L28 – Inherited & Acquired Bleeding Disorders

Question 1

List the endothelial factors that inhibit blood coagulation?

Answer 1

Antithrombin, tissue factor pathway inhibitor, protein S, protein C, Thrombomodulin

Question 2

List endothelial factors that cause vasodilation and inhibit platelet aggregation?

Answer 2

Prostacyclin, nitric oxide

Question 3

List endothelial factors that initiate coagulation?

Answer 3

• Von Willebrand factor
• Tissue factor (rich in thromboplastin, can be used to check prothrombin time (PT))

Question 4

List 4 functions of platelets in forming blood clot?

Answer 4

Form a primary plug to close vascular defect (+ve feedback)

Release serotonin, thromboxane = stimulate vascular constriction

Release ADP, TXA2 for platelet aggregation

Provide a pro-coagulant surface for coagulation reactions to generate fibrin clot

Question 5

Which coagulants are produced by the liver?

Answer 5

All except VWF, Factor VIII

Question 6

2 functions of Von Willebrand factor (VWF)?

Answer 6

 Bridges between platelet and collagen in platelet adhesion

 Carrier protein = protects factor VIII from degradation in circulation

Question 7

Describe the structure involved in platelet to platelet adhesion?

Answer 7

• Glycoprotein IIb/IIIa complex bind plt together

Question 8

List the coagulation factors with longest and shortest t1/2

Answer 8

Longest = Factor 1

Shortest = factor 7

Question 9

Thrombin activates which coagulation factors to form a positive feedback loop?

Answer 9

Factor 5,8,11

Question 10

What is the convergence point of the intrinsic and extrinsic pathway for clot?

Answer 10

Extrinsic and intrinsic pathways converge at Factor X

Question 11

What is the end product of the final common coagulation pathway

Answer 11

Fibrin

Question 12

3 principle mechanisms of bleeding disorders?

Answer 12

• Defective blood vessel
• Defective Platelets
• Defective coagulation factors and VWF

Question 13

Define the 2 patterns of bleeding?

Answer 13

Platelet/vessel type: Mucocutaneous bleeding*

Coagulation type: Delayed bleeding, Deep-seated bleeding*

Question 14

Give examples of mucocutaneous and deep-seated bleeding?

Answer 14

Muco = petechiae & bruises, gum bleeding, menorrhagia, retinal hemorrhage

Deep-seated = joint (haemarthrosis), soft tissue (muscle haematoma)

Question 15

What is the most important prelim. evaluation of bleeding disorder?

Answer 15

Bleeding history

• Age of onset of bleeding disorder
• Severity and progression
• Family members affected?

Question 16

Acquired bleeding disorders are more common than inherited. T or F?

Answer 16

True

Question 17

List some types of drugs that can cause bleeding disorders.

Answer 17

• Oral anticoagulants
• Anti-platelet drugs
• Chemotherapy

Question 18

List the 3 functional tests for coagulation factors.

Answer 18

1. Prothrombin time (PT)
2. Activated partial thromboplastin time (APTT)
3. Thrombin time (TT)

Question 19

Define what is tested in PT?

Answer 19

Extrinsic pathway = factor 7

Common pathway = factor 10 ,factor 5, prothrombin (F2), Fibrinogen (F1)

Question 20

What defect is indicated in Isolated Prolonged PT?

How about concurrent APTT prolong?

Answer 20

isolated = factor VII deficiency

PT + APTT prolonged = intrinsic/ final common pathway defects

Question 21

List 3 common causes of prolonged PT?

Answer 21

Vitamin K deficiency

Vitamin K antagonists (e.g. warfarin)

liver disease

Question 22

Define what is tested in APTT?

Answer 22

intrinsic pathway = Factor 12,11,9,8

final common pathway = 10,5, prothrombin, fibrinogen

Question 23

What defects are indicated in isolated prolonged APTT?

Answer 23

• Intrinsic pathway: Deficiencies of Factor 8,9,11,12
• Inhibitors of factor 8 or others or lupus anticoagulant
• Contact factor def. ((Pre)Kallikrein, Factor 12, HMWK)
• Unfractionated/ contam. heparin

Question 24

Define what is tested in Thrombin Time?

Answer 24

evaluates fibrinogen

Question 25

What defects are indicated in prolonged TT?

Answer 25

Low fibrinogen:

1) Deficiency / dysfunction of fibrinogen (hypofibrinogenemia / afibrinogenaemia/ dysfibrinogenemia)
2) Inhibition of thrombin by heparin (e.g. contamination)
3) DIC consuming clotting factors
4) Liver disease = defect synthesis of fibrinogen

Question 26

List some causes of Increased fibrinogen levels?

Answer 26

• Hormone-related: female sex, pregnancy, oral contraception
• Acute phase reaction (e.g. infection, lupus)

Question 27

Difference in the initiation of clotting in vitro and in vivo?

Answer 27

In vitro = need contact factors like Prekallikrein to start

In vivo = need tissue factor and platelets to start

Question 28

Describe the ddx of prolonged APTT?

Answer 28

Question 29

What type of bleeding is asso. with platelet disorders

Answer 29

Mucocutaneous bleeding

Question 30

List 3 causes of thrombocytopenia?

Answer 30

1. Decreased platelet production from the marrow: e.g. due to malignancies
2. Increased consumption of platelets (immune and non-immune causes)
3. Others: Abnormal pooling in spleen, or dilutional (e.g. massive blood transfusion).

Question 31

Does drug-induced platelet disorder create functional or numerical disorder?

Answer 31

Functional

Question 32

List 3 tests to assess platelet disorders

Answer 32

• CBC platelet count
• PBS morphology
• Platelet function test: aggregometry that measures aggregation response of the platelets to different agonists

Question 33

Indication for platelet function test?

Answer 33

if normal platelet count, normal PT and APTT, but mucocutaneous bleeding persists