: Objective: Patients with hyperleukocytic leukaemia were graded according to the severity of symptoms possibly caused by leukostasis to evaluate the effectiveness of therapy and to test the ...relative contribution of blast type and count of blasts and promyelocytes in the development of leukostasis syndrome. Methods: Ninety‐five patients (59 male, 36 female, median age 52 yr) with hyperleukocytic leukaemia leukocytes above 50 × 109/L, 48 acute myeloid leukaemia (AML), 31 chronic myeloid leukaemia (CML), 13 acute lymphoblastic leukaemia (ALL), three chronic myelomonocytic leukaemia (CMML) were grouped according to the presence or absence and severity of neurologic, pulmonary and other symptoms into four categories (no, possible, probable and highly probable leukostasis syndrome). Age, white blood count (WBC), haemoglobin, blast count and total of blasts plus promyelocytes of these groups were compared by Mann–Whitney U‐test. Results: Patients with myeloid leukaemia (AML M1/M2, CML) which scored as highly probable leukostasis showed significantly higher WBC (P = 0.011), lower haemoglobin (P = 0.004), higher peripheral blast counts (P = 0.004) and higher total of peripheral blasts plus promyelocytes (P < 0.001) compared with the lower probability groups. In leukaemia involving the monocytic lineage (AML M4/M5, CMML) no significant differences were found in any of these factors between patients with highly probable leukostasis and the other patients. Conclusions: Our results show that a four‐stage clinical grading scale is a valuable tool for analysing hyperleukocytic patient populations and evaluate the effectiveness of therapy more precisely. We further demonstrate that the mechanisms of leukostasis are different in myeloid leukaemia as compared with leukaemia with involvement of the monocytic lineage.
The aim of the proposed concept is to use anticoagulant therapy in prophylaxis and therapy of thromboembolic events only to an extent that the coagulation activation is just not any longer ...detectable. It results an individualized anticoagulation tailored to the coagulation activation of the patient (individualized "minimal invasive" anticoagulation). Intensity and control of efficiency are to be monitored by measurement of in vivo coagulation activation, e.g. by D-dimer-antigen measurement. Especially with the use of the new oral anticoagulants such a saver anticoagulant therapy - as far as possible from bleeding risk - could open up new indications, which so far are not used because of safety reasons. More patients at risk could be prevented from thromboembolic events. The proposed concept is based on pathophysiological considerations and own clinical experience. It should be evaluated for efficiency in clinical studies.
Hereditary spherocytosis is a common hemolytic anemia with an estimated incidence of 1 / 2500 births. It is caused by a molecular defect in one or more of the proteins of the red blood cell ...cytoskeleton. Mutations in the ABCB11 gene, encoding the bile salt export pump, can entail progressive familial intrahepatic cholestasis and benign recurred intrahepatic cholestasis. A 18 year old Turkish patient with hereditary spherocytosis was admitted to hospital with pruritus and severe jaundice. Ultrasound examination presented stones in gallbladder and bile duct. After endoscopic retrograde cholangiography with extraction of small bile duct stones abdominal pain resolved and liver enzymes normalized within a few days, but bilirubin and bile acids remained highly elevated. Liver biopsy revealed a severe canalicular cholestasis. Genetic analysis showed the compound heterozygous variants ABCB11 A 444V and 3084A > G. Treatment with ursodesoxycholic acid and intermittent therapy with prednisone reduced pruritus and jaundice with concomitant improvement of blood test. Here we report the first case of a patient with combined hereditary spherocytosis and compound heterozygous ABCB11 gene variants predisposing to intrahepatic cholestasis. Therefore, patients with hemolytic disorders should be investigated for bile acid transporter diseases in case of hyperbilirubinemia and severe cholestasis.
Based on the concept that the so-called resistance to anti-platelet drugs is meant to describe a phenomenon where the drug does not hit its direct pharmacodynamic target, assays, used to evaluated ...the effects of anti-platelet drugs, should as closely as possible measure the direct pharmacodynamic effect of a particular drug. Thus, for the detection of aspirin effects, thromboxane concentrations or arachidonic acid-induced responses (light aggregometry, whole-blood aggregometry) should be measured. For the detection of clopidogrel actions, VASP phosphorylation (flow cytometry) or ADP-induced responses (light aggregometry, whole blood aggregometry) should be analysed.
The optimum therapy for patients with relapsed or refractory aggressive non-Hodgkin's lymphomas (NHL) not qualifying for platinum-based and/or high-dose chemotherapy is not known. We conducted a ...prospective phase II study evaluating a regimen consisting of gemcitabine (1 g/m2, days 1 and 8), vinorelbine (30 mg/m2, days 1 and 8) and prednisone (100 mg/day, days 1-8) (GVP) given every 21 days. Fifteen patients with a median age of 68 years and a median of three previous therapies were enrolled. Diagnoses included B lymphoblastic (n=1), diffuse large B cell (n=10), anaplastic large T cell (n=2) and peripheral T-cell NHL (n=2). The median international prognostic index score was 3 (six patients with a score of 4 or 5). Five patients achieved a complete remission and three patients a partial remission. The median overall survival was 13.8 months, and the median time to next treatment was 4.4 months. Haematological toxicities of World Health Organisation grades 3/4 were leucopenia in 58%, thrombocytopenia in 33% and anaemia in 17% of all courses. Three patients had grade 3 infections. There was no treatment-related mortality. GVP shows substantial activity in poor prognosis relapsed or refractory aggressive lymphomas and is generally well tolerated, but haematological toxicity is dose limiting.
In cardiopulmonary bypass (CPB) surgery high dose heparin is necessary to inhibit the clotting cascade which is activated through damage to the vessels (extrinsic pathway) as well as contact ...activation of the blood with the various artificial surfaces of the CPB machine (intrinsic pathway). In most European heart surgery centres, the fibrinolytic activation that always occurs in CPB due to contact activation is reduced by the proteinase inhibitor aprotinin. Monitoring of anticoagulation during CPB is performed with the activated whole blood clotting time (ACT). The two machines commonly used for this purpose, Hemotec and Hemochron, use different contact system activators, kaolin and celite. These activators displayed highly significant differences, in both in vitro tests (modified APTT with whole blood in a neutral coagulometer), and ACT in both machines where aprotinin and heparin were used, as well as with parallel measurements with the two machines with blood from patients undergoing CPB with high dose aprotinin therapy (P < 0.001). The Hemotec machine with kaolin as activator was not affected by aprotinin throughout surgery, while the Hemochron clotting times almost doubled as soon as aprotinin and heparin were combined. Our studies show that for the determination of ACT in CPB were high dose aprotinin therapy is used only ACT determinations with machines using kaolin as activator yield accurate results.
Aims:
Thrombophilic diathesis may cause severe problems in cardiac surgical patients. Protein S deficiency is a coagulation disorder associated with recurrent thromboembolic events. We analysed our ...experience with seven patients with protein S deficiency who underwent cardiac surgery between 1999 and 2005.
Methods:
We retrospectively reviewed the clinical data, operative and postoperative courses, and the mid-term results of seven patients who were diagnosed to have protein S deficiency. In three of them, a past medical history of thromboembolic events and subsequent laboratory screening lead to the preoperative diagnosis of protein S deficiency. Four patients were diagnosed perioperatively after a thromboembolic event. Six of the patients were operated using cardiopulmonary bypass, one was operated off-pump.
Results:
Procedures performed were emergent pulmonary embolectomy (patient 1), aortic valve replacement and coronary artery bypass grafting (CABG, patient 2), Re-CABG (patients 3 and 7) and CABG (patients 4, 5 and 6). Patients 4, 5 and 6 had known protein S deficiency and underwent cardiac surgery under continous coumadin therapy. At follow up (mean follow up of 12±17 months), all but one patient were on continous coumadin, well and without any further thromboembolic events.
Conclusions:
In case of a past medical history of thromboembolic events we suggest careful laboratory screening to identify an underlying thrombophilic disorder. We then operate the patient under coumadin therapy with a target INR of 2.0, in order to minimize the risk of perioperative thromboembolism. Though rare, protein S deficiency and other coagulation disorders can be a critical issue in cardiac surgery.
Resistance to acetylsalicylic acid (ASA) or clopidogrel is understood from the clinical point of view as failure of the drugs to prevent recurrent vascular occlusions. Non-response to ASA and ...clopidogrel is defined from the laboratory aspect as an inability to cause in vitro detectable platelet function inhibition. It would be beneficial to monitor non-response to ASA or clopidogrel with platelet function methods, which detect the specific effect of these drugs, and thus prevent clinical events caused by failure of therapy. Non-response to ASA and clopidogrel are detected with different platelet function methods, which are not always clinically standardized and are assessing only the global platelet function and not the specific drug effect. Although various studies reporting 5 to 59% non-response for both drugs, support a clinical relevance of ASA and clopidogrel non-response, well-designed clinical prospective trials are required to identify patients with antiplatelet drug resistance. Furthermore, mechanisms explaining this phenomenon of drug resistance are still unknown.
Immune thrombocytopenia (ITP) is a common disorder in children and adults. In a patient with newly diagnosed ITP, the treatment strategy is relatively well defined. Second-line treatments are more ...controversial, and the management of chronic ITP is even more so. During the 3rd ICIS Expert Meeting on Consensus and Development of Strategies in ITP, held in Basel on September 3-5, 2009, a group of experts were tasked with reaching a consensus on some frequently asked questions relating to diagnosis and management of children and adults with chronic ITP. The content of this article is designed to provide a practical support to trained haematologists in their care of patients with chronic ITP.
