Haemostasis and coagulopathies

Question 1

What is primary haemostasis and how does it work

Answer 1

Formation of the platelet plug
Injury to vessel -> reflex vasoconstriction + exposure of vWF on subendothelial matrix -> platelets can bind to vWF and become activated -> this recruits more platelets + exposes -ve charged phospholipids upon which coagulation factors can assemble

Question 2

Which clotting factors require activation by vitamine K

Answer 2

2, 7, 9, 10
II, VII, IX, X

Question 3

What is secondary haemostasis

Answer 3

Stabilisation of the primary plug via series of enzymatic reactions mediated by clotting factors
Ends with production of thrombin which can catalise conversion of fibrinogen to fibrin to form clot

Question 4

What does the fact that many mammals have mutations in factor XII but no bleeding tendencies show us

Answer 4

INtrinsic activation pathway less important than extrinsic in vivo

Question 5

How does extrinsic pathway activation work

Answer 5

Tissue factor exposure causes activation of factor VII (with Ca2+ present as cofactor)
–> Thrombin (II) burst which activates factor XII and platelets; leads to +ve feedback on factors V and VII

= major INITIATOR of secondary coagulation

Question 6

How does intrinsic pathway activation work

Answer 6

Initiated by contact of factors to -ve charged surfaced e.g phospholipids

Important for AMPLIFICATION

Question 7

Common pathway in secondary haemostasis

Answer 7

Thrombin (II) catalyses conversion of fibrinogen to fibrin
+ activates factors V, VII and IX for amplification and their inhibitors (protein C and S) which prevent system overrive

Also activates factor XIII which forms covalent bonds to cross link fibrin

Question 8

Which inhibitors act to inhibit haemostasis

Answer 8

anti-thrombin III, protein C and protein S

Question 9

What causes fibrinolysis

Answer 9

PLasmin (activated by plasminogen) breaks down fibrin

Question 10

What are D dimers

Answer 10

break-down products from CROSS-LINKED FIBRIN (i.e final stage clot)

Question 11

Signs of a primary haemostasis disorder

Answer 11

Petechiae, epistaxis, melaena

Question 12

Causes of disorders of primary haemostasis

Answer 12

Marked thrombocytopaenia (i.e <30-50x10^9/L), vWF deficiency, thrombocytopathia (i.e dysfunction)

Question 13

When should we avoid doing a buccal mucosal bleeding time test

Answer 13

In suspecting thrombocytopaenia

Question 14

How to test primary haemostasis i.e platelet function

Answer 14

Buccal mucosal bleeding test

Question 15

Which breed is prone to vWD

Answer 15

Doberman

Question 16

Causes of thrombocytopathia

Answer 16

1) Inherited: Chediak-Higashi syndrome in Persian cats
2) Acquired: DIC, neoplasia, NSAIDs, severe liver/kidney disease, marked hyperglobulinaemia

Question 17

What is treatment/care for vWD

Answer 17

Before surgery: give prophylactic blood products, give desmopressin to cause vWF release for 4 hours

Question 18

Whcih clotting factor has the shortest half life

Answer 18

VII

Question 19

DIfferent tests for assessing secondary haemostasis

Answer 19

whole blood clotting time, activated clotting time, activated partial thromboplastin time, one stage prothrombin time

Question 20

WBCT test

Answer 20

Simple but crude
Put blood in glass tube (-ve charged surface); time until clot formed
Prolonged = >6 mins; only see in VERY SEVERE deficiency i.e <5% normal amounts

Affected by: temp, size of tubes, number of platelets available

Question 21

ACT test for secondary haemostasis

Answer 21

Similar to WBCT but ad known amount of diatomaceous earth to activate intrinsic pathway + controlled temp; prolonged when <10% normal amount left

Question 22

APTT test for secondary haemostasis

Answer 22

Perform on plasma not whole blood
- Supply contact activator kaolin, phospholipid source (so no effect of low platelets), Ca2+, controlled temp

Consider abnormal when time to clot 20% over RI

Question 23

OSPT test for secondary haemostasis

Answer 23

Similar to APTT but uses tissue factor as activator
Also supplies phospholipids, ca2+
Again 20% over RI is abnormal
Most sensitive to fall in factor VII

Question 24

Causes of acquired coagulopathy

Answer 24

1) Hepatic disease: not making enough factors
2) Vit K antagonist (rat poisoning) or deficiency (diet, exocrine pancreatic insufficiency, GI disease)
3) Consumption of coagulation factors; DIC or angiostronglus vasorum infection

Question 25

How does rodenticide poison cause a coagulopathy

Answer 25

Inhibits epoxide reductase enzymes so vitK remains in inactive form

Most sensitive test = OPST; because factor VII is tested and this one has the shortest half life

Question 26

Effect of DIC on coagulation

Answer 26

From marked inflammatory response e.g pancreatitis, neoplasia, heat stroke

At first: hypercoagulation phase; endothelial damage, platelet activation etc etc
THEN: hypocoagulative phase; activation of fibrinolysis –> inactivation and depletion of clotting factors

Question 27

Clinical findings with DIC

Answer 27

Inflammatory leukogram, thrombocytopaenia, prolonger OSPT and APTT, elevated D diners

Question 28

What is haemophilia A

Answer 28

Factor VIII deficiency
- See prolonged APTT but normal OSPT
Seen in German shepherds; more so males

Question 29

WHat type of blood for coagulation testing

Answer 29

citrated blood

Question 30

In what conditions might D dimers be raised (unrelated to coagulopathy)

Answer 30

Renal or liver disease; since they clear D dimers

Question 31

What is ‘very high’ levels of D dimers

Answer 31

> 2000mg/ml –> indicates fibrinolysis, DIC or thrombus
Vs mid range values; neoplasia, inflammation, renal or liver disease, thromboembolic disease