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Year 2 - MCD - Haematology > Disorders of Haemostasis > Flashcards

Disorders of Haemostasis Flashcards

1
Q

What is abnormal bleeding?

A
  • Easy bruising (e.g. w/o apparent trauma)
  • Gum bleeding
  • Frequent nosebleeds (and duration >10 min)
  • Bleeding after tooth extraction
  • Post operative bleeding
  • Heavy, prolonged or recurrent bleeding after surgery or dental extractions.
  • 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.
    In women
  • Menorrhagia (e.g requiring treatment)
  • Post partum bleeding
  • Family history
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2
Q

What categories of causes can cause problems with haemostasis?

A

Lack of a specific factor

  • Failure of production: congenital and acquired
  • Increased consumption/clearance

Defective function of a specific factor

  • Genetic defect
  • Acquired defect – drugs, synthetic defect, inhibition

(more commonly due to drugs than do to genetic defects)

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3
Q

What factors are important for platelet aggregation?

A

ADP, thromboxane

-> the first step in primary heamosuasis is adhesion and then the platelets are activated more which leads to aggregation.

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4
Q

How do platelets bind to WVF and collagen

A

WVF: Glp1b / Gp1b

Collagen: Glp1a, GPVI, alpha1beta1

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5
Q

Name some disorders of primary haemostasis related to thrombocytes

A

Low numbers: “thrombocytopenia”

  • BM failure eg: leukaemia, B12 deficiency
  • Accelerated clearance eg: immune (ITP), DIC.
  • pooling and destruction in an enlarged spleen

Impaired function

  • Hereditary absence of glycoproteins or storage granules
  • Acquired due to drugs: aspirin, NSAIDs, clopidogrel
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6
Q

What are the 3 main factors that can cause problems with primary haemostasis?

A
  • platelets
  • WVF
  • Vessel Wall
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7
Q

auto-ITP

A

Autoimmune thrombocytopenic purpura

  • very common cause of thrombocytopenia
  • ABs cover the platelet and then it is phagocytksed by macrophages.
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8
Q

What are the 3 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
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9
Q

Hereditary platelet defects

A
  • missing surface glycoproteins (Gp2b/3a; Gp1b)
  • missing granules (i.e. dense granules)

Examples:

  • Glanzmann’s thrombasthenia (recessive severe bleeding)
  • Bernard Soulier syndrome (GPIB binding to VWF is impaired)
  • Storage Pool disease (problem with dense granule release)
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10
Q

VWF - what can lead to problems with haemostasis

A

VWD:

  • Hereditary decrease of quantity +/ function (common)
  • Acquired due to antibody (rare)

VWD is usually hereditary

  • Deficiency of VWF (Type 1 (not recessive, you don’t make enough) or 3 (recessive, you don’t make any))
  • VWF with abnormal function (Type 2)
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11
Q

What are the 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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12
Q

Problems with the vessles leading to problems with primary haemostasis

A

Inherited (rare) Hereditary haemorrhagic telangiectasia Ehlers-Danlos syndrome and other connective tissue disorders

Acquired:

  • Scurvy
  • Steroid therapy
  • Ageing (senile purpura)
  • Vasculitis
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13
Q

Ehlers-Danlos syndrome

A

(stretchy velvety skin. Atypical ears: prominent “winged”, small, round, lobeless, lobe attached to face, ears with different shapes: kidney shape, “Dumbo ears”, “Mr. Spock ears”, soft ears, with bent helix.
Abnormal nose: with a lump in the union of the bone and the cartilage, nasal septum deviation)

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14
Q

Briefly summarise the disorders of primary haemostasis

A

Platelets

  • Thrombocytopenia
  • Drugs

Von Willebrand Factor
- Von Willebrand disease

The vessel wall

  • Hereditary vascular disorders
  • Scurvy, steroids, age
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15
Q

Summarise the typical features of primary haemostasis disorders

A

Typical primary haemostasis bleeding:

  • Immediate
  • Prolonged bleeding from cuts
  • Epistaxes
  • Gum bleeding
  • Menorrhagia
  • Easy bruising
  • Prolonged bleeding after trauma or surgery
  • Mucotaneous: gums, nose, menstrual bleeding.

Thrombocytopenia – Petechiae
Severe VWD – haemophilia-like bleeding

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16
Q

Tests for disorders of primary haemostasis

A
  • Platelet count, platelet morphology
  • Bleeding time (PFA100 in lab)
  • Assays of von Willebrand Factor
  • Clinical observation
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17
Q

FVI

A

activated factor V

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18
Q

What are the effects of haemophilia on thrombin production

A
  • very reduced thrombin production

- thrombogram curve Is a lot flatter

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19
Q

Why is coagulation important in injuries?

A
  • The role of the coagulation cascade is to generate a burst of thrombin which will convert fibrinogen to fibrin
  • Deficiency of any coagulation factor results in a failure of thrombin generation and hence fibrin formation
  • platelet plug is enough for small injuries but for bigger ones you need fibrin.
  • The primary platelet plug is sufficient for small vessel injury
  • In larger vessels it will fall apart
  • Fibrin formation stabilises the platelet plug
20
Q

Summarise disorders of coagulation

A

Deficiency of coagulation factor production

  • Hereditary failure of production
    - Factor VIII/IX: haemophilia A/B
  • Acquired
    - Liver disease
    - Dilution
    - Anticoagulant drugs – warfarin

Increased consumption

  • Acquired
    • Disseminated intravascular coagulation (DIC)
    • Immune - autoantibodies (very rarely there are ABs to clotting factors)

Consumption
- Disseminated intravascular coagulation
increased consumption
- Generalised activation of coagulation – Tissue factor
- Associated with sepsis, major tissue damage, inflammation
- Consumes and depletes coagulation factors
- Platelets consumed
- Activation of fibrinolysis depletes fibrinogen
- Deposition of fibrin in vessels causes organ failure

21
Q

DIC - how do you treat it?

A
  • treat DIC by treating the underlying cause

- you can support by replacing these things but you cannot turn the process off without removing the cause

22
Q

Name 4 coagulation factor deficiencies and what problems they cause.

A

Factor VIII and IX (Haemophilia)

  • Severe but compatible with life
  • Spontaneous joint and muscle bleeding

Prothrombin (Factor II)
- Lethal

Factor XI
- Bleed after trauma but not spontaneously

Factor XII
- No excess bleeding at all

=> not all factor deficiencies are the same.

23
Q

Acquired coagulation disorders - coagulation factor production

A

Liver failure – decreased production
- Most coagulation factors are synthesised in the liver

Dilution

  • Red cell transfusions no longer contain plasma
  • Major transfusions require plasma as well as rbc and platelets (otherwise you have a dilutional effect)

Anticoagulant drugs
- e.g. warfarin

24
Q

Summarise DIC

A

= disseminated intravascular coagulation

  • commonly seen with sepsis, obstetric problems, cancer.
  • there is an unregulated activation of the coagulation system
  • all the clotting factors are being used up, platelet activation
  • blood clots form in small vessels
  • fibrin in organs can cause organ failure
  • because all coagulation factors are used up you get bleeding
  • you have uncontrolled coagulation and bleeding
  • treat it by treating the cause.
25
Q

What factors are deficient in haemophilia A and B?

A

A: factor 8 (on X chromosome)

B: factor 9 (0n X chromosome)

26
Q

Bleeding pattern in coagulation disorders

A
  • superficial cuts do not bleed (platelets)
  • bruising is common, nosebleeds are rare
  • spontaneous bleeding is deep, into muscles
    and joints
  • bleeding after trauma may be delayed and is prolonged
  • frequently restarts after stopping
27
Q

what is a joint hallmark of haemophilia?

A

haemarthrosis

28
Q

What clinical procedure should you avoid in people with hameophilia?

A
  • i.m. injections

- can cause large area bruising

29
Q

Is haemophilia serious?

A

YES

  • people can bleed to death
  • most people with haemophilia don’t have access to adequate treatment
30
Q

Clinical Distinction Between Bleeding due to Platelet and Coagulation Defects

A

Platelet defects:

  • Superficial bleeding into skin, mucosal membranes
  • Bleeding immediate after injury

Coagulation Defects:
- Bleeding into deep tissues, muscles, joints
- Delayed, but severe bleeding after injury. Bleeding
often prolonged.

Either can be life threatening!!

31
Q

Summarise tests for clotting disorders

A

Screening tests (‘clotting screen’)

  • Prothrombin time (PT)
  • Activated partial thromboplastin time (APTT)
  • Full blood count (platelets)
  • Factor assays (for Factor VIII etc)
  • Tests for inhibitors

Important e.g. before surgery.

32
Q

APTT

A

= activated partial thromboplastin time

  • tests intrinsic pathway and common pathway (XII, XI, VIII, IX)
33
Q

PT

A

= prothrombin time

  • tests extrinsic pathway and common pathway(VII, TF)
34
Q

TT

A

= thrombin time

  • tests common pathway
35
Q

Which bleeding disorders are not detected by routine. bleeding 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)
36
Q

Disorders of fibrinolysis

A
  • Disorders of fibrinolysis can cause abnormal bleeding but are rare

Hereditary
- antiplasmin deficiency

Acquired

  • drugs such as tPA
  • Disseminated intravascular coagulation
37
Q

which drug is given as a clot buster?

A

tPa

38
Q

what is antiplasmin?

A

Alpha 2-antiplasmin is a serine protease inhibitor responsible for inactivating plasmin.

39
Q

Why do. carriers of haemophilia have different phenotypes?

A

lionisation

  • FVIII Normal range 0.5 -1.5 iu/ml
  • you can have different low. ranges
40
Q

inheritance of VWD

A

autosomal dominant

  • Type 2, (Type 1) AD
  • Type 3 AR
41
Q

inheritance of haaemophilia

A
  • X linked recessive
42
Q

Inheritance of less common bleeding disorders

A
  • All the rest (V, X etc.)
  • Autosomal recessive (AR)
  • And therefore much less common
43
Q

How do you treat haemostatic disorders?

A

Failure of production/function

  • Replace missing factor/platelets (e.g. in haemophilia)
  • Prophylactic
  • Therapeutic
  • Stop drugs

Immune destruction

  • Immunosuppression (eg prednisolone)
  • Splenectomy for ITP (because a lot of platelets are being destroyed)

Increased consumption

  • Treat cause
  • Replace as necessary
44
Q

Factor replacement treatment for bleeding disorders

A

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 FVIII and FIX are available.

45
Q

What are the main therapeutic approached for bleeding disorders? (4)

A
  • factor replacement
  • platelet replacement
  • Gene therapy
  • Novel approaches
46
Q

DDAVP

A

= desmopressin

  • Vasopressin derivative
  • 2-5 fold rise in VWF-VIII (VIII>vWF)
  • Releases endogenous stores - Hence only useful in mild disorders
47
Q

Tranexamic acid

A
  • Inhibits fibrinolysis
  • Widely distributed – crosses placenta
  • Low concentration in breast milk
  • useful in adjunctive therapy

Year 2 - MCD - Haematology (11 decks)

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