Macrothrombocytopenia (MTP) is a heterogeneous group of disorders characterized by enlarged and reduced numbers of circulating platelets, sometimes resulting in abnormal bleeding. The clinical presentations of MTP-affected individuals vary considerably and range from no symptoms to a severe bleeding tendency. MTP-causing mutations have been reported in several genes, involved in various functions such as cell signaling, cytoskeleton organization, and gene expression. Among these, the most common is MYH9, which is responsible for MYH9-related disease. The second most common are GP1BA, GP1BB, and GP, which are responsible for Bernard-Soulier syndrome. It has been reported that some patients with platelet-type bleeding disorder (BDPLT) [DS:H01235] have macrothrombocytopenia.
Category
Hematologic disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
03 Diseases of the blood or blood-forming organs
Coagulation defects, purpura or other haemorrhagic or related conditions
3B64 Thrombocytopenia
H01740 Macrothrombocytopenia
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06515 Regulation of kinetochore-microtubule interactions
H01740 Macrothrombocytopenia
nt06541 Cytoskeleton in neurons
H01740 Macrothrombocytopenia
Immune system
nt06514 Coagulation cascade
H01740 Macrothrombocytopenia
Kunishima S, Okuno Y, Yoshida K, Shiraishi Y, Sanada M, Muramatsu H, Chiba K, Tanaka H, Miyazaki K, Sakai M, Ohtake M, Kobayashi R, Iguchi A, Niimi G, Otsu M, Takahashi Y, Miyano S, Saito H, Kojima S, Ogawa S
Title
ACTN1 mutations cause congenital macrothrombocytopenia.
Freson K, Matthijs G, Thys C, Marien P, Hoylaerts MF, Vermylen J, Van Geet C
Title
Different substitutions at residue D218 of the X-linked transcription factor GATA1 lead to altered clinical severity of macrothrombocytopenia and anemia and are associated with variable skewed X inactivation.
Platelet-type von Willebrand disease (PT-VWD) is an autosomal dominant bleeding disorder caused by gain-of-function mutations of GP1BA gene coding for the platelet surface glycoprotein Ib alpha protein, the receptor for the adhesive protein von Willebrand factor (VWF). PT-VWD is unique among platelet disorders because of platelet hyperresponsiveness rather than decreased function. In PT-VWD patients, platelets bind the VWF and agglutinate spontaneously. This results in thrombocytopenia and reduction of plasma VWF as platelets are removed from circulation. Of note, there is a very similar disorder, type 2B von Willebrand disease (VWD) [DS:H02092], to be taken into consideration in differential diagnosis.
Category
Hematologic disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
03 Diseases of the blood or blood-forming organs
Coagulation defects, purpura or other haemorrhagic or related conditions
3B62 Qualitative platelet defects
H02093 Platelet-type von Willebrand disease
Pathway-based classification of diseases [BR:br08402]
Immune system
nt06514 Coagulation cascade
H02093 Platelet-type von Willebrand disease
Pseudo-von Willebrand's disease. An intrinsic platelet defect with aggregation by unmodified human factor VIII/von Willebrand factor and enhanced adsorption of its high-molecular-weight multimers.
