Primer 12 - Platelets

Question 1

How long do platelets live?

Answer 1

From eight to ten days.

Question 2

What is the end product of the coagulation cascade?

Answer 2

Fibrin mesh.

Question 3

What are the stages of platelet during a blood vessel injury?

Answer 3

1. Adhesion.
2. Activation.
3. Aggregation.

Question 4

What are 4 factors inside endothelium that are relevant in coagulation?

Answer 4

1. von Willebrand Factor (vWF).
2. Thromboplastin.
3. tPA.
4. PGI2.

Question 5

What is the von Willebrand factor and what does it do?

Answer 5

It is made up of several subunits linked by disulfide bonds, synthesized by endothelial cells and megakaryocytes.
Function: Two.
-Complexes with and stabilizes Factor VIII (deficiency of this leads to increase in PTT).
-Platelet adhesion to vessel wall and other platelets (deficiency leads to increase in bleeding time).

Question 6

What are the contents of platelets relevant to coagulation?

Answer 6

1. vWF.
2. Fibrinogen.
3. Cyclooxygenase.
4. Thromboxane A2.

Question 7

What happens in adhesion during endothelial damage?

Answer 7

Damage to the endothelium exposes the collagen underneath. The vWF that leaked out of the ruptured endothelium binds to the subendothelial collagen. The exposed side of the vWF attaches to the Glycoprotein Ib (Gp1b) that is on the surface of platelets, leading to platelet adhesion to the injured site.

Question 8

What happens in activation phase in endothelial damage?

Answer 8

• Secretion of ADP, PDGF, serotonin, fibrinogen, lysosomal enzymes, thromboxane A2, calcium, thrombin.
• Thrombin: Fibrinogen that leads to fibrin.
• Thromboxane A2 that leads to vasoconstriction and platelet aggregation.

Question 9

What happens in the aggregation phase in endothelial damage?

Answer 9

The activated platelets secrete ADP and on the surface of platelets there is a ADP receptor, triggering the expression of Gp IIb/IIIa from inside the platelet to outside the platelet. Then the glyprotein binds to the free fribrinogen and other platelets binds to that same fibrinogen with their glycoprotein IIb/IIIa receptor, making a series of crosslinks making the plug.

Question 10

What does Aspirin inhibit?

Answer 10

Inhibits COX, the enzyme that blocks arachidonic acid to thromboxane A2.

Question 11

What does Ticlopidine, clopidogrel block?

Answer 11

Block the ADP receptor on platelet surface.

Question 12

What do Abciximab, epitofibatide, tirofiban inhibit?

Answer 12

They inhibit Gp IIb/IIIa directly in the platelet surface.

Question 13

What labs are going to be abnormal in platelet disfunction?

Answer 13

-Bleeding time.

Question 14

What are the symptoms of platelet disorders?

Answer 14

1. Bleeding from the mucous membranes.
2. Epistaxis.
3. Petechiae.
4. Purpura.

Question 15

What are four important platelet disorders?

Answer 15

1. Immune thrombocytopenia purpura (ITP).
2. Thrombotic thrombocytopenic purpura (TTP).
3. Bernard-Soulier syndrome.
4. Glanzmann thrombasthenia.

Question 16

What is the treatment for immune thrombocytopenia purpura (ITP)?

Answer 16

• Steriods.
• IV immunoglobulin (IVIG).
• Splenectomy.

Question 17

What is the underlying pathophysiology of Thrombotic thrombocytopenic purpura (TTP)?

Answer 17

• Deficiency of the metalloprotease called ADAMTS13 (zinc containing enzyme that cleaves the von Willebrand factor multimers into smaller active units). This causes excessive platelet activation/aggregation which in turn causes widespread thrombosis.
• With this widespread thrombosis, it causes consumption of platelets, leading to thrombocytopenia.
• And the activation of coagulation cascade, leads to excessive fibrin mesh, which causes microangiopathic hemolytic anemia.

Question 18

What is the classic triad of Hemolytic Uric Syndrome?

Answer 18

-a milder form of TTP, causes Hemolysis, Uremia, and Thrombocytopenia.

Question 19

What is the classic pentad of TTP?

Answer 19

[Neuritic Fever Torched His Kidneys]

-Fever, anemia(hemolysis), thrombocytopenia, renal failure, and neurological symptoms.

Question 20

What is the cause of Bernard-Soulier Syndrome?

Answer 20

Defect in Gp Ib, the one that binds the platelet to the von Willebrand factor.
-Platelets are defected, so their numbers will only be slightly low.

Question 21

What is the cause of Glanzmann Thrombasthenia?

Answer 21

A defect in glycoprotein(Gp) IIb/IIIa, affecting platelet aggregation.

Question 22

What are some Mixed platelet and coagulation disorders?

Answer 22

• von Willebrand Disease.

- DIC.

Question 23

What is the most common inherited bleeding disorder?

Answer 23

-von Willebrand Disease.

Question 24

What is the treatment for von Willebrand disease?

Answer 24

DDAVP (desmopressin).

Question 25

What is ironic about the labs in DIC?

Answer 25

Although there is widespread coagulation, it is using all the platelets and coagulation factors, leaving you in a HIPOcoagulative state, making bleeding easier: Prolonged bleeding time, PT, and PTT.

Question 26

What are the causes of DIC?

Answer 26

[STOP Making Thrombi] | Sepsis (usually G-), trauma, OB complication, Pancreatitis, Malignancy, Transfusion.

Question 27

What do we see in the lab in DIC?

Answer 27

- Schistocytes (macroangiopathic hemolytic anemia). - Fibrin split products and D-dimers (protein leftovers when you break down fibrin). - Decreased fibrinogen.

Question 28

What does bleeding time measure?

Answer 28

Platelet function.

Question 29

What are some aspiring indications?

Answer 29

-Reduced fever, pain, anti-inflammatory, anti-platelet, acute MI, Acute coronary syndromes, acute thrombotic stroke, MI prevention.

Question 30

What are the side effects of aspirin?

Answer 30

-Peptic ulcers, bleeding, hyperventilation, Reye syndrome (hepatoencephalopathy syndrome), tinnitus.

Question 31

What are the symptoms of Reye syndrome?

Answer 31

Liver problems, encephalopathy, and hypoglycemia.

Question 32

What are 4 ADP receptor inhibitors?

Answer 32

Clopidogrel, ticlopidine, ticagrelor, prasugrel.

Question 33

What are three Glycoprotein IIb/IIIa inhibitors?

Answer 33

Abciximab, Tirofiban, Eptifibatide.

Question 34

What is the cause of ITP?

Answer 34

Anti-glycoprotein IIb/IIIa antibodies.

Question 35

What molecules are expressed in the surface of platelets after it becomes activated?

Answer 35

Glycoprotein IIb/IIIa.

Question 36

NSAIDs inhibit the production of which substance that is important in platelet aggregation?

Answer 36

Thromboxane A2.

Question 37

After a normal vaginal delivery, a mother bleeds profusely from her vagina and later bleeding from her gums. What abnormal findings do you expect in the lab?

Answer 37

This is DIC: increased bleeding time, increased PT and PTT, decreased platelets, increased D-dimer.

Question 38

What is the mechanism of action of streptokinase?

Answer 38

Converts plasminogen to plasmin.

Question 39

What is the mechanism of action of aspirin?

Answer 39

Irreversibly inhibits COX-1.

Question 40

What is the mechanism of action of clopidrogel?

Answer 40

Blocks ADP receptors.

Question 41

What is the mechanism of action of abciximab?

Answer 41

Gp IIb/IIIa.

Question 42

What is the mechanism of action of Tirofiban?

Answer 42

Gp IIb/IIIa.

Question 43

What is the mechanism of action of Ticlopidine?

Answer 43

Blocks ADP receptors.

Question 44

What is the mechanism of action of enoxaparin?

Answer 44

-LMWH (low molecular weight), inhibits factor Xa.

Question 45

What is the mechanism of action of Eptifibatide?

Answer 45

Gp IIb/IIIa inhibitor.

Question 46

RFF: anti-platelet antibodies.

Answer 46

Immune thrombocytopenic purpura (ITP).

Question 47

RFF: bleeding disorder with Gp Ib deficiency.

Answer 47

Bernard-Soulier disease.

Question 48

RFF: Most common inherited bleeding disorder.

Answer 48

von Willebrand disease.

Question 49

Where do platelets come from?

Answer 49

From megakareocytes.