|Year : 2017 | Volume
| Issue : 4 | Page : 196-198
A rare case of bleeding disorder: Glanzmann's thrombasthenia
Jami Swathi1, A Gowrishankar1, SA Jayakumar1, Karun Jain2
1 Department of Internal Medicine, Stanley Medical College, Chennai, Tamil Nadu, India
2 Department of Orthopaedics, JSS Medical College, Mysore, Karnataka, India
|Date of Web Publication||16-Oct-2017|
1st Floor, House No. 102, Vigyan Lok Society, Karkardooma, New Delhi - 110 092
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Glanzmann's thrombasthenia (GT) is a rare bleeding disorder, which is characterized by a lack of platelet aggregation. It is characterized by qualitative or quantitative abnormalities of the platelet membrane glycoprotein IIb/IIIa. Physiologically, this platelet receptor normally binds several adhesive plasma proteins, and this facilitates attachment and aggregation of platelets to ensure thrombus formation at sites of vascular injury. The lack of resultant platelet aggregation in GT leads to mucocutaneous bleeding whose manifestation may be clinically variable, ranging from easy bruising to severe and potentially life-threatening hemorrhages. Objective: To highlight this rare but potentially life-threating disorder, GT. Case Report: We report a case of GT that was first detected because of the multiple episodes of gum bleeding. The patient was an 18-year-old girl who presented with a history of repeated episodes of gum bleeding since childhood. Till the first visit to our hospital, she had not been diagnosed with GT despite a history of bleeding tendency, notably purpura in areas of easy bruising, gum bleeding, and prolonged bleeding time after abrasions and insect stings. GT was diagnosed on the basis of prolonged bleeding time, lack of platelet aggregation with adenosine di phosphate, epinephrine and collagen. Conclusion: GT should always be considered as differential diagnosis while evaluating any case of bleeding disorder.
| Abstract in French|| |
Contexte: La thrombasthénie de Glanzmann (GT) est un trouble de saignement rare, qui se caractérise par un manque d'agrégation plaquettaire. C'est caractérisé par des anomalies qualitatives ou quantitatives de la glycoprotéine IIb / IIIa de la membrane plaquettaire. Physiologiquement, ce récepteur plaquettaire se lie normalement à plusieurs protéines plasmiques adhésives, ce qui facilite la fixation et l'agrégation des plaquettes pour assurer la formation de thrombus sur les sites de lésions vasculaires. Le manque d'agrégation plaquettaire résultante dans GT entraîne un saignement mucocutaneous dont la manifestation peut être cliniquement variable, allant de meurtrissures faciles à des hémorragies sévères et potentiellement mortelles. Objectif: mettre en évidence ce rare mais désordre potentiellement thérapeutique, GT. Rapport de cas: Nous rapportons un cas de GT qui a d'abord été détecté en raison des multiples épisodes de gomme saignement. Le patient était une fille de 18 ans qui a présenté une histoire d'épisodes répétés de saignement des gencives depuis l'enfance. Jusqu'à la première visite à notre hôpital, elle n'a pas été diagnostiquée avec GT malgré une histoire de tendance saignante, notamment le purpura dans les zones de meurtrissures faciles, le saignement des gencives et le temps de saignement prolongé après les abrasions et les piqûres d'insectes. GT a été diagnostiqué sur la base d'un temps de saignement prolongé, le manque de l'agrégation plaquettaire avec ADP, épinéphrine et collagène. Conclusion: GT doit toujours être considéré comme un diagnostic différentiel tout en en évaluant tout cas de trouble hémorragique.
Mots-clés: thrombasthénie de Glanzmann, saignement des gencives, transfusion de plaquettes
Keywords: Glanzmann's thrombasthenia, gum bleeding, platelet transfusion
|How to cite this article:|
Swathi J, Gowrishankar A, Jayakumar S A, Jain K. A rare case of bleeding disorder: Glanzmann's thrombasthenia. Ann Afr Med 2017;16:196-8
| Introduction|| |
Glanzmann's thrombasthenia (GT) was first documented in 1918 by Dr. Eduard Glanzmann, who described a novel platelet abnormality with defective clot retraction and abnormal appearance on stained film.,, It has since been more specifically described as an autosomal recessive genetic disorder, in which the platelet count is normal or subnormal, the bleeding time is prolonged, and platelet aggregation is deficient or absent., Due to this deficiency of platelet function, it manifests as a bleeding disorder characterized by mucocutaneous hemorrhage of varying severity. Globally, it is extremely rare, but it has a relatively high incidence in consanguineous populations where intermarriage is common., Despite its rarity, it has gained attention since the discovery of its pathophysiology, due to the consequent development of antiplatelet agents now commonly used during percutaneous coronary interventions., GT is associated with clinical variability: some patients have only minimal bruising while others have frequent, severe, and potentially fatal hemorrhages. The site of bleeding in GT is clearly defined: purpura, epistaxis, gingival hemorrhage, and menorrhagia are nearly constant features; gastrointestinal bleeding and hematuria are less common. In this report, we describe a case of GT.
| Case Report|| |
An 18-year-old female patient presented with repeated episodes of gum bleeding since childhood. She also had a history of prolonged bleeding on minor trauma. There was no history of bone pain. She was given blood transfusion many times in the past, the details of which were not known. She was born out of a consanguineous marriage. On examination, she had pallor and gum bleeding. Vital signs were stable. Cardiovascular, respiratory, and other system examination were unremarkable. Her investigations revealed hemoglobin - 7 g/dl, total leukocyte count - 4200, differential count polymorphs - 74, lymphocytes - 23, eosinophils - 3, platelets - 2.1 lakhs, red blood cell (RBC) count - 2.82 lakhs, hematocrit - 19.3, mean corpuscular volume - 68.4, mean corpuscular hemoglobin - 18.4, mean corpuscular hemoglobin concentration - 26.9, erythrocyte sedimentation rate - 15/32, peripheral smear-microcytic hypochromic RBCs, white blood cell count normal, no immature cells seen, platelets count adequate, normal size, and morphology. Bleeding time - >15 min, activated partial thromboplastin Time - 27 s (control - 27 s), and prothrombin time/INR - 1. Serum fibrinogen was 200 mg/dL. Hence, the patient was found to have gum bleeding with a normal platelet count, normal platelet morphology, and a prolonged bleeding time. Clot retraction test was done, in which blood is allowed to clot in a test tube, and clot retraction noted after 24 h. It was absent, i.e., no clot retraction was seen after 24 h. It was suggestive of GT. The next step in the evaluation of the patient was to assess Von Willebrand factor, the level of which could not be assessed because of nonavailability of the test. With this background, the next step in the analysis was platelet aggregation studies. Platelet aggregation was induced with ristocetin, ADP, and collagen. Absent platelet aggregation was seen with ADP [Figure 1]; however, it was seen with ristocetin and collagen. This led to the final diagnosis of GT.
She was given oral tranexamic acid 500 mg thrice daily and platelet transfusion to control the current bleeding episode. Since her hemoglobin was low, she was given packed cell transfusion and followed by oral iron for maintenance. She was given advise about the maintenance of dental hygiene to prevent episodes of gingivitis which tend to precipitate gum bleed. During the course of follow-up, she came with gum bleed for which she was given platelet transfusion. She even attained menarche during the same period. She had episodes of menorrhagia which were treated with platelet transfusion. She was counseled regarding the use of oral contraceptive pills to prevent future episodes. Since she was in need of repeated transfusions. She was immunized with Hepatitis B vaccine to prevent transfusion associated hepatitis.
| Discussion|| |
GT is a rare inherited bleeding disorder. The frequency of consanguinity in affected families is noticeable, and GT has an increased incidence in populations in whom marriage among close relatives is an accepted custom., In certain ethnic groups, such as South Indian Hindus, Iraqi Jews, French gypsies, and Jordanian nomadic tribes, thrombasthenia may actually be a common hereditary hemorrhagic disorder, whereas not so common in other parts of the world. For these reasons, it would be not easy to give an estimation of worldwide prevalence.,
GT is an autosomal recessive condition caused by a deficiency in platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa (CD41/CD61) complex. This protein complex is a member of the integrin family of adhesion., Formation of complexes of GPIIb with GPIIIa protects these glycoproteins from proteolysis. A defect in either GPIIb or GPIIIa causes the degradation of the other subunit and results in the same functional defect. Most of the encountered mutations are missense mutations or deletions in the GPIIb or GPIIIa gene., GT is classified into three subtypes. In type 1, there is a total absence of the GPIIb–GPIIIa complex, whereas, in type II, there is only partial deficiency of GPIIb and GPIIIa, usually in the range of 5%–20% of normal values. In the variant type, GPIIb and GPIIIa are functionally impaired., Affected patients exhibit a lifelong moderate-to-severe bleeding tendency and may cause epistaxis (73%), gingival bleeding (55%), and menorrhagia (98%) at menarche.
GT is characterized by normal platelet morphology and normal platelet count, prolonged bleeding time, absent or decreased clot retraction, and normal platelet aggregation in the presence of ristocetin., Platelet aggregation is absent in the presence of epinephrine, collagen, arachidonic Acid, ADP, due to the dependence of these factors on fibrinogen attachment to the platelet for aggregation., Platelet aggregation occurs normally in response to ristocetin due to its independence from fibrinogen. Flow cytometry can also be used to detect the presence of the GPIIb and GPIIIa complex, GPIIb (CD41), GPIIIa (CD61), and fibrinogen using monoclonal antibodies. This method can also be used to rapidly predict the carrier status of family members of patients with the disorder., DNA analysis is the most accurate in carrier detection but only when the defect is known, limiting its clinical utility. GPIIb-IIIa quantification by monoclonal antibodies and platelet antigen detection may be used for prenatal diagnosis of Type I GT and heterozygous state.
There is no known cure for GT. The overall morbidity and mortality have been difficult to estimate due to its rarity, but in most studies, the prognosis has proven to be very good., Hemorrhage is naturally the main clinical concern and supportive care is critical. Platelet transfusion is necessary before any invasive procedure or heavy bleeding episode., Platelet alloimmunization against HLA group and/or GPIIb/IIIa glycoproteins is a genuine concern, but the risk is no greater than for any transfused patient, and it is not a contraindication to this therapy. Other than transfusion, management is primarily preventive care. Drugs that affect platelet function, such as NSAIDS or aspirin, should be avoided. Immunizations for hepatitis B should be given due to the infectious risks of frequent transfusion. Oral contraceptives may be taken to treat menorrhagia. Regular dental visits are encouraged to avoid gingivitis and gingival bleeding, and iron supplements are suggested during early childhood and adolescence to avoid iron deficiency anemia which is commonly caused by such bleeding. Desmopressin (dDAVP) has been attempted as therapy but has not shown any proven clinical usefulness., Bone marrow transplants have been used successfully in rare cases though this remains a drastic treatment.,
Patients have a normal platelet count, but increased bleeding time and abnormal platelet function assays. Genetically, GT has an autosomal recessive pattern and may arise from a number of mutations that affect GPIIb, GPIIIa, and/or the GPIIb/IIIa complex.,, The classification of type I and type II GT is based on the amount of GPIIb/IIIa complex present on the platelet surface, whereas the variant form is classified by an abnormal GPIIb/IIIa complex present at normal or subnormal amounts.
Our understanding of the pathogenesis of GT and the function of αIIbβ3 has improved substantially since Glanzmann first described the disease; however, the treatment of GT remains unsatisfactory. Control and prevention of bleeding among patients with GT is imperative and remains challenging. Local measures, including antifibrinolytic therapy, with or without platelet transfusions, used to be the mainstay of therapy. However, in recent years, the use of recombinant factor VIIa has increased significantly, with excellent response rates in treating and preventing hemorrhage among GT patients. Gene therapy and stem cell transplantation offer a potential cure of this disease, but both are expensive and remain experimental at this point. Bone marrow transplants have been used successfully in rare cases.
| Conclusion|| |
GT is a rare inherited bleeding disorder. It is primarily found in a limited number of populations, in which consanguineous marriage is common. Patients usually present with easy bruising and bleeding from epistaxis and dental extractions. With proper supportive care, GT has a very good prognosis. GT should always be considered as differential diagnosis while evaluating any case of bleeding disorder.
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