Primary Hemostasis and Related Bleeding Disorders

Question 1

By what process are blood vessels repaired?

Answer 1

Hemostasis

Question 2

What is primary hemostasis?

Answer 2

Formation of a weak platelet plug and is mediated by interaction

Question 3

What is secondary hemostasis?

Answer 3

Stabilization of the platelet plug and is mediated by coagulation cascade

Question 4

What are the 4 steps of primary hemostasis?

Answer 4

Transient vessel vasoconstriction, platelet adhesion to surface of disrupted blood vessel, platelet degranulation, platelet aggregation

Question 5

What are the two mediators of transient vessel vasoconstriction in primary hemostasis?

Answer 5

Endothelin released by endothelium and neural stimulation

Question 6

Describe the process of platelet adhesion

Answer 6

Von Willebrand factor binds exposed subendothelial collagen. Platelets bind vWF using the GPIb receptor.

Question 7

In order of importance, where does Von Willebrand factor come from?

Answer 7

Weibel-Paladie bodies of endothelial cells and Alpha-granules of platelets.

Question 8

What process does plate adhesion induce.

Answer 8

Adhesion induces platelet degranulation and the release of ADP and TXA2.

Question 9

Describe platelet degranulation and the release of associated mediators

Answer 9

Adhesion causes platelets to change shape and release ADP which promotes exposure of GIIb/IIIa receptor. Platelets also release TXA2 which promotes further platelet aggregation.

Question 10

Where do ADP and TXA2 come from, respectively?

Answer 10

Platelet dense granules and platelet cyclooxygenase.

Question 11

Describe the process of platelet aggregation

Answer 11

Platelets aggregate by GPIIb/IIIa receptor crosslinking via fibrinogen forming the platelet plug. Coagulation cascade eventually strengthens this weak plug.

Question 12

Clinical Symptoms of disorders in primary hemostasis

Answer 12

Mucosal bleeding, epistaxis, hemoptysis, GI bleeding, hematuria, menorrhagia.

Question 13

When is intracranial bleeding highly probable?

Answer 13

With severe thrombocytopenia

Question 14

Symptoms of skin bleeding and sizes

Answer 14

Petechiae 1-2 mm, purpura >3 mm, ecchymoses >1 cm

Question 15

Are petechiae commonly seen with quantitative or qualitative disorders?

Answer 15

Quantitative disorders

Question 16

4 Useful laboratory studies and their normal findings

Answer 16

Platelet count 150-400K/uL, Bleeding time 2-7 mins, Blood smear to assess number/size of platelets, Bone marrow biopsy to asses megakaryocytes

Question 17

What is Immune Thrombocytopenic Purpura?

Answer 17

Autoimmune production of IgG against platelet antigens such as GPIIb/IIIa

Question 18

Describe the process of ITP

Answer 18

Spleen produces auto Abs against platelet antigen (GPIIb/IIIa), spleen macrophages consume platelet-IgG complex causing thrombocytopenia

Question 19

Describe acute and chronic ITP

Answer 19

Acute - often arises in children weeks after viral infections/immunizations, self-limiting; Chronic - most commonly found in women of childbearing age, may be primary or secondary.

Question 20

What is the concern of pregnant women who have ITP?

Answer 20

IgG Abs to platelet antigens can cross the placenta and cause the offspring to have transient thrombocytopenia

Question 21

3 Laboratory findings in ITP

Answer 21

Platelet count <50K/uL, Normal PT/PTT, Increased megakaryocytes in bone marrow

Question 22

Tx for ITP

Answer 22

Corticosteroids, IVIG competes with platelet-IgG complex so that spleen only consumes IgG, Splenectomy - removes site of Ab production and platelet-IgG consumption

Question 23

What is Microangiopathic Hemolytic Anemia?

Answer 23

Pathologic formation of platelet microthrombi in small vessels (uangiopathic) which shear RBCs forming schistocytes (hemolytic)

Question 24

In which two conditions is microangiopathic hemolytic anemia observed?

Answer 24

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS)

Question 25

Describe pathology of TTP

Answer 25

ADAMTS13 deficiency (either autoAb or genetic) cannot cleave VWF multimers resulting in abnormal platelet adhesion and uthrombi.

Question 26

Describe pathology of HUS

Answer 26

E. coli O157:H7 releases veratoxin which causes systemic endothelial damage, resulting in platelet microthromi and RBC shearing

Question 27

Clinical findings of TTP and HUS

Answer 27

Skin/mucosal bleeding, uangiopathic hemolytic anemia, fever

• Renal Insufficiency (More common in HUS)
• CNS abnormalities (More common in TTP)

Question 28

What does TTP and HUS stand for?

Answer 28

Thrombotic Thrombocytopenic Purpura and Hemolytic-Uremic Syndrome

Question 29

Laboratory findings for TTP and HUS

Answer 29

Thrombocytopenia, increased bleeding time, Normal PT/PTT, Anemia w/ schistocytes, Increased megakaryocytes on BM biopsy (Body responds to thrombocytopenia by increase MK activity)

Question 30

TTP and HUS Tx

Answer 30

Plasmapheresis (to remove Abs) and corticosteroids (to reduce production of Ab)

Question 31

What is Bernard-Soulier syndrome?

Answer 31

Genetic GPIb deficiency and therefore impaired platelet adhesion, mild thrombocytopenia because platelets get destroyed, enlarged platelets (platelets released as immature) BS = “Big suckers”

Question 32

What is Glanzmann thrombasthenia?

Answer 32

Genetic GPIIb/IIIa deficiency; platelet aggregation is impaired

Question 33

Explain the mechanism of aspirin

Answer 33

Irreversibly inactivates COX resulting in low TXA2. Impairs platelet aggregation.

Question 34

How does uremia cause platelet dysfunction?

Answer 34

Adhesion and aggregation are impaired by nitrogenous waste products which build up during kidney failure