L10. Platelets Flashcards
Where are the cells that platelets are produced from
Megakaryocytes are found next to bone marrow sinusoidal endothelial cells and develop long filopodia that extend into marrow capillaries
Describe the steps in platelet formation from stem cell
- Stem cell -> megakaryoblast matures by enlarging cytoplasm and endomitotic synchronous nuclear replication.
- Megakaryoblast undergoes cytoplasmic granulation producing components for the mature platelet
- Megakaryocyte filopodia in the capillaries will fragment to produce~4000 platelets
Describe the structure and contents of a platelet
lifespan= 7-10 days
Discoid, anuclear, but have mitochondria
Platelet phospholipid Membrane has open canilicular systems with submembranous filaments
Alpha granules
Electron dense granules
What are the steps for platelets to make platelet plug at the site of injury
(1’ haemostasis platelet function)
and what are the receptor sites
- After blood vessel injury there is vasoconstriction
- VWF in blood (von willebrand factor) binds to Exposed subendothelial collagen, allowing it to bind to
Glycoprotein 1b 9 5 on platelet - a)Activation: Because of binding there is platelet shape and phospholipid layer change-
b) Platelets release granules to recruit more platelets (PLATELET AGGREGATION) and form a surface for coagulation cascade
c) they become more spherical and extrude long pseudopods to enhance interaction between adjacent platelets - Phospholipid layer change exposes integrin a2b B3 which allows crosslinking platelets together with help of cofactors like fibrinogen (in blood and granules)
What is the function of platelets
Platelets become activated and aggregate at the site of injury forming a temporary loose platelet plug - maintain endovascular homeostasis
What is the role of thromboxane , ADP and Fibrinogen in platelet aggregation. What triggers TXA2 production
- Thromboxane production by platelet (via prostaglandin synthesis) is triggered by thrombin + when platelets adhere to collagen.
- TA2 lowers platelet cAMP levels–> initiates release reaction of granules
The granules contain:
a) ADP: helps Integrin a2b, B3 fibrinogen receptor expression
b) Fibrinogen binds to receptors on activated platelets and crosslinks them together
What are the causes of thrombocytopenia - reduced platelet numbers (3.7)
+ examples
- Reduced production
- viral infection eg. EBV, hep
- drugs
- bone marrow failure shows as a general cytopenia: aplastic, leukaemia, carcinoma, megaloblastosis - Increased destruction
- immune thrombocytopenic purpura (1’ autoimmune)
- 2nday autoimmune eg. SLE
- Drugs, eg heparin
- DIC
- hypersplenism
- massive transfusion
- viral infection
What are the causes of increased platelet number= Thrombocytosis (3)
- Increased production
- Reactive to infection and inflammation,
- Response to bleeding and iron deficiency
- Reactive to myeloproliferative disorders: eg. essential thrombocythemia
What is purpura, petechiae, haematoma
Purpura is rash looking purple spots. Wet purpura looks like bruises on the gums. Caused by internal bleeding from small bv
Petechiae is non painful pinpricks red/purple spots caused by capillary bleeding into the subcutaneous tissue
Haematoma is a solid swelling of clotted blood within tissues
What is the main treatment of Immune thrombocytopenia if severe bleeding or very low platelets and what are not good treatments
- Prednisone 1mg/kg/day . Suppress antibody formation
- IV immunoglobulin may be used to urgently increase platelet count
- Platelet infusion not very helpful as antibodies also effect donor platelets
- TPO receptor agonist drugs help to mature more megakaryocytes and increase platelets to stop anti-megakaryocyte action by antibodies
- Splenectomy no longer 2nd line treatment, but can help young well patients
What do alpha granules vs electron dense granules do
Alpha granules
- coagulation factors,
- growth factors for angiogenesis
- heparin neutralising factor (platelet factor 4)
- thrombospondin
Electron dense granules
-recruiting more platelets to site of injury eg. ADP, serotonin
+ Ca2+ for clotting processes
