Thrombotic disorders

Question 1

What are the 3 main elements of haemostasis?

Answer 1

Primary haemostasis

Blood coagulation

Fibrinolysis

Question 2

Primary haemostasis is triggered by tissue damage and involves what processes?

Answer 2

Vasoconstriction (mediated mainly by NO?)

Platelet adhesion

Platelet aggregation

Basically - involves diverting blood flow elsewhere through vasoconstriction and plugging the exposed collagen bit with platelets

Question 3

Coagulation occurs following primary haemostasis and involves which processes>

Answer 3

Insoluble fibrin formation

Fibrin cross-linking

Question 4

Fibrinolysis occurs when plasminogen in converted to plasmin by the actions of what molecules?

Answer 4

Factors XIa and XIIa

Tissue plasminogen activator (t-PA)

Urokinase plasminogen activator (u-PA)

Question 5

What is Virchow’s triad?

Answer 5

Stasis

Hypercoagulability

Vessel damage

If one or more of these occurs then it leads to the formation of a thrombus - an unwanted thrombosis

Question 6

Considering virchows triad - what might cause each of these thingies to occur?

Answer 6

Stasis = bed rest, travel

Vessel damage = atherosclerosis

Hypercoagulability = pregnancy, trauma and lots of others

Question 7

What are the 3 main types of thrombosis?

Answer 7

Arterial

Venous

Microvascular

Question 8

What are the features of an arterial thrombus?

Answer 8

Arterial thrombi are called ‘white clots’

Clot is made up of Platelets and fibrin

They tend to be secondary to atheroscleroses and cause ischaemia and infarction downstream

Question 9

Give examples of arterial thrombotic disease

Answer 9

Coronary thrombosis:

• MI
• unstable angina

Cerebrovascular thromboembolism:

• Stroke
• TIA

Peripheral embolisms:

• acute limb ischaemia

Question 10

What are risk factors for arterial thromboembolic disease

Answer 10

Age

Smoking

Sedentary lifestyle

Hypertension

Diabetes mellitus

Obesity

Hypercholesterolaemia

Question 11

Describe the management for arterial thromboembolic disease

Answer 11

Primary prevention:

• modify lifestyle factors
• treatment of vascular risk factors eg atheros

Acute presentation:

• thrombolysis
• antiplatelets/anticoagulant therapy

Secondary prevention

Question 12

What are the features of a venous thrombus?

Answer 12

‘Red thrombus’

Made up of fibrin and red cells

Results in clogging up and increasing pressure upstream

Principally due to stasis and hypercoagulability

Question 13

What are the main types of venous thromboembolic disease

Answer 13

Limb deep vein thrombosis

Pulmonary embolism

visceral venous thrombosis

intracranial venous thrombosis

superficial thrombophlebitis

Question 14

Venous thrombus formation generally occurs due to stasis and hypercoagulability

What are the risk factors for venous thrombus formation?

Answer 14

Increasing age, Immobility

Pregnancy

Surgery or trauma

Obesity

Family history

Systemic disease

Hormonal therapy - COCP, HRT

Question 15

What systemic diseases are risk factors for venous thrombosis?

Answer 15

Cancer

Myeloproliferative Neoplasm (MPNs)

Autoimmune disease:

• Inflammatory bowel disease
• Connective tissue disease e.g SLE
• Antiphospholipid syndrome: arterial and venous thrombosis

Question 16

How is a diagnosis of venous thrombosis and VTE made?

Answer 16

Pretest probability scoring (Geneva or Wells score) followed by either:

1) Lab testing - if probability score low
2) Imaging - if high

Question 17

What modalities of imaging are used for diagnosing VT and VTE?

Answer 17

Suspected Upper and lower limb VT:

• Doppler US

Suspected pulmonary embolism:

• CT pulmonary angiogram (CTPA) - gold standard
• V/Q scan

Question 18

What are the aims of management for Venous thrombosis?

Answer 18

Prevent clot extension (growing)

Prevent embolisation

Prevent recurrence in long term management

Question 19

What drugs are used to treat venous thromboembolism?

Answer 19

Anticoagulants - to prevent extension of clot:

• DOACs - apixaban/rivaroxaban
• LMWH - dalteparin
• warfarin

For massive PE - thrombolysis eg Streptokinase, alteplase etc

Question 20

Heritable thrombophilia conditions predispose individuals to VT and VTE

What are the heritable thrombophilias?

Answer 20

Factor V Leiden

Prothrombin G20210A

Antithrombin deficiency

Protein S deficiency

Protein C deficiency

Question 21

Describe how Factor V leiden predisposes an individual to VT

Answer 21

Protein C and Protein S normally inhibit Factor IIIa which blocks the coagulation cascade (when we dont need it)

Factor V Leiden gene mutation means that there is Protein C resistance so its inhibition is far less effective and coagulation happens more readily

Question 22

Under what circumstances is thrombophilia screened for?

Answer 22

Screening is limited to high risk heritiable thrombophilia - such as antithrombin deficiency

Question 23

What are the main features of microvascular thrombi?

Answer 23

Made up of platelets and/or fibrin

Reults in diffuse ischaemia

Principally occurs in DIC

Question 24

What is DIC?

What can precipitate DIC?

Answer 24

Disseminated intravascular coagulation

basically clots form absolutely everywhere - its really not good

Can be caused by:

• septicaemia (esp Meningitis)
• malignancy
• eclampsia

Question 25

Why is DIC a coagulation disorder and a bleeding disorder at the same time?

Answer 25

Shit tons of clotting uses up all the platelets and clotting factors in the body

This means theres none left - so bleeding occurs uncontrollably