Pamela Dudkiewicz

Increased procoagulant cell-derived microparticles (C-MP) in splenectomized patients with ITP ☆

BACKGROUND Splenectomy is frequently employed for therapeutic and diagnostic purposes in various clinical disorders. However its long-term safety is not well elucidated. Although risk of infection by encapsulated organisms is widely recognized, less well-known are risks of thrombosis and cardiovascular disease. METHODS We investigated levels of cell-derived microparticles (C-MP) in 23 splenectomized ITP (ITP-S) and 53 unsplenectomized ITP patients (ITP-nS). Assay of C-MP derived from platelets (PMP), leukocytes (LMP), red cells (RMP) and endothelial cells (EMP) were performed by flow cytometry. Coagulation parameters included PT, aPTT and activities of FVIII, IX and XI. Results of all measures were compared between the two groups, ITP-S vs ITP-nS. RESULTS Levels of all C-MP were higher in ITP-S than ITP-nS but only RMP and LMP reached statistical significance (p = 0.0035 and p < 0.0001, respectively). The aPTT was significantly shorter in ITP-S (p = 0.029). Interestingly, correlation analysis revealed that RMP, but not other C-MP, were associated with shortening of aPTT (p = 0.024) as well as with increased activities of factors VIII (p = 0.023), IX (p = 0.021) and XI (p = 0.0089). CONCLUSIONS RMP and LMP were significantly elevated in splenectomized compared to non-splenectomized ITP patients. This suggests that the spleen functions to clear procoagulant C-MP, and that elevation of C-MP might contribute to increased risk of thrombosis, progression of atherosclerosis and cardiovascular disease following splenectomy.

Interleukin-11 for treatment of hepatitis C-associated ITP

Background: Immune thrombocytopenic purpura (ITP) is frequently associated with chronic hepatitis C (HpC-ITP). Methods: Recombinant interleukin-11 (rIL-11), which has both thrombopoietic and anti-inflammatory properties, was evaluated in 12 patients with HpC-ITP in this pilot study. Group 1 (7 patients) was treated at high dose (50 µg/kg daily) while group 2 (5 patients) at low dose (15–35 µg/kg three/week). Results: In group 1, mean platelet counts rose from initial 54 × 109/l to 103 × 109/l (p = 0.02) and in group 2, from an initial 51 × 109/l to 74 × 109/l (p = 0.04). Antiplatelet antibody (aPlt-Ab) decreased in group 1. LFT improved in both groups. The mean HCV-RNA decreased in group 1 (p = 0.04), not in group 2. Side effects were common and troublesome, but were minimized with individualized dosing. One patient achieved good remission of both ITP and HpC lasting >2 years with low-dose maintenance. Conclusion: When used based on individual tolerance, rIL-11 appears useful in HpC-ITP.

Danazol therapy combined with intermittent application of chemotherapy induces lasting remission in myeloproliferative disorder (MPD): an alternative for the elderly with advanced MPD

Abstract There is no good alternative therapy available for elderly patients with advanced myeloproliferative disorders (MPD) who failed on conventional therapies and are not candidates for bone marrow transplant. We report here an effective therapy that induced exceptionally long‐lasting remissions and improved quality of life. Eighteen elderly patients (mean age: 70·6 years) (16 myelofibrosis and 2 thrombocythemia) who had failed on conventional therapies were treated. Danazol was administered daily at 200–800 mg throughout the study. Chemotherapy was applied intermittently as needed to reduce spleen size and blood counts. Busulfan (2–4 mg/day) was used most often and 6‐mercaptopurine (6‐MP) (50–100 mg/day) and/or cytarabine (100–200 mg/m2) if the white blood cell (WBC) count rose rapidly. When MPD stabilized, chemotherapy was discontinued and dosage of danazol was reduced. Therapy was well tolerated. Overall, 61% of patients responded with unexpectedly long‐lasting remissions and improved quality of life. Three (17%) had excellent (E) response, defined by normalization of blood counts and non‐palpable spleen, while eight (44%) had good (G) response, defined by rise of Hct by ⩾7% and ⩾50% reduction of spleen. Mean duration of remission was 45 months (10–78 months) in E responders and 11 months in G responders (2–22 months). This regimen offers a safe and effective alternative for advanced MPD in the elderly.

Interstitial lung disease (ILD) and severe ITP

Abstract Introduction: Platelets play an important role in inflammatory and immune responses. We report interstitial lung disease (ILD) developing during the acute phase of severe thrombocytopenia in 3 patients with severe refractory ITP. Methods and Results: We identified 3 cases with severe ITP who developed ILD in the course of refractory chronic ITP. The thrombocytopenia was severe in all cases. ILD was an incidental finding at the presentation and often misdiagnosed as lung infections. ILD was documented by lung biopsy in cases 1 and 2, supplemented by serial chest X-rays and/or CAT scan. As the ITP improved, ILD regressed in case 1, persisted in case 2, and progressed to advanced pulmonary fibrosis in case 3. Conclusion: We report an association of ILD with severe refractory ITP. ILD was detected in acute phase of platelet destruction, suggesting that platelet destruction may have triggered inflammation in the lung, leading to ILD.

Atypical chronic myeloid leukemia following organ transplants

Abstract:  Secondary malignancy frequently develops among recipients of organ transplants, most commonly malignancies of the lymphoid system and skin. However, chronic myeloid leukemia (CML) is rare following transplant, with only a handful of cases reported, all of whom had kidney transplant and received azathioprine for immunosuppression. We report three cases of post‐transplant CML seen at a single institution within a two‐yr period. Two had received liver and one a kidney transplant. None were on azathioprine but all had tacrolimus. CML is a rare hematological malignancy, usually presenting with high white counts and splenomegaly. In all three of our subjects, presentation of CML post‐transplant was so atypical that their diagnosis could easily be missed. All had rapid and excellent response to imatinib, and underwent clinical remission. This is the first report of CML developing in the course of tacrolimus therapy among liver transplant recipients. Presentations of CML were highly atypical and easy to miss in early stage. Awareness of atypical CML developing post‐transplant is important since early and timely therapeutic intervention with imatinib is critical for improving quality of life and overall prognosis.