GLANZMANN THROMBASTHENIA

AR disorder characterized by defective invitro platelet aggregation and life long

bleeding tendency due to qualitative or quantitative abnormality of platelet
glycoprotein GPIIb/IIIa receptor also known as intigrin alpha IIB3.

ETIOLOGY

Biochemical basis is defect in glycoprotein GPIIb/IIIa.Itbis a calcium dependent

heterodimer that preferentially binds to fibrinogen or vWF, but also to fibronectin
or vitronectin.

Incidence is 1 in 1 million .

Genes for both GPIIb/IIIa are located on long arm of chromosome 17.Defect in any of
these genes will cause decreased synthesis of subunit and decrease fibrinogen
receptor and defective binding of fibrinogen after platelet activation.So platelet
aggregation is defective or completely absent.

There are around 100 different mutations that can lead to this disease.

Isoantibodies specific for deleted

GPIIb/IIIa have been demonstrated in blood of multiple transfused patients,which can
produce thrombesthania defect in normal transfused patient.

CLINICAL FEATURES :-

Commonly associated with consanguinous marriages,

Hemorrhagic manifestations are seen in patient homozygous for GT mutation,

heterozygous condition is mostly asymptomatic.

Sites of bleeding:-
Purpura ,epistaxis, gingival bleeding menorrhagia
.

GI bleeding and menorrhagia is less common.

Epistaxis is a common cause of severe bleeding and is typically seen in childhood.

Bleeding tendency decrease with age

.

Post traumatic and postoperative hemorrhage can be serious and pregnancy and delivery
cause serious hemorrhagic risk.

Prognosis usually good with careful supportive care.

Deaths due to bleeding is rare unless associated with trauma, other disease and
chronic isoimmunization.

LAB FINDINGS :-

Prolonged bleeding time.

Deficient clot retraction.

Deficient platelet aggregation with ADP, collagen,epinephrine and thrombin.

Normal Ristocetin induced aggregation and coagulation

Platelet counts are almost normal and they are normal in morphology

TREATMENT:-

Localised bleeding can be treated by Limited measures like fibrin sealants or topical
thrombin and antifibrinolytic Agents.

Epistaxis and gingival bleed:-

nasal packing for application of gel foam soaked in topical thrombin.

Regular proper Dental Care to decrease risk of gingival bleed.

Severe menorrhagia is common and can be treated with high dose of progesterone
followed by maintenance treatment of birth control pills.

Iron deficiency anaemia can develop insidiously with gingival oozing or minor
menorrhagia.

A significant number of transfused patients develop HLA specific alloantibodies or GP

IIb/IIIa specific autoantibodies which complicate transfusion therapy and limit
future treatment.

These isoantibodies can block normal transfused platelet aggregation and lead to
Rapid removal by immune mechanisms.

Pregnancy and delivery pose a serious hemorrhagic risk.

Multiple platelet transfusion are required before and after delivery.

An alternative approach for patients who are refractory to platelet transfusion, is

use of rf VIIa.

It enhances the deposition of AlphaIIb beta 3 deficient platelets on subendothelial

matrix through an interaction with fibrin formed by increased trombin generation
leading to clot stability.

For patient with severe recurrent bleeding episodes,allogenic Bone Marrow

transplantation may be done.