Platelet Function and Disorders Flashcards
Platelets are shed from what cells?
Megakaryocytes
What is the hormone that controls platelet production?
Thrombopoietin
Life span of platelets
7-10 days
Structure of platelet plasma membrane
Invaginations increase surface area for coagulation factor absorption
Phospholipids provide critical template for coagulation cascade
2 types of granules in platelets and what they contain
Alpha: proteins associated with adhesion and clotting
Dense: Ca, nucleotides, serotonin
What is the primary function of platelets? 3 general steps to do it
Formation of initial hemostatic plug at site of vascular injury
Steps: adhesion to vessel wall, secretion of granule contents, aggregation
How do platelets adhere to the vessel wall?
Normal platelet flow is halted by engagement of Gp1a2a with exposed collagen in subendothelium
Subendothelial microfibrils bind vWF - it then binds to platelet Gp1b9
How does platelet morphology change when they are activated?
Platelets become more spherical
Extrude pseudopods
Form a monolayer
How is the secretion of granule contents triggered, and what does the release cause?
Collagen binding activates prostaglandin synthesis
Thromboxane A2 is formed, and the activated PLC causes granule release
The release of ADP, serotonin, fibrinogen and enzymes triggers further conformational change and activation
How is platelet aggregation triggered?
Gp1b9 binding causes activation of Gp2b3a, which exposed binding sites for fibrinogen
Fibrinogen binds platelets to each other
NOT the coagulation cascade
ADP and TXA2 recruit other platelets
3 components of primary hemostasis
Vessel wall
Platelet
Von Willebrand factor
Qualitative vs quantitative platelet defect
Qual: defect in platelet function
Quan: insufficient numbers
3 ways to break up a congenital qualitative platelet disorder
Receptor defect: defective adhesion or aggregation
Storage pool defect: impaired platelet activation
Secretory defect: defective signal transduction, mimics ASA
3 ways to break up an acquired platelet function defect (qualitative)
- Drugs (NSAIDs, ASA, heparin, etc)
- Systemic conditions (renal failure, bypass)
- Hematologic disease (MDS, etc)
Are quantitative or qualitative platelet disorders more common?
Quantitative
So get the platelet count!
And look at the morphology
Causes of thrombocytopenia: reduced production
Congenital (rare): family history, may also have a function defect
Acquired: B12/folate deficiency, infiltrative, marrow failure, meds
Platelet transfusions are effective, rarely required though
Causes of thrombocytopenia: sequestration (hypersplenism)
Congestive: cirrhosis, portal HTN
Reactive: infections, some autoimmune diseases
Infiltrative: benign or malignant
Platelet transfusions will have limited effect
Causes of thrombocytopenia: increased consumption
Immune
Drug induced
MAHA (microangiopathic hemolytic anemia)
Non specific: sepsis, DIC, significant blood loss
Immune thrombocytopenia
Platelet equivalent of AIHA: RES/spleen mediated clearance of Ab coated platelets
Antibody is not readily identifiable
Spleen not enlarged!!!
Clinical manifestations are rare unless platelets really low (bruising, petechiae, etc)
Treat with immune suppression
Platelet transfusions are ineffective
Heparin induced thrombocytopenia
Immune response that onsets 4-14 days after starting heparin
Makes an antibody to heparin that cross reacts with platelets
High chance of venous/arterial thromboembolism at 30 days
Treatment: stop heparin and usually give alternate anticoagulant
Microangiopathic hemolytic anemia (MAHA)
Group of disorders with similar pathophys
Microvascular occlusive disorders: systemic or intrarenal aggregation of platelets, thrombocytopenia, mechanical injury to RBCs
Triggered by: HUS, TTP
Thrombotic thrombocytopenia purpura (TTP)
When the enzyme that cleaves vWF into smaller pieces (ADAMTS13) isnt working
Because of an autoantibody
VWF sticks out of endothelial cells and in small vessels where the flow is slow platelets can get stuck and form a clot
Medical emergency - treat with plasma exchange
Platelet transfusions are contraindicated
Classic pentad for TTP
Thrombocytopenia (stuck inside vessels) Microangiopathic hemolytic anemia (MAHA) Fever Neurologic signs and symptoms Renal impairment
