No treatment for low-risk thrombocythaemia:results from a prospective study

Essential thrombocythaemia (ET) is a chronic myeloproliferative disorder characterized by the occurrence of thromboembolic episodes, particularly in patients aged > 60 years or with a previous history of thrombosis, and/or by haemorrhages in patients with an exceedingly high platelet count. In these subgroups of patients the use of cytoreductive therapy is beneficial in terms of risk/benefit ratio. Only limited anecdotal data are available on the thrombotic or haemorrhagic risk and survival in young asymptomatic ET patients with a platelet count < 1500 × 10⁹/l. Therefore the optimal management of these patients is unknown.
To assess the incidence of thrombosis and haemorrhages in this group of patients we carried out a prospective observational study in a cohort of 65 patients with ET, aged < 60 years, with no history of thrombosis or haemorrhage and platelet count < 1500 × 10⁹/l, and in 65 age- and sex-matched controls. Patients were not treated with cytoreductive therapy until the occurrence of thrombosis or haemorrhage. Arterial or venous thrombotic events were objectively documented both in cases and in controls.
The median follow-up was 4.1 years, with an incidence of thrombosis in patients and controls of 1.91 and 1.50 cases/100 patient-years, respectively. The age- and sex-adjusted risk rate ratio was 1.43 (95% CI 0.37–5.4). Only three minor haemorrhagic episodes occurred in patients, with an incidence of 1.12 cases/100 patient-years.
Pregnancy and surgery were not associated with thrombosis in these patients.
We conclude that the thrombotic risk in young ET patients, with no thrombotic history and a platelet count < 1500 × 10⁹/l, is not increased compared to the normal population and that a conservative therapeutic approach should therefore be considered in these patients.     

Uncontrolled thrombocytosis in chronic myeloproliferative disorders

S ummary . A retrospective study was performed to examine the natural course of uncontrolled thrombocytosis associated with chronic myeloproliferative disorders. Thirty-eight patients with polycythaemia rubra vera (PV), myelofibrosis/myeloid metaplasia (MM), chronic myelogenous leukaemia (CML) or essential thrombocythaemia (ET) had platelet counts greater than 1000 × 10⁹/1 and were followed closely for a total of 246 patient years. Eleven of the patients experienced haemorrhagic episodes. Bleeding was twice as frequent in patients over 59 years old as in those younger and no bleeding occurred in those less than 51 years of age. There was no correlation between frequency of bleeding and extent of thrombocytosis. Bleeding events occurred concurrently with use of anti-inflammatory agents in 32% of episodes. The gastrointestinal tract was the most frequent site. Documented thrombotic events occurred in three patients, two of whom had PV with haematocrits greater than 53%. This study suggests that the thrombocytosis of myeloproliferative processes may pose a less serious threat than originally thought and that aggressive lowering of the platelet count may not be indicated in all cases.     

Interferon alpha-2b as treatment for Philadelphia-negative chronic myeloproliferative disorders with excessive thrombocytosis

Summary. We treated 32 patients with Ph¹-negative chronic myeloproliferative disorders (CMD) with excessive thrombocytosis with Interferon α-2b (IFN α-2b): 26 had essential thrombocythaemia, ET (18 previously untreated, eight pretreated); one thrombocythaemia after treatment for Hodgkin's disease (HD); two thrombocythaemia associated with non-Hodgkin's lymphoma (NHL); three stage II idiopathic myelofibrosis (IM). IFN was given at daily doses of 1−4 × 10⁶ IU. Twenty-seven patients (84%) responded, 17 (53%) achieved complete haematologic response after a median time of 12 weeks, and 10 (31%) partial haematologic response. Median platelet levels declined in complete haematologic response patients from 1190 to 335 × 10⁹/I. Normalization of megakaryocyte (MK) levels was observed in 8/17 complete haematologic response patients treated for 9–12 months, with decreased bone marrow (BM) cellularity. Side effects requiring dose reduction or discontinuation of treatment occurred in 28% of cases with IFN doses of 2 or 4 × 10⁶ IU. After 1 year of continuous IFN treatment, responses were maintained with conventional chemotherapy or low-dose IFN. This study demonstrates that IFN has definite therapeutic activity in CMD with excessive thrombocytosis. This biological agent, either alone or in combination with other antineoplastic treatment, may represent a new therapeutic approach for these disorders.     

Anagrelide in the treatment of thrombocythemia essential (ET)

Essential thrombocythaemia (ET), the most often occurring myeloproliferative disorder is a clonal malignant disorder arising from stem cell. The course of the disease is complicated by some severe thrombotic events and far less commonly by haemorrhagic phenomena. Treatment of ET consist of antiplatelet drugs (e.g. aspirin) and lowering platelet count (hydroxyurea or interferon alpha). Anagrelide (anagrelide hydrochloride) is an imidazoquinazoline derivative which lowers platelet count probably by inhibiting thrombopoiesis and reduces platelet aggregation. The aim of the study was to evaluate the efficacy and side effects of anagrelide in patients with ET refractory to prior treatment with hydroxyurea. Anagrelide (Agrylin or Thromboreductin) was used in 40 patients with ET from Jan. 1999 to June. 2003. Out of 40 patients, there were 29 females and 11 males, (median age 52.0 +/- 14.25 years; range, 21-72). Median follow up was 23 months (range, 8 to 54 months). Anagrelide in the average dose of 2,0 mg (range, 1,0-3,5 mg) reduced platelet count in all patients. Median time of response was 3-4 weeks. Complete remission (platelet count < or =450 G/l) achieved 22 persons (55%) and partial remission 17 persons, and only one patient had platelet count slightly above 600 G/l (627 G/l). There was a significant (p < 0.05) reduction in platelet count from a mean of 1136.05 +/- 295.09 G/l to 480.98 +/- 72.26 G/l (56%) Despite platelet count reduction <500 G/l in 3 patients reappeared symptoms of low extremities deep venous thrombosis and in one transient ischaemic cerebral stroke was found. Hemoglobin level in a single case was lower than 12 g/dL (10.8 g/dL), and neither leukopenia nor disturbances of hepatic or renal function were observed. During the first two months of treatment with anagrelide some mild and transient side effects were noticed, eg. headache in 10 (25%), fluid retention in 8 (20%), palpitations in 4 (10%), and diarrhoea in 2 (5%) patients, but all of them continued therapy. Achieved platelet count reduction allowed in 2 ET patients safe performance of planned surgery (cholecystectomy, partial thyroidectomy) and in 1 balloon coronary angioplasty. Anagrelide proved to be an effective drug for of ET patients refractory to hydroxyurea.     

Prevention and treatment of thrombotic complications in essential thrombocythaemia: efficacy and safety of aspirin

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.     

A Complex Ph1 Translocation in a Patient with Primary Thrombocythaemia

S ummary . Routine blood examination of a 27-year-old female revealed a platelet count of 2000 10⁹/1. Bone marrow cells showed the Philadelphia chromosome which was one product of a complex rearrangement of chromosomes 9, 22 and X. Her platelet count was lowered by plateletphoresis and chemotherapy. She remains in good health 19 months later, but her thrombocythaemia is considered to be an early manifestation of chronic myeloid leukaemia.     

Transient normal platelet counts and decreased requirement for interferon during pregnancy in essential thrombocythaemia

We report on the remarkable decrease in the platelet counts during pregnancy in two women with essential thrombocythaemia following treatment with recombinant interferon-α (r-IFN-α). Prior to pregnancy, the first patient was treated for 10 months with r-IFN-α 3×10⁶ units/d six times per week, and the platelet count ranged between 750 and 800×10⁹/l. Starting from the sixth week of gestation, the platelet count decreased to normal levels and remained so, resulting in a lower r-IFN-α requirement. Following successful delivery of a healthy newborn an abrupt rise of the platelet count to pre-gestation values was observed, necessitating increased r-IFN-α dosage as before pregnancy. The second patient when she became pregnant had been treated with r-IFN-α 3×10⁶ units/d six times per week for 10 weeks. Starting from the 24th week of gestation the platelet count decreased, and despite reduction in the dose of r-IFN-α reached normal values at the time of delivery. The exact mechanism for the platelet count normalization during pregnancy is unclear, and several possibilities are discussed.     

Immunomagnetic selection of CD34+peripheral blood stem cells for autografting in patients with breast cancer

Contamination of transplants with tumour cells may contribute to relapse after peripheral blood stem cell transplantation (PBSCT). We studied the feasibility of CD34⁺ cell selection from blood-derived autografts obtained following G-CSF-supported cytotoxic chemotherapy in a group of 25 patients with breast cancer (10 with high-risk stage II/III and 15 with stage IV without bone or bone marrow involvement).
Using immunomagnetic beads (Isolex 300 SA, Baxter) CD34⁺ cells were enriched and released by chymopapain resulting in a median purity of 95% (range 82–99%) and a median recovery of 80% (range 27–132%). The enrichment procedure did not change the proportion of CD34⁺ subsets coexpressing HLA-DR, CD38 and Thy-1, while L-selectin was removed from the cell surface following selection. Using a sensitive immunocytological technique with a cocktail of epithelial-specific antibodies (anti-cytokeratin 8, 18 and 19; HEA125; BM7 and BM8), five leukaphereses products contained epithelial cells, whereas the selected CD34⁺ cell fraction was free of tumour cells. A neutrophil count of 0.5×10⁹/l and a platelet count of 20×10⁹/l was reached after a median time of 14 and 10 d following 40 high-dose chemotherapy (HDC) cycles. Our results indicate that immunomagnetic selection of CD34⁺ cells yields highly purified autografts devoid of tumour cells whereas the engraftment ability of the progenitor and stem cells is fully retained.     

Factors influencing haematological recovery in 53 patients with acute myeloid leukaemia in first remission after autologous bone marrow transplantation

Summary The kinetics of haematological recovery were retrospectively analysed in 53 patients with acute myeloid leukaemia in first remission after myeloablative chemoradiotherapy followed by autologous bone marrow transplantation. The median time to achieve a neutrophil count of 1 × 10⁹/1 was 46d (22–196 d) and median time to achieve unsupported platelet counts of 20 × 10⁹/1 and 50 × 10⁹/1 was 70 d (24–310 d) and 126 d (29–497 d) respectively. Multivariate analysis revealed two factors that were significantly associated with delayed neutrophil and platelet recovery: (1) use of high dose fractionated TBI and mononuclear cell cryopreservation, and (2) low platelet count at the time of bone marrow harvest. There was no correlation with: number of courses of chemotherapy, remission to ABMT interval, CMV status, indices of autograft quality or the development of elevated platelet associated immunoglobulin. Delayed haematological recovery did not predict for relapse or death. Delayed platelet recovery did, however, present significant problems with increased blood and platelet requirements and lengthening of hospital stay.     

Acquired cyclic thrombocytopenia-thrombocytosis with periodic defect of platelet function

Summary A periodic fall of platelet number characterizes an acquired pathological condition named cyclic thrombocytopenia. We observed a patient in whom the episodes of thrombocytopenia (platelet number less than 50×10⁹/l) were followed regularly by thrombocytosis (700–2 300 × 10⁹ platelets/l). The period of platelet count fluctuation was about 30 d. Morphological examination of bone marrow showed the cyclic disappearance of mature and immature megakaryocytes: bone marrow cultures revealed a periodic severe defect of both multilineage and single-lineage progenitor cell growth. When platelet count was falling, a mild defect of platelet aggregation and ATP release was observed. while platelet function was normal when platelet count was rising. Prednisone. thymopentine. high-dose intravenous γ-globulin and splenectomy were without effect. After 4 years of cyclic platelet and megakaryocyte fluctuations, stable amegakaryo-cytic thrombocypenia developed and the patient died of haemorrhagic stroke.     

G-CSF alone mobilizes sufficient peripheral blood CD34+ cells for positive selection in newly diagnosed patients with myeloma and lymphoma

We have evaluated CD34⁺ cell positive selection from granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPC) in 26 patients with either multiple myeloma (MM, n  = 18) or follicular non-Hodgkin's lymphoma (NHL, n  = 8). 26 PBPC were collected with two leukaphereses: 16 contained sufficient numbers of CD34⁺ cells and were selected. The absolute number of CD34⁺ cells in the leukapheresis products was found to be significantly related to the duration of underlying disease and exposure to prior treatment. CD34⁺ cell positive selection allowed recovery of a median of 35% of CD34⁺ cells, the selected fraction containing a median number of 1.43 × 10⁶/kg CD34⁺ cells/kg (range 0.48–41.5). 10 patients were transplanted and received a median dose of 1.51 × 10⁶ CD34⁺ cells (range 0.48–4.2). The median time to granulocyte (>0.5 × 10⁹/l) and platelet (>20 × 10⁹/l) engraftment was 12 and 13 d respectively (ranges 10–13 and 0–95). Lymphoma cells were found by a sensitive polymerase chain reaction technique in four out of five CD34⁺ cell fractions tested.     

The risk of spinal haematoma following neuraxial anaesthesia or lumbar puncture in thrombocytopenic individuals

Neuraxial anaesthesia is increasingly performed in thrombocytopenic patients at the time of delivery of pregnancy. There is a lack of data regarding the optimum platelet count at which spinal procedures can be safely performed. Reports are often confounded by the presence of other risk factors for spinal haematomata, such as anticoagulants, antiplatelet agents and other acquired or congenital coagulopathies/platelet function defects or rapidly falling platelet counts. In the absence of these additional risk factors, a platelet count of 80 × 10⁹/l is a 'safe' count for placing an epidural or spinal anaesthetic and 40 × 10⁹/l is a 'safe' count for lumbar puncture. It is likely that lower platelet counts may also be safe but there is insufficient published evidence to make recommendations for lower levels at this stage. For patients with platelet counts of 50–80 × 10⁹/l requiring epidural or spinal anaesthesia and patients with a platelet count 20–40 × 10⁹/l requiring a lumbar puncture, an individual decision based on assessment of risks and benefits should be made.     

Occurrence, Predictors, and Outcomes of Post-Percutaneous Coronary Intervention Thrombocytopenia in an Unselected Population

Objectives: We sought to determine the occurrence, predictors, and prognostic impact of post-percutaneous coronary intervention (post-PCI) thrombocytopenia on an unselected real-world patient population.
Background: Thrombocytopenia after PCI has been shown to portend worse prognosis in clinical trials. The significance of post-PCI thrombocytopenia has not previously been examined outside the clinical trial setting.
Methods: The study cohort consisted of 1,302 consecutive patients with normal baseline platelet count (150 × 10⁹/L). Post-PCI thrombocytopenia was defined as nadir platelet count < 100 × 10⁹/L or a drop > 50% from baseline. The primary outcomes were in-hospital and 6-month rates of death and major adverse cardiovascular events (MACE), and the secondary outcomes were bleeding, need for blood transfusion, and length of hospital stay. Logistic regression was performed to identify independent predictors.
Results: Post-PCI thrombocytopenia developed in 41 patients (occurrence 3.1%). Independent predictors were baseline creatinine clearance (odds ratio [OR] 1.02 for every unit decrease, 95% confidence interval [CI] 1.01–1.03, P = 0.001), failed PCI (OR 3.8, CI 1.6–9.4, P = 0.003), and use of intraaortic balloon pump (OR 2.8, CI 1.1–6.8, P = 0.024). All study outcomes were significantly higher in patients with post-PCI thrombocytopenia. Post-PCI thrombocytopenia independently predicted MACE at 6 months (hazard ratio 2.7, CI 1.3–5.5, P = 0.0069) and all the secondary outcomes.
Conclusions: Post-PCI thrombocytopenia occurred in 3.1% of patients in an unselected real-world population and carried a significant detrimental impact on prognosis. Failed PCI was the strongest correlate identified.     

Laboratory abnormalities in thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura is an uncommon disorder that requires prompt recognition and intervention to prevent death. To date, information regarding the classic laboratory abnormalities in the disease has been derived from small numbers of patients whose laboratory tests have been done at many different sites. We report the laboratory findings in 135 patients who presented with thrombotic thrombocytopenic purpura to 17 Canadian centres. 50 men and 85 women had a mean platelet count of 25.3 ± 19.4 × 10⁹/l. The initial platelet count correlated with mortality; 32% of patients with a platelet count of 20 × 10⁹/l or less died compared with 18% of patients with a platelet count >20 × 10⁹/l ( P  = 0.058). The platelet-associated IgG was elevated in 88% at presentation whereas the indirect platelet suspension immunofluorescence test was positive in only 18%. 93% of the sera showed reactivity against platelets following protein blotting. All sera tested also showed reactivity against endothelial cells. Immune complexes were seen in all patients, whereas the platelet aggregating factor was detected in 59%. Although the von Willebrand factor was elevated in the majority of patients at entry, the multimer pattern was variable and showed no predictive pattern. Renal dysfunction was common (18%).     

BCR-ABL oncoprotein is expressed by platelets from CML patients and associated with a special pattern of CrkL phosphorylation

Constitutive tyrosine phosphorylation of CrkL was recently demonstrated in platelets from chronic myelogenous leukaemia (CML) patients but BCR-ABL tyrosine kinase could not be detected in the platelet lysates. We studied platelets from 14 CML patients with different types of BCR-ABL mRNA and with maximal platelet counts ranging from 149 to 3069 × 10⁹/l. P2l0^BCR-ABL protein was detected by Western blotting in platelet lysates of 12/13 CML patients with active disease but not in the lysate of platelets from a Ph-positive acute lymphoblastic leukaemia (ALL) patient in remission or eight BCR-ABL-negative controls including one essential thrombocythaemia (ET) patient. Immunoblotting of p2l0^BCR-ABL-positive platelets lysates with anti-CrkL antibody revealed a CrkL triplet consisting of one unphosphorylated and two phosphorylated forms of the protein. This CrkL phosphorylation pattern was not observed in normal platelets or CML platelets treated with ABL tyrosine kinase inhibitor CGP57148B. The presence of BCR-ABL provides an explanation for the constitutive tyrosine phosphorylation of CrkL in CML platelets. As no correlation was observed between platelet counts and platelet BCR-ABL protein expression, thrombocytosis or thrombocythaemia in CML cannot be explained by constitutive BCR-ABL-mediated CrkL tyrosine phosphorylation.     

Regeneration of peripheral blood cells following allogeneic bone marrow transplantation for severe aplastic anaemia

S ummary . We have studied the pattern of regeneration of peripheral blood cells following ABO compatible bone marrow transplantation for severe aplastic anaemia. 18 patients were treated with cyclosporin A and six with methotrexate for post graft immunosuppression. The number of days taken for the neutrophil count to reach 0.5 × 10⁹/l, the lymphocyte count to reach 1.0 x 10⁹/l, the platelet count to reach 100 × 10⁹/l and the reticulocytes to reach 1% was shorter in the CyA treated patients. This finding reached statistical significance for all types of cells except the platelets (neutrophils, P < 0.001; lymphocytes, P < 0.02; platelets, P > 0.05; reticulocytes, P < 0.001).     

Peripheral blood stem cells (PBSCs) collected after recombinant granulocyte colony stimulating factor (rhG-CSF): an analysis of factors correlating with the tempo of engraftment after transplantation

Factors affecting mobilization and engraftment were analysed in 54 patients undergoing transplant using autologous PBSCs mobilized with high-dose recombinant granulocyte stimulating factor (rhG-CSF). Patients received 5-7 d of rhG-CSF. 16 μg/kg/d, administered subcutaneously. PBSCs were harvested by leukapheresis using automated continuous-flow blood cell separators beginning on day 4 of rhG-CSF, processing 10 litres of whole blood, for 2-6 consecutive days. Transplants were performed for the following diseases: breast cancer (n = 22), non-Hodgkin's lymphoma (n = 18), multiple myeloma (n = 7) and other (n = 7). Engraftment was rapid with patients reaching a neutrophil count of 1 × 10⁹/1a median of 12 d (range 9-22) after transplant. Platelets > 20 × 10⁹/1 independent of transfusion support were achieved a median of day 10 (range 7-60) after infusion. Multiple factors potentially influencing engraftment were examined using a Cox regression model. The number of CD34⁺ cells per kg was highly correlated with the time to achievement of granulocyte and platelet recovery (P < 0.012, 0.0001). The use of a post-infusion growth factor and a radiation preparative regimen was important for neutrophil recovery, and a diagnosis of breast cancer was important for platelet recovery. In an analysis by linear regression of the logarithm of CD34⁺ cells collected, lower age, marrow without disease, no prior radiation, and lower number of prior chemotherapy regimens, were important factors influencing larger numbers of CD34⁺ cells in collections.     

Factors predictive of disease progression and death in AIDS-related Kaposi's sarcoma

Background   The natural history of Kaposi's sarcoma (KS) is poorly documented. We attempted to identify factors predictive of progression and survival in HIV-infected patients with KS and CD4⁺ cell counts greater than 100/μL.
Patients and Methods   We studied retrospectively 78 HIV-infected patients diagnosed as having KS between 1989 and 1995. The following variables were assessed as potential predictors of progression and death, in a Cox proportional hazards model: age, sex, ethnic group, transmission group, site of the first KS lesions, duration of KS, concomitant opportunistic infections or malignancies, antiretroviral drug therapy (excluding protease inhibitors), antiherpes treatments, neutrophil counts, CD4⁺ and CD8⁺ cell counts, plasma HIV load, p24 antigenaemia, β₂-microglobulinaemia and immunoglobin A and G serum levels.
Results   During a median follow-up of 22 months (3–81 months), KS progressed in 66 of the 78 patients. The median survival time after progression was 68 months (9–126 months). Multivariate analysis identified only visceral KS, a high neutrophil count and a high serum immunoglobulin (Ig) level as independent predictors of progression ( P  < 0.05). Previous and concomitant opportunistic diseases ( P  = 0.003) and low CD4⁺ cell counts ( P  = 0.013) were independently associated with shorter survival; in contrast KS therapy did not independently influence survival.
Conclusion   Progression of KS is predicted by markers of KS severity, while overall survival is best predicted by markers of immunodeficiency (opportunistic diseases and the CD4⁺ cell count).     

Pleural tuberculosis in Harare, Zimbabwe: the relationship between human immunodeficiency virus, CD4 lymphocyte count, granuloma formation and disseminated disease

objective   To elucidate the relationship between HIV, CD4¹ count and pleural TB. method   In a prospective study, 94 patients presenting at two large Harare hospitals with clinically suspected pleural TB were enrolled over a 10-month period. All underwent standardized evaluation, closed pleural aspiration and biopsy. Patients receiving directly observed anti-TB therapy were followed-up. results   Pleural TB was diagnosed in 90 individuals (median age 33 years; range 18-65; 64 males); the seroprevalence of HIV was 85%. HIV-positive patients were older than HIV-negative individuals (median age 33 vs 23 years, P = 0.013) and had a significantly lower median CD4¹ count (191 vs 1106 × 10⁶/l respectively, P = 0.004). A CD4¹ count of <200 × 10⁶/l was associated with a length of illness >30 days (65% vs 37%; P = 0.05), a positive pleural fluid smear (37% vs 0%; P = 0.0006) and a positive pleural biopsy Ziehl-Neelsen stain (35% vs 7%; P = 0.021). However, a relationship between CD4¹ count and either pleural granuloma formation or radiological evidence of disseminated disease was not observed. conclusion   In sub-Saharan Africa, TB pleural effusions have become associated with older age, a chronic onset, and an increased mycobacterial load. These data emphasize the complex relationship between pleural TB, HIV infection and a low CD4¹ count.     

Pulsed high-dose dexamethasone in refractory chronic idiopathic thrombocytopenic purpura: a report on 10 cases

Summary. We treated 10 patients who had chronic refractory idiopathic thrombocytopenic purpura (ITP) with high-dose dexamethasone (DXM, 40mg/d for 4 sequential days every month). The interval from diagnosis ranged from 49 to 300 months, and patients had previously received a median of 5.5 treatments (including splenectomy in nine cases). Median platelet count was 14 × 10⁹/1 (range 6-26 × 10⁹/1) at the onset of DXM and eight patients had bleeding symptoms. Eight patients received at least three cycles of DXM.
Five patients had a response (i.e. platelet count at least doubled and increased by >20 × 10⁹/1), including one almost complete remission and four minor responses (MR).
Of the MR, one was probably due to concurrent IVIg administration, and all four MR were transient, in spite of further cycles of DXM. In three patients DXM was a failure after three or four cycles. In two patients DXM had to be stopped after one course because of major side-effects (systemic hypertension with stroke and insulin-dependent diabetes, respectively).
In our experience, high-dose DXM had a relatively limited effect in chronic refractory ITP and was associated with severe side-effects in some cases.