Platelets

Question 1

how are platelets formed?

Answer 1

produced in the bone marrow from fragments of megakaryocytes

Question 2

What regulates platelet production?

Answer 2

thrombopoietin produced by the liver

Question 3

what is the lifespan of a platelet?

Answer 3

7-10 days

Question 4

what organ removes platelets from the blood?

Answer 4

the spleen

Question 5

name some surface proteins on platelets

Answer 5

ABO
HPA
HLA Class I (not class II)
Glycoproteins e.g. GP1a

Question 6

how are platelets activated?

Answer 6

a) Adhesion to collagen via GPIa

b) Adhesion to vWF via GPIb and IIb/IIIa

Question 7

what does activation of platelets lead to?

Answer 7

release of substances from alpha and dense granules

membrane phospholipids activate clotting factors

Question 8

what substance cross-links activated platelets?

Answer 8

fibrin

Question 9

what substances can bind to the activated platelet surface and what does this lead to?

Answer 9

coagulation factors - this enhances the clotting cascade

Question 10

Name some substances released by platelet granules

Answer 10

ADP
thrombin
calcium
PDGF
fibrinogen
vWF
PF4
serotonin

Question 11

How can we investigate platelet problems?

Answer 11

a) number- FBC
b) appearance - blood film
c) function: bleeding time and PFA - platelet function analyser
d) surface proteins- flow cytometry

Question 12

what are the clinical features of platelet dysfunction?

Answer 12

a) mucosal bleeding eg epistaxis, gum bleeding and menorrhagia
b) easy bruising
c) petechiae, purpura
d) traumatic haematomas eg subdural haematoma

Question 13

What are the categories of causes of low platelet count?

Answer 13

production failure
increased removal
(artifact)

Question 14

What are the causes of low platelet production?

Answer 14

congenital

acquired: Drugs, Marrow suppression, Marrow failure, Marrow replacement

Question 15

What are the causes of increased removal of platelets?

Answer 15

immune
consumption
splenomegaly

Question 16

what are the causes of impaired platelet FUNCTION?

Answer 16

congenital: storage pool disorders, Glanzmann, Bernard Soulier, von Willebrand disease
acquired: uraemia, drugs

Question 17

What are the causes of thrombocytopenia that are due to decreased production of platelets?

Answer 17

1. congenital thrombocytopenia
2. infiltration of the bone marrow
3. reduced platelet production by the bone marrow
4. dysfunctional production of platelets in the bone marrow

Question 18

What happens in congenital thrombocytopenia?

Answer 18

absent/ reduced or malfunctioning megakaryocytes in BM

Question 19

Give examples of conditions where there is an infiltration of the BM

Answer 19

leukaemia 
metastatic malignancy 
lymphoma 
myeloma
myelofibrosis

Question 20

What are some reasons why the BM would produce less platelets apart from infiltration?

Answer 20

Low B12 / folate
Reduced TPO (e.g. liver disease)
Medication: Methotrexate, chemotherapy 
Toxins: e.g. Alcohol
Infections: e.g. viral (e.g. HIV) TB 
Aplastic anaemia (auto immune)

Question 21

What are the causes of thrombocytopenia due to increased destruction of platelets?

Answer 21

autoimmune - immune thrombocytopenic purpura 
post transfusion purpura
sequestration
massive transfusion
hypersplenism 
drug-related immune destruction
DIC
thrombotic thrombocytopenic purpura 
HUS 
haemolysis with elevated liver enzymes and low platelets - HELLP
major haemorrhage

Question 22

Name an autoimmune condition that results in thrombocytopenia due to increased destruction of platelets

Answer 22

immune thrombocytopenia

ITP

Question 23

Name some targets of medication in the platelet

Answer 23

P2Y12
Gp IIbIIIa
COX1

Question 24

If a pt presents with easy bruising after a viral infection, what is the most likely diagnosis and by what mechanism does the platelet count decrease?

Answer 24

immune thrombocytopenia - increased destruction

Question 25

What is the pathophysiology of immune thrombocytopenia?

Answer 25

IgG antibodies form to platelet and megakaryocyte surface glycoproteins these opsonised platelets are removed by the RES

Question 26

What are the triggers for primary immune thrombocytopenia?

Answer 26

following viral infection | following immunisation

Question 27

What are the secondary causes of immune thrombocytopenia?

Answer 27

malignancy eg CLL | infections HIV, Hep C

Question 28

What are the treatments available for immune thrombocytopenia?

Answer 28

1. immunosuppression eg steroids 2. IV immunoglobulin 3. treat the underlying cause 4. if bleeding, give platelets 5. Tranexamic acid - inhibits the breakdown of fibrin

Question 29

What is done to investigate immune thrombocytopenia?

Answer 29

try and find an underlying cause

Question 30

If a 3 year old presents with easy bruising and gum bleeding, with low platelets and small cervical lymph nodes palpable with a widened mediastinum on X-ray, what is the likely diagnosis?

Answer 30

ALL - acute lymphoblastic leukaemmia

Question 31

Why does ALL cause thrombocytopenia?

Answer 31

due to bone marrow infiltration

Question 32

If a diabetic has gram negative sepsis and low platelets with very raised CRP, raised WBCs, raised PT, low fibrin and the blood film shows toxic neutrophils, what is the diagnosis? Why is the platelet count reduced?

Answer 32

DIC - due to increased consumption of platelets

Question 33

What is the pathophysiology of DIC?

Answer 33

production of cytokines in SIRS causes systemic activation of the clotting cascade, consumption of platelets and clotting factors, causing bleeding but also microvascular thrombosis which causes organ failure

Question 34

What are the investigations done for DIC?

Answer 34

``` blood test to check for: thrombocytopenia prolonged PT and APTT low fibrinogen high D dimers ``` evidence for organ failure find out what the underlying cause is

Question 35

What conditions can cause SIRS?

Answer 35

``` sepsis malignancy obstetric emergency pancreatitis trauma ```

Question 36

What are the treatments for DIC?

Answer 36

a) platelets b) fresh frozen plasma - which contain clotting factors d) cryoprecipitate - which contains fibrinogen and some clotting factors e) treat the underlying cause

Question 37

What platelet condition does a pt who has fever, dysarthria and left sided weakness have? They are found to have an infarct in the MCA - middle cerebral artery. What is the mechanism whereby the platelet count reduces?

Answer 37

Thrombotic thrombocytopenic purpura increased consumption of platelets

Question 38

what is the pathophysiology of TTP?

Answer 38

antibodies are produced against ADAMTS13 which is a metalloprotease that is responsible for cleaving large multimers of vWF into smaller units. This means there is an increase in circulating multimers of vWF, which increases platelet adhesion to areas of endothelial injury. This means small thrombi form, decreasing the overall number of circulating platelets this increases the risk of life-threatening bleeds red blood cells passing the microscopic clots are damaged and form schistocytes (like shredding the RBCs)

Question 39

What are the treatments of TTP?

Answer 39

urgent plasma exchange to replace ADAMTS 13 and remove Ab produced by the body immunosuppression to reduce the Ab level - methylprednisolone

Question 40

What should you NOT give to sb with TTP?

Answer 40

platelets

Question 41

what is the function of platelets?

Answer 41

primary haemostasis