Clinical Disorders Of Haemostasis

Front 1

Three types of Clinical disorders of haemostasis?

Back 1

Vascular disorders

Platelet disorders

Coagulation disorders

Front 2

What is purpura?

Back 2

Subcutaneous bleeding

Caused by atropy of supporting tissues of cetaneous blood vessels

Front 3

What is Petechiae?

What is the cause?

Back 3

Red, flat pinhead spots

Due to localised microvasculature haemorrhage

Front 4

What is Ecchymoses?

Back 4

Bruises

Localised haemorrhage, often involving multiple microvessels

Front 5

What is Epistaxis?

Back 5

Nose bleed

Front 6

What is Haemarthrosis?

Back 6

Bleeding into joints

Front 7

What is Telangectasia?

Back 7

Increase in size of microvessels, usually in skin

Front 8

What is Haematoma?

Back 8

Localised collection of blood

Ccan occur in any tissue, e.g. deep within a muscle

Front 9

Cause of vascular disorders?

Back 9

May be inherited or acquired

Front 10

Name an inherited vascular disorder?

Back 10

Hereditary haemorrhagic telangiectasia

- Autosomal dominant inheritance

- malformed and thin walled capillaries

- –Spontaneous bleeding into skin and mucosa

–Defects can lead to haemorrhage andanaemia – (due to repeated haemorrhages)

Front 11

What is the cause of acquired vascular disorders?

What are the symptoms?

Back 11

Allergic reactions , infection or nutrition

Results in purpuras with mucous membrane bleeding

Tendency to bruise following minimaltrauma

Front 12

Give an example of an acquired vascular disorder

Back 12

Allergic purpura

- autoimmune inflammation

- effusion of blood into skin

- insect bites, food

Infection induced purpura - scarlet fever leads to autoimmune damage

Front 13

Give an example of a acquired, nutritional vascular disorder

Back 13

Scurvy

- Inadequate collagen synthesis

- Cell-cell adhesion breaks down in endothelium- Also causes platelet defects

Petechiae, bruising and mucosal haemorrhage

Front 14

Give an example of a disorder due to platelet numbers?

What is the cause

Back 14

Thrombocytopaenia

Can be caused by immune or non-immune reasons

Front 15

cause of ITP

Back 15

Formation of autoimmune Ab against platelets- destroys platelets (only last hours),- inhibits megakarypoiesis - impair platelet function

Chronic - associated with SLE, HIV

Front 16

What is Immune thrombocytopaenic purpura, ITP?

Effects

Back 16

F:M = 3:1, 20-30 years in chronic

Hl of platelets - 2 days

Half life of platelets - minutes from 2-3 days

Front 17

What is the treatment for ITP?

Back 17

Do nothing - 90% recover. chronic - no recovery

Chronic - aim to maintain platelet count to stop spontaneous bruising

Corticosteroids and immmunosuppressives - block inflammatory response so can form primary haemostatic response

Splenectomy - stop sequestration of platelets . 50-90% remission

•Thrombopoietin agonists have been used toincrease platelet production

Front 18

Example of Druginduced thrombocytopaenia

Back 18

Penicillin, paracetamol - •Induction of anti-platelet antibodies

Front 19

Non-immunethrombocytopaenia

Back 19

TTP

•Microthrombiformed in arterioles and capillaries

–Plateletsactivated and deposited at multiple sites leads to massive consumption

Front 20

Give an example of a hereditary and acquired disorder of platelet function

Back 20

Hereditary - Glanzmann’s thrombasthenia - defect in platelet aggregation due to GPIIb:GPIIIa. petechial rash. •Autosomal recessive

Acquired - aspirin - inhibits granule release, irreversible for 7 days. Binds COX (low Kd) + ibuprofen

Front 21

Types of coagulation disorders

Back 21

•X-linked coagulation disorders–HaemophiliaA–HaemophiliaB

•Autosomal recessive coagulation disorders–Afibrinogenaemia(most common) – can’t form crosslinked fibrin. treat - purifiedfibrinogen

•Autosomal dominant coagulation disordersvon Willebrandsdisease – vWfactor defect. Affects primary and secondary haemastasis

Front 22

Give an example of a Hereditary coagulation disorder and mutation

10% of patient have what?

Back 22

Often single gene defect

X-linked coagulation disorders- Haemophilia A

Half of the patients have missense or frameshift mutations or deletions in factor VIII gene

–10%Haemophilia A patients have antibodies to factor VIII

Front 23

When is HaemophiliaA possible in females?

Back 23

–spontaneousmutant father, carrier mother

–haemophiliacfather, carrier mother

Front 24

What is the pathology of Haemophilia A?

Back 24

Traumatic bleeding

Haemarthrosis - Bleeding into joints from synovial vessels

Haematomas - Subcutaneous and muscular bleeding

Front 25

What is the treatment for Haemophilia A?

Back 25

Factor VIII replacement

Fresh plasma - best if fresh, but can transmit disease

So use Cryoprecipitate - Freezeand slow thaw

Best method - Recombinant Factor VIII. Expensive

Front 26

Cause of Haemophilia B?

Back 26

Deficiency or mutation in factor IX- modulates extrinsic coagulation

Similar symptoms

Front 27

What is the cause and symptoms of vW disease?

Back 27

Defect/deficiency in vW factor

Dominant autosomal disorder

Front 28

What is the effect of vW disease?

Back 28

Primary - Poor platelet adhesion to wounds

Secondary - reduced factor VIII levels
as vWf stabilises VIII

Front 29

Treatment for vW disease?

Back 29

Small daily doses of plasma will increase factor VIII

Front 30

What is the result of Acquired coagulation disorders?

Back 30

Multiple failure in coagulation cascade

Involves thrombocytopaenia and/or vascular defects

Spontaneous skin purpura

Front 31

What are 4 major causes of Acquired coagulation disorders?

Back 31

Vitamin K deficiency

Liver disease

Inhibitors of coagulation

Drug induced

Front 32

What is vitamin K needed for?

Back 32

Synthesis of active prothrombin, factors VII, IX and X and proteins C and S are dependent on vitamin K

Required for g-carboxylation of glutamic acid

Front 33

What is the cause of liver disease?

Back 33

Deficient synthesis and secretion of coagulation factors by liver

Correlates with decrease in albumin production

•Deficient clearance of activatedcoagulation factors - diffuseintravascular coagulation

Front 34

Druginduced bleeding disorders

Back 34

Antibiotics - –interfere with fibrin polymerisation–May affect platelet function

Front 35

What is a platelet-related side effect of aspirin treatment?

Back 35

Inhibits cyclo-oxygenase - impaired thromboxane A2 synthesis

Impairs release reaction and aggregation of arachidonic acid, collagen, adrenaline and ADP

Front 36

What is a source of vitamin K?

Back 36

Green vegetables and bacterial synthesis in the gut