Sex-Linked Hereditary Thrombocytopenia with Immunological Defects

1975 ◽  
Vol 25 (4) ◽  
pp. 309-317 ◽  
Author(s):  
J. Cohn ◽  
M. Hauge ◽  
V. Andersen ◽  
K. Henningsen ◽  
Staub Nielsen ◽  
...  
Keyword(s):  
Hereditary Thrombocytopenia

An operation on a follicular dental cyst performed on a patient with hereditary thrombocytopenia

1997 ◽  
Vol 26 ◽  
pp. 50-51
Author(s):  
S. Fujimoto ◽  
Y. Ono ◽  
K. Kimura ◽  
C. Fukushima ◽  
T. Kanazawa
Keyword(s):  
Hereditary Thrombocytopenia

Hereditary Thrombocytosis: The Thrombopoietin Receptor c-MPL Can Activate Its Downstream Pathway without Full Glycosylation and Membrane Expression

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2374-2374
Author(s):  
Clemens Stockklausner ◽  
Nicole Echner ◽  
Anne-Christine Klotter ◽  
Isabelle Nadine Kuhlee ◽  
Andreas E Kulozik
Keyword(s):  
Plasma Membrane ◽  
Ligand Binding ◽  
Signaling Pathway ◽  
Conflicts Of Interest ◽  
Direct Consequence ◽  
Compound Heterozygous ◽  
Membrane Expression ◽  
Receptor Dimerization ◽  
Hereditary Thrombocytopenia ◽  
And Function

Abstract Abstract 2374 Thrombopoiesis is tightly regulated by the interaction between thrombopoietin (TPO) and its receptor c-Mpl. Receptor binding also leads to the clearance of TPO from the plasma thus establishing a negative feedback loop. However, it is still an open question how the receptor activates its downstream pathway. Alternative models posit that ligand binding either results in receptor dimerization in the plasma membrane or leads to conformational change of preformed receptor dimers. Several mutations in the TPO and the c-Mpl receptor genes have been linked to either hereditary thrombocytopenia or thrombocytosis. We focused on mutations in the extracellular part of the c-Mpl receptor, where ligand binding and receptor dimerization occur. Mutated homozygous c-Mpl R102P and compound heterozygous R102P/F104S receptors cause severe hereditary thrombocytopenia. In contrast, the homozygous c-Mpl P106L mutation was found in patients with hereditary thrombocytosis. We now addressed the question of how the disparate phenotype of mutations in the same domain of the c-Mpl receptor can be explained. We first functionally analyzed and compared normal with mutated R102P, F104S and P106L c-Mpl receptors in transfected HeLa and BA/F3 cells and found that the normal and the F104S c-Mpl receptors are glycosylated normally by the Golgi apparatus and reach the plasma membrane. In contrast, the R102P and P106L mutated receptors are not fully glycosylated, do not reach the plasma membrane and are atypically distributed in the ER. Functional analysis of the TPO/c-Mpl signaling pathway in BA/F3 cells showed decreased phosphorylation of Stat3, Stat5 and Erk1/2 with the R102P and F104S mutants when compared to normal. By contrast, TPO/c-Mpl signaling was up-regulated in cells transfected with the P106L-mutated receptor. Moreover, the P106L mutant, but not the other mutant receptors, enhanced ligand-independent growth of transfected BA/F3 cells. Despite of their opposite function, the TPO plasma levels of patients carrying both, homozygous R102P and P106L mutations were elevated 10 to 20-fold compared to normal and heterozygous individuals. This finding, together with their impaired glycosylation and inability to reach the plasma membrane, suggests that these mutants do not bind and internalize their ligand. TPO binding and degradation thus requires the receptor to be expressed at the plasma membrane, whereas, surprisingly, c-Mpl P106L activated its signaling pathway in a ligand independent fashion. Correct receptor processing and function can thus be separated. This indicates that TPO binding is required for regulation but that the constitutive activation of c-Mpl P106L is a likely direct consequence of premature receptor dimerization in the ER, auto-phosphorylation and subsequent activation of downstream targets. Disclosures: No relevant conflicts of interest to declare.

Hereditary Thrombocytopenia

2009 ◽  
Vol 4 (6) ◽  
pp. 441-452 ◽  
Author(s):  
G. Myllylä ◽  
R. Pelkonen ◽  
E. Ikkala ◽  
J. Apajalahti
Keyword(s):  
Hereditary Thrombocytopenia

Case forum: Hereditary MDS of hereditary thrombocytopenia?

2006 ◽  
Vol 30 ◽  
pp. S10
Author(s):  
E. Bergsträße ◽  
M. Schmugge
Keyword(s):  
Hereditary Thrombocytopenia

scholarly journals The case of rare hereditary thrombocytopenia with a predisposition to the development of acute myeloid leukemia in twin children

2019 ◽  
Vol 17 (4) ◽  
pp. 51-56
Author(s):  
F. R. Khajieva ◽  
P. A. Zharkov ◽  
D. V. Fedorova ◽  
E. V. Raykina ◽  
A. A. Ignatova ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Rare Disease ◽  
Myeloid Leukemia ◽  
Clinical Observation ◽  
Runx1 Gene ◽  
Hereditary Thrombocytopenia ◽  
Twin Children ◽  
Acute Myeloid

Family thrombocytopenia/thrombocytopathy with a predisposition to the development of acute myeloid leukemia (AML) is a rare disease associated with a mutation in the RUNX1 gene. To date, there are data on this disease in no more than 70 families. We present a description of the clinical observation of this pathology in two twin children, and also offer an analysis of available literature on the pathogenetic aspects and prevalence of this rare disease. Patient's parents agreed to use personal dats and photos in research and publications.

Peripartum Management of Women with Suspected Hereditary Thrombocytopenia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3224-3224
Author(s):  
Cynthia M. Wu ◽  
Mohan K. Pai ◽  
Uma Athale ◽  
John G. Kelton ◽  
Donnie M. Arnold
Keyword(s):  
Platelet Count ◽  
Post Partum ◽  
Tertiary Care ◽  
Diagnostic Testing ◽  
Bleeding Complications ◽  
Severe Thrombocytopenia ◽  
Care Hospital ◽  
Count Response ◽  
Hereditary Thrombocytopenia ◽  
Platelet Transfusions

Introduction: Hereditary macrothrombocytopenic disorders are rare syndromes characterized by mild to moderate thrombocytopenia, large platelets, and a variable bleeding phenotype. In general, the diagnosis must be made clinically and management is empiric. Because of the autosomally inherited nature of these disorders, peripartum management must take into account the risk of bleeding for both mother and baby, during the pregnancy and at delivery. Study Purpose: To describe the peripartum management and bleeding complications in pregnant women with suspected inherited macrothrombocytopenic disorders and their children. Study Design: We performed a retrospective review of all mothers referred to our tertiary care hospital from 2004 to 2007 for evaluation of macrothrombocytopenia in pregnancy where hereditary thrombocytopenia was suspected. The diagnosis was confirmed if at least 2 of the following clinical features were present: life-long thrombocytopenia; family history of thrombocytopenia that spanned at least 2 generations; and the lack of a platelet count response to IVIG or corticosteroids. Data relating to bleeding and therapies used to treat or to prevent bleeding before or during delivery for mother and child were extracted from medical charts. Blood films were reviewed with experts in morphology, and diagnostic testing was performed when possible. Results: A total of 5 mothers and 8 babies were included. The median platelet count of mothers at delivery was 54 x 109/L (range 15–83 x 109/L) and the median MPV was 9.8 fL (range 7.4–11.3 fL). Of the 8 babies, 4 were thrombocytopenic with a median platelet count at birth of 50 x 109/L (range 9–93 x 109/L) and a median MPV of 9.4 fL (range 8.9–9.6fL). One mother and her baby had neutrophilic Dohle body inclusions, and none had skeletal, neurologic or renal abnormalities. Three mothers were previously treated with IVIG, including one who also received prednisone, with no platelet count response. During pregnancy, fetal blood sampling for platelet count measurements was not done. None of the mothers had epidural anesthesia, all delivered vaginally and 7 of 8 labours were induced. Two mothers received prophylactic tranexamic acid at the time of active labour and 1 received DDAVP. Prophylactic platelet transfusions were not given. One mother had bleeding associated with spontaneous rupture of membranes, and one had a post partum hemorrhage associated with uterine atony and vaginal laceration. The latter was repaired surgically and treated with platelet transfusions and DDAVP. None of the babies bled, but 1 was given a platelet transfusion because of severe thrombocytopenia at birth (platelet count = 9 x 109/L) with persistent platelet clumping. Conclusions: The frequency of pregnancy-related bleeding in mothers with hereditary macrothrombocytopenia was low in this cohort even in the absence of prophylaxis. There is a need for improved diagnosis and risk stratification of mothers with hereditary macrothrombocytopenia. A multicentre prospective study would assist in determining optimal peripartum management.

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