MedGen

MYH9-related disease (MYH9-RD) is characterized in all affected individuals by hematologic features present from birth consisting of platelet macrocytosis (i.e., >40% of platelets larger than 3.9 µm in diameter), thrombocytopenia (platelet count <150 x 109/L), and aggregates of the MYH9 protein in the cytoplasm of neutrophil granulocytes. Most affected individuals develop one or more additional extrahematologic manifestations of the disease over their lifetime, including sensorineural hearing loss, renal disease (manifesting initially as glomerular nephropathy), presenile cataracts, and/or elevation of liver enzymes. [from GeneReviews]

Thrombocythemia, or thrombocytosis, is a myeloproliferative disorder characterized by excessive platelet production resulting in increased numbers of circulating platelets. Thrombocythemia can be associated with thrombotic or hemorrhagic episodes and occasional leukemic transformation (summary by Wiestner et al., 1998). Genetic Heterogeneity of Thrombocythemia THCYT2 (601977) is caused by germline or somatic mutation in the THPO receptor gene (MPL; 159530) on chromosome 1p34, and THCYT3 (614521) is caused by germline or somatic mutation in the JAK2 gene (147796) on chromosome 9p. Somatic mutations in the TET2 (612839), ASXL1 (612990), SH2B3 (605093), and SF3B1 (605590) genes have also been found in cases of essential thrombocythemia. Somatic mutation in the CALR gene (109091) occurs in approximately 70% of essential thrombocythemia patients who lack JAK2 and MPL mutations (Klampfl et al., 2013; Nangalia et al., 2013). [from OMIM]

Glanzmann thrombasthenia is a bleeding disorder that is characterized by prolonged or spontaneous bleeding starting from birth. People with Glanzmann thrombasthenia tend to bruise easily, have frequent nosebleeds (epistaxis), and may bleed from the gums. They may also develop red or purple spots on the skin caused by bleeding underneath the skin (petechiae) or swelling caused by bleeding within tissues (hematoma). Glanzmann thrombasthenia can also cause prolonged bleeding following injury, trauma, or surgery (including dental work). Women with this condition can have prolonged and sometimes abnormally heavy menstrual bleeding. Affected women also have an increased risk of excessive blood loss during pregnancy and childbirth.

About a quarter of individuals with Glanzmann thrombasthenia have bleeding in the gastrointestinal tract, which often occurs later in life. Rarely, affected individuals have bleeding inside the skull (intracranial hemorrhage) or joints (hemarthrosis).

The severity and frequency of the bleeding episodes in Glanzmann thrombasthenia can vary greatly among affected individuals, even in the same family. Spontaneous bleeding tends to become less frequent with age. [from MedlinePlus Genetics]

Platelet-type bleeding disorder-17 is an autosomal dominant disorder characterized by increased bleeding tendency due to abnormal platelet function. It is a type of 'gray platelet syndrome' because the platelets appear abnormal on light microscopy. Electron microscopy shows decreased or absent alpha-granules within platelets, and bone marrow biopsy shows increased numbers of abnormal megakaryocytes, suggesting a defect in megakaryopoiesis and platelet production. The bleeding severity is variable (summary by Monteferrario et al., 2014). [from OMIM]

Quebec platelet disorder is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins. The disorder shows a favorable therapeutic response to fibrinolytic inhibitors (summary by Diamandis et al., 2009). [from OMIM]

Bleeding disorder due to CalDAG-GEFI deficiency is a rare hematologic disease due to defective platelet function and characterized by mucocutaneous bleeding starting in infancy (around 18 months of age), presenting with prolonged and severe epistaxis, hematomas and bleeding after tooth extraction. Massive menorrhagia and chronic anemia have also been reported. [from ORDO]

Platelet-type bleeding disorder-24 (BDPLT24) is an autosomal dominant form of congenital macrothrombocytopenia associated with platelet anisocytosis. It is a disorder of platelet production. Affected individuals may have no or only mildly increased bleeding tendency. In vitro studies show mild platelet functional abnormalities (summary by Kunishima et al., 2011 and Nurden et al., 2011). For a discussion of genetic heterogeneity of Glanzmann thrombasthenia-like with macrothrombocytopenia, see 187800. [from OMIM]

Glanzmann thrombasthenia-2 (GT2) is an autosomal recessive bleeding disorder characterized by failure of platelet aggregation and by absent or diminished clot retraction. The abnormalities are related to quantitative or qualitative abnormalities of the GPIIb (607759)/IIIa platelet surface fibrinogen receptor complex resulting from mutations in the GPIIIa gene (Rosenberg et al., 1997). For a general phenotypic description and a discussion of genetic heterogeneity of Glanzmann thrombasthenia, see 273800. [from OMIM]

Abnormal response to epinephrine as manifested by reduced or lacking aggregation of platelets upon addition of epinephrine. [from HPO]