Hemostasis

Question 1

What is the first step of primary hemostasis?

Answer 1

Step 1: transient VASOCONSTRICTION of damaged vessel

–> Mediated by reflex neural stimulation and endothelin released from endothelial cells

Question 2

What is the second step of primary hemostasis?

Answer 2

Step 2: platelet ADHESION to surface of disrupted vessel

• • Von Willebrand factor (vWF) binds exposed subendothelial collagen
• -> vWF is derived from the Weibel-Palade bodies of endothelial cells & alpha-granules of platelets

– Platelets bind vWFusing the GpIIb receptor

Question 3

What is the third step of primary hemostasis?

Answer 3

Step 3: platelet ACTIVATION/ DEGRANULATION
– Adhesion induces shape change in platelets and degranulation with release of multiple mediators

• -Exposure of GpIIb/IIIa on platelets
• -> Mediated by ADP release from dense granules of platelets

–TXA2 synthesized by platelets cyclooxygenase (COX) and released –> promotes platelet aggregation

Question 4

What is the fourth step of primary hemostasis?

Answer 4

Step 4: PLATELET AGGREGATION
–PLATELET PLUG: platelets aggregate at the site of injury via Gp IIb/ IIIa using fibrinogen (from plasma) as a linking molecule —> results in formation of platelet plug

–STABILIZATION: platelet plug is weak: coagulation cascase (secondary hemostasis) stabilizes it

Question 5

What is the etiology of disorders of primary hemostasis?

Answer 5

Abnormalities of platelets, qualitative and quantitative

Question 6

What is the clinical presentation of disorders of primary hemostasis?

Answer 6

Mucosal and skin bleeding
–> intracranial bleeding: seen in severe thrombocytopenia

–> Epistaxis: most common overall symptom

–> hemoptysis

–> GI bleeding

–> hematuria & menorrhagia

Skin, symptoms of bleeding
–> petechiae 1-2 mm: a sign of thrombocytopenia– not usually seen in qualitative disorders

–> Purpura > 3 mm

–> Ecchymoses > 1 cm

Question 7

At platelet value does a person typically become symptomatic?

Question 8

What is the normal bleeding time?

Answer 8

Normal 2-7 min, prolong in quantitative and qualitative platelet disorders

Question 9

What is the etiology of ITP?

Immune thrombocytopenic purpura

Answer 9

Autoimmune production of IgG against platelet antigens (i.e. GpIIb/ IIIa)

Question 10

What is the pathophysiology of ITP?

Answer 10

• Autoantibodies are produced by plasma cells in the spleen

- Antibody-bound platelets are consumed by splenic macrophages, resulting thrombocytopenia

Question 11

What is the epidemiology of ITP?

Answer 11

The most common cause of thrombocytopenia in children and adults

Question 12

Describe and distinguish acute and chronic immune thrombocytopenic purport (ITP).

Answer 12

Acute form:
=>arises in children weeks after a viral infection or immunization; self-limited, usually resolving within weeks of presentation

Chronic form:
=> arises in adults, usually women of childbearing age.

=> may be primary or secondary (i.e. SLE)

=> May cause short-lived thrombocytopenia in offspring since anti platelet IgG can cross the placenta

Question 13

What are the lab findings in ITP?

Answer 13

1. Decreased platelet count, often

Question 14

What is the treatment for ITP?

Answer 14

Initial treatment is corticosteroids. Children respond well; adults may show early response, but often relapse

1. IVIG is used to raise the platelet count in symptomatic bleeding, but its effect is short lived
2. Splenectomy eliminates the primary source of antibody and the site of platelet destruction (performed in refractory cases))

Question 15

What is the etiology of Microangiopathic Hemolytic Anemia?

Answer 15

Pathologic formation of platelet micorthrombi in small vessels

Question 16

What is the pathophysiology of Microangiopathic Hemolytic Anemia?

Answer 16

• Platelets are consumed in the formation of microthrombi

- RBCs are “sheared” as they cross micro thrombi, resulting in hemolytic anemia with schistocytes

Question 17

Provide examples of microangiopathic hemolytic anemia.

Answer 17

–> TTP: thrombotic thrombocytopenic purpura

–> HUS: hemolytic uremic syndrome

Question 18

What is the etiology of TTP?

Answer 18

TTP is due to decreased ADAMTS13, an enzyme that normally cleaves vWF multimers into smaller monomers for eventual degradation.

Question 19

What is the specific pathophysiology of TTP?

Answer 19

TTP is due to decreased ADAMTS13, an enzyme that normally cleaves vWF multimers into smaller monomers for eventual degradation.

–> Large, uncleaved multimers lead to abnormal platelet adhesion, resulting in micro thrombi

–> Decreased ADAMTS13 is usaully due to an acquired antibody; most commonly seen in adult females

Question 20

What is the epidemiology of TTP?

Answer 20

most commonly seen in adult females

Question 21

What is the epidemiology of HUS?

Answer 21

HUS is due to endothelial damage by drugs or infection.

–> Classically seen in children with E. coli O157: H7 dysentery, which results from exposure to undercooked beef

–> E. coli verotoxin damages endothelial cells resulting in platelet microthrombi

Question 22

What is the clinical presentation of HUS and TTP?

Answer 22

Clinical findings (HUS and TTP) include

1. Skin and mucosal bleeding
2. Microangiopathic hemolytic anemia
3. Fever
4. Renal insufficiency (more common in HUS) – thrombi involve vessels of the kidney
5. CNS abnormalities (more common in TTP) – thrombi involve vessels in the CNS

Question 23

What are the laboratory findings in microangiopathic hemolytic anemia?

Answer 23

Laboratory findings include:
1. Thrombocytopenia with increased bleeding time

2. Normal PT/ PTT ( coagulation cascade not activated)
3. Anemia with schistocytes
4. Increased in megakaryocytic on bone marrow biopsy

Question 24

What is the treatment for microangiopathic hemolytic anemia?

Answer 24

Treatment involves plasmapheresis and corticosteroids, particularly in TTP

Question 25

List the qualitative platelet disorders and their respective etiologies.

Answer 25

Bernard- Soulier Syndrome: due to a genetic GpIb deficiency; platelet adhesion is impared
–> Blood smear shows mild thrombocytopenia with enlarged platelets

Glanzmann thrombasthenia: due to a genetic GpIIb/ IIIa deficiency; platelet aggregation is impaired

Aspirin irreversibly activates cyclooxygenase; lack to XA, impairs aggregation

Uremia disrupts platelet function; both adhesion and aggregation are impaired