Simona Raso

Residual vein thrombosis for assessing duration of anticoagulation after unprovoked deep vein thrombosis of the lower limbs: The extended DACUS study

The safest duration of anticoagulation after idiopathic deep vein thrombosis (DVT) is unknown. We conducted a prospective study to assess the optimal duration of vitamin K antagonist (VKA) therapy considering the risk of recurrence of thrombosis according to residual vein thrombosis (RVT). Patients with a first unprovoked DVT were evaluated for the presence of RVT after 3 months of VKA administration; those without RVT suspended VKA, while those with RVT continued oral anticoagulation for up to 2 years. Recurrent thrombosis and/or bleeding events were recorded during treatment (RVT group) and 1 year after VKA withdrawal (both groups). Among 409 patients evaluated for unprovoked DVT, 33.2% (136 of 409 patients) did not have RVT and VKA was stopped. The remaining 273 (66.8%) patients with RVT received anticoagulants for an additional 21 months; during this period of treatment, recurrent venous thromboembolism and major bleeding occurred in 4.7% and 1.1% of patients, respectively. After VKA suspension, the rates of recurrent thrombotic events were 1.4% and 10.4% in the no‐RVT and RVT groups, respectively (relative risk = 7.4; 95% confidence interval = 4.9–9.9). These results indicate that in patients without RVT, a short period of treatment with a VKA is sufficient; in those with persistent RVT, treatment extended to 2 years substantially reduces, but does not eliminate, the risk of recurrent thrombosis. Am. J. Hematol. 2011.

Cancer patients requiring interruption of long-term warfarin because of surgery or chemotherapy induced thrombocytopenia: The use of fixed sub-therapeutic doses of low-molecular weight heparin

No data are available regarding the management of cancer patients requiring interruption of long‐term vitamin‐K antagonist (VKA) therapy. For this purpose, we tested the efficacy and safety of fixed doses of low‐molecular weight heparin (LMWH) in substitution of VKA because of invasive procedures or chemotherapy‐induced thrombocytopenia. In cancer patients on VKA, therapy was discontinued 5 ± 1 days before surgery or chemotherapy. Heparin was given at prophylactic dosage in patients at low risk and at fixed subtherapeutic doses (3,800 or 4,000 UI anti‐FXa, b.i.d.) in those at high‐risk for thrombosis. LMWH was reinitiated 12 hr after surgery and VKA the day after. In patients receiving chemotherapy, LMWH was reinitiated 12/24 hr after obtaining a stable platelet count ≥ 30,000 mmc3 and VKA after a stable platelet count ≥ 50,000 mmc3. Thromboembolism and major bleeding events were recorded from the time of VKA suspension to 30 ± 2 days postprocedure or until the next chemotherapy. Overall, 156 patients (56.4% at low risk and 43.5% at high risk for thrombosis) were enrolled; 34.6% underwent major surgery, 40.4% nonmajor surgery, and 25% chemotherapy. Thrombotic events occurred in five patients [3.2%, 95% confidence interval (CI): 1.41–7.27], four belonging to the high‐risk and one to the low‐risk group. Major bleeding occurred in five patients (3.2%, 95 CI: 1.41–7.27), all belonging to the high‐risk group (three during major surgery and two during chemotherapy). In conclusion, LMWH given at fixed subtherapeutic is a feasible and relatively safe approach for bridging therapy in cancer patients on long‐term VKA. Am. J. Hematol., 2012.

Absolute lymphocyte count is unrelated to overall survival in newly diagnosed elderly patients with multiple myeloma treated with immunomodulatory drugs

1 Cattedra ed U.O. di Ematologia con trapianto, Policlinico Universitario di Palermo, Palermo, Sicily, 2 Divisione di Ematologia, Ospedale Ferrarotto, Universit à di Catania, Catania, Sicily, 3 Azienda Ospedaliera “ Ospedali Riuniti Villa Sofi a-Cervello ” , Palermo, Sicily, 4 Cattedra ed U.O. di Ematologia con trapianto, Policlinico Universitario di Bari, Bari, Italy and 5 Istituto Italiano di Statistica (ISTAT)-Palermo, Palermo, Sicily

Safety of plasma-derived protein C for treating disseminated intravascular coagulation in adult patients with active cancer†

Cancer-related disseminated intravascular coagulation (DIC) is a life-threatening condition for which no effective treatment is currently available. Protein C (PC), a modulator of coagulation as well as the inflammatory system, has been successfully tested (in its activated recombinant form [a-rPC]) in sepsis-related coagulopathy, but with an increased risk for major bleeding. Plasma-derived PC (pd-PC) is more suitable than a-rPC in patients at high risk from bleeding due to its self-limiting process. We carried out a single-arm study evaluating the role of pd-PC in adult cancer patients with overt DIC. Over a period of 3 years, we treated 19 patients with overt DIC and a PC plasma concentration <50%; all received PC concentrate (Ceprotin(®), Baxter) for 72 hr in adjusted doses to restore normal PC values (70-120%). Blood coagulation, haematological tests, and the DIC score were recorded after 12, 24, 48 hr, 7 and 10 days, while clinical outcomes (bleeding, thrombosis and mortality) were recorded up to 28 days. Within 48 hr of starting pd-PC therapy, laboratory tests as well as the DIC score improved in all patients. At 28-days follow-up, no bleeding or thrombosis was observed. This is the first study to investigate the use of pd- PC for treatment of cancer-related overt DIC.

Abdominal aortic thrombosis secondary to reactive thrombocytosis in a patient with iron deficiency anemia.

Dear Editor, A 42-year-old Caucasian female came to our attention with a diagnosis of abdominal aortic thrombosis. Few months before the visit, the patient experienced vomiting and abdominal pain refractory to symptomatic therapy. The patient was referred to the emergency room, and she underwent laboratory and radiological examinations. Complete blood cells count (CBC) showed an extreme thrombocytosis (PLT = 1,133,000/ mmc); an abdominal computed tomography scan showed abdominal aortic thrombosis above the celiac artery and multiple infarctions of the spleen and the left kidney. Past medical history was unremarkable; all known risk factors for arterial thrombosis were ruled out. The patient was hospitalized and treated with unfractionated heparin by continuous intravenous infusion plus platelet-antiaggregating medication (acetyl salicylic acid, ASA). Serum ferritin levels on admission were very low (ferritin = 4 ng/ml). At the time she came to our Regional Reference Center for Thrombosis, 2 weeks after hospital discharge, the following laboratory test results were available: moderate microcytic anemia (Hb 8.2 g/dl; MCV 60.2 fl) thrombocytosis (PLT 932,000/mmc) with normal white blood cell count. Biochemical parameters including inflammation markers, protein electrophoresis, coagulation profile, and oncological serum markers were found in the normal range. Second level diagnostic tests and oral iron supplementation were prescribed. The patient refused a bone marrow biopsy. Research of JAK-2 (V617F and exon 12), calreticulin, and MPL genemutations resulted negative. Genetic thrombophilia tests (factor V Leiden and prothrombin mutation) and autoimmunity markers were negative. An abdominal ultrasonography scan revealed residual intra-aortic thrombus (6–7 mm) along the right side profile of the vessel wall, cranially to the origin of the celiac artery. Endoscopy investigations were performed in order to better define the etiology of iron deficient anemia in an asymptomatic subject. Esophagogastroduodenoscopy revealed signs of gastroesophageal reflux disease; colonoscopy showed diverticular and hemorrhoidal disease. During monthly follow-up visits, hemoglobin levels grew up, and after 3 months of oral iron supplementation, laboratory parameters were all normalized. In particular, in agreement with the increase of hemoglobin levels, platelet count decreased progressively and returned to stable normal values (PLT=300,000/mmc). At the 3-month follow-up after thrombosis, abdominal ultrasound scan showed a complete recanalization of the abdominal aortic vessel. At a 2 years follow-up visit, the patient is under secondary prophylaxis with ASA, CBCs remains within the normal range. Stable clinical and laboratory findings confirm the diagnosis of thrombocytosis secondary to iron deficiency. Thrombocytosis is a not rare event in iron deficiency anemia, and this association seems attributable to a complex interrelationship between erythropoietic and thrombotic growth factors [1, 2]. Iron supplementation usually treats anemia and decreases back platelets to a normal count [3]. * Simona Raso raso.simona@libero.it

Drug-related cardiotoxicity for the treatment of haematological malignancies in elderly.

Several publications have focused on the cardiotoxicity of specific classes of hematological therapeutic agents such as antracyclines and cyclofosfamide. Cardiotoxicity of cancer chemotherapeutics is a problem for patients of all ages, but it increases with age. Toxicity can also develop months after the last chemotherapy dose, and late reactions can be seen years later when they present as new-onset cardiomyopathy. No data are available about the cardiotoxicity of non-chemotherapy agents currently used as preferred therapy for hematological malignancy in elderly. In this review we have provided a summary of the cardiovascular toxic effects produced by different drugs and therapeutic agents. Early identification of patients who are at risk for cardiotoxicity should be a primary goal for hematologists in the development of personalized antineoplastic therapeutic strategies or interventions. Thus, the discovery of new biomarkers to identify patients at a high risk for the development of these complications is a high priority. Although targeted therapies such as imatinib and anti-CD20 antibody such rituximab are considered less toxic and better tolerated by patients compared with classic chemotherapy drugs, certain cardiological complications can be very serious and as these agents have been in use for a limited period of time.

Buffy coat-derived platelets cryopreserved using a new method: Results from in vitro studies

Cryopreservation for the long-term storage of platelets (PLTs) is a useful method to overcome the limits of platelet shortage. This is an in vitro prospective study to evaluate the count, viability, and function of buffy coat-derived pooled platelet concentrates (BC-PLTs), treated with dimethyl sulphoxide (DMSO) and cryopreserved (CRY BC-PLTs) at -80 °C with a modified Valeri method. PLTs were stored in 6% DMSO with a patented kit. Overall, 49 BC-PLTs from 245 healthy volunteer donors were prepared, cryopreserved, and analysed before and after 3, 6, and 9 months of storage. In flow cytometry, a statistically significant reduction in CD 42b (92.7 ± 4.29% at T0 vs. 23.6 ± 27.5% at T3, 16.38 ± 12.54% at T6, and 17.3 ± 9.6% at T9) and PAC-1 (1.9 ± 1.34% at T0 vs. 0.62 ± 0.4% at T3, 0.63 ± 0.83% at T6, and 0.49 ± 0.48% at T9) was observed after storage. CRY BC-PLTs showed a good and stable endogenous thrombin generation potential (nM min): 529.25 ± 98.64 at T0 vs. 533.04 ± 103.15 at T9 months. CRY BC-PLTs showed a good viability in vitro, according to currently accepted criteria for cryopreserved PLTs.

Immunosenescence and lymphomagenesis

One of the most important determinants of aging-related changes is a complex biological process emerged recently and called “immunosenescence”. Immunosenescence refers to the inability of an aging immune system to produce an appropriate and effective response to challenge. This immune dysregulation may manifest as increased susceptibility to infection, cancer, autoimmune disease, and vaccine failure. At present, the relationship between immunosenescence and lymphoma in elderly patients is not defined in a satisfactory way.This review presents a brief overview of the interplay between aging, cancer and lymphoma, and the key topic of immunosenescence is addressed in the context of two main lymphoma groups, namely Non Hodgkin Lymphoma (NHL) and Hodgkin Lymphoma (HL). Epstein Barr Virus (EBV) plays a central role in the onset of neoplastic lymphoproliferation associated with immunological changes in aging, although the pathophysiology varies vastly among different disease entities. The interaction between immune dysfunction, immunosenescence and Epstein Barr Virus (EBV) infection appears to differ between NHL and HL, as well as between NHL subtypes.

Late onset of unilateral optic disk edema secondary to treatment with imatinib mesylate

Prompt ophthalmology evaluation and immediate imatinib suspension should be suggested at any time of tyrosine kinase inhibitor therapy in patients with visual deficit, as it may be a clinical manifestation of optic disk edema, and suspension may help in prompt recovery.