Disorders of Platelet Secretion

Question 1

most common of the hereditary platelet function defects

Answer 1

Storage pool and release reaction defects

Question 2

Px with storage pool & release reaction defects present with:

Answer 2

mucocutaneous hemorrhage,
hematuria,
epistaxis,
easy and spontaneous bruising

Question 3

Dense Granule Deficiencies

Answer 3

Hermansky-Pudlak syndrome
Chédiak-Higashi syndrome
Wiskott-Aldrich syndrome Thrombocytopenia–absent radius (TAR) syndrome

Question 4

a-Granule Deficiencies

Answer 4

Gray platelet syndrome

Question 5

dense granules are the storage site for:

Answer 5

serotonin
nucleotides (ADP & ATP)
calcium
pyrophosphate

Question 6

Dense granule deficiencies can be subdivided into deficiency:

Answer 6

associated with albinism & nonalbinos

Question 7

platelets of _ there is evidence for the presence of dense granule membranes in normal to near-normal numbers, which suggests that the disorder arises from an in- ability to package the dense granule contents

Answer 7

nonalbinos

Question 8

plays a major role in platelet activation, recruitment, and aggregation and growth of the hemostatic plug

Answer 8

ADP

Question 9

In the platelet function tests, addition of _ to platelet-rich plasma fails to induce an aggregation response from platelets with dense granule deficiency

Answer 9

arachidonic acid

Question 10

characterized by tyrosinase- positive oculocutaneous albinism, defective lysosomal function in a variety of cell types, ceroid-like deposition in the cells of the reticuloendothelial system, and a profound platelet dense granule deficiency

Answer 10

Hermansky-Pudlak syndrome

Question 11

Several of the mutations responsible for Hermansky-Pudlak syndrome have been mapped to _. Mutations in _ genes individually can give rise to Hermansky-Pudlak syndrome.

Answer 11

chromosome 19;

at least seven

Question 12

most bleeding episodes in _ are not severe, lethal hemorrhage has been reported, and in one series hemorrhage accounted for 16% of deaths in affected patient

Answer 12

Hermansky-Pudlak syndrome

Question 13

HPS

For extensive surgery or prolonged bleeding both _ & _ are required.

_ can be used to treat skin wounds that fail to spontaneously clot.

Answer 13

red blood cell (RBC) and platelet transfusions;

Thrombin-soaked Gelfoam

Question 14

characterized by partial oculocutaneous albinism, frequent pyogenic bacterial infections, giant lysosomal granules in cells of hematologic and nonhematologic origin, platelet dense granule deficiency, and hemorrhage

Answer 14

Chédiak-Higashi syndrome

Question 15

accompanied by severe immunologic defects and progressive neurologic dysfunction in patients who survive to adulthood

Answer 15

Chédiak-Higashi syndrome

Question 16

The gene for the Chédiak-Higashi syndrome protein is located on

Answer 16

chromosome 1

Question 17

disorder of generalized cellular dysfunction involving fusion of cytoplasmic granules;

marked by lymphocytic proliferation in the liver, spleen, and marrow with macro- phage accumulation in tissues.

Answer 17

Chédiak-Higashi syndrome

Question 18

This is a rare X-linked disease caused by mutations in the WAS gene on the short arm of the _ that encodes for a 502-amino acid protein – the Wiskott-Aldrich syndrome protein (WASp) – that is found exclusively in hematopoietic cells, including lymphocytes

Answer 18

X chromosome Xp11.23

Question 19

plays a crucial role in actin cytoskeleton remodeling

Answer 19

WASp

Question 20

classic form of WAS characterized by susceptibility to infections associated with immune dysfunction, with recurrent bacterial, viral, and fungal infections, microthrom- bocytopenia, and severe eczema

Answer 20

eczema- thrombocytopenia immunodeficiency syndrome

Question 21

Wiskott-Aldrich platelets are also structurally _. The number of dense granules is decreased, and the platelets are small (microthrombocytes)

Answer 21

abnormal

Question 22

The platelets show a decreased aggregation response to ADP, collagen, and epinephrine and lack a secondary wave of aggregation in response to these agonists

Answer 22

Wiskott-Aldrich syndrome (WAS)

Question 23

treatment for the thrombocytopenia!

Answer 23

splenectomy
platelet transfusion (hemorrhagic episodes)
bone marrow transplantation

Question 24

congenital absence of the radial bones (the most pro- nounced skeletal abnormality), numerous cardiac and other skel- etal abnormalities, and thrombocytopenia (90% of cases)

Answer 24

Thrombocytopenia with absent radii syndrome (TAR)

Question 25

are the storage site for proteins produced by the megakaryocyte (e.g., platelet-derived growth factor, thrombospondin, and platelet factor 4) or present in plasma and taken up by platelets

Answer 25

a-granules

Question 26

lifelong mild bleeding tendencies, moderate thrombocytopenia, fibrosis of the marrow, and large platelets whose gray appearance on a Wright-stained blood film

Answer 26

Grey Platelet Syndrome

Question 27

lifelong mild bleeding tendencies, moderate thrombocytopenia, fibrosis of the marrow, and large platelets whose gray appearance on a Wright-stained blood film: More recently, a mutation in region 3p21.31 involving the gene _ has been identified. This gene is crucial for the devel- opment of !-granules.

Answer 27

Gray Platelet Syndrome NBEAL2

Question 28

in gray platelet syndrome, the plasma levels of _ and _ are increased, because although the proteins normally contained in !-granules are produced, storage in those granules is not possible

Answer 28

platelet factor 4 and B- thromboglobulin

Question 29

Gray Platelet Syndrome Treatments:

Answer 29

platelet transfusions - severe bleeding Cryoprecipitate - control bleeding Desmopressin acetate - shorten the bleeding time

Question 30

rare disorder in which both a-granules and dense granules are deficient

Answer 30

a -dense storage pool deficiency.

Question 31

results from a deficiency of multimerin (a multi- meric protein that is stored complexed with factor V in a-granules)

Answer 31

Quebec platelet disorder