Primary Hemostasis And Related Bleeding Disorders

Question 1

What are the two stages of hemostasis?

Answer 1

Primary is a platelet plug which is weak

Secondary stabilizes the platelet plug via the coagulation cascade

Question 2

What are the 4 steps of primary hemostasis?

Answer 2

Reflex vasoconstriction
Platelet adhesion
Platelet degranulation
Platelet aggregation

Question 3

2 things that cause the reflex VC?

Answer 3

When the endothelial layer of the blood vessel is damaged, neural stimulation and endothelin released by the endothelial layer lead to the VC

Question 4

How do the platelets stick to the damaged surface?

Answer 4

VWF comes along and can bind to the collagen. Platelets then bind to vWF via 1b receptor

Question 5

How do we go from the adhesion step to the degranulation step?

Answer 5

Adhesion causes a shape change in the platelet which enables it to release multiple factors. ADP is released to promote expression of 2b3a receptor which allows for aggregation. TXA2 is also released to promote platelet aggregation.

Question 6

How is platelet aggregation accomplished?

Answer 6

Platelets use fibrinogen as the linking molecule via 2b3a to bind to one another to create the platelet plug. Remember this is a weak plus. The coagulation cascade will make the strong fibrin clot.

Question 7

Disorders of primary hemostais is usually due to what and what are the two ways we sort of look at this cause/problem?

Answer 7

Usually due to abnormalities in platelets. We can have a quantitative problem where we don’t have enough or a qualitative problem where the platelets aren’t functioning correctly.

Question 8

Major clinical features of abnormalities in platelets?

Answer 8

Mucosal and skin bleeding, nose bleeding being most common. Severe low platelets can lead to intracranial bleeds.

Question 9

Talk about the 3 different clinical signs/symptoms of skin bleeds?

Answer 9

Petechiae 1-2mm this is due to thrombocytopenia so not usually qualitative disorders
Purpura over 3 mm
Ecchymoses greater than 1 cm

Question 10

What 4 lab studies can help in diagnosing platelet disorders?

Answer 10

Get a platelet count 150-400
Bleeding time
Blood smear to look at the platelets
Bone marrow biopsy to check megakaryocyte count

Question 11

Explain what is going on with immune thrombocytopenic purpura? What’s the cause, who is causing the problems?

Answer 11

IgG is being produced by plasma cells in the spleen that are going around binding to antigens on platelets like 2b/3a and then macros in the spleen are eating these dudes up causing thrombocytopenia. Most common cause of thrombocytopenia is kids and adults

Question 12

What are the two forms of ITP, who is affected, what causes it?

Answer 12

Acute form occurs in kids after a viral infection or immunization. Self limiting
Chronic phase occurs in adults, usually women of child bearing age. Can be primary or secondary to autoimmune diseases like lupus. Can cause short lived low palettes in fetus.

Question 13

3 lab findings for ITP?

Answer 13

Low platelets
Normal PT/PTT
Increases megakaryocytes

Question 14

What is initial treatment of ITP and what are two other treatments if there is relapse?

Answer 14

Corticosteroids. Kids respond good, adults may relapse.
IVIG to distract the spleen macros.
Take the spleen out to remove source of auto antibodies and the destroyers, the macros.

Question 15

What is going on with microangiopathic hemolytic anemia and what are the two conditions we see this in?

Answer 15

Problems in small blood vessels where we have hemolysis of RBCs causing anemia. The problem is that the body is forming microthrombi using platelets and those thrombi cut up the RBCs as they pass by causing shistocytes.
TTP and HUS

Question 16

What is TTP, what causes it, what is the typical patient, etc?

Answer 16

Thrombotic thrombocytopenia purpura. So small clots using up platelets causing bleeds in the skin.
The cause is usually an acquired autoantibody that decreases the amount of ADAMTS13, which is responsible for breaking down vWF. Don’t break it down, it will cause platelets adhesion and small thrombi. Adult females most commonly seen in.

Question 17

What is HUS, what is the cause, typical presenting patient?

Answer 17

Endothelial damage by drugs of infection. Most common cause is ECOLI 0157:H7 which has a toxin that damages the endothelium and causes micro platelet thrombi.

Question 18

Clinical findings in both TTP and HUS?

Answer 18

Skin and mucosal bleeds
Fever
Kidney problems, more common in HUS
CNS problems, more common in TTP

Question 19

4 lab findings for microangiopathic hemolytic anemia? What is the treatment

Answer 19

Thrombocytopenia with increased bleeding times
Normal PT/PTT
Anemia with schistocytes 
Increased megakarocytes 
Plasmapheresis and corticosteroids

Question 20

What are the 4 common qualitative platelet disorders and what is going on with each?

Answer 20

1. Bernard soulier syndrome which is a genetic deficiency in 1b so platelet adhesion is impaired. Enlarged platelets is key here.
2. Glanzmann thrombasthenia is due to 2b3a genetic deficiency so platelet aggregation is impaired
3. Aspirin leads to a lack of TXA2, so aggregation is impaired
4. Uremia disrupts platelet function which impairs both adhesion and aggregation

Question 21

Explain secondary hemostatis and the major players?

Answer 21

The whole point here is to go in and stabilize the platelet plug and make it stronger by creating thrombin to convert fibrinogen to fibrin.
Clotting factors are produced by the liver and they float around in the blood inactivated.
3 things activate these guys
1. Exposure to an activating substance like 7 or 12
2. Calcium
3. Phospholipid surface of platelets

Question 22

Secondary disorders are usually due to what?2 clinical features to all these disorder big picture? What are the laboratory studies for these disorders and how to interpret them?

Answer 22

Clotting factor deficiencies/defects/abnormalities
Deep bleeding, like in muscles and joints
PTT: measures intrinsic pathway and common pathway. Also measures heparin use
PT: extrinsic factor and common pathway and measures warfarin use