Haemostasis: acquired disorders

Question 1

Acquired vascular bleeding disorders

Answer 1

Senile Purpura
Scurvy (Vitamin C deficiency)
Steroid Purpura

Question 2

Causes of thrombocytopenia

Answer 2

Failure of platelet production
-vit B12 or folate deficiency
-bone marrow infiltration (leukaemia or metastases)
-radiation, cytotoxic therapy
Increased consumption of platelets
-immune thrombocytopenia (ITP)
-disseminated intravascular coagulation (DIC)
-HIV infection
Hypersplenism

Question 3

Immune thrombocytopenia (ITP): adults

Answer 3

-cause usually unclear
chronic
-treat if there is bleeding

Question 4

Immune thrombocytopenia (ITP): children

Answer 4

Usually follows acute infection

Self limiting so usually not treated

Question 5

Immune thrombocytopenia (ITP): diagnosis

Answer 5

Thrombocytopenia
Exclusion of other causes of thrombocytopenia
Bone marrow examination

Question 6

Immune thrombocytopenia (ITP): treatment

Answer 6

Steroids
Intravenous immunoglobulin
Splenectomy
Thrombopoietin receptor analogues

Question 7

Disseminated intravascular coagulation (DIC)

Answer 7

Breakdown of haemostatic balance
Simultaneous bleeding and microvascular thrombosis
Life threatening condition

Question 8

Disseminated intravascular coagulation (DIC): causes

Answer 8

sepsis
obstetric
malignancy

Question 9

Disseminated intravascular coagulation (DIC): treatment

Answer 9

Remove underlying cause

Give plasma and platelets if bleeding

Question 10

Platelet function abnormalities: acquired

Answer 10

Antiplatelet drugs
Renal disease
Liver disease
DIC

Question 11

Antiplatelet drugs

Answer 11

Aspirin
Clopidogrel
Preasugrel

Question 12

Aspirin as an antiplatelet drugs

Answer 12

Inhibits cyclo-oxygenase (platelet enzyme) irreversibly

Act for lifetime of platelet ie 7-10 days

Question 13

Clopidogrel as an antiplatelet drugs

Answer 13

Blocks ADP receptor (on platelet surface) irreversibly

Acts for lifetime of platelet ie 7-10 days

Question 14

Prasugrel as an antiplatelet drugs

Answer 14

Blocks ADP receptor irreversibly
Acts for lifetime of platelet ie 7-10days
More rapid and consistent inhibition than clopidogrel

Question 15

Renal disease

Answer 15

Increased bleeding
-anaemia
-thrombocytopenia in autoimmune renal disease
-uraemia
-treat with DDAVP and/or dialysis
Increased thrombotic risk
-in nephrotic syndrome
-acquired antithrombin deficiency

Question 16

Liver disease

Answer 16

Site of synthesis of coagulation factors and fibrinogen
Liver disease often associated with bleeding and prolonged prothrombin time
Often more than one cause for bleeding in liver disease

Question 17

Causes of bleeding in liver disease

Answer 17

Reduced clotting factors
-due to poor synthesis or vitamin K deficiency
Thrombocytopenia due to hypersplenism
Platelet function defect
Portal hypertension – bleeding from varices
Dysfibrinogenemia
Increased fibrinolysis

Question 18

Vitamin K deficiency

Answer 18

Vitamin K necessary for the correct synthesis of coagulation factors II, VII, XI and X.
Vitamin K fat soluble vitamin
-deficiency in malabsorption, esp obstructive jaundice
-all babies born with vit K deficiency so must have it at birth
Manifests as prolonged prothrombin time
Treat with vitamin K
-in malabsorption must be given intravenously

Question 19

Drugs as causes of acquired bleeding disorders

Answer 19

Antiplatelet drugs such as Aspirin
-affect platelet function
Anticoagulants such as Heparin and warfarin
-affect coagulation cascade
Steroids make tissues thin and cause bruising and bleeding
Many drugs can affect liver, kidneys and bone marrow

Question 20

Two types of thrombosis

Answer 20

In the arterial circulation (eg MI or Stroke):
-high pressure system
-platelet rich
In the venous circulation (eg DVT or PE):
-low pressure system
-fibrin rich

Question 21

Arterial thrombosis treatment

Answer 21

Antiplatelet drugs

Question 22

Venous thrombosis treatment

Answer 22

Anticoagulant drugs

Question 23

Antiplatelet drugs

Answer 23

Aspirin
Clopidogrel
Prasugrel
Ticagrelor

Question 24

Anticoagulants

Answer 24

Intravenous
-unfractionated heparin
Subcutaneous
-low molecular weight heparin
Oral
-warfarin, 
-dabigatran, rivaroxaban, apixaban, edoxaban

Question 25

Oral anticoagulants

Answer 25

``` Vitamin K antagonists -96% warfarin in the UK -4% acenocoumarol Direct oral anticoagulants -Dabigatran -Rivaroxaban -Apixaban -Edoxaban ```

Question 26

Heparin

Answer 26

Glycosaminoglycan Binds to antithrombin and increases its activity Indirect thrombin inhibitor Not absorbed from the gut so given iv or sc Monitor with the APTT test Given by continuous infusion

Question 27

Low molecular weight heparin

Answer 27

Glycosaminoglycan Binds to antithrombin and increases its activity Indirect thrombin inhibitor Not absorbed from the gut so given iv or sc Monitor with the APTT test Given by continuous infusion

Question 28

Warfarin: pharmacology

Answer 28

Given by mouth completely and rapidly absorbed 99% plasma protein bound Inhibits the production of factors II, VII, IX, X Peak effect 3-4 days after starting, and effect still present 4-5 days after stopping -ie slow on and slow off action

Question 29

Side effects of warfarin

Answer 29

Bleeding, embryopathy

Question 30

Warfarin: monitoring

Answer 30

Measure the INR (International Normalised Ratio) Dose of warfarin is based on the INR Target for first DVT/PE: 2.0-3.0 Frequency of monitoring depends on the stability of the patient’s INR -eg can be 1 per week up to 1 every 8 weeks. INR must be measured before surgery

Question 31

The direct oral anticoagulants

Answer 31

``` Oral No monitoring Aiming to replace heparin and warfarin Standard dosing No alcohol or food interactions Very few drug interactions Short half life (10-15hours) More expensive than warfarin ```

Question 32

Advantages of DOACs over warfarin

Answer 32

Rapid onset of action Fixed oral dosing with predictable anticoagulant effect Low potential for food or alcohol interactions Low potential for drug interactions No need for blood monitoring

Question 33

Disadvantages of DOACs over warfarin

Answer 33

Renal elimination No specific antidotes for the Xa inhibitors Licensed for only specific indications Recently introduced