BL- Platelet disorders

Question 1

4 events in the formation of a platelet plug

Answer 1

Platelet adhesion
Platelet activation
Platelet aggregation
Fibrin formation and support of local coagulation

Question 2

Platelet Precursor

Answer 2

Megakaryocyte in bone marrow

Question 3

How long do platelets circulate

Answer 3

Bud off, circulate 7-10 days

Question 4

TPO: thrombopoietin

Answer 4

main growth and maturation factor for megakaryocytes

Question 5

Platelet adhesion
Platelet activation
Platelet aggregation
Fibrin formation and support of local coagulation

Answer 5

4 events in the formation of a platelet plug

Question 6

• inhibits coagulation
• prevents platelet aggregation
• promotes clot breakdown
• provides barrier to reactive elements in the vessel wall

Answer 6

Normal Endothelium:

Question 7

main growth and maturation factor for megakaryocytes

Answer 7

TPO: thrombopoietin

Question 8

Glycoproteins on _____ are receptors for adhesive proteins present in the vessel wall and in plasma

Answer 8

platelet surface

Question 9

Who attracts platelets well?

Answer 9

Von Willebrand factor

*Temporary bond between GPIb (platelet) and vWF

Question 10

Granules of Plts

Answer 10

Dense Granules
Lysosomes
Alpha granles

Question 11

_______granules release serotonin ( vasoconstriction) , ADP platelet activation, calcium (further activation, adhesions and aggregation) of other platelets

Answer 11

Dense

Question 12

_________stick to activated platelets and are themselves activated through release of compounds that further amplify platelet activation

Answer 12

New platelets

Question 13

Platelets adhere to damaged vessel wall directly via collagen or indirectly via von Willebrand factor

Answer 13

Plt Adhesion

Question 14

Excitatory agonists (collagen, thromboxane A2, etc.) cause a conformational change in platelet to expose Glycoprotein IIbIIIa binding sites for fibrinogen

Answer 14

Plt activation

Question 15

Platelets are laced together through fibrinogen bridges

Answer 15

plt Aggregation

Question 16

Locally, thrombin converts the fibrinogen to fibrin stabilizing

Answer 16

Fibrin formation

Question 17

Thrombocytopenia

Answer 17

(decreased numbers of platelets)

Question 18

Normal platelet count between

Answer 18

150,000-400,000/ul

Question 19

may see spontaneous hemorrhage and increased risk of hemorrhage with trauma or surgery

Answer 19

Platelets 20–50,000

*Platelets <10,000-20,000: can see life-threatening spontaneous hemorrhage

Question 20

1. Decreased production of platelets
2. Increased destruction of platelets
3. Distribution disorders (Increased sequestration of platelets due to splenomegaly)
4. Dilution (massive transfusion)

Answer 20

Causes of Thrombocytopenia

Question 21

Low platelets in the setting of pancytopenia

Answer 21

~In the elderly think of Myelodysplastic syndrome (high MCV) and other hem malignancies (non-Hodgkin’s Lymphoma)

~Nutritional deficiencies (B12/Folate)

Question 22

Very common cause of low platelets
Can be seen in bacterial and viral infections
Viral: HIV, hepatitis C

Answer 22

Infection- common cause of low platelets

Question 23

Disease of children or young adults following viral infection
Sudden onset severe thrombocytopenia with petechiae and nosebleeds
Recovery in 2-6 weeks without treatment or after steroids

Answer 23

Acute ITP

Question 24

Adults
Often have concurrent autoimmune disorders (e.g. SLE, RA), lymphoma, or HIV, though most cases idiopathic
Primary ITP is therefore a diagnosis of exclusion
Treatment options include steroids, IVIG, splenectomy, TPO receptor agonists

Answer 24

Chronic ITP ( by definition >12 months):

Question 25

a disorder that can lead to easy or excessive bruising and bleeding. The bleeding results from unusually low levels of platelets — the cells that help your blood clot.

Answer 25

Idiopathic thrombocytopenic purpura (ITP)

Question 26

``` Most common congenital bleeding disorder Usually autosomal dominant Abnormality in platelet/endothelial interaction Clinical problems: Mucosal bleeding Nose bleeds GI bleeds Menorrhagia Bleeding after surgery if no correction ```

Answer 26

Von Willebrand Disease

Question 27

Adhere platelets to exposed collagen that acts as scaffolding for vWF at the site of a wound or vessel disruption

Answer 27

Von Willebrand protein fx

Question 28

Carry Factor VIII | Without this protein, Factor VIII has a VERY short half-life

Answer 28

Von Willebrand protein fx

Question 29

Platelet Function Analyzer (PFA) (measures 1st function of the vW protein)

Answer 29

Tests for von Willebrand’s Disease: | Screening test

Question 30

Type 1: Partial quantitative vWF deficiency. 70-80% cases Type 2: Qualitative defects – either decreased (2A) or increased (2B) adhesion to platelets with latter accelerating vWF clearance. 15-30% cases Type 3: Almost complete absence vWF. Rare

Answer 30

Types of von Willebrand’s Disease

Question 31

Factor VIII level normal or decreased (measures 2nd function of vW protein)

Answer 31

Tests for von Willebrand’s Disease:

Question 32

Qualitative defects – either decreased (2A) or increased (2B) adhesion to platelets with latter accelerating vWF clearance. 15-30% cases

Answer 32

Type 2- Types of von Willebrand’s Disease

Question 33

measures amount of vW protein

Answer 33

Tests for von Willebrand’s Disease:

Question 34

Partial quantitative vWF deficiency. 70-80% cases

Answer 34

Type 1- von Willebrand’s Disease

Question 35

Almost complete absence vWF. Rare

Answer 35

Type 3- von Willebrand’s Disease

Question 36

Von Willebrand Disease Treatment - DDAVP

Answer 36

DDAVP (arginine vasopressin) enhances already synthesized vWF release from endothelial stores so effective in type 1 but not type 2 or type 3 disease

Question 37

Other platelet function disorders

Answer 37

1. Congenital 2. Drug induced ( aspirin, NSAIDs, Plavix) 3. Uremia 4. Liver disease 5. Myeloproliferative disorders

Question 38

__________ from obvious trauma suggests local vascular defect

Answer 38

Brisk bleeding

Question 39

____________ is more likely a generalized hemostatic disorder

Answer 39

Prolonged or recurrent bleeding

Question 40

___________ from injured site raises the possibly of excessive fibrinolysis or abnormal crosslinking of fibrin

Answer 40

Sudden resumption of bleeding

Question 41

_________ suggests a more severe, generalized hemostatic disorder

Answer 41

Multiple site bleeding

Question 42

Disorders can be classified as either qualitative (abnormal function) or quantitative (not enough or too many platelets). They can be further classified as congenital or ________.

Answer 42

acquired

Question 43

Qualitative Platelet Disorders

Answer 43

``` Von Willebrand disease (vWD) Bernard-Soulier syndrome gray platelet syndrome afibrogenemia Glanzmann thrombasthenia ```

Question 44

Quantitative Platelet Disorders

Answer 44

immune thrombocytopenic purpura (ITP) Alloimmune thrombocytopenia DIC, sepsis, thrombotic thrombocytopenic purpura (TTP), and hemolytic uremic syndrome (HUS)

Question 45

Disorders can be classified as either qualitative (abnormal function) or _____(not enough or too many platelets). They can be further classified as congenital or acquired.

Answer 45

quantitative

Question 46

the most common congenital bleeding disorder.

Answer 46

Von Willebrand disease (vWD)

Question 47

a rare autosomal recessive disorder where expression of GP1b on the platelet surface is reduced, leading to a defect in platelet adhesion. Platelet aggregation studies only show abnormal aggregation with ristocetin.

Answer 47

Bernard-Soulier syndrome

Question 48

Storage pool deficiencies can occur, with a deficiency of either dense granules or α-granules. Deficiency of α-granules is known as

Answer 48

gray platelet syndrome

Question 49

leads to both primary (platelet plug formation) and | secondary (formation of cross-linked fibrin) hemostatic defects.

Answer 49

afibrogenemia

Question 50

rare autosomal recessive bleeding disorder caused by absent or defective GPIIb-IIIa

Answer 50

Glanzmann thrombasthenia

Question 51

Thrombocytopenia (a low platelet count) can be due to decreased platelet production, increased platelet destruction or consumption, or _______ of platelets in the spleen.

Answer 51

sequestration

Question 52

The most common cause of thrombocytopenia due to increased destruction is:

Answer 52

immune thrombocytopenic purpura (ITP)

Question 53

occurs when a patient develops antibodies to platelet antigens not present on the patient’s own platelets

Answer 53

Alloimmune thrombocytopenia

Question 54

Other nonimmune-mediated | causes of thrombocytopenia include:

Answer 54

DIC, sepsis, thrombotic thrombocytopenic | purpura (TTP), and hemolytic uremic syndrome (HUS).

Question 55

Platelet count and blood smear to evaluate for thrombocytopenia or other hematologic abnormalities

Answer 55

Basic screening tests when evaluating excessive bleeding

Question 56

Mild cases of ______disease may require repeated testing to establish a diagnosis if clinical suspicion remains.

Answer 56

von Willebrand

Question 57

Thrombin clotting time (TCT) to evaluate for fibrinogen defects, the presence of fibrin split products, or heparin effects Fibrinogen level

Answer 57

Basic screening tests when evaluating excessive bleeding

Question 58

Bleeding time or platelet function analyzer (PFA-100) to evaluate primary hemostasis

Answer 58

Basic screening tests when evaluating excessive bleeding

Question 59

APTT as a screening test for the intrinsic coagulation pathway PT/INR as a screening test for the extrinsic coagulation pathway

Answer 59

Basic screening tests when evaluating excessive bleeding