1/67. Hereditary nephritis, deafness and abnormal thrombopoiesis. Study of a new kindred.A fourth kindred displaying the triad of hereditary nephritis, deafness and thrombocytopenia with giant platelets is described. Renal involvement, a common cause of death amongst afflicted subjects, appears to have a better prognosis in the affected members of this family. Although the electron microscopic appearance of the megakaryocytes in the present case appears similar to that in previously reported cases, we suggest that the "giant" platelets may result from a degenerative process of megakaryocytes leading to nuclear regression and cytoplasmic fragmentation, rather than the usual blebbing process.- - - - - - - - - - ranking = 1keywords = giant (Clic here for more details about this article) |
2/67. Sebastian syndrome: case report and review of the literature.Macrothrombocytopenias (MTCP) are a heterogeneous group of disorders associated with thrombocytopenia and giant platelets, and may include other clinical or laboratory findings such as hereditary nephritis, sensorineural deafness, leukocyte inclusions, and cataracts. patients with MTCP may have mild to moderate bleeding symptoms or be completely asymptomatic. The most recently described MTCP is the Sebastian syndrome (SS), which consists of thrombocytopenia with giant platelets and leukocyte inclusions. Only three previous reports about this syndrome have been published. Herein, we report the first African-American family with SS. The propositus is a 4-week-old male born to a mother carrying the diagnosis of chronic idiopathic thrombocytopenia purpura (ITP). His 4-year-old brother also has thrombocytopenia. There is no history of bleeding symptoms in any of the family members. The diagnosis was established by demonstrating thrombocytopenia with giant platelets and leukocyte inclusions on both peripheral smear and by electron microscopy. This report illustrates the importance of obtaining a family history when evaluating thrombocytopenia with special emphasis on a history of thrombocytopenia, renal disease, deafness, and cataracts. It is important to differentiate between MTCP and chronic ITP to avoid the unnecessary diagnostic studies, and, more critically, unneeded and potentially harmful therapy.- - - - - - - - - - ranking = 1.5keywords = giant (Clic here for more details about this article) |
3/67. Mapping of a gene for May-Hegglin anomaly to chromosome 22q.May-Hegglin anomaly (MHA) is a rare autosomal dominant platelet disorder characterized by the triad of giant platelets, thrombocytopenia and leukocyte inclusions. Both the molecular and the genetic defects responsible for this disorder remain unknown. In order to map the gene responsible for MHA, we performed a genome-wide linkage study using highly polymorphic short tandem repeat markers in a single Japanese MHA family. Significant linkage was obtained for the markers on the long arm of chromosome 22 (22q12.3-q13.2), with a maximum two-point lod score of 4.52 at a recombination fraction of 0.00 for the markers D22S1142 and D22S277. Haplotype analysis mapped a critical region for the disease locus to a 13.6-centimorgan region, between D22S280 and D22S272. The relative proximity of the platelet GPIbbeta gene (22q11.2) to this region, as well as its involvement in an isolated giant platelet disorder, suggested a possible involvement of GPIbbeta mutations in MHA. However, dna-sequencing analysis in two patients revealed no abnormality in the sequence of the GPIbbeta gene. This is the first report of linkage for MHA, and further analysis of this locus may lead to the identification of a gene the product of which regulates platelet and leukocyte morphology.- - - - - - - - - - ranking = 1keywords = giant (Clic here for more details about this article) |
4/67. Successful transcutaneous arterial embolization of a giant hemangioma associated with high-output cardiac failure and kasabach-merritt syndrome in a neonate: a case report.We describe the case of a patient with a neonatal giant cutaneous hemangioma with high-output cardiac failure and kasabach-merritt syndrome and successfully treated with transcutaneous arterial embolization aimed at controlling severe congestive heart failure and consumption coagulopathy. A patient was admitted to the neonatal care unit on the first day of age because of a large hemangioma on his right lateral chest wall and respiratory distress, associated with cardiac failure resulting from arteriovenous shunting. On the second day of age the platelet count decreased to 5.7 x 10(4)/microliter and fibrinogen level was 85 mg/dl. The values of prothrombin time and activated partial thromboplastin time were prolonged. Intravenous predonisone therapy was started immediately, but bleeding tendency was getting worse and the evidence of congestive heart failure persisted. On the third day the patient then underwent embolization of feeding arteries with microcoils. The cardiac failure and thrombocytopenic coagulopathy had improved significantly without complications. We conclude that transcutaneous arterial embolization is an effective and safe treatment in this neonate and should be considered for the treatment of control high-output cardiac failure and coagulopathy in infants with hemangioma and kasabach-merritt syndrome.- - - - - - - - - - ranking = 2.5keywords = giant (Clic here for more details about this article) |
5/67. Sebastian platelet syndrome: two Japanese families originally diagnosed with May-Hegglin anomaly.Ultrastructural studies of granulocytes were performed on two unrelated patients with hereditary thrombocytopenia, giant platelets, and inclusion bodies in granulocytes. Each patient had been diagnosed with May-Hegglin anomaly. In both cases, inclusion bodies in granulocytes consisted of clusters of ribosomes and small segments of rough endoplasmic reticulum. Additional clinical features suggesting Alport syndrome were lacking in these propositi and their family members. These observations imply that the patients were affected not with May-Hegglin anomaly but with Sebastian platelet syndrome. They would thus represent the seventh and eighth families known to carry this hereditary disease.- - - - - - - - - - ranking = 0.5keywords = giant (Clic here for more details about this article) |
6/67. Inherited macrothrombocytopenia with distinctive platelet ultrastructural and functional features.We report a family with inherited macrothrombocytopenia and characteristic large membrane complexes in the platelets. Two affected subjects had platelet counts of 40 and 65 x 10(9)/L respectively as assessed by contrast phase microscopy. Ultrastructural studies revealed giant spheroid platelets with characteristic large membrane complexes and/or giant vacuoles containing platelet organelles. Immunohistochemical studies of actin and tubulin showed a disorganization of the microtubule and actin systems. These abnormalities were absent in leukocytes, indicating a platelet-specific cytoskeleton disorder. Platelet autoantibodies were repeatedly absent. Nevertheless, in the peripheral blood we observed several figures of platelet phagocytosis by macrophages and neutrophils. The in vitro aggregometric response of platelets to ADP, collagen, thrombin, ristocetin was present, but shape change was absent. The urinary excretion of thromboxane a2 metabolites of the affected subjects were approximately 2 standard deviations above control values, in spite of a reduced maximal biosynthetic capacity of thromboxane from giant platelets assessed in vitro during whole blood clotting. This inherited platelet disorder shows structural and functional features which allow to distinguish it from other syndromes associated with giant platelets. We also propose to include ultrastructural and cytoskeletal studies in the diagnosis as well as in the classification of inherited giant platelet disorders.- - - - - - - - - - ranking = 2.5keywords = giant (Clic here for more details about this article) |
7/67. Multivessel coronary thrombosis, acute myocardial infarction, and no reflow in a patient with essential thrombocythaemia.Essential thrombocythaemia (ET) has been reported rarely to cause coronary thrombosis, but the management is still undefined. A 63 year old woman with multivessel coronary thrombosis, acute myocardial infarction (MI), and no reflow in reperfused coronary artery in association with ET is presented. The patient's platelet count was only moderately raised at the onset of MI, but peripheral blood smear and bone marrow evaluation revealed clumping giant platelets and numerous large hyperploid megakaryocytes. Long term prophylaxis with antiplatelet agents in patients with ET is recommended, even if the platelet count is not largely raised. Cytoreductive treatment may also be effective for secondary prevention when thrombotic complications occur.- - - - - - - - - - ranking = 0.5keywords = giant (Clic here for more details about this article) |
8/67. Fechtner syndrome: physiologic analysis of macrothrombocytopenia.Fechtner syndrome is a rare autosomal dominant disorder consisting of macrothrombocytopenia and leukocyte inclusions, associated with Alport's syndrome (hereditary nephropathy, sensorineural hearing loss, and ocular anomalies). We describe a 71-year-old Caucasian male with a history of hearing loss and asymptomatic macrothrombocytopenia incidentally noted in 1985. Several challenges to hemostasis were uneventful, including total hip arthroplasty. He subsequently developed progressive renal failure, with 'nil lesions' by light and electron microscopy, which was responsive to corticosteroid therapy. Eight family members are affected variably by either thrombocytopenia or renal failure. Laboratory testing gave the following results: hemoglobin, 10.2 g/dl; leukocytes, 5.0 x 109/l; platelets, 64 x 109/l (mean platelet volume, 13.3 fl; normal platelet volume, 7.6-10.8 fl). Peripheral blood smear revealed thrombocytopenia and leukocytes with inclusions. Electron microscopy of the buffy coat confirmed Fechtner inclusions within the patient's leukocytes. Whole mount and thin section electron microscopy revealed a population of large, although not giant, platelets. Despite thrombocytopenia, platelet aggregation was normal. flow cytometry of dilute platelets revealed normal glycoprotein alphaII beta beta3 activation and alpha-granule p-selectin secretory response to 10 nmol/l human alpha-thrombin. Dense granule adenosine triphosphate secretory response to thrombin was likewise normal. This case illustrates that 'giant' platelets are not universally present in Fechtner syndrome cases, although the platelets are enlarged. Finally, renal pathology other than Alport's nephropathy may be associated with this syndrome.- - - - - - - - - - ranking = 1keywords = giant (Clic here for more details about this article) |
9/67. Metastatic angiosarcoma of the liver preoperatively presenting as giant hemangioma.BACKGROUND: Hepatic angiosarcomas are rare tumors most often associated with exposure to vinyl chloride or other carcinogens. Only a few cases have been published without such a history. CASE REPORT: We report the case of a 73-year-old woman who was admitted to our medical department with unclear upper abdominal pain, thrombocytopenia and anemia. Both computed tomography and magnet resonance imaging revealed a giant hemangioma in the right liver with multiple small hemangiomas. To cure the problem of thrombocytopenia due to sequestration of blood cells in the hemangioma, we decided to resect the large tumor. Intraoperatively, however, the diagnosis of angiosarcoma with multiple metastases was made. The patient died 6 weeks after surgery. CONCLUSION: Problems in diagnosing angiosarcoma include the brief duration of antecedent symptoms, difficulties in radiological diagnosis, and patients without a history of professional exposure to carcinogens.- - - - - - - - - - ranking = 2.5keywords = giant (Clic here for more details about this article) |
10/67. Macrothrombocytopenia with abnormal demarcation membranes in megakaryocytes and neutropenia with a complete lack of sialyl-Lewis-X antigen in leukocytes--a new syndrome?A new megathrombocytopenic syndrome with giant platelets in peripheral blood and severe thrombocytopenia was diagnosed in a 4-month-old boy. His clinical course included repeated hemorrhagic incidents leading to death at age 37 months. bone marrow ultrastructural analysis revealed numerous dystrophic megakaryocytes with giant membrane complexes. Although these features were similar to those described for megakaryocytes in mice lacking the gene for transcription factor p45-NF-E2, no abnormalities in the p45-NF-E2 gene could be documented. Platelet membrane analysis showed a reduction in glycoprotein (GP) Ib, but normal content of GPIIb and GPIIIa. Analysis of genes encoding for GPIb alpha and beta, GPV, and GPIX ruled out the possibility that the observed platelet abnormality is a variant of bernard-soulier syndrome. A moderate neutropenia was associated with a complete lack of expression of sialyl-Lewis-X on the surface of polymorphonuclear neutrophils. A common defect in posttranslational modification of glycoproteins could account for the diverse cellular abnormalities.- - - - - - - - - - ranking = 1keywords = giant (Clic here for more details about this article) |
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