Thrombasthenia (Glanzmann’s thrombasthenia, GT) is a rare inherited platelet disease with an incidence of approximately one in a million worldwide. Patients present with varying degrees of bleeding in skin, mucous membranes and other parts of the body since childhood, and severe

2024/05/2608:58:32 regimen 1577

Thrombasthenia (Glanzmann’s thrombasthenia, GT) is a rare inherited platelet disease with an incidence of approximately one in a million worldwide. Patients present with varying degrees of bleeding in skin, mucous membranes and other parts of the body since childhood, and severe  - DayDayNews

Thrombasthenia (Glanzmann’s thrombasthenia, GT) is a rare inherited platelet disease with an incidence of approximately one in a million worldwide. Patients present with varying degrees of bleeding in skin, mucous membranes and other parts of the body since childhood, and severe cases can be life-threatening. The patient's platelet number and morphology are normal, but the aggregation response to physiological agonists such as collagen, arachidonic acid and ADP is low or absent, and the response to ristocetin is normal. The inheritance mode of the disease is autosomal recessive inheritance . Patients with heterozygous generally have no bleeding symptoms, while patients with homozygous have obvious bleeding. Patients with homozygous mutations are more common in families with consanguineous marriages.

Brief medical history

Patient, female, 23 years old, suffered from abnormal uterine bleeding, non-stop bleeding for 16 days after menstruation, heavy volume with blood clots, and a history of thrombothenia. After questioning, the patient had gum bleeding, nosebleeds, ear bleeding, pharyngeal bleeding, and skin ecchymosis since childhood. He had no gastrointestinal or urinary system bleeding. His family had no history of similar bleeding. His parents were consanguineous, and In 2010, he was diagnosed with thrombothenia in Ruijin Hospital. In January 2019, he was hospitalized due to rupture of the corpus luteum.

Laboratory test

Laboratory phenotypic test results (2010)

Thrombasthenia (Glanzmann’s thrombasthenia, GT) is a rare inherited platelet disease with an incidence of approximately one in a million worldwide. Patients present with varying degrees of bleeding in skin, mucous membranes and other parts of the body since childhood, and severe  - DayDayNews

Genetic test results (2010)

The family diagram is as follows:

Thrombasthenia (Glanzmann’s thrombasthenia, GT) is a rare inherited platelet disease with an incidence of approximately one in a million worldwide. Patients present with varying degrees of bleeding in skin, mucous membranes and other parts of the body since childhood, and severe  - DayDayNews

Thrombasthenia (Glanzmann’s thrombasthenia, GT) is a rare inherited platelet disease with an incidence of approximately one in a million worldwide. Patients present with varying degrees of bleeding in skin, mucous membranes and other parts of the body since childhood, and severe  - DayDayNews

A 4

Thrombasthenia (Glanzmann’s thrombasthenia, GT) is a rare inherited platelet disease with an incidence of approximately one in a million worldwide. Patients present with varying degrees of bleeding in skin, mucous membranes and other parts of the body since childhood, and severe  - DayDayNews

B

Thrombasthenia (Glanzmann’s thrombasthenia, GT) is a rare inherited platelet disease with an incidence of approximately one in a million worldwide. Patients present with varying degrees of bleeding in skin, mucous membranes and other parts of the body since childhood, and severe  - DayDayNews

C

Thrombasthenia (Glanzmann’s thrombasthenia, GT) is a rare inherited platelet disease with an incidence of approximately one in a million worldwide. Patients present with varying degrees of bleeding in skin, mucous membranes and other parts of the body since childhood, and severe  - DayDayNews

Figure A shows the exon Exon15 of the proband, 14103 14104insT, 14105AC, 14106GC, 14107AT homozygous mutations . (indicated by arrow). Figure B shows the heterozygous mutations in Exon15, 14103, 14104insT, 14105AC, 14106GC, and 14107AT in the exon of the proband's father. (indicated by arrow). Picture C shows the sequencing map of this site in exon Exon15 of the healthy control.

The test results of abnormal uterine bleeding on June 2 were:

Thrombasthenia (Glanzmann’s thrombasthenia, GT) is a rare inherited platelet disease with an incidence of approximately one in a million worldwide. Patients present with varying degrees of bleeding in skin, mucous membranes and other parts of the body since childhood, and severe  - DayDayNews

Thrombasthenia (Glanzmann’s thrombasthenia, GT) is a rare inherited platelet disease with an incidence of approximately one in a million worldwide. Patients present with varying degrees of bleeding in skin, mucous membranes and other parts of the body since childhood, and severe  - DayDayNews

Thrombasthenia (Glanzmann’s thrombasthenia, GT) is a rare inherited platelet disease with an incidence of approximately one in a million worldwide. Patients present with varying degrees of bleeding in skin, mucous membranes and other parts of the body since childhood, and severe  - DayDayNews

Result analysis and treatment

From the patient's phenotype and genotype, it can be diagnosed as thrombothenia. The patient has been bleeding since childhood. The patient had menstruation when he was 12 years old. The doctor gave him the treatment at that time. The plan is: treatment with norethindrone , 1 tablet/qdx21d, stop for 7 days, take after menstruation; if bleeding is severe, platelet suspension can be transfused. I went to the hospital on June 2, 2022, 16 days after menstruation. The blood routine showed secondary anemia, and the coagulation routine was normal. The TEG result showed platelet function abnormality . After ruling out negative HCG, the doctor recommended transfusion of platelet suspension. And take iron orally.

Discussion

Thrombocytthenia (GT) is caused by a genetic defect in platelet glycoprotein IIb (GPIIb) or IIIa (GPIIIa), which causes platelets to respond to various inducers (such as adenosine diphosphate, collagen, arachidonic acid, epinephrine) Congenital and hereditary reactions are reduced or even non-responsive. This disease is a platelet dysfunction disease inherited from autosomal recessive . Thrombasthenia is divided into 3 types based on the reduction in the amount or qualitative abnormality of the GPIIb/IIIa complex: Type I GT (IIb/IIIa 5%) accounts for the majority (78%). Type II GT (IIb/IIIa accounts for 5%-25%) accounts for about 4%. Type III GT (IIb/IIIa), also known as variant GT, accounts for about 40%-100%. Current reports of GT gene defects include gene point mutations, deletions, insertions, and rearrangements, and the vast majority are point mutations .

integrin αIIbβ3 is the most abundant glycoprotein expressed on platelet membranes. When platelets are in an activated state, it can bind fibrinogen , von Willebrand factor (vWF) and fibronectin , etc. A variety of adhesion molecules play a key role in the process of platelet adhesion and aggregation.Integrin αIIbβ3 is a calcium ion-dependent heterodimer, which forms a complex in a 1:1 ratio with the participation of calcium ions . Mutations in either αIIb or β3 subunit will affect the formation of the complex and cells. Surface expression, resulting in thrombothenia.

The proband had a homozygous T insertion in exon 15 of the αIIb gene near the 3' end between positions 14103 and 14104, resulting in a frameshift mutation, and at the same time, the subsequent three nucleotides were homozygous. The point mutations are 14105AC, 14105GC, and 14107AT respectively. The proband's parents were consanguineous, and both parents had the same heterozygous mutation as the proband. Flow cytometry results showed that αIIb and β3 were both reduced to about 1%. It is speculated that this insertion mutation and point mutations at multiple sites may change the spatial structure of αIIb glycoprotein, affect the formation of αIIbβ3 complex, and lead to the occurrence of type I GT.

Thrombasthenia treatment

Treatment principles

There is currently no specific treatment for thrombothenia. It is mainly symptomatic and supportive treatment and hemostasis. Drug treatment or platelet transfusion is usually used to slow down the progression of the disease.

General treatment

During bleeding, reduce activities, avoid trauma, and rest in bed. Avoid taking drugs that affect platelet function .

drug treatment

(1) Common drugs: vitamin K1, ethylamine , hemocoagulase , etc.;

bleeding of skin and mucous membranes can be given hemostatic drugs, bed rest, and reduced activity. Commonly used drugs can be vitamins. K1, ethylamine sulfonate, hemocoagulase, etc.

(2) Infusion of platelet

local treatment cannot effectively stop bleeding, you can choose to infuse apheresis platelet suspension.

(3) Recombinant activated factor VII: Suitable for patients whose platelet transfusion is ineffective or who produce platelet antibodies, and has better hemostatic effect.

Symptomatic treatment

(1) For nosebleeds: nasal cavity packing can be treated with gauze strips, sponges and ephedrine cotton pads.

(2) People with bleeding gums: local compression is required to stop bleeding, or use gelatin sponge to compress, or apply thrombin to control.

(3) People with menorrhagia: You can choose Fukang tablets and norethindrone for oral administration.

(4) People with long-term chronic blood loss: Oral ferrous succinate tablets, folic acid tablets and adenosylcobalamin tablets can be taken orally.

Surgical treatment

Allogeneic bone marrow transplantation: suitable for patients with severe bleeding and platelet transfusion failure. But the risk is greater.

Conclusion

Thrombocytthenia (GT) is a rare hereditary platelet disease. Phenotypic screening of the disease can be done through platelet aggregation function testing, bleeding time (BT) and thromboelastography testing. However, at the basic level of Hospitals rarely carry out platelet aggregation testing, and BT is also difficult to operate. We can judge platelet function by significantly reducing the MA value of thromboelastogram (excluding antiplatelet drug treatment and thrombocytopenia ). Of course, the final confirmation method is DNA Testing.

There is no radical cure for this disease, which requires active hemostasis and symptomatic treatment. However, after active and formal treatment, most prognosis is good . After consulting some relevant literature, it is found that the disease is more common in families with incest. The author believes that for the health of the next generation, the best preventive measure is to strictly prohibit incest.

References:

(1) Gao Min, Su Yongchun. Pathogenesis and treatment progress of hereditary thrombothenia. Journal of Clinical Pediatrics, 2015 (05) Volume 33, Issue 5.

(2) Shen WZ, QL. Ding,PP Jin,et al. A novel Pro126His beta propeller mutation in integrin alphaIIb causes Glanzmann thrombasthenia by impairing progression of pro-alpha IIb beta3 from endoplasmicreticulum to Golgi[J]. Blood cell,molecules,and disease[J],2009,42(1):44.

(3) N.ROSENBERG, H.HAUSCHNER, H.PERETZ, et.al.A 13bp deletion in aIIb gene is a founder mutation that predominated in Palestinian Arab patients with Glanzmann thrombasthenia [J]. Thromb Haemost, 2005, 5( 3):2746.

(4) Wang Zhaoyue, Ruan Changgeng. Current status and prospects of platelet therapy. Chinese Journal of Hematology. 2016 (5) Volume 37 Issue 5.

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