterns of bleeding associated with disorders of secondary haemostasis?

A

Deficiency or defect of coagulation factors, poor thrombin burst and poor fibrin mesh.

  • Often delayed (after primary haemostasis)
  • Prolonged – but may come into hospital several times due to stop-start bleeding
  • Deeper - joints and muscles – spontaneous bleeding is deep, into muscles and joints
  • Don’t tend to get excessive bleeding from small cuts (primary haemostasis is ok)
  • Small vessels are generally ok – superficial cuts do not bleed due to platelets
  • Bruising is common
  • Nosebleeds are rare
  • Bleeding after trauma/surgery may be delayed, and is prolonged
  • Bleeding after intramuscular injections
  • HAEMARTHROSIS is the hallmark of HAEMOPHILIA

NOTE: Easy Bruising is a feature of pretty much ALL BLEEDING DISORDERS

35
Q

What is haemarthosis?

A

HAEMARTHROSIS

It is the hallmark of HAEMOPHILIA

It is bleeding into the joints

This is a characteristic feature of severe haemophilia A and B

They bleed into joints

  • pressure builds up
  • the joint becomes swollen and painful

People with haemophilia are generally fine when dealing with SMALL CUTS

Haemophiliac patients have prophylaxis to prevent this

36
Q

Why would you never give an intramuscular injection to a person with a clotting factor deficiency?

A

They will suffer a large ecchymosis

Ecchymosis is a discoloration of the skin resulting from bleeding underneath, typically caused by bruising.

37
Q

In summary, what bleeding patterns are associated with platelet/vascular defects?

A

Superficial bleeding into the skin and mucosal membranes

Bleeding immediately after injury

38
Q

In summary, what bleeding pattern are associated with coagulation?

A

Bleeding into deep tissues, muscles and joints

Delayed, but severe bleeding, after injury (bleeding often prolonged)

39
Q

What tests are done for disorders of secondary haemostasis?

A

Screening tests (‘clotting screen’):

  • PT
  • APTT
  • Full blood count (platelets)

Factor assays

  • for Factor VIII etc.

Tests for inhibitors

40
Q

What would be the results of a typical clotting screen for haemophilia?

A

APTT is prolonged

  • because you are not making factor 8 or 9

PT will be normal

  • extrinsic pathway not affected
41
Q

What bleeding disorders are not detected by routine clotting tests?

A
  • Mild factor deficiencies
  • Von Willebrand disease
  • Factor XIII deficiency (cross linking)
  • Platelet disorders
  • Excessive fibrinolysis
  • Vessel wall disorders
  • Metabolic disorders (e.g. uraemia)
  • (Thrombotic disorders)
42
Q

Other than disorders of primary and secondary haemostasis, what other conditions can cause abnormal bleeding?

A

DISORDERS OF FIBRINOLYSIS –

  • can cause abnormal bleeding
  • they are rare
  • Hereditary: antiplasmin deficiency
  • Acquired: drugs such as tPA, Disseminated intravascular coagulation
43
Q

What common bleeding disorders have a genetic component?

A

HAEMOPHILIA

  • Sex-linked recessive disorder
  • Haemophilia A and B are both X-linked
  • The genes tend to be carried by females
  • The disease tends to affect males
  • The varying degrees of lyonization results in the varying levels of genes being carried

VON WILLEBRAND DISEASE

Autosomal Dominant Disorder

  • Type 1 can be dominant
  • But Type 3 is recessive (rarely seen)
  • Type 2 von Willebrand disease is autosomal dominant
44
Q

What targets do bleeding disorder treatments target?

A

Failure of production/function

  • Replace missing factor/platelets (Prophylactic or Therapeutic)
  • Stop drugs causing this

Immune destruction (e.g. immune thrombocytopenia)

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

Increased consumption

  • Treat the cause of the DIC
  • Replace what is missing as necessary
45
Q

What does DIC stand for?

A

Disseminated Intravascular Coagulation

46
Q

List the treatments used for bleeding disorders

A

FACTOR REPLACEMENT THERAPY

Plasma

  • Contains all coagulation factors

Cryoprecipitate

  • Rich in Fibrinogen, FVIII, VWF, Factor XIII

Factor Concentrates

  • Concentrates available for all factors except factor V

Prothrombin Complex Concentrates (PCCs)

  • Factors II, VII, IX, X

Recombinant Forms of Factors

  • FVIII and FIX are available

GENE THERAPY

  • For haemophilia A and B

NOVEL APPROACHES IN DEVELOPMENT

  • Bispecific antibodies
  • Anti-TFPI antibodies
  • Antithrombin RNAi

PLATELET REPLACEMENT THERAPY

  • Pooled platelet concentrates available

DDAVP (desmopressin)

  • Release the body’s own stores of VWF and F8
  • For von Willebrand Disease

TRANEXAMIC ACID

  • Anti-fibrinolytic

FIBRIN GLUE/SPRAY

47
Q

How does DDAVP work as haemostatic treatment?

A

DDAVP is a vasopressin derivative (analogue)

It causes a 2-5 fold rise in VWF and VIII (there is a secondary rise in F8)

It causes the release of these from endogenous stores

  • hence it is only useful in mild disorders

This can be given as a nasal spray or intravenously

Intranasally:

  • 300 micrograms administered
  • peak response seen in 60-90 minutes

Intravenously:

  • 0.3 micrograms/kg
  • peak response seen in 30-60 minutes
48
Q

How does Tranexamic Acid work as haemostatic treatment?

A

Inhibits fibrinolysis

  • competitively inhibits binding of tPA to fibrin

Widely distributed, and crosses the placenta

  • but low concentration detected in breast milk

Useful adjunctive therapy, that can be administered in many ways

Intravenous: 0.5g tds

Oral: 1.5g tds

o Mouthwash: 1g (10ml 5%) qds

Yr 2 MCD - Haem (12 decks)

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