Cyclosporine (CsA) is associated with thrombotic micro-angiopathy and endothelial dysfunction. Markers of endothelial dysfunction may serve to identify patients at risk for development of vascular ...injury. In this study we measured von Willebrand Factor (vWF) and sP-selectin as possible markers for endothelial dysfunction in renal transplant recipients at different concentrations of CsA. Because sP-selectin can also be derived from platelets an additional in vitro study was performed to study the potential effect of CsA on the expression of P-selectin on platelet surface, while the effects of CsA on the interaction of platelets with Endothelial Cell Matrix (ECM) were studied under flow conditions in a perfusion chamber model.
CsA was stepwisely replaced by mycophenolate mofetil (MMF) in 15 renal transplant recipients (more than 6 months after transplantation). VWF and sP-selectin were measured at normal CsA (median trough level 130 microg/l), low CsA (trough level 45 microg/l) and after stopping CsA. MMF 2 g daily was added while lowering and stopping CsA. Platelet activation was investigated by measurement of P-selectin on platelet surface by flow-cytometry (FACS), after incubation with CsA (0, 2, 20 and 200 mg/l) in vitro and after perfusion of whole blood over ECM with CsA (0 or 2 mg/l, peak levels).
Stepwise withdrawal of CsA gave a dose-related decrease of both vWF and sP-selectin, suggesting reversible endothelial dysfunction. FACS showed no expression of P-selectin on platelets by CsA. Also perfusion studies over ECM demonstrated no platelet activation by CsA but even inhibition of platelet adhesion and aggregation.
The use of CsA is not accompanied by platelet activation. However endothelial dysfunction induced by CsA does occur as reflected by increased vWF and sP-selectin. (See Editorial p. 1).
Patients with inflammatory bowel disease (IBD) are at increased risk for thromboembolic events. Hyperhomocysteinemia, which is an established risk factor for arterial as well as venous thrombosis, ...may be more prevalent in IBD because of vitamin deficiencies.
In this retrospective study, we studied the concentrations of total homocysteine (tHcy), cobalamin, folate, and pyridoxine in 231 consecutive patients with IBD, of whom 16 patients had a history of venous thrombosis, and nine a history of arterial thrombosis. Age- and gender-matched healthy volunteers served as controls (n = 102).
Homocysteine concentrations in patients were higher (12.3 micromol/L range 4.6-51.3 vs 11.1 micromol/L range 3.9-27.6, p = 0.001) and hyperhomocysteinemia tended to be more prevalent in patients than in the controls (11.1% vs 5%, p = 0.07). Folate, cobalamin, creatinine, and pyridoxine concentrations were correlated with tHcy. Folate deficiency was infrequently encountered in IBD patients (4.3%). The tHcy concentration in patients with a history of venous or arterial thrombosis was not higher than in patients without a history of thrombosis (12.7 micromol/L range 4.6-40.1 and 15.2 micromol/L (range 10.5-26.8) vs 12.3 micromol/L range 10.5-26.8, not significant). Hyperhomocysteinemia was found in 18.8% of the patients with venous thrombosis, 11.1% of the patients with arterial thrombosis, and 10.5% of the patients without thrombosis (not significant).
Hyperhomocysteinemia is a common phenomenon in IBD and correlates with serum folate, cobalamin, creatinine, and pyridoxine concentrations. No correlation between tHcy and a history of venous or arterial thromboembolic complications is found. Hyperhomocysteinemia does not seem to be a major contributory factor in the development of venous or arterial thrombosis in IBD patients.
BACKGROUNDThe Gram-negative bacillus Capnocytophaga canimorsus may cause a severe illness resembling thrombotic thrombocytopenic purpura (TTP). The pathogenesis and optimal therapy of this secondary ...thrombotic microangiopathy (TMA) remain uncertain.CASE REPORTA 63-year-old Caucasian man was admitted with suspicion for TTP, but blood cultures grew C. canimorsus. Initial investigations revealed severe thrombocytopenia, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity level of less than 1%, and strongly elevated D-dimer and lactate dehydrogenase levels. He made a full recovery with antibiotics and plasma infusion for 3 days. Plasmapheresis was not performed. Retrospective determination of serial ADAMTS13 activity levels revealed that ADAMTS13 activity had already increased to 25% at the start of plasma infusion.CONCLUSIONThis case highlights that a C. canimorsus sepsis may cause a secondary TMA with a severe ADAMTS13 deficiency. It also illustrates that the adjunctive role of plasma exchange or plasma infusion is doubtful as ADAMTS13 activity levels increased with antibiotics alone.
Thrombotic thrombocytopenic purpura (TTP) after bone marrow transplantation (BMT) is a serious complication that, in contrast to classic TTP, is generally not responsive to therapeutic plasma ...exchange. We describe the remission of TTP after autologous BMT by administration of cyclosporin in four patients, either after failure of plasmapheresis (two patients) or as primary treatment modality (two patients). Cyclosporin may be an attractive drug for post autologous BMT‐TTP.
Thrombotic thrombocytopenic purpura (TTP) after bone marrow transplantation (BMT) differs from classic TTP in its clinical course and therapy. A characteristic of classic TTP is the inhibition of a ...plasma protease that specifically cleaves von Willebrand factor (vWF), thus reducing its multimeric size. We investigated whether this protease was also inhibited in BMT-associated TTP. Plasma from patients with classic or BMT-associated TTP was incubated with recombinant vWF R834Q, a vWF mutant with enhanced sensitivity to the protease. The proteolysis of vWF multimers was analyzed and quantified on Western blot. Metalloprotease activity was strongly inhibited in the classic TTP patient group. However, metalloprotease activity was normal in the BMT-associated TTP patient group. The difference in activity between the two patient groups was highly significant (P = .0016). The results indicate that the etiologies of classic and BMT-associated TTP are indeed different and provide an explanation for the lack of success of plasma exchange in BMT-associated TTP.
A 27-year-old male chimpanzee (Pan troglodytes verus) developed signs of thrombotic thrombocytopenic purpura (TTP). ADAMTS13 deficiency appeared to be the cause of disease. After treatment with ...high-dose prednisone, haematological values and clinical signs recovered. This is the first description of spontaneous TTP associated with ADAMTS13 deficiency in a non-human primate.
Summary
It is well known that the function of platelets decreases progressively during storage of platelet concentrates at room temperature. To investigate this phenomenon in more detail, we have ...resuspended platelets that had been stored for 24 h or 72 h in fresh plasma, and we have measured the aggregation response and the ATP secretion. Conversely, the effect of plasma in which platelet concentrates (PC) had been stored for 24 h or 72 h, was tested on fresh platelets. Both the aggregation response to collagen and ADP and the collagen-induced ATP secretion of stored platelets partially recovered after incubation with fresh plasma (
p
<0.05). The same parameters measured with fresh platelets incubated in stored PC-plasma were found to be significantly reduced in comparison with the response of fresh platelets in fresh plasma (
p
<0.05). Finally, platelets were stored in a plasma-free medium, suitable for platelet storage and the supernatant was tested. This supernatant inhibited the function of fresh platelets in a storage time-dependent fashion. Boiling of these supernatants did not change the inhibiting capacities, whereas filtration over active charcoal did. Analysis of this supernatant revealed AMP and diadenosine tetraphosphate, which both inhibit platelet function.
These data show that stored platelets release nucleotides that inhibit platelet function in a reversible manner. This phenomenon may contribute to the decrease of platelet function during storage and the recovery of platelet function after transfusion.
An invasive process in the pancreas was found in a 60-year-old woman and a 50-year-old man with abdominal symptoms. Generally, such findings turn out to be adenocarcinoma. However, these patients had ...lymphoma. Primary pancreatic lymphoma or localization of lymphoma in the pancreas are rare and chemotherapy may be curative. Therefore, obtaining tissue for histopathological confirmation of the diagnosis is very important. Both patients underwent chemotherapy. The first patient was in complete remission one month after the last chemotherapy cycle. In the second, the disease went into remission, but he suddenly died of sepsis after the fourth chemotherapy cycle.
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