Ketty Lee

Autoimmune Thrombocytopenic Purpura and Helicobacter pylori Infection

BACKGROUND The mechanisms triggering the production of platelet autoantibodies in autoimmune thrombocytopenic purpura (AITP) are poorly understood. Recently, marked improvements in platelet counts have been reported in patients with AITP and concurrent Helicobacter pylori infection after eradication of H pylori by a standard antibiotic regimen. We looked for an association between H pylori infection and AITP in adults. METHODS Fifty-one adults of white French origin, negative for human immunodeficiency virus (mean +/- SD age, 40 +/- 19.8 years), with AITP and a platelet count of less than 50 x 10(3)/microL at onset were included. Thirty-five consecutive nonthrombocytopenic patients (mean +/- SD age, 43 +/- 22 years) of the same origin and with unknown H pylori status served as control subjects. Antibodies against H pylori were detected by means of an agglutination method in both patients and control subjects. Sex ratio, mean age, hemorrhagic manifestations, response to corticosteroid therapy, and final outcome were compared in H pylori-negative and H pylori-positive patients with AITP. To test for a possible molecular mimicry mechanism, we also used an immunoblot assay to look for specific H pylori antibodies in platelet eluates from 3 H pylori-positive patients with AITP. RESULTS Seroprevalence of H pylori in patients with AITP (15 [29%]) was not significatively different from that in control subjects (10 [29%]). The H pylori-positive and H pylori-negative patients with AITP did not differ in main characteristics at AITP onset, response rate to corticosteroids, and final outcome. None of the 3 patients investigated had H pylori antibodies in platelet eluates. CONCLUSION Although the role of H pylori in a subgroup of patients with AITP cannot be excluded, we found no evidence of an association between H pylori infection and AITP.

Preventive treatment of priapism in sickle cell disease with oral and self-administered intracavernous injection of etilefrine

OBJECTIVES Priapism is a common and currently unsatisfactorily managed complication of sickle cell disease (SCD). In June 1994, 6 SCD patients received a new therapeutic regimen to prevent the occurrence and recurrence of priapism. METHODS The patients (5 with SS and 1 with SC) were adults and had frequent episodes of stuttering priapism (SP), and two of them had had acute episodes (AP) lasting more than 3 hours. The treatment consists of preventive oral administration of the alpha-adrenergic agent etilefrine, and self-administered intracavernous injection (SICI) of the same agent to reverse episodes lasting more than 1 hour. RESULTS Since the beginning of treatment, all patients were protected against AP, 4 patients had no recurrence with the oral treatment alone, 2 had to use SICI, 1 occasionally and 1 constantly. There was no modification of sexual activity and no complications. Blood pressure was unaffected. CONCLUSIONS This treatment is simple, cheap, and self-administered. It should be proposed to all patients with SCD in all geographic areas as part of an educational program for active prevention of this severe complication.

Detection of platelet-reactive antibodies in patients who are refractory to platelet transfusions, and the selection of compatible donors

Although the frequency of alloimmunization against platelets, i.e. against human leucocyte antigens (HLA) class Iand platelet-specific human platelet alloantigens (HPA), has decreased as a result of leucocyte depletion of plateletand red-cell concentrates, refractoriness to platelet transfusions remains problematic [1]. There are still several points of interest concerning this, such as: the optimal technique(s) required to detect the alloantibodies; the actual association between the alloantibodies detected and refractoriness; the optimal policy for selecting compatible platelets for alloimmunized patients, and the impact of universal leucocyte depletion. To obtain information on these matters, the questions listed below were sent to experts in the field. Answers were obtained from 11. Question 1. Which techniques do you use to detect HLA class I antibodies in patients suspected of immunological refractoriness to platelet transfusions? Could you explain the reason for your choice of technique(s)? What is the frequency of cytotoxic and non-cytotoxic antibodies? Question 2. Which technique do you use to detect HPA antibodies? Could you explain your choice of technique(s)? What is the frequency of such antibodies in isolation and in combination with HLA class I antibodies? Question 3. What are your requirements for the cell panels used to detect HLA class I or HPA antibodies, e.g. number of cells, phenotypes required, etc? Question 4. Could you indicate the association you found between the antibodies detected and refractoriness? Question 5. Which policy do you apply to select compatible donors for refractory patients: (a) Selection of matched platelets? (b) Selection based on the specificity of the detected antibodies? (c) Cross-matching (please indicate techniques used)? Question 6. If you have implemented universal leucocyte depletion of cell concentrates, have you found a decrease in the frequency of alloimmunization?

Platelet autoantibodies and lupus-associated thrombocytopenia

Summary. To characterize the antigenic targets of anti‐platelet antibodies (APA) found in systemic lupus erythematosus (SLE)‐associated thrombocytopenia, 48 patients with immune thrombocytopenia and SLE were compared with 20 patients with SLE who had never been thrombocytopenic. Both cases and controls were tested for circulating APA by an indirect platelet suspension immunofluorescence assay (PSIIFT) and by indirect monoclonal antibody specific immobilization of platelet antigens (MAIPA). A direct platelet suspension immunofluorescence assay (PSIFT) was also used for antibodies bound to platelets in vivo in thrombocytopenic patients; 13 of them with high titres of platelets‐bound APA were investigated by direct and indirect MAIPA and platelet eluate analysis. Circulating APA were detected by PSIIFT in 88% of cases and 55% of controls (P = 0·0066) and platelet‐bound antibodies were detected by PSIFT in 90% of cases. Indirect MAIPA detected specific APA (mainly directed against GpIIbIIIa) in 36% of cases and only 5% of the controls (P = 0·0076). Nine out of the 13 fully investigated thrombocytopenic patients (69%) had a positive direct MAIPA and/or APA detected in platelet eluates. In conclusion, the production of specific anti‐platelet autoantibodies, mainly directed against GpIIb/IIIa, and their binding to platelet membrane plays an important role in the pathogenesis of SLE‐associated thrombocytopenia.

Transplantation for liver failure in patients with sickle cell disease: Challenging but feasible

Sickle cell disease (SCD) frequently affects the liver; if acute liver failure (ALF) develops, the only potentially effective therapeutic option is liver transplantation (LT). Only 12 patients for whom LT was performed for SCD‐related ALF have been described so far. We report a retrospective series of 6 adult patients with SCD (3 men and 3 women, median age = 40.1 years) who underwent emergency LT. The indication for LT was ALF complicating cirrhosis in 5 patients (hepatitis C/iron overload–induced cirrhosis in 3 and iron overload–induced cirrhosis in 2); one patient had autoimmune hepatitis. The median follow‐up was 52.7 months (0.5‐123 months). The 1‐, 3‐, 5‐, and 10‐year survival rates were 83.3%, 66.7%, 44.4%, and 44.4%, respectively. One patient died of hepatocellular failure precipitated by hyperacute allograft rejection on post‐LT day 10. Soon after LT, 2 patients developed seizures; in 1 case, the seizures were a complication of early calcineurin inhibitor–induced leukoencephalopathy. Four long‐term survivors benefited from specific management of SCD; specifically, the hemoglobin S fraction was maintained below 30% and the total hemoglobin level was maintained between 8 and 10 g/dL. Two patients had mild vaso‐occlusive crises. Three patients experienced a recurrence of hepatitis C virus (HCV) infection; 2 of these patients experienced reversible neurological complications while they were receiving antiviral treatment. Carefully selected patients with SCD may benefit from emergency LT. However, such patients seem to be particularly susceptible to neurological complications after LT. In contrast, severe SCD‐related crises do not seem to recur if specific management is provided. Outcomes may be improved if the neurological complications can be minimized; for example, the administration of a calcineurin inhibitor can be delayed, and the management of HCV infection recurrence can be improved. Liver Transpl, 2011.

Clinical Follow-Up of Hydroxyurea-Treated Adults with Sickle Cell Disease

Hydroxyurea-derived clinical and biological benefits and safety were retrospectively studied for 123 adult patients from 2 sickle cell disease referral centers during a total follow-up of 654 patient-years and total hydroxyurea exposure of 549 patient-years. Fifty-six adverse events occurred (incidence: 12%/patient-year), with leg ulcers being the most frequent. Adverse events could arise at any time and were usually reversible. No malignancy was observed. Clinical and biological benefits of our cohort were similar to those previously reported. Based on this relatively long retrospective study, the risk/benefit ratio for moderate hydroxyurea doses was satisfactory.

Methylprednisolone-induced immune thrombocytopenia

To the editor: Drug-induced immune thrombocytopenia (DITP) may occur after exposure to many medications and is sometimes indistinguishable from idiopathic thrombocytopenic purpura (ITP).[1][1]–[3][2] When suspected, the causative drug must be stopped and the platelet count returns to normal in