Glanzmann Thrombasthenia

Author: Arun Gupta, MD,MBBS, 12/23/2019
Category: Platelet and Megakaryocyte Disorders > Hereditary Platelet Disorders > Glanzmann Thrombasthenia (glycoprotein IIb-IIIa deficiency)
Published Date: 01/08/2020

A 22-year-old female patient was referred to Hematology department with history of muco-cutaneous bleeding since childhood. She confirmed episodes of mild and occasional epistaxis and easy bruising in past. She also gave history of menorrhagia since menarche, for which she used to receive trexanemic acid and NSAIDs. Her laboratory investigations revealed following results:

CBC:  Hb -11g%,  WBC -7600/cumm, Platelets -210,000/cumm

Coagulation:  Prothrombin time: 13.1 sec ( control : 14 sec )  INR 0.99 ( normal :      

                        0.9-1.01 ),  APTT: 30 sec (control: 30 sec ), VWF Ag : 209% ( N: 61.3-

                       158 ), VWF activity : 226.8 % ( Normal : 49-170 ), Factor XIII : 88.2% (

                      normal : 70-155% )

PFA-200 :  Collagen/Epi : More than 289 sec ( normal : 82-150 sec ),

                  Collagen/ADP : More than 180 sec ( normal : 60-100 )

Platelet aggregation tests were  performed which showed aggregation with Ristocetin only ( 1.2 mg/ml ). No aggregation response was observed with Arachidonic Acid, ADP, Collagen or Epinephrine, thus establishing a diagnosis of Glanzmann Thrombasthenia.

 

Learning points:

1.      Glanzmann Thrombasthenia is a rare platelet function disorder which results from quantitative and/or qualitative abnormality of αIIbβ3 integrin

( previously known as glycoprotein 11b/111a ). It is inherited in autosomal recessive manner.  The αIIbβ3 receptors are important for attachment with fibrinogen and/or VWF, thus forming cross links between adjacent platelets. So its defect results in bleeding.  The platelet count and morphology are usually normal.

2.      The patients give history of excessive muco-cutaneous bleeding since childhood, most commonly following trauma, excessive bleeding after dental extractions or menorrhagia. Less commonly, joint bleeds, gastrointestinal or genitourinary bleeding is observed. Many patients have family history of similar pattern of bleeding.

3.      Diagnostic investigations include a CBC, coagulation profile, assay of coagulation factors, mild deficiency of which can result in similar type of bleeding, PFA-200 and platelet aggregometry. Bleeding time, which was used to be done in past, has been discarded by many centers as there is debate over its reproducibility and validity. Flow cytometry is an  additional helpful  investigation for confirmation of diagnosis.

4.      Treatment in patients who require active management include transfusion of fresh platelets, preferably from HLA matched donor. Recombinant factor V11 ( rFV11) has been approved for use in patients who become refractory to platelet transfusions. For control of menorrhagia, NSAIDs, trexanemic acid and oral contraceptives are recommended.