5. Bleeding disorders

Question 1

which tests are used to measure platelet no. and activity

Answer 1

platelet count and bleeding time

Question 2

which parts of the clotting cascade do the APTT, PT and INR tests measure

Answer 2

APTT = intrinsic and common pathway

PT and INR (P’s PT/mean PT) = extrinsic pathway

Question 3

which medication should be used to:

1. treat arterial thrombi (eg unstable angina, MI)
2. treat venous thrombi (eg DVT or PE)
3. prophylaxis in AF, valvular heart disease, artificial heart valves or antiphospholipid syndrome

Answer 3

1. anti-platelets: aspirin
2. anti-coagulants: warfarin or heparin
3. anti-coagulants: warfarin or heparin

Question 4

describe the MOA of aspirin

Answer 4

Irreversibly inactivates platelet cyclooxygenase… suppresses production of thromboxane A2 (platelet aggregator)… inhibits platelet aggregation

Question 5

describe the MOA of warfarin

Answer 5

Inhibits vitamin K epoxide reductase… no recycling of oxidised VitK… no activation of coagulation factors II, VII, IX and X.

Question 6

describe the MOA of heparin

Answer 6

Enhances activity of anti-thrombin III… inactivates thrombin and factor X

Question 7

what are the effects of aspirin, warfarin and heparin on coagulation tests

Answer 7

1. aspirin: increased bleeding time (as measure of platelet activity)
2. warfarin: increased PT and INR
3. heparin: increased APTT

Question 8

P presents with following lab tests:

• increased PT and INR
• increased APTT
• decreased fibrinogen
• increased fibrin degradation products

what is the likely diagnosis and why

Answer 8

Disseminated intravascular coagulation:

• fibrinogen consumed in microthrombi formation (decreased fibrinogen)… then broken down by fibrinolysis… release of fibrin degradation products, e.g. D-dimers
• run out of of coagulation factors, etc. (increased PT, INR and APTT)

Question 9

describe the pathophysiology of DIC

Answer 9

Thrombohaemorrhagic disorder occurring as a secondary complication in a variety of disorders.

A clotting activator gets into blood and causes microthrombi formation throughout circulation… consumes platelets, fibrin and coagulation factors, and activates fibrinolysis… haemorrhage.

i) microthrombi formation… tissue ischaemia
ii) haemorrhage - can be severe, from mucous membranes and into skin/internal organs
iii) microangiopathic haemolytic anaemia - as RBCs squeeze through narrow vessels narrowed by microthrombi

Question 10

name 5 different causes of DIC

Answer 10

1. infection and sepsis - esp. by gram negative as GNB produce endotoxins that damage emdothelium and activate clotting
2. severe trauma - esp. to brain as contains large amounts of thromboplastin (tissue factor), or extensive burns
3. obstetric complications (50%) - e.g. amniotic fluid embolism (pro-coagulant), retained dead foetus (releases thromboplastin)
4. malignancy (33%) - e.g. mucin-secreting adenocarcinoma: release mucin (pro-coagulant), produce inflammation and tissue damage
5. snake bite

Question 11

a P presents with:

• frequent mucosal bleeding, e.g. epistaxis, menorrhagia
• prolonged bleeding time
• prolonged APTT

what is the likely diagnosis

Answer 11

von Willebrand disease (most common inherited bleeding disorder)

• prolonged bleeding time as affects platelet aggregation
• prolonged APTT as affects F8, part of intrinsic pathway

Question 12

describe the pathophysiology of vWB disease

Answer 12

Autosomal dominant inherited deficiency in von Willebrand factor.

Involves impaired platelet plug and fibrin clot formation and thus inefficient haemostasis, as vWF is a glycoprotein with 3 functions:

1. platelet adhesion to vessel walls (vWF binds to collagen and platelets)
   2. platelet aggregation
   3. stability and transport of Factor VIII

Question 13

a P presents with:

• petechiae
• low platelet count
• prolonged bleeding time

what is the likely diagnosis

Answer 13

thrombocytopenia = platelet count <100 x 10^9/L

Question 14

describe different causes for thrombocytopenia

Answer 14

1. decreased platelet production - due to BM infiltration by malignancy, cytotoxic drugs, infections (e.g. measles and HIV) or B12 and folate deficiency (required for platelet production)
2. decreased platelet survival - due to immunologic destruction (eg ITP) or non-immunological destruction (eg DIC)
3. platelet sequestration - due to hypersplenism
4. dilutional - due to massive blood transfusions

Question 15

a P presents with:

• prolonged APTT
• low F8 assay

what is the likely diagnosis and what are the associated symptoms

Answer 15

Haemophilia A (most common inherited disease associated with serious bleeding)

Signs and symptoms:

1. easy bruising
2. massive haemorrhage after trauma/surgery
3. “spontaneous” haemorrhages in areas subject to minor trauma, e.g. joints - haemarthrosis
4. joint deformities (due to recurrent haemarthrosis)

Question 16

describe the pathophysiology of haemophilia A

Answer 16

X-linked recessive (affects males and homozygous females) inherited deficiency in Factor VIII… reduced efficiency of blood clotting cascade

Question 17

what is haemophilia B

Answer 17

X-linked recessive deficiency in Factor IX

Question 18

what is immune thrombocytopenic purpura - how would it present

Answer 18

Auto-antibody production (primary or secondary to other auto-immune diseases) against platelet surface glycoproteins… platelet destruction

Signs and symptoms :

• bruising and petechiae
• mucosal bleeding, eg epistaxis, menorrhagia, GI bleeding
• haematuria
• intracranial bleeding (v rare)