Bhl Week 2: Disorders Of Platelet Number And Function

Front 1

How are platelet granules released?

Back 1

Canalicular system

(When activated, the platelet granules move to the center of the platelet and then release their contents into the canalicular system, and the granule contents gets to the exterior of the platelet via the canalicular system)

Front 2

What type of bleeding occurs with dysfunction of the primary hemostatic system?

Back 2

1. Immediate bleeding
2. Mucocutaneous bleeding

Front 3

What type of bleeding occurs with dysfunction of the secondary hemostatic system?

Back 3

1. Delayed bleeding
2. Deep visceral hematomas, hemarthroses

Front 4

Describe how platelets initially adhere to collagen

Back 4

Mediated primarily by vWF binding to subendothelial collagen and the GP Ib complext

Front 5

How do platelets aggregate?

Back 5

Mediated by GP IIb/IIIa and fibrinogen
(fibrinogen acts as a bridge)

Front 6

How is arachidonic acid synthesized?

Back 6

Platelet membrane phospholipid is converted to arachidonic acid via Phospholipase A

Front 7

What is the function of cyclooxygenase?

Back 7

Converts arachidonic acid to prostaglandin endoperoxides

(Necessary for the production of TXA2)

Front 8

What is the mechanism of action of Aspirin?

Back 8

Acetylates and irreversibly inhibits COX enzyme.
(platelets are unable to synthesize new enzyme)

Front 9

Which clinical syndrome involves the lack of von Willebrand factor receptor?

Back 9

Bernard-Soulier syndrome

Front 10

Which clinical syndrome involves the lack of the fibrinogen receptor?

Back 10

Glanzmann's thrombasthenia

Front 11

What is probably the most common cause of acquired platelet disorders?

Back 11

Drug-induced

Front 12

List 3 common causes of acquired platelet disorders.

Back 12

1. Drug-induced
2. Uremia
3. Cardiopulmonary bypass

Front 13

List 5 drugs commonly induce platelet dysfunction.

Back 13

1. Aspirin (and other NSAIDs)
2. Clopidogrel (Plavix)
3. Ticlopidine
4. Prasugrel
5. RheoPro (anti-GP IIb/IIIa antibody)

Front 14

What type of test must be run on patients before prescribing Clopidogrel (Plavix)?

Back 14

Genetic testing
(to predict responsiveness to the drug)

Front 15

How does uremia lead to anemia?

Back 15

Due to defective clearance of nitric oxide by RBCs, causing damage.
*Nitric oxide is a platelet antagonist and vasodilator, so elevated NO leads to bleeding problems

Front 16

List 4 ways to treat platelet dysfunction caused by uremia.

Back 16

1. Erythropoietin (raise Hb)
2. Dialysis
3. Cryoprecipitate
4. DDAVP

(Platelet transfusions usually NOT effective, but may be used if severe bleeding)

Front 17

What platelet count generally defines thrombocytosis?

Back 17

>440,000 /uL

(Value used at OUMC)

Front 18

Artifactual thrombocytosis can be caused by...?

Back 18

1. Schistocytes (RBC fragments)
2. WBC fragments
3. Cryoglobulins
4. Microorganisms

Front 19

T or F

Secondary thrombocytosis predisposes patients to thrombosis

Back 19

FALSE

Secondary thrombocytosis poses no threat of thrombosis

Front 20

Is iron deficiency characteristically associated with thrombocytosis or thrombocytopoenia?

Back 20

Thrombocytosis

Front 21

What platelet count generally defines thrombocytopenia (at OUMC)?

Back 21

< 140,000 /uL

Front 22

List 3 general mechanisms that result in thrombocytopenia.

Back 22

1. Impaired platelet production
2. Accelerated destruction
3. Increased sequestration

Front 23

The platelet count in thrombocytopenia due to hypersplenism is usually greater than what value?

Does hypersplenism usually result in bleeding problems?

Back 23

50,000 /uL

*Not low enough to cause significant bleeding problems.

Front 24

Thrombocytopenia due to hypersplenism is usually associated with which other conditions?

Back 24

1. Anemia
2. Leukopenia

Front 25

Besides a low platelet count, what other abnormal lab values would you expect to find in a patient with hypersplenism?

Back 25

1. Low Hb
2. Low WBC count

Front 26

Inherited thrombocytopenias are often associated with what kind of physical abnormalities?

Back 26

Skeletal abnormalities
(absent radii)

Front 27

What must you exclude before starting on workup or treatment for thrombocytopenia?

Back 27

Pseudothrombocytopenia

1. Platelet clumping
2. Platelet satellitism
3. Giant platelets
4. Clotted specimen
5. Old specimen

Front 28

What causes platelets to clump, resulting in artifactual thrombocytopenia?

Back 28

Agglutination of platelets in blood anticoagulated with EDTA.
IgG antibody aggregates platelets in the presence of extremely low calcium

Front 29

What should you do to get an accurate platelet count if platelet clumping is causing falsely low platelet values?

Back 29

Repeat platelet count on specimen anticoagulated with citrate

Front 30

What is probably the most common cause of thrombocytopenia in neonates?

Back 30

Infections
(Rubella, CMV, varicella, hepatitis)

Front 31

List 5 causes of immune thrombocyteopenia.

Back 31

1. Idiopathic immune thrombocytopenic purpura
2. Drugs
3. Infections (esp HIV)
4. Autoimmune diseases (SLE)
5. Lymphoproliferative disorders

Front 32

List 5 drugs that commonly cause immune thrombocytopenia.

Back 32

1. Heparin
2. Quinine
3. Quinidine
4. Rifampin
5. Trimethoprim-sulfamethoxazole (Bactrim)

Front 33

How is the diagnosis of drug-related immune thrombocytopenia made?

Back 33

Diagnosis of exclusion

Front 34

What is the treatment for drug-related immune thrombocytopenia?

Back 34

1. STOP the drug
2. For acute bleeding, IVIG or plasmapheresis can be used

Front 35

What's the difference between Type 1 and Type 2 Heparin-Induced thrombocytopenia?

Back 35

Type 1 -->
Common
Onset within the FIRST FEW DAYS
No significant sequela

Type 2 -->
Rare
Onset usually AFTER 5 - 7 DAYS
Associated with thrombosis

Front 36

What is HITT?

Back 36

Heparin-Induced Thrombocytopenia with Thrombosis

(Type II HIT)

Front 37

Describe the mechanism behind HITT.

Back 37

1. Heparin binds to platelet factor 4 (PF4 is exposed when platelets aggregate)
2. Antibodies develop against Heparin-PF4 complex
3. Platelets are activated --> thrombosis

Front 38

Is the risk of HITT higher with unfractionated or low-molecular weight heparin?

Back 38

Unfractionated heparin poses higher risk

Front 39

Is venous or arterial thrombosis more common in HITT?

What are the most common sites involved?

Back 39

Venous thrombosis is more common

*Lower extremities and cerebral sinuses are common sites involved

Front 40

If HITT has developed while a patient is on unfractionated heparin, can the prescription be changed to low-molecular weight heparin to fix the problem?

Back 40

No.

The antibodies will also react to low-molecular weight heparin.

Front 41

Type 2 HIT usually develops within how many days after heparin therapy is started?

Back 41

5 - 7 days

Front 42

What laboratory tests can you run to diagnose Type 2 HIT?

Back 42

1. Immunoassays (HIT antibody)
2. Serotonin release assay

Front 43

If you are suspecting HIT and the HIT antibody test is positive, what should you do?

Back 43

1. Stop heparin
2. Use alternative anticoagulant such as a direct thrombin inhibitor (argatroban)

Front 44

Does a positive HIT antibody test "rule in" HIT?

Back 44

No.

The test is sensitive, but no specific. A negative test result will rule out HIT, but a positive test does not rule in HIT.

Front 45

If a patient develops Type 2 HIT, can Warfarin be used instead of heparin?

Back 45

No.
Warfarin is considered contraindicated--may actually INCREASE thrombosis

*Treatment of choice is a direct thrombin inhibitor (argatroban)

Front 46

Idiopathic (immune) thrombocytopenic purpura is a diangosis of exclusion. What possibilites must you exclude before making the diagnosis?

Back 46

1. Infection (*HIV, sepsis)
2. Systemic autoimmune disease (SLE)
3. Drug-related
4. Primary hematologic disease (acute leukemia, CLL, MDS, TTP-HUS)

Front 47

If schistocytes are present on a blood smear and the LDH is elevated, is Immune Thrombocytopenic Purpura an appropriate diagnosis?

Back 47

NO.

These findings would be evidence of mechanical damage, such as anemia caused by TTP-HUS.

*Schistocytes should NOT be present in ITP and the LDH should be NORMAL

Front 48

What is the difference in duration between acute and chronic ITP?

Back 48

Acute --> less than 6 months

Chronic --> more than 6 months

Front 49

Which type of ITP (acute or chronic) is more common in children?

Back 49

Acute ITP is more common in children

Chronic ITP is more common in adults

Front 50

Acute ITP often follows what sort of condition?

Back 50

Viral infection
(or vaccination)

Front 51

Which type of ITP is more prone to relapse (acute or chronic)?

Back 51

Chronic ITP

Front 52

Thrombocytopenia with normal Hb and WBC count is most commonly caused by..?

Back 52

ITP
(usually chronic)

Front 53

Should splenomegaly or lymphadenopathy be present in primary ITP?

Back 53

May have MODEST splenomegaly
NO lymphadenopathy

Front 54

When looking at a CBC and blood smear, what cells should be absent in order for you to suspect ITP as a diagnosis?

Back 54

1. No immature or abnormal WBCs
2. No schistocytes
3. WBC count normal
4. Hb count normal

Front 55

What is the first line of treatment for ITP?

What used to be the second-line of treatment, and what is considered second-line now?

Back 55

Corticosteroids

Splenectomy used to be considered second line of treatment (now considered 3rd choice)
Rituximab is now considered second line

Front 56

What is the mechanism of action of Rituximab?

Back 56

Antibody against B-cell antigen-- decreases B-cell production, resulting in decreased autoantibodies

*Second line therapy for ITP

Front 57

What type of therapy can be used for ITP to rapidly increase platelet counts (but are too expensive to use chronically)?

Back 57

Intravenous immunoglobulins or anti-D antibody

Front 58

How does anti-D antibody treat ITP?

Back 58

(*Useful only in Rh D-(+) patients)

Induces mild hemolytic anemia. The macrophages are so busy phagocytizing the anti-D coated RBCs that they ignore the antibody-coated platelets

Front 59

What treatment is very effective in raising the platelet count in chronic ITP which is refractory to corticosteroids and splenectomy?

Back 59

TPO agonists
(Romiplastin--Nplate, Eltrombopag--Promacta)

Front 60

Thrombotic microangiopathies is a heterogeneous group of conditions characterized by the combination of..?

Back 60

1. Microangiopathic hemolysis
2. Thrombocytopenia
3. +/- Systemic manifestations

Front 61

Thrombotic Thrombocytopenic Purpura (TTP) results from a deficiency of which enzyme?

Back 61

Von Willebrand factor cleaving enzyme (ADAMTS13)

Front 62

Are TTP and HUS both systemic diseases?

Back 62

TTP is a systemic disease

HUS has prominent renal manifestations

Front 63

What is the treatment for TTP?

Back 63

Plasma exchange
(Remove patient plasma, replace with fresh frozen plasma)

Front 64

Describe the difference in treating children and adults with HUS.

Back 64

Children---> primary supportive care (hemodialysis, control BP). *Plasma exchange NOT shown to be beneficial

Adults --> Plasma exchange appears to be beneficial

Front 65

When does gestational thrombocytopenia generally occur during pregnancy?

The platelet count usually remains above what value?

Back 65

Third trimester

Platelet count usually >100,000 / uL