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Medicine Year 1 - Semester 2 - Part 1 > Coagulation - Normal and Abnormal > Flashcards

Coagulation - Normal and Abnormal Flashcards

1
Q

Describe the term haemostasis

A

Haemostasis is the mechanism that leads to cessation of bleeding from a blood vessel.

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2
Q

Describe the ideal coagulation system

A

Allows blood to flow through vessels

Cope with leaks, big and small, whilst allowing the rest to flow.

Repair mechanisms to dissolve clots

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3
Q

Main constituents of coagulation

A

Vessel wall lined by endothelium

Platelets derived from megakaryocytes in marrow.

Coagulation factors in pre-activated state

Inhibitors of coagulation

Fibrinolytic system and inhibitors

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4
Q

Function of endothelial cells

A

Line blood vessels and form a barrier

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5
Q

What do endothelial cels produce ?

A

Produce thrombomodulin and heparin sulphate to inhibit thrombin production.

Enzymes to degrade platelet granule-derived moleucles

Prostacyclin and nitric oxide to reduce platelet adhesion.

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6
Q

Describe the production of platelets

A

Fragments of megakaryocytic
Budded off into lumen of marrow sinusoids

Production stimulated by thrombopoetin (TPO) which is liver derived.

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7
Q

Describe the function of platelets

A

Form a plug when attracted by lowered prostacyclin and by collagen exposure.

Thromboxane A2 and serotonin from platelets cause vasoconstriction.

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8
Q

State the lifespan of platelets

A

Circulate for 5-10 days with around 30% stored in spleen

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9
Q

Location of platelets

A

Adhere to vessel wall via Von Willibrand’s factor and Glycoprotein Ib.

Adhere to each other via Glycoprotein IIb-IIa and fibrinogen

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10
Q

State the 2 pathways of the coagulation cascade

A

Intrinsic Pathway - endothelial collagen

Extrinsic Pathway - Trans-membrane protein in connective tissue around vessels named tissue factor

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11
Q

Outline the main elements of the coagulation cascade

A

Fibrin is the final product of the clotting cascade.

Fibrinogen is the precursor for fibrin, and is activated by thrombin (IIa).

Thrombin is activated in 2 ways :

  • Intrinsic
  • Extrinsic
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12
Q

What does the common pathway to produce thrombin involve ?

A

Involves Factor 5 (Va) and Factor 10 (Xa), which generate thrombin

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13
Q

What slows down the coagulation cascade ?

A

TFPI
Antithrombin
Active Protein C

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14
Q

Describe protein C

A

Activated by thrombomodulin thrombin complex

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15
Q

Describe antithrombin

A

Inhibits Xa and IIa

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16
Q

Function of heparin

A

Heparin stimulates antithrombin and heparin cofactor II

Heparin cofactor II inhibits IIa

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17
Q

Co-factor (factor S)

A

Va and VIIIa are degraded

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18
Q

How is plasminogen activated ?

A

Activated to plasmin by tissue plasminogen activator - from endothelial cells

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19
Q

What is a measurement of fibrinolysis ?

A

Fibrin broken down into fibrin degradation products - including D dimers

20
Q

Therapeutic use of the fibrinolytic system

A

Use with streptokinase or tPA for clot busting

e.g. Acute myocardial infarction to thrombotic stroke.

21
Q

Measurement of coagulation

A

Full blood count
Bleeding time
Prothrombin time

22
Q

Reference range for FBC

A

150-400 x 10^9/L

Easy bruising and purport <30-50

Risk of major bleeding <10

23
Q

Describe bleeding time

A

In vivo test of overall clotting - mainly platelet function

Lots of poorly controlled variables so not often done.

24
Q

Prothrombin Time

(measures extrinsic pathway)

A

Done on citrated plasma which removes Ca2+

At 37C thromboplastin and Ca2+ are added

Measure the time until clot forms

Prolonged by levels of II, X, VII

25
Q

Function of citrated plasma

A

Removed Ca2+

Ionised calcium makes things clot

26
Q

Describe the activated partial thromboplastin test

A

Ca2+, kaolin and phospholipids are added to citrated plasma.

Measure of the intrinsic and common pathway

Prolonged in haemophilia and by heparin

27
Q

PT time
APPT

A

Extrinsic pathway
Intrinsic / Common pathway

28
Q

How can prolonged PT or APTT be tested ?

A

50:50 mix with normal plasma to see if prolongation corrects.

29
Q

How can fibrinogen be measured ?

A

BY measuring clot density

OR

Thrombin time - thrombin and calico added to citrated plasma

30
Q

Inherited blood disorder

A

Haemophilia - X linked defect in VIII or IX gene

31
Q

Haemophilia stats

A

Approx 1:5000 of males

Female carriers not affected
can be mild - chance finding or issue from surgery

32
Q

Severe haemophilia

A

<1% VIII level

Frequent bleed into joints and soft tissues

33
Q

Treatment of haemophilia

A

Prophylaxis or Treatment
Clotting factors

Gene Therapy - factor 9 deficiency

34
Q

Be aware of examples of congenital and acquired coagulation disorders

A

Von Willebrand disease
Haemophilia

Acquired coagulation disease :

  • liver
  • disseminated intra-vascular coagulation (DIC)
35
Q

Von Willebrand

A

Usually autosomal dominant
Defect in platelet adhesion and binding of VIII

Up to 1% of pop

36
Q

Acquired coagulation disease - liver

A

Liver disease - alcohol, autoimmune, viral hepatitis

PT and fibrinogen abnormal
Bleeding due to abnormal clotting, low platelets

Portal hypertension causing oesophageal varices ad uper GI bleeding

37
Q

Where are coagulation factors produced ?

A

Liver

38
Q

Acquired coagulation disease - DIC

A

Activation of clotting cascade

Causes depletion of clotting factors and damage due to clot.

Treat the cause and replace clotting factors

39
Q

Describe factors which increase risk of clotting

A

Trauma
Malignancy e.g. prostate cancer
Sepsis
Amniotic fluid embolism

40
Q

Thrombocytopenia

A

Low platelets

Could be due to :

  • under production
  • increased use
  • abnormal distribution
41
Q

Causes of low platelet count

A

Abnormal marrow function

Drug adverse effete

Cytotoxic chemotherapy

Immune thrombocytopenia

Splenomegally
Large haemangioma

42
Q

Increased risk of clotting

A

Abnormal :

  • vessel wall
  • flow
  • blood component
43
Q

Thrombophilia

A

Increased risk of clotting

  • inherited defect in coagulation inhibitors
44
Q

Abnormal vessel wall

A

Atheroma
Plaque
Varicose veins
Aneurysm

45
Q

Abnormal flow

A

Atrial fibrillation
Immobile - plane flight, surgery
Varicose veins

46
Q

Abnormal blood components

A

Increased haemoglobin/ RBC count
Increased platelet / WBC count

Increased viscosity of plasma
Reduced coagulation factor inhibitors

Medicine Year 1 - Semester 2 - Part 1 (51 decks)

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