Chapter 4.1 Primary Hemostasis and Related Bleeding Disorders

Question 1

Distinguish between primary and secondary hemostasis. Describe the crucial interactions/mediators of each stage.

Answer 1

endothelial cells line blood vessels sit on top of basement membrane

damage of tube is repaired by hemostasis (thrombus/clot will form at site of injury)

primary hemostasis: form weak platelet plug- adhesion and aggregation of platelets in place of injury (interaction platelets and vessel wall)

secondary hemostatsis stabilizes the platelet plug; mediated by coagulation cascade

Question 2

When there is disruption of blood vessel, what is the first step/reaction of primary hemostasis?

What mediates this process (2 things)?

Answer 2

1. transient vasoconstriction of damaged vessels (blood vessel will rapidly constrict) sort of knee-jerk reaction, gets damaged and clamps down quickly.

mediated by neural stimulation (neural reflex)

endothelial cells themselves have molecule called endothelin that will be released upon damage and cause quick transient vasoconstriction of damaged factor

Question 3

What is step 2 of primary hemostasis? Describe the mechanism.

Answer 3

Platelet adhesion to surface of disrupted vessel:
Von willibrand factor binds exposed subendothelial collagen

platelets bind vWF using GP1b receptor

(when endothelial cells disrupted, BM exposed and connective tissue underneath exposed, both contain collagen which allows vWF to bind and vWF acts as a linker molecule for platelets to bind to this region

platelets use GP1B to bind vWF

Question 4

Where does Von Wilibrand Factor come from?

Answer 4

1. platelet itself
2. endothelial cells (vast majority of VWF comes from endothelial cell)

within endothelial cell its the Weibel-Palade body that holds VWF.

vWF is derived from Weibel-Palade bodies of endothelial cells and alpha granules of platelets

WP bodies contain P selectin (selectin speed bump) and VWF

Question 5

What is step 3 of primary hemostasis?

Answer 5

once binding occurs, platelets activated, undergo shape change, and degranulate

Step 3: Platelet degranulation

adhesion to VWF causes shape change which allows for dumping of mediators to move process forward

mediators are ADP (present in dense core granules) promotes exposure of GPIIb/IIIa receptor on platelets

and Thromboxan A2 (TXA2- derivative of platelet cyclooxygenase) promotes platelet aggregation

ADP induces platelets to express another receptor; Gp2b3a which is essential for platelet aggregation (when all platelets join together at spot)

adhesion-platelet binding to area of exposed sub-eendothelial collagen via VWF, aggregation (when platelets aggregate on top of those adhesed platelets

TXA2 is signal for further platelet aggregation

important linker molecule for platelets to aggregate is fibrinogen

Question 6

Platelet adhesion to VWF causes shape change which allows for dumping of mediators to move process forward. What are the mediators and where do they come from?

Answer 6

mediators are ADP (present in dense core granules) and Thromboxan A2 (TXA2- derivative of platelet cyclooxygenase)

Question 7

What is the role of ADP and TXA2?

Answer 7

ADP induces platelets to express another receptor; Gp2b3a which is essential for platelet aggregation (when all platelets join together at spot)

TXA2 is signal for further platelet aggregation

Question 8

What is step 4 of primary hemostasis?

Answer 8

Platelet aggregation

Platelets aggregate at site of injury via GpIIb/IIIa using fibrinogen as a linking molecule

results in formation of platelet plug

important linker molecule for platelets to aggregate is fibrinogen

Question 9

What will stabilize the weak platelet plug?

Answer 9

coagulation cascade (secondary hemostasis) stabilizes it

Question 10

When patients have disorders of primary hemostasis they present with classic signs and symptoms, desscribe.

Answer 10

mucosal and skin bleeding

epistaxis (nose bleeding) most common
hemoptysis (coughing up blood)
GI bleeding
hematuria (blood in urine
menorrhagia (heavy menstrual bleeding bc endometrial also is mucosal surface)

Question 11

What is a feared consequence of low platelet count?

Answer 11

intracranial bleeding occurs with severe thrombocytopenia

Question 12

What are some symptoms of skin bleeding?

Answer 12

varying sizes of bleeding in skin:

petechiae (pin-point bleeding in the skin)

purpura (larger, 3mm or greater)

ecchymoses (approx greater than 1 cm)

easy bruising

Question 13

What type of bleeding is a sign of thrombocytopenia?

Answer 13

petechiae (pin-point bleeding in the skin) -presents w quantitative disorders

sign of thrombocytopenia and are not usually seen with qualitative disorders

Question 14

When a patient has a disorder of primary hemostasis with skin and mucosal bleeding, what are some useful laboratory studies?

Answer 14

platelet count - 150,000-400,000/microliter is normal

bleeding time- prick patient, see how long before they stop bleeding (2-7 minutes is normal)

blood smear - look at blood on slide, assess number in rough estimate, assess size of platelets

bone marrow biopsy (megakaryocytes are cells prod. platelets… are there megakaryocytes in bone marrow?)

Question 15

What is the most common cause of thrombocytopenia in children and adults?

Answer 15

ITP:
Autoimmune production of IgG against platelet antigens (like GPIIb/IIIa)

CPIIb/IIIa (used for cross linking of platelets via fibrinogen)

acute form- children
chronic form

Question 16

Where are the antibodies (IgG in ITP) produced?

Answer 16

autoantibodies are produced by plasma cells in the spleen

IgG that cause ITP prod. by plasma cells in spleen, goes out into blood, binds platelets, then macrophages in spleen eat the antibody bound platelets

anitbodies made in spleen and platelets bound to antibody are consumed in spleen

(antibody-bound platelets are consumed by splenic macrophages, resulting in thrombocytopenia)

Question 17

Describe how ITP usually manifests in children.

Answer 17

acute form arises in children

see thrombocytopenia weeks after viral infection or immunization (due to antibody IgG binding platelets and consuming them)

self-limited, usually resolves within weeks of presentation

Question 18

What will ITP show in labs?

Answer 18

low platelet count (bc platelets are being consumed) often less than 50K/ul

Normal PT/PTT

increase/hyperplasia in megakaryocytes on bone marrow biopsy (bone marrow trying to increase platelets)

Question 19

What will the labs show in a patient with ITP? (Platelet count? PT/PTT? megakaryocytes?)

Answer 19

low platelet count (bc platelets are being consumed) often less than 50K/ul

Normal PT/PTT

increase/hyperplasia in megakaryocytes on bone marrow biopsy (bone marrow trying to increase platelets)

Question 20

If you’re worried that intracranial bleeding may occur in a patient with thrombocytopenia, what treatment can you offer?

Answer 20

IVIG can raise platelet count

give Ig (splenic macrophages will eat that Ig instead of the Ig bound to platelets)
basically overrun spleen with IVIG so it'll leave the platelets alone

once IVIG consumed, spleen will eat the platelets again so effect is short lived

(do this to help w symptomatic bleeding)

Question 21

What effect will a splenectomy have for patients with ITP?

Answer 21

eliminates the source of antibody and the site of destruction

performed in refractory cases

Question 22

What is microangiopathic hemolytic anemia?

Answer 22

microangio-small blood vessels

pathologic formation of platelet microthrombi in small vessels (get abnormal aggregation of platelets), RBC have to pass across that platelet microthrombus which is partially occluding, you get shearing of RBC - you’ve destroyed the RBC = hemolysis

leads to hemolytic anemia

Question 23

What is microangiopathic hemolytic anemia?

Answer 23

microangio-small blood vessels

pathologic formation of platelet microthrombi in small vessels (get abnormal aggregation of platelets), RBC have to pass across that platelet microthrombus which is partially occluding, you get shearing of RBC - you’ve destroyed the RBC = hemolysis

platelets are consumed in the formation of microthrombi, RBC are “sheared” as they cross microthrombi, resulting in hemolytic anemia with schistocytes

leads to hemolytic anemia

Question 24

In what two classic disorders is microangiopathic hemolytic anemia seen?

Answer 24

Seen in TTP and HUS