111 Platelet Disorders

Question 1

What is the treatment of ITP with severe thrombocytopenia without significant bleeding?

Answer 1

Prednisone

Question 2

Dynamic process in which platelets and blood vessel wall play key roles

Answer 2

Hemostasis

Question 3

Major regulator of platelet production and where is it synthesized?

Answer 3

Thrombopoietin TPO which is synthesized in the liver

Question 4

Increased synthesis of platelet is associated with inflammation and what interluekin?

Answer 4

Interluekin 6

Question 5

What is the average lifespan of platelets?

Answer 5

7 to 10 days

Question 6

Large multimeric protein present in both plasma and extracellular matrix of the sub endothelial vessel wall which platelet adhere to

Answer 6

VWF

Question 7

Signals platelet aggregation

Answer 7

Glycoprotein IIb/IIIa

Question 8

Stabilized platelet plug and develops simultaneously as product of coagulation cascade

Answer 8

Fibrin

Question 9

Processes that leads to thrombocytopenia

Answer 9

1. Decreased bone marrow production
2. Sequestration in the spleen
3. Increased platelet destruction

Question 10

Key step in evaluating a patient with thrombocytopenia

Answer 10

Review the peripheral blood smear

Question 11

What is pseudothrombocytopenia?

Answer 11

In vitro artifact resulting from platelet agglutination via antibodies form the calcium content in the blood collection
(EDTA anticoagulated blood)
Remedy: collect blood in sodium citrate (blue top tube) or heparin (green top tube)

Question 12

Platelet count to maintain vascular integrity in the microcirculation

Answer 12

Platelet count of 5-10K

Question 13

Pinpoint non blanching hemorrhages and are usually a sign of decreased platelet number and not platelet dysfunction

Answer 13

Petechaie

Question 14

Most common noniateogenic cause of thrombocytopenia

Answer 14

Viral and bacterial infection

Question 15

Platelet count less than 150K. Hgb and WBC count abnormal. Whats the next step?

Answer 15

Bone marrow examination

Question 16

Platelet count less than 150K. Hgb and WBC count normal. Whats the next step?

Answer 16

Peripheral blood smear

Question 17

Platelet count less than 150K. Hgb and WBC count normal. PBS show clumped platelets. What’s the next step?

Answer 17

Redraw in sodium citrate or heparin

Question 18

Platelet count less than 150K. Hgb and WBC count. PBS fragmented RBC. What’s the diagnosis?

Answer 18

Micrioangiopathic hemolytic anemia (DIC, TTP)

Question 19

Platelet count less than 150K. Hgb and WBC count normal. PBS normal RBC. Normal Platelets. What are the considerations?

Answer 19

Drug induced thrombocytopenia
Infection induced thrombocytopenia
Idiopathic immune thrombocytopenia
Congenital thrombocytopenia

Question 20

What differentiates HIT from other drug induced thrombocytopenia

Answer 20

1. In HIT, thrombocytopenia is not usually severe with nadir counts rarely less than 20K
2. Hit is not associated with bleeding but with markedly increased risk for thrombosis

Question 21

Pathophysiology of HIT

Answer 21

Antibody formation to heparin. Protein platelet factor 4 (PF4) attached to heparin to form a complex. The anti hepatrin/PF4 antibody activates platelets through the FcYRIIa receptor and also activates monocyte and endothelial cells

Question 22

True or false. HIT is more common in UFH than in LWH.

Answer 22

True

Question 23

When do patient manifest HIT?

Answer 23

5-10 days after exposure to heparin

Question 24

4T in the diagnostic algorithm of HIT

Answer 24

Thrombocytopenia
Timing of drop of platelet count
Thrombosis such as localized skin reaction
Other cause if thrombocytopenia not evident

Question 25

How is HIT diagnosed? What laboratory tests are used for HIT?

Answer 25

``` HIT remains a clinical diagnosis Test for HIT ELISA with PF4/polyanion complex IgG ELISA Platelet activation assat (serotonin release) ```

Question 26

Why is ELISA PF4/polyanion has low specificity in what population of patient?

Answer 26

Low specificity among patibes who undergone cardiopulmonary bypass surgery where 50% develop antibodies postoperatively

Question 27

Common complication of HIT

Answer 27

Thrombosis both arterial and venous

Question 28

Drugs effective in HIT thrombosis. How long should it ge given?

Answer 28

Direct thrombin inhibitors like argatroban, bivalirudin Anti thrombin binding polysaccharides like fondaparinux Then transitions to warfarin Given a few days after platelet recovery for for 1 month

Question 29

Can you give warfarin immediately to HIT thrombosis?

Answer 29

No as aspirin may lead to venous gangrene due to Clotting activation and severely reduced level of protein C and S

Question 30

Acquired disorder in which there is immune mediated destruction of platelets and possibly inhibition of platelet release from megakaryocyte

Answer 30

Idiopathic thrombocytopenia purpura

Question 31

Autoimmune disease commonly associated with secondary ITP

Answer 31

SLE

Question 32

Infections commonly associated with ITP

Answer 32

HIV and hepatitis C

Question 33

Pathogen assosciated with ITP

Answer 33

H. Pylori

Question 34

Autoimmune hemolytic anemia with ITP

Answer 34

Evan's syndrome

Question 35

Mechanism of action is production of limited hemolysis with antibody coated cells saturating the Fc receptors, inhibiting FC receptor function

Answer 35

Rh0D immune globulin

Question 36

Rare complication of Rh0D immune Globulin

Answer 36

Severe intrvascular hemolysis

Question 37

Treatment options for ITP

Answer 37

1. Glucocorticoids: prednisone 2. Rh0D immune Globulin 3. IVIg 4. TPO receptor agonist: romiplostim (SQ) and eltrombopag (oral)

Question 38

Common feature among inherited thrombocytopenia

Answer 38

Large platelets

Question 39

Group of disorders characterized by thrombocytopenia, micrioangiopathic hemolytic anemia evident by fragmented RBCs. Examples?

Answer 39

Thrombotic thrombocytopenic micrioangiopathies | Examples: TTP, hemolytic uremic syndrome

Question 40

Differentiate between DIC and thrombocytopenic micrioangiopathies

Answer 40

DIC: consumption of Clotting factors | TTP and HUS: normal PT and aPTT

Question 41

Other name of inherited TTP

Answer 41

Upshaw-Schulman syndrome

Question 42

Pathophysiology of TTP

Answer 42

Deficiency of metalloprotease ADAMTS13 which cleaves VWF

Question 43

Findings to support TTP?

Answer 43

``` Increased LDH Increased Indirect bilirubin Decreased haptolgobin Increased Reticulocyte count Negative antiglobulin tests ```

Question 44

Main stay treatment of TTP

Answer 44

Plasma exchange

Question 45

Syndrome characterized by acute renal failure, micrioangiopathic hemolytic anemia and thrombocytopenia. Often preceeded by an episode of diarrhea

Answer 45

Hemolytic Uremic Syndrome

Question 46

Most frequut etiologic serotype of HUs

Answer 46

E coli O157:H7

Question 47

Primary treatment of HUS

Answer 47

Supportive

Question 48

Humanized monoclonal antibody against C5 that blocks terminal complement and has efficacy in resolution of HUS

Answer 48

Eculizumab

Question 49

Causes of thrombocytosis

Answer 49

``` Iron deficiency Inflammation Cancer Infection Essential thrombocythemia Rarely: 5q- Myelodysplastic process ```

Question 50

True or false. Thrombocytosis in response to acute or chronic inflammation is associated with increased thrombotic risk

Answer 50

False.

Question 51

Inherited disorder absence of platelet Gp Ib-IX-V receptor

Answer 51

Bernard Soulier

Question 52

Inherited disorder. Absence of platelet Gp IIb/IIIa receptor

Answer 52

Glanzmann thrombasthenia

Question 53

Classic autosomal dominant qualitative platelet disorder resulting from abnormalities of platelet granule formation

Answer 53

Platelet storage pool disorder

Question 54

Most common inherited disorders of platelet function prevent normal secretion of granule content

Answer 54

Secretion disorders

Question 55

Treament for inherited disorders of platelet dysfunction

Answer 55

Platelet transfusion Tranexamic acid Desmopressin/DDAVP

Question 56

Treament for inherited disorders of platelet dysfunction

Answer 56

Platelet transfusion Tranexamic acid Desmopressin/DDAVP

Question 57

Common cause of acquired platelet dysfunction

Answer 57

Medication: antiplatelet or penicillins

Question 58

What is the platelet dysfunction in Uremia?

Answer 58

Defective adhesion and activation improved by dialysis or increasing hematocrit by 27-32% DDAVP

Question 59

Most common inherited bleeding disorder

Answer 59

Von willebrand disease

Question 60

What is the role of VWF

Answer 60

1. Major adhesion molecule that tethers the platelet to the exposed subendothelium 2. Binding protein for FVIII resulting in significant prolongation of the FVIII half life circulation

Question 61

Most common type of VWD

Answer 61

Type 1: parallel decrease in VWF protein, VWF function and FVII level

Question 62

Common manifestation of VWD in female

Answer 62

Menorrhagia

Question 63

Which blood type has decreased levels of VWF

Answer 63

Blood type O

Question 64

VWD variant where gene affecting binding of FVIII; also known as autosomal hemophilia

Answer 64

Type 2N

Question 65

VWD variant describes patient with virtually no VWF and FVIII levels less than 10%

Answer 65

Type 3

Question 66

VWD variant describes increased susceptibility to cleavage by ADAMTS13

Answer 66

Type 2A

Question 67

VWD variant describes increased spontaneous binding of VWF to platelets in circulation

Answer 67

Type 2B

Question 68

Aortic stenosis with GI bleeding; attributed to prescience of angiodysplasia of the GI tract

Answer 68

Heyde Syndrome

Question 69

Treatment of VWD

Answer 69

DDAVP: releases VWF and FVIII from the endothelial stores

Question 70

True or false. DDAVP has 2h peak activity when given intranasally compared to 30 mins if IV.

Answer 70

True

Question 71

Major side effect of DDAVP

Answer 71

Hyponatremia

Question 72

What the use of vitamin C

Answer 72

Synthesize hydroxy proline which is an essential constituent of collagen