Question

Explain the pathophysiology of the following, and why each typically has normal coagulation screening tests.

Bernard-Soulier syndrome

Glanzmann's thrombasthenia

?-Storage pool disease

Gray platelet syndrome

Answer 1

Bernard soulier syndrome ;

Also called hemorrhagiparous thrombocytic dystrophy

Blood test;

Platelets aggregation test

Large platelets

Lower platelet count (thrombocytopenia )

Prolonged bleeding time (difficult in clotting )

Giant platelet

Platelet aggregation in response to ADP,collagen,and epinephrine is normal.

Absent platelet aggregation in response to vWF and ristocetin.

Affect individual tend to bleed excessively and bruise easily.

Pathophysiology;

Platelets play a critical role in normal primary haemostatic and clot formation.

The platelets members contains specific glycoprotein receptors which function in platelet adhesion, activation, and aggregation.

The GPIb_IX_V receptors complex is responsible for platelet adhesion through its interaction with von will brand factors on the exposed subendothelium.

Glanzmanns thrombasthenia;

Abnormal integrin alpha iib beta3 formely knowe as glycoprotein which is an integrin aggregation receptors on platelet. This receptors is activated when the platelets is stimulated by ADP, epinephrine, collagen or thrombin.

Pathophysiology;

Deficiency of platelet membranes GPllb_lala

Absent platelet aggregation with all agonists agglutination by ristocetin intact.

Blood test;

Defective platelet aggregation

Decreased GPllb_llla expression

Platelets aggregation test

Normal PLT count

And morphology

Greatly prolonged bleeding time

Absence of PLT aggregation in response to ADP,collagen, epinephrine or thrombin

Flow cytometry CD41 and CD61

Studies of GPIIb/Iiia receptors on the PLT membranes.

Storage pool disease

The platelets granules are affected. Granules are storage spaces inside each platelet. During the process of making a platelet plug,the platelets change shape. Chemicals inside the granules are pushed out into the blood stream.

Dense granules deficiency;

Decreased or absence of dense granules on EM

Normal appearing platelets on peripheral blood smear

Prolonged PFA/BT

Abnormal aggregation due to lack of ADP in dense granules

Lower levels of collagen. Collagen require endogenous ADP and this is lacking.

Platelet aggregation studies

Flow cytometry

Bleeding time

Gray platelets syndrome;

Platelets alpha granules deficiency is a rare Congenital autosomal recessive bleeding disorder caused by reduction or absence of alpha granules in blood platelet and release protein normally contained in these granules into the marrow causing myelofibrosis.

Congenital platelet disorder

Blood test;

Decreased and absence of platelet alpha granules

Large platelets with few granules giving the gray appearance

Normal platelet count with variable morphology

Platelets aggregation shows normal primary wave but absence of secondary wave when stimulate with ADP, epinephrine, arachidonic acid

Ristocein agglutination is normal.

Hypogranular platelets

Thrombocytopenia

Giant platelet

Absence alpha granules

Pathophysiology;

Empty platelet alpha granules .

Is a rare inherited disorders in which peripheral blood platelet are relatively large, vascuolated and almost devoid of cytoplasmic granulation. GPS to determine precisely which organelles are missing from their cell's. The lack of alpha granules.