Heme - Platelets

Front 1

What is the marrow precursor cell for platelets? What stimulates platelet growth?

Back 1

Megakaryocytes. Platelet growth is stimulated by Thrombopoeitin

Front 2

What effect might a large spleen have on circulating platelets? No spleen?

Back 2

1/3 of circulating platelets are sequestered in the spleen. Splenomegaly is cause of low circulating platelets. Asplenic patients will have higher than average circulating platelet counts.

Front 3

What's the lifespan of a circulating platelet?

Back 3

9-10 days.

Front 4

What are the two internal membrane systems of platelets?

Back 4

1) Open Canalicular System - route for degranulation
2) Dense Tubular System - stores calcium required for platelet activation

Front 5

What do Platelet Dense Granules contain?

Back 5

ADPP

Front 6

What do platelet Alpha Granules contain?

Back 6

vWF, Fibrinogen

Front 7

What are four proteins involved in platelet adhesion?

Back 7

1) vWF
2) Fibronecin
3) Laminin
4) Thrombospondin

Front 8

What is the main receptor for vFW?

Back 8

Glycoprotein 1b

Front 9

What are two INHIBITORS of protein adhesion?

Back 9

1) Prostacyclin
2) NO
(Both released by intact endothelium.)

Front 10

Name four platelet activation AGONISTS:

Back 10

1) Collagen
2) Thrombin
3) Calcium
4) Thromboxane A2
5) ADP
6) Epinepherine

Front 11

Why does aspirin have an anti-clotting effect?

Back 11

Aspirin inhibits cyclooxygenase. Platelets need CO to produce Thromboxane A2, a clotting agonist.

Front 12

What are the THREE STEPS in platelet activations?

Back 12

1) Platelet calcium mobilization and granule secretion
2) Cyclooxygenase formation of Thromboxane A2
3) Platelet contraction

Front 13

How do platelets AGGREGATE after activation?

Back 13

Exposure of glycoprotein IIb-IIIa receptor complexes are exposed, binding fibrinogen. Fibrinogen networks bridge between platelets.

Front 14

How do platelets enhance COAGULATION?

Back 14

Activated platelets form surface complexes (collectively called Platelet Factor 3), which enhance the activation of Factors IX, X and Thrombin

Front 15

Are platelets involved in anti-coagulation?

Back 15

Yes - they carry Protein S, an anticoagulant.

Front 16

Name four causes of thrombocytopenia caused by marrow suppression or decreased platelet production.

Back 16

1) Radiation
2) Leukemia
3) Aplastic anemia
4) Folate/B12

Front 17

What are the marrow and platelet characteristics of a thrombocytopenia from increased platelet destruction?

Back 17

1) Normal to increased Megakaryocytes
2) "Young" circulating platelets, peripheral blast
3) (Hepatosplenomegaly)

Front 18

What is the most common immune thrombocytopenia?

Back 18

Idiopathic Thrombocytopenic Purpura

Front 19

What causes ITP?

Back 19

Auto-antibodies recognize and bind circulating platelet. They are then destroyed by the SPLEEN, liver and marrow (reticuloendothelial system)

Front 20

What is the natural history of ITP?

Back 20

PEDS: spontaneous resolution in 90% of cases
ADULTS: chronic. most common in young women, esp. surrounding pregnancy

Front 21

How is ITP diagnosed?

Back 21

Thrombocytopenia with normal to elevated # of megakaryocytes in the marrow, after exclusion of other causes (i.e. DIC). Response to corticosteroid therapy is supportive of the diagnosis.

Front 22

How is ITP treated?

Back 22

1) Corticosteroids
2) Splenectomy
3) Refractory: other immunosuppressives, IgG

Front 23

Other than ITP, name additional disease triggers associated with auto-immune destruction of platelets.

Back 23

1) HIV
2) Hepatitis C
3) SLE
4) Lymphoma, CLL

Front 24

What is the classic drug-induced thrombocytopenia?

Back 24

Quinine and quinine derivatives. Drug-antibody complexes deposit on the platelet surface.

Front 25

What is the most important part of treatment for a drug-induced thrombocytopenia?

Back 25

Removal of the offending drug. Immunosuppressives have little effect in these cases.

Front 26

Use of what common anticoagulant can result in a low platelet count?

Back 26

Heparin Induced Thrombocytopenia may be caused by even trace amounts heparin in the system.

Front 27

What is the pathophysiology of heparin-induced thrombocytopenia?

Back 27

Heparin use can induce formation of anti-platelet antibodies.

Front 28

What serious complication can develop from heparin-induced thrombocytopenia?

Back 28

Thrombosis due to formation of platelet plugs. Prolonged treatment with a direct thrombin inhibitor is required.

Front 29

What are the two major ways in which thrombocytopenia may develop in HIV-infected patients?

Back 29

1) Decreased Platelet Production - virus directly affects marrow production of platelets
2) Chronic ITP

Front 30

What are the two main thrombotic microangiopathies?

Back 30

1) TTP - thrombotic thrombocytopenic purpura
2) HUS - hemolytic uremic syndrome

Front 31

What is the fundamental pathology in TTP?

Back 31

Inhibitory autoantibodies against ADAMTS13 prevent cleavage of multimer vWF strands, leading to platelet agglutination.

Front 32

Does TTP affect the RBCs?

Back 32

Yes. The microangiopathy leads to RBC sheer stress,

Front 33

Name the classic pentad of TTP:

Back 33

1) Thrombocytopenia
2) Neurologic problems
3) Microangiopathic hemolytic anemia
4) Renal abnormalities
5) Fever

Front 34

What are the two main classes of TTP?

Back 34

1) Idiopathic
2) Secondary, caused by cancer, pregnancy, HIV, etc.

Front 35

What is the mainstay of treatment for TTP?

Back 35

1) *PLASMA TRANSFUSION*
2) Plasmapheresis
3) Splenectomy (refractory disease)

Front 36

What microangiopathy is associated with a bacterial toxin?

Back 36

Hemolytic Uremic Syndrome is commonly triggered by Shigatoxin-producing bacteria (E. coli O157:H7)

Front 37

What's the treatment for HUS?

Back 37

Supportive care. HUS is self-resolving.

Front 38

What blood pathway is NOT activated with microangiopathies?

Back 38

Coagulation pathways are not activated with TTP, HUS or vasculitis-associated platelet consumption.

Front 39

Is thrombocytopenia in pregnancy always concerning?

Back 39

No. Approx. 5-10% of women with a normal pregnancy may develop incidental thrombocytopenia, with no evidence of an autoantibody. (ITP commonly presents with pregnancy as well.)

Front 40

Name four common causes for Thrombocytopenia due to SEQUESTRATION.

Back 40

Congestive: portal hypertension, CHF
Infiltrative: myeloproliferative
Infections: TB, sarcoid
Hyperplastic: hemolytic anemias

Front 41

What are the two main causes for thrombocytosis?

Back 41

1) Increased Production
2) Decreased Sequestration

Front 42

Thrombocytosis due to Increased Production may be split into two groups:

Back 42

1) Primary (Essential Thr)
2) Reactive (Low Iron)

Front 43

Essential Thrombocytosis is...

Back 43

a myeloproliferative disease where the major manifestation is increased platelet count.

Front 44

What are the bone marrow characteristics of ET?

Back 44

Increased # of megakaryocytes, fibrosis.

Front 45

What other cell lines may be affected in ET?

Back 45

Many patients have neutrophilia, and a small increase in hematocrit.

Front 46

What are the four myeloproliferative disorders?

Back 46

1) Essential thrombocytosis
2) Chronic myelogenous leukemia
3) Polycythemia vera
4) Myelofibrosis

Front 47

What enzyme mutation has been associated with ET?

Back 47

JAK2 kinase mutations have been associated with ET.

Front 48

What platelet morphology may be found in ET?

Back 48

Platelets may be extremely large in ET, and they may clump on the smear.

Front 49

What drug helps to lower platelet counts in ET w/out an increased risk of malignancy?

Back 49

Anagrelide helps to lower the platelet count in ET, without long-term risk of malignancy.

Front 50

What were the two Platelet Adhesion Defects mentioned in class?

Back 50

1) Bernard Soulier
2) Thrombasthenia

Front 51

What are the characteristics of Bernard Soulier?

Back 51

* Platelet adhesion problem
* Problem with Glycoprotein 1 complex
* Normal vWF and Factor VIII levels

Front 52

What are "exhausted platelets?"

Back 52

Activation of the platelet membrane and release of storage pool depletes platelet of functional capacity.

Front 53

What are some of the causes for "exhausted platelets?"

Back 53

Heart-lung bypass, valvular heart disease, DIC, burns

Front 54

What class of disorders might lead to platelets with an increased volume? (MPV?)

Back 54

Myelodysplastic syndromes or with increased platelet production.

Front 55

What does an abnormal "bleeding time" signify?

Back 55

An abnormally long bleeding time indicates a problem with platelet plug formation. This may be caused by thrombocytopenia, or a disorder with platelet function.

Front 56

What assay is NORMAL in congenital disorders of coagulation (i.e. the hemophilias?) In which coag. problem is it prolonged?

Back 56

The bleeding time is NORMAL in congenital coag factor deficiencies. Bleeding time is LONG in vWF diseases, as vWF is required for platelet plug formation.