Platelet Function and Disorders

Question 1

Platelets are shed from what cells?

Answer 1

Megakaryocytes

Question 2

What is the hormone that controls platelet production?

Answer 2

Thrombopoietin

Question 3

Life span of platelets

Answer 3

7-10 days

Question 4

Structure of platelet plasma membrane

Answer 4

Invaginations increase surface area for coagulation factor absorption
Phospholipids provide critical template for coagulation cascade

Question 5

2 types of granules in platelets and what they contain

Answer 5

Alpha: proteins associated with adhesion and clotting
Dense: Ca, nucleotides, serotonin

Question 6

What is the primary function of platelets? 3 general steps to do it

Answer 6

Formation of initial hemostatic plug at site of vascular injury
Steps: adhesion to vessel wall, secretion of granule contents, aggregation

Question 7

How do platelets adhere to the vessel wall?

Answer 7

Normal platelet flow is halted by engagement of Gp1a2a with exposed collagen in subendothelium
Subendothelial microfibrils bind vWF - it then binds to platelet Gp1b9

Question 8

How does platelet morphology change when they are activated?

Answer 8

Platelets become more spherical
Extrude pseudopods
Form a monolayer

Question 9

How is the secretion of granule contents triggered, and what does the release cause?

Answer 9

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

Question 10

How is platelet aggregation triggered?

Answer 10

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

Question 11

3 components of primary hemostasis

Answer 11

Vessel wall
Platelet
Von Willebrand factor

Question 12

Qualitative vs quantitative platelet defect

Answer 12

Qual: defect in platelet function
Quan: insufficient numbers

Question 13

3 ways to break up a congenital qualitative platelet disorder

Answer 13

Receptor defect: defective adhesion or aggregation
Storage pool defect: impaired platelet activation
Secretory defect: defective signal transduction, mimics ASA

Question 14

3 ways to break up an acquired platelet function defect (qualitative)

Answer 14

1. Drugs (NSAIDs, ASA, heparin, etc)
2. Systemic conditions (renal failure, bypass)
3. Hematologic disease (MDS, etc)

Question 15

Are quantitative or qualitative platelet disorders more common?

Answer 15

Quantitative
So get the platelet count!
And look at the morphology

Question 16

Causes of thrombocytopenia: reduced production

Answer 16

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

Question 17

Causes of thrombocytopenia: sequestration (hypersplenism)

Answer 17

Congestive: cirrhosis, portal HTN
Reactive: infections, some autoimmune diseases
Infiltrative: benign or malignant
Platelet transfusions will have limited effect

Question 18

Causes of thrombocytopenia: increased consumption

Answer 18

Immune
Drug induced
MAHA (microangiopathic hemolytic anemia)
Non specific: sepsis, DIC, significant blood loss

Question 19

Immune thrombocytopenia

Answer 19

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

Question 20

Heparin induced thrombocytopenia

Answer 20

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

Question 21

Microangiopathic hemolytic anemia (MAHA)

Answer 21

Group of disorders with similar pathophys
Microvascular occlusive disorders: systemic or intrarenal aggregation of platelets, thrombocytopenia, mechanical injury to RBCs
Triggered by: HUS, TTP

Question 22

Thrombotic thrombocytopenia purpura (TTP)

Answer 22

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

Question 23

Classic pentad for TTP

Answer 23

Thrombocytopenia (stuck inside vessels)
Microangiopathic hemolytic anemia (MAHA)
Fever
Neurologic signs and symptoms
Renal impairment