The Thrombon

Question 1

What are the precursor cells to platelets in the bone marrow prior to release from the Bone marrow?

Answer 1

Megakaryocytes

Question 2

How are platelets released from the bone marrow

Answer 2

The cytoplasmic extensions of megakaryocytes extend into the venous sinuses of the bone marrow. Constriction and fragmentation of the magakaryocyte occurs releasing many platelets.

Question 3

How long does it take for platelets to be produced in the bone marrow?

Answer 3

4-5 days

Question 4

What is the average life span of a platelet? What is its circulation time?

Answer 4

Life span = 10 days

Circulation time = 7-9 days

Question 5

Why do platelets not adhere to intact healthy endothelium?

Answer 5

Endothelial cells produce nitric oxide and prostaglandins to prevent platelets from adhering to healthy endothelial cells

They degrade ADP and vasoactive amines as well as inactivating thrombin

The endothelium has a net negative charge and therefore the mostly negatively charged phospholipid layer of the platelets do not adhere.

Heparin sulfate & proteoglycans prevent adhesion

Question 6

What is the role of von willebrands factor in platelet plug formation?

Answer 6

Von Willebrands factor assists in the adherence of platelets to the exposed sub-endothelium.

Question 7

How do platelets cause aggregation at the site of vascular injury?

Answer 7

Platelets, once activated release ADP (contained in their dense granules) which attracts more platelets to the site of platelet adherence.

Question 8

What is the role of phosphatidylserine (platelet factor 3) in platelet plug formation?

Answer 8

Normally the platelet membrane is composed of negatively charged phospholipids with phosphatidylserine in the inner membrane leaflet. When the platelet becomes activated, this phosphatidylserine flips to the outer membrane leaflet. Phosphatidylserine allows for the binding of coagulation factors as well as amplifying their activity!

Question 9

What is the name of the receptor on the platelet membrane for fibrinogen?

Answer 9

GPIIb/IIIa is a receptor that is normally present on the inactivated platelets but cannot bind fibrinogen. When the platelet becomes activated, intracellular signalling results in conformational change to the GPIIb/IIIa receptor allowing for fibrinogen to bind!

Question 10

What are the main components of the alpha granules that are pre-formed in platelets?

Answer 10

• Von Willebrands factor
• Factor V (platelet factor 1)
• anti-Antithrombin III (platelet factor 2)
• neutrophil and monocyte chemotactic factor (Platelet factor 4)
• fibrinogen (Platelet factor 5)
• antiplasmin (platelet factor 6)
• beta thromboglobulin
• fibroblast activating peptide
• high molecular weight kininogen (HMWK)
• IgG
• fibronectin
• cationic protein

Question 11

How do granule contents get into and out of the platelet?

Answer 11

An Open canalicular system — allow for exocytosis, endocytosis and phagocytosis (can pull bacteria through but does not kill them)

Question 12

What does the term “empiripoiesis” mean?

Answer 12

The active penetration of one cell by another cell which remains intact

• usually seen with transmigration of neutrophils across megakaryocytes
• this is seen increasing in frequency with AIHA, IHA, myelosclerosis and paraneoplastic hemorrhage

Question 13

What are the 3 mechanisms of thrombocytopaenia ?

Answer 13

1. Reduced production of platelets
2. Increased destruction or loss of platelets
3. Abnormal pooling of platelets

Question 14

What is pseudothrombocytopaenia in cats?

Answer 14

Cat platelets tend to clump more easily compared to other species and can result in what appears to be thrombocytopaenia but in reality is just platelets clumping together due to platelet activation and ineffectiveness of anticoagulants in cats. This occurs in 2/3 cat blood samples.
These appear as large clumps at the feathered edge of the blood smear

Question 15

What is pseudothrombocytopaenia in sight hounds?

Answer 15

Sighthounds such as greyhounds, deerhounds, whippets etc often appear to be thrombocytopaenic but this is actually due to a combination of:

• hyperaggregable platelets (predisposition to aggregate)
• lower platelet numbers as an adaptation for running

It appears to be related to an increased Hct in these dogs - RBC and platelet numbers are inversely related

Question 16

What can occur to platelet numbers when the sample is taken with EDTA?

Answer 16

This can result in a pseudothrombocytopaenia — EDTA unmasks antigens on the surface of platelets resulting in platelet aggregation and “sticking” of platelets to the surrounding neutrophils. The platelet count therefore appears as falsely low.

Question 17

Which viruses can cause thrombocytopaenia due to DIC?

Answer 17

Canine adenovirus and infectious canine hepatitis (herpesvirus) can cause DIC resulting in low platelet numbers — thrombocytopaenia

Question 18

How does canine parvovirus cause thrombocytopaenia?

Answer 18

Due to bone marrow suppression — reduced megakaryocytes production

Question 19

How does Babesia canis cause thrombocytopaenia?

Answer 19

Infection with Babesia canis results in sequestration of platelets in the spleen and liver due to hepatosplenomegaly.

Question 20

What fungal infections can result in thrombocytopaenia?

Answer 20

Histoplasmosis

Disseminated candidiasis

Question 21

How does Bovine viral diarrhea virus and hog cholera cause thrombocytopaenia?

Answer 21

They have a direct effect on the production of platelets. The virus can directly infect megakaryocytes causing cell death or decreased platelet production

** canine distemper virus can also directly infect megakaryocytes causing a direct reduction in platelets - thrombocytopaenia

Question 22

How do Rickettsial agents cause thrombocytopaenia ?

Answer 22

Rickettsial diseases result in stem-cell suppression or myelofibrosis. They can also cause splenic sequestration, consumption of platelets due to vasculitis.
Examples: Ehrlichia canis, Ehrlichia equi, Ehrlichia platys, Hemobratonella canis, Rickettsia ricketsii

Question 23

What can cause immune mediated thromboctopaenia (ITP)?

Answer 23

• associated with immune mediated hemolytic anemia
• certain drugs
• secondary to neoplasia
• secondary to septicaemia

Question 24

What is the treatment for immune mediated thrombocytopaenia (ITP)?

Answer 24

• steroids
• vincristine
• azathioprine
• cyclosporine

Question 25

What happens to the MPV in immune-mediated thrombocytopaenia?

Answer 25

The MPV initially decreases then it increases which normalizes it

Question 26

What do you see at the level of the bone marrow with immune-mediated thrombocytopaenia?

Answer 26

Hyperplasia of megakaryocytes but there is decreased platelet production from sinusoidal cytoplasmic extensions.

Question 27

How does aspirin work?

Answer 27

Aspirin irreversibly inhibits COX-1 thereby preventing the formation of thromboxane A2.
Thromboxane A2 is important in vasoconstriction as well as platelet aggregation.
Aspirin will permanently prevent COX-1 activity in the platelet for its lifespan (8-10 days). But an animal will have normal Hemostasis if only 20% of their platelets are affected.

Question 28

What effect does Aspirin have in cattle and sheep?

Answer 28

Aspirin does not inhibit platelet aggregation in these species as they do not produce much thromboxane for platelet aggregation.

Question 29

What is the name of the disease characterized by “ giant platelets syndrome”?

Answer 29

Bernard Soulier platelet defect
Causes defective adhesion of platelets
Patients often present as thrombocytopaenic

Question 30

What is Glanzmann’s Thrombocytopaenia?

Answer 30

This is a thrombocytopaenia characterized by a deficiency in GPIIb/IIIa (fibrinogen receptor) on the surface of platelets resulting in an inability for fibrinogen to bind.

Question 31

What clinical signs would you see in Glanzmann’s thrombocytopaenia?

Answer 31

Platelet numbers are normal but there is an increased bleeding time. The severity of bleeding is unpredictable and does not correlate with the severity of the deficiency.