The efficacy and safety of aspirin in the prevention and treatment of thrombosis in essential thrombocythaemia (ET) was retrospectively analysed in a cohort of 68 ET patients. 41 patients presented with thrombosis, five patients with bleeding; two patients had a paradoxical combination of bleeding and thrombosis at presentation. At presentation, patients with bleeding had significantly higher platelet and leucocyte counts than patients with thrombosis. During long‐term follow‐up the incidence of thrombosis was significantly reduced in patients receiving aspirin, either as monotherapy or in combination with cytoreduction. However, treatment with aspirin (500 mg/d) was associated with an increase in (minor) bleeding complications. In patients receiving aspirin, bleeding occurred particularly at platelet counts exceeding 1000×109/l. The overall 5‐ and 10‐years survival probability was 93% and 84% respectively, indicating that life expectancy in ET is close to normal. Although our data need confirmation in prospective clinical trials, they suggest that aspirin, particularly in lower doses (100 mg/d), may be a safe antithrombotic agent in ET with an acceptable risk for bleeding, if applied to patients with a platelet count <1000×109/l and/or absence of a bleeding history.
Summary. Patients with essential thrombocythaemia (ET)exhibit a decrease of large von Willebrand factor (VWF) multimers in plasma, which is inversely related to the platelet count. In the present study we investigated whether the decrease of large VWF multimers in plasma with increasing platelet counts is the consequence of increased turnover of large VWF multimers in vivo. To that end we measured the half-life times of endogenously released VWF:Ag and VWF:CBA (collagen binding activity) after intravenous administration of desmopressin (DDAVP) to nine ET patients and nine control subjects (N). In addition, the half-life times of VWF:Ag and VWF:CBA were also measured in four ET patients after cytoreduction of the increased platelet count to normal or nearly normal values. Estimated half-life times of VWF:Ag did not differ between ET patients and normals (11·0 Ϯ 4·0 h v 12·4 Ϯ 2·5 h, P > 0·05). Estimated half-life times of VWF:CBA were significantly lower in ET patients as compared with normal individuals (6·1 Ϯ 2·0 h v 8·4 Ϯ 2·5 h, P < 0·05). After cytoreduction of the increased platelet count to (nearly) normal values in all four ET patients the half-life time of VWF:CBA significantly (P ¼ 0·014) increased from 5·2 Ϯ 1·2 h to 8·7 Ϯ 2·0 h. Our data suggest that platelets may play a role in the homeostasis of circulating von Willebrand factor, which may compromise normal haemostasis at fairly increased platelet counts.
Patients with essential thrombocythemia (ET), who frequently have bleeding complications, may manifest an excessive prolongation of the bleeding time (BT) after ingestion of aspirin (ASA). The reason for this excessive prolongation of the BT is unknown, but it is attributed to qualitative platelet defects. Since patients with ET may also have acquired abnormalities of plasma and platelet von Willebrand factor (vWF), we questioned whether the excessive prolongation of the BT by ASA was related to changes in either plasma or platelet vWF. To that end, we studied BT and plasma and platelet vWF in ten ET patients, ten patients with reactive thrombocytosis (RT), and ten normal individuals, both before and after administration of 500 mg ASA for 7 days. In a second study, the effect of DDAVP infusion on plasma vWF in relation to the BT was studied in ten normal individuals and ten ET patients after treatment with 100 mg ASA for 3 days. In the first study, treatment with ASA resulted in a significant prolongation of the BT in normal subjects, RT patients, and ET patients. However, in five ET patients an excessive (`2 SD) prolongation of the BT by ASA was observed. Although ASA induced no direct changes in either plasma or platelet vWF levels in either normal subjects, RT patients, or ET patients, all five ET patients who showed an excessive prolongation of the BT by ASA had significantly decreased levels of large vWF multimers in plasma. In the second study, infusion with DDAVP resulted in a significant increase in plasma large vWF multimers, paralleled by a normalization of (excessively) prolonged BT. Our data suggest that in ET inhibition of platelet function by ASA in the presence of concurrently decreased levels of large vWF multimers in plasma may have provoked the excessive BT prolongation.
Summary:We describe an infant with severe combined immunodeficiency syndrome and an ␣-thalassemia trait who developed a renal Fanconi syndrome after his first stem cell transplantation. This syndrome consists of a generalized failure of proximal tubular reabsorption, which leads to a large number of metabolic disturbances. The etiology varies from inherited causes, including an idiopathic form, to acquired causes such as intoxications, immunological disorders and hemoglobinopathies. In this case report we discuss possible explanations of the Fanconi syndrome in our patient. Bone Marrow Transplantation (2000) 26, 97-99. Keywords: immunodeficiency; ␣-thalassemia; bone marrow transplantation; Fanconi syndromeThe de Toni-Debré-Fanconi syndrome is characterized by a general dysfunction of the proximal tubule, leading to an excessive urinary loss of amino acids, glucose, bicarbonate, phosphate and other solutes normally absorbed in the proximal tubule. The consequences of these losses are hyperchloremic metabolic acidosis, decreased plasma phosphate levels, electrolyte imbalance, which can lead to severe dehydration, rickets, and growth retardation. The syndrome was first described by Lignac in 1924.1 In 1943, McCune et al 2 abbreviated the name to Fanconi syndrome. We describe a boy with severe combined immunodeficiency syndrome (SCID), ␣ 0 -thalassemia and Fanconi syndrome, a combination of rare diseases not previously reported. Case reportA 1-month-old Turkish boy, born 20 March 1998, was admitted to our hospital in April 1998 for a cord blood transplantation from a matched unrelated donor for his RAG-2 point mutation (deletion of a guanin nucleotide at position 1913, which causes a frame shift and a stop codon at amino acid position 247) autosomal recessive SCID (non T, non B). He was born after an uneventful pregnancy and delivery from consanguineous parents (first cousins), who lost their first born female child, also affected by SCID without signs of Fanconi syndrome. The diagnosis of our patient was established from cord blood. The father was heterozygous for ␣-thalassemia (--SEA) and the mother was heterozygous for -thalassemia (IVS1-6 T→C). Hbelectrophoresis of blood from our patient revealed only an ␣-thalassemia trait. He was prepared for stem cell transplantation with antithymocytic globulin 5 mg/kg/day (20 mg/day) for 5 consecutive days because of circulating maternal T cells. He received cyclosporin A to prevent GVHD. On 25 May 1998, he received 80 ml MUD-cord blood without T or B cell depletion, which contained 15.2 ϫ 10 7 NBC/kg body weight. After stem cell transplantation he was treated with methotrexate 2.5 mg/day on days ϩ1 and ϩ3 and cyclosporin A was continued for GVHD prophylaxis. There were no complications during his hospital stay. Unfortunately, no engraftment of T or B cells was documented. He remained in good physical condition with length and weight measurements at the 10th percentile. In December 1998 he received a second stem cell transplant. This time he received bone marrow from a ma...
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