Platelets Flashcards
how are platelets formed?
produced in the bone marrow from fragments of megakaryocytes
What regulates platelet production?
thrombopoietin produced by the liver
what is the lifespan of a platelet?
7-10 days
what organ removes platelets from the blood?
the spleen
name some surface proteins on platelets
ABO
HPA
HLA Class I (not class II)
Glycoproteins e.g. GP1a
how are platelets activated?
a) Adhesion to collagen via GPIa
b) Adhesion to vWF via GPIb and IIb/IIIa
what does activation of platelets lead to?
release of substances from alpha and dense granules
membrane phospholipids activate clotting factors
what substance cross-links activated platelets?
fibrin
what substances can bind to the activated platelet surface and what does this lead to?
coagulation factors - this enhances the clotting cascade
Name some substances released by platelet granules
ADP thrombin calcium PDGF fibrinogen vWF PF4 serotonin
How can we investigate platelet problems?
a) number- FBC
b) appearance - blood film
c) function: bleeding time and PFA - platelet function analyser
d) surface proteins- flow cytometry
what are the clinical features of platelet dysfunction?
a) mucosal bleeding eg epistaxis, gum bleeding and menorrhagia
b) easy bruising
c) petechiae, purpura
d) traumatic haematomas eg subdural haematoma
What are the categories of causes of low platelet count?
production failure
increased removal
(artifact)
What are the causes of low platelet production?
congenital
acquired: Drugs, Marrow suppression, Marrow failure, Marrow replacement
What are the causes of increased removal of platelets?
immune
consumption
splenomegaly
what are the causes of impaired platelet FUNCTION?
congenital: storage pool disorders, Glanzmann, Bernard Soulier, von Willebrand disease
acquired: uraemia, drugs
What are the causes of thrombocytopenia that are due to decreased production of platelets?
- congenital thrombocytopenia
- infiltration of the bone marrow
- reduced platelet production by the bone marrow
- dysfunctional production of platelets in the bone marrow
What happens in congenital thrombocytopenia?
absent/ reduced or malfunctioning megakaryocytes in BM
Give examples of conditions where there is an infiltration of the BM
leukaemia metastatic malignancy lymphoma myeloma myelofibrosis
What are some reasons why the BM would produce less platelets apart from infiltration?
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)
What are the causes of thrombocytopenia due to increased destruction of platelets?
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
Name an autoimmune condition that results in thrombocytopenia due to increased destruction of platelets
immune thrombocytopenia
ITP
Name some targets of medication in the platelet
P2Y12
Gp IIbIIIa
COX1
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?
immune thrombocytopenia - increased destruction
What is the pathophysiology of immune thrombocytopenia?
IgG antibodies form to platelet and megakaryocyte surface glycoproteins
these opsonised platelets are removed by the RES
What are the triggers for primary immune thrombocytopenia?
following viral infection
following immunisation
What are the secondary causes of immune thrombocytopenia?
malignancy eg CLL
infections HIV, Hep C
What are the treatments available for immune thrombocytopenia?
- immunosuppression eg steroids
- IV immunoglobulin
- treat the underlying cause
- if bleeding, give platelets
- Tranexamic acid - inhibits the breakdown of fibrin
What is done to investigate immune thrombocytopenia?
try and find an underlying cause
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?
ALL - acute lymphoblastic leukaemmia
Why does ALL cause thrombocytopenia?
due to bone marrow infiltration
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?
DIC - due to increased consumption of platelets
What is the pathophysiology of DIC?
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
What are the investigations done for DIC?
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
What conditions can cause SIRS?
sepsis malignancy obstetric emergency pancreatitis trauma
What are the treatments for DIC?
a) platelets
b) fresh frozen plasma - which contain clotting factors
d) cryoprecipitate - which contains fibrinogen and some clotting factors
e) treat the underlying cause
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?
Thrombotic thrombocytopenic purpura
increased consumption of platelets
what is the pathophysiology of TTP?
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 ofendothelialinjury. 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)
What are the treatments of TTP?
urgent plasma exchange to replace ADAMTS 13 and remove Ab produced by the body
immunosuppression to reduce the Ab level - methylprednisolone
What should you NOT give to sb with TTP?
platelets
what is the function of platelets?
primary haemostasis
