Cyclosporin therapy for idiopathic thrombocytopenic purpura

Nine adult patients with chronic idiopathic thrombocytopenic purpura (ITP) were treated with cyclosporin. Their platelet counts were all below 5 x 10(4)/microliters. It was administered orally at 5 mg/kg/day for 8 weeks. In one patient, the platelet count increased over 10 x 10(4)/microliters in 4 patients it did over 5 x 10(4)/microliters. Gingival hyperplasia was observed in one patient. Renal dysfunction was not observed in any patients. The elevation of PAIgG declined during the period of treatment. These results suggest that this therapy may be useful in refractory idiopathic thrombocytopenic purpura.     

Colchicine therapy for refractory idiopathic thrombocytopenic purpura

Fourteen patients with idiopathic thrombocytopenic purpura (ITP) refractory to splenectomy and corticosteroids (prednisone, 1 to 2 mg/kg of body weight per day) received at least 1.2 mg of oral colchicine daily for a minimum of two weeks. Three patients had complete responses and one had a partial response (response rate, 29%). Responses were evident within two weeks of commencing therapy. Only the patient with a partial response was receiving concomitant therapy, a stable dose of prednisone. Responsiveness to colchicine did not seem to correlate with responsiveness to vincristine sulfate. Side effects of colchicine therapy were mild and complications did not occur. A possible mechanism of action for colchicine in ITP is decreased clearance of opsonized platelets secondary to inhibition of microtubule-dependent events in macrophages. Colchicine is useful in the treatment of ITP resistant to standard treatment.     

Low-dose prednisolone therapy for idiopathic thrombocytopenic purpura

Prednisolone (PSL) is widely used for the treatment of idiopathic thrombocytopenic purpura (ITP). We compared the effects of a relatively low dose (0.5 mg/kg/day, LD group) of PSL and the conventional dose (1.0 mg/kg/day, CD group) on 59 ITP patients. Twenty-six patients were treated with low-dose PSL, and 23 patients with the conventional dose. No statistically significant difference was observed in the complete remission rates for the LD group (35%) and the CD group (39%). However, the mean duration of hospitalization was significantly (p < 0.001) shorter for LD group patients than for patients in the CD group (20 days versus 50 days, respectively). In conclusion, low-dose PSL may be as effective as the conventional dose and capable of reducing the cost of hospitalization, thus, improving the quality of life for patients with ITP.     

Kaposi's sarcoma developing during corticosteroid therapy in idiopathic thrombocytopenic purpura

A case of Kaposi's sarcoma developing during corticosteroid therapy for idiopathic thrombocytopenic purpura is reported. The patient is a 58-year-old female who was admitted to Sapporo City General Hospital for bleeding tendency in March 1987. She had been treated before admission with prednisolone (over 40 mg/day) for idiopathic thrombocytopenic purpura since October 1986, but her platelet count was below 40,000/microliters. In April 1987, several dark red or blue nodules appeared on the tip of her nose, left forearm, right shoulder, trunk and tongue. These nodules rapidly grew. Biopsy specimens from the nodule of the left forearm showed the histologic changes of Kaposi's sarcoma. She was treated with irradiation. Splenectomy was done in May 1987 and prednisolone was decreased to 5 mg/day. Her platelet count was continually kept 50,000/microliters or more. Her Kaposi's sarcoma completely regressed in January 1988. The relationship of immunosuppressive therapy to Kaposi's sarcoma is discussed.     

Immunosuppressive therapy of chronic idiopathic thrombocytopenic purpura

The results of 17 courses of immunosuppressive therapy in 12 adult patients with chronic idiopathic thrombocytopenic purpura were compared to those reported in 94 patients in the literature. About 50 per cent of the reported patients with chronic idiopathic thrombocytopenic purpura treated with immunosuppressive drugs have had a successful response. In most of these, however, the idiopathic thrombocytopenic purpura was of short duration which suggests that many of the responses were spontaneous. The probability of response to immunosuppressive agents is much greater in the splenectomized patient than in the nonsplenectomized patient.Azathioprine and cyclophosphamide are the drugs of choice for the immunosuppressive therapy of chronic idiopathic thrombocytopenic purpura. The immunosuppressive effects of cyclophosphamide probably are better, but the potential complications of this drug in patients with chronic idiopathic thrombocytopenic purpura are more serious. Nonsteroidal immunosuppressive therapy should be used as the primary form of treatment only in patients with serious disease who fail to respond to corticosteroid therapy and who are poor risks for splenectomy. One or more courses of nonsteroidal immunosuppressive therapy may be indicated in patients with chronic refractory idiopathic thrombocytopenic purpura with life-threatening disease. It is expected that from 15 to 35 per cent of adults and probably more children with chronic refractory idiopathic thrombocytopenic purpura will have a successful response.The use of nonsteroidal immunosuppressive drugs in patients with chronic idiopathic thrombocytopenic purpura remains experimental and involves uncertain risks to the patient.     

Interferon therapy of idiopathic thrombocytopenic purpura]

The authors evaluated the efficacy of a daily administration of recombinant human alpha 2a interferon (IFN), given at a dose of 300MU for 12 consecutive days, in patients with steroid-nonresponsive or -dependent idiopathic thrombocytopenic purpura (ITP). Nine patients received courses of IFN therapy. Mean platelet counts rose from 1.39 to 10.9 x 10(4)/microliters and PAIgG decreased from 151.7 to 59.7 ng/10(7) cells. The maximum rise in platelet counts occurred from 10 to 42 days (mean 19.1) after the initiation of IFN. Complete response (CR) was achieved in 3 of 13 courses (23.1%), and partial response (PR) in 8 (61.5%). One CR case continued for longer than 20 months without further treatment, but intermittent IFN therapy was necessary for the other. The increment of the platelet counts was transient in all of the partial responders. No severe side effect requiring interruption of the course of IFN was experienced. Both serum IgG and PAIgG significantly correlated with the increment of platelet counts, therefore the mechanism of IFN on ITP was presumed to be associated with the inhibition of autoantibody production. Daily administration of IFN appears to be an effective and safe treatment protocol for refractory ITP.     

Low-dose danazol therapy in idiopathic thrombocytopenic purpura

Danazol was administered orally at a dosage of 50 mg/day to 17 patients (11 females and 6 males) with idiopathic thrombocytopenic purpura refractory to steroids and/or splenectomy. The patients had not been treated with conventional dosages of danazol. The drug was suspended in four patients because of adverse effects of danazol. In 13 patients (8 females and 5 males, mean age 44 y. o.) who received the danazol therapy for more than 6 months, there were no patients with an excellent response, and one patient had a good response to the therapy. The rest of the patients did not respond to danazol.     

Diagnosis and therapy of idiopathic thrombocytopenic purpura

To the diagnostics of the idiopathic thrombopenia caused by autoantibodies belong: 1. the clinical findings such as type of haemorrhage and the controls of the capillary function. 2. the proof of antibodies, in which case positive findings are proving, but negative ones do not exclude the immune thrombopenia, 3. smear of the sternal marrow with judgment of the megakaryocytes and formation of thrombocytes, 4. isotopic control of the survival time of the thrombocytes, which is reserved to special insitutions. As therapy essentially three forms have developed: 1. Therapy with glucocorticoids, 2. Immunosuppressive drugs, 3. Splenectomy. In own observations of 48 patients the glucocorticoids bring an actual improvement only for 7 patients, the others fail in therapy or show only a partial remission. The least prospects are in the immunosuppressive drugs, being equal whether preceding or accompanying a glucocorticoid therapy was performed. Most successes (11 out of 16 patients) are to be stated in splenectomy. Following an after-control of all therapeutic methods together a successful therapy results only in one third, in the next two thirds the therapy either fails or at most evokes a partial remission.     

Low-dose danazol therapy in idiopathic thrombocytopenic purpura

Although danazol is effective in the treatment of idiopathic thrombocytopenic purpura, its long-term safety and optimal dosage are not well established. We compared low (50 mg/d) and conventional (400 to 800 mg/d) dosages in 24 patients. Thirteen patients received the low dose 1 to 24 months after conventional doses had been discontinued (group 1). Five patients received low doses immediately after the conventional doses (group 2). Six patients were treated with low doses from the outset (group 3). In group 1, similar responses to either dose were seen in 9 patients, whereas there were better responses to conventional doses in 3 and to the lower dose in 1. All patients in group 2 maintained remissions with low doses. There were two excellent-good responses, one fair, and three poor responses in group 3. Side effects were generally less frequent and severe with the low doses. Low-dose danazol is better tolerated but took longer to obtain remissions, and is useful for maintenance therapy in the management of idiopathic thrombocytopenic purpura.     

High-dose gammaglobulin therapy for idiopathic thrombocytopenic purpura in adults

High-dose gammaglobulin therapy for patients with idiopathic thrombocytopenic purpura (ITP), introduced by Imbach et al., was applied to 5 adults with chronic refractory ITP to investigate the mechanism of the increase in platelet counts. In 4 of the 5 cases, transient increase in platelet count was observed. Platelet-associated IgG was decreased in 3 cases, increased in 1 case and unchanged in 1 case after treatment. In 4 cases having a variety of autoantibodies, the antibody titers decreased after treatment. No significant changes in antiplatelet antibody titers in serum, or in circulating immune complexes were observed during or after these treatments. No side effects were noted in any of the cases. These results indicate that the treatment is suitable for the treatment of patients prior to surgery and of patients at high risk of intense bleeding and death. It can be reasonably assumed that the increased platelet count is mainly due to a defective removal of antibody-coated platelets.     

Acute disseminated encephalomyelitis during treatment for idiopathic thrombocytopenic purpura

A 54-year-old woman had an episode of sudden oral bleeding and generalized petechiae 1 week after a sore throat and diarrhea. On admission, the platelet count was 0.1 x 10(4)/microl, and the platelet-associated IgG level was elevated. Hyperplasia of megakaryocytes in a bone marrow specimen and aberrant Epstein-Barr virus (EBV) antibody patterns led to a diagnosis of EBV-associated idiopathic thrombocytopenic purpura (ITP). Prednisolone (PSL) promptly restored her platelet count; however, she developed disorientation and affective lability soon after PSL was tapered. Subsequently, she ran a high fever and developed convulsive seizures. T2-weighted MRI demonstrated a high signal area in the subcortical white matter, and no abnormal findings were found on examination of the cerebrospinal fluid. The diagnosis of acute disseminated encephalomyelitis (ADEM) was made and steroid pulse therapy was started, which resulted in remission of the symptoms without recurrence in the following months. This is the first reported case of ADEM following EBV infection during treatment for ITP. Administration of PSL for ITP might mask the presenting clinical picture of ADEM. The possibility of ADEM should be investigated in patients of ITP following viral infection who develop acute encephalopathy.     

High-dose dexamethasone therapy in chronic idiopathic thrombocytopenic purpura

 A high-dose pulse of dexamethasone has been described as a current option for the treatment of refractory idiopathic thrombocytopenic purpura (ITP), but the results are controversial. Here we describe the use of a high dose of dexamethasone (40 mg per day for 4 days every month) in 18 patients with chronic ITP. The median age of the patients was 42.5 years (range, 16–77 years); 13 were female and five male. The duration of the disease ranged from 5 to 480 months, and splenectomy was carried out in six of the 18 patients.The overall results obtained revealed a satisfactory response (platelet counts higher than 50×10⁹/l) in eight of the 18 patients. However, a long-term remisson was achieved in only three of the eight patients with a follow up of 7–16 months. We were not able to identify any clinical or laboratory prognostic parameters or previous treatment which would allow one to predict a successful outcome of this treatment. These results suggest that a high dose of dexamethasone may provide an alternative, be it a poor one, for the treatment of refractory IPT, in which the use of a low-cost drug with limited side effects is an important consideration. Received: 18 March 1996 / Accepted: 2 July 1996     

High-dose cepharanthin therapy of idiopathic thrombocytopenic purpura]

Clinical efficacy of oral high-dose cepharanthin (40-60 mg/day) was evaluated in nine patients with idiopathic thrombocytopenic purpura who were unable to discontinue the administration of adrenocorticosteroids or immunosuppressive drugs. Mean platelet counts significantly (p less than 0.05) rose from 4.5 +/- 0.9 x 10(4)/microliters to 8.9 +/- 4.2 x 10(4)/microliters without any side effects. Two to five months after the initiation of this therapy, 4 patients, including 3 who could discontinue adrenocorticosteroids, kept their platelet counts over 10 x 10(4)/microliters. It was suggested that the oral administration of cepharanthin could be a beneficial and safe strategy for ITP.     

Improvement of idiopathic thrombocytopenic purpura by antithyroid therapy

Here we report a case of idiopathic thrombocytopenic purpura accompanied by Graves' disease. Improvement in thyroid function with methimazole led to the spontaneous recovery of the platelet count from 8 x 10(9)/L to 84 x 10(9)/L. Furthermore, the second fall and recovery of the platelet count well coincided with the recurrence of hyperthyroidism after the discontinuation of methimazole and its normalization by resumption of the drug, respectively. These parallel fluctuations of platelet and thyrotropin because of the cessation and resumption of antithyroid therapy suggests that correction of hyperthyroidism may be beneficial to the control of an imbalance in the immune system which impairs not only thyroid but also the platelet.     

Splenic embolization therapy of idiopathic thrombocytopenic purpura]

21 patients with chronic idiopathic thrombocytopenic purpura (ITP) and 3 patients with Evan's syndrome underwent partial splenic embolization (PSE). 22 patients underwent PSE once, while 2 patients were treated twice, thus a total of 26 procedures were carried out. Follow-up 3 months after embolization was available in all the 24 patients for their response to embolization therapy. 16 patients (67%) achieved complete remission (platelets greater than 100 x 10(9)/L) and 4 (17%) partial remission (platelets greater than 84 x 10(9)/L) after splenic embolization. A total efficacy rate of 83% was observed. This response to embolization after transcatheter vessel occlusion 3 months after is similar to the reported results of splenectomy. Not only may the morbidity and mortality associated with surgical splenectomy be avoided, but also the noninfarcted spleen may continue to provide immunologic functions. The most important experience in this series, however, was the emphasis on partial (60-70%) rather than total splenic arterial embolization. The sequestration site of platelets was associated with the outcome of splenic embolization. More splenic sequestration sites were found in responders, to the therapy.