Hematol. Rev., Volume 1, Issue 2 (July 2009) – 12 articles

The β-globin gene mutation in sickle cell anemia results in anemia and repeated bouts of vascular occlusion. The cumulative effect of these vasocclusive events is progressive damage to many organs including the kidneys, lungs, and brain. The transfusion of red blood cells (RBC) can ameliorate many of these complications, but can be associated with both acute and chronic complications, including iron overload. The objective of the Best Practices in Transfusion Medicine for Patients with Sickle Cell Disease (SCD) Conference was to review the available published evidence and clinical experience surrounding the use of RBC transfusions for sickle cell disease by a panel of experts. The expert panel developed explicit clinical guidelines for the use of RBC in SCD patients. The panel also made recommendations for further research. A set of guidelines were produced for dissemination to pertinent stakeholders. If implemented, these clinical pathways have the potential to optimize the use of red blood cell transfusions in SCD. Full article

Warfarin is the most widely used medicine for oral anticoagulant therapy (OAT). It inhibits the synthesis of coagulation factors II, VII, IX, and X in the liver and results in the production of inactive or partially active versions of these factors. Inactive coagulation factors interfere with prothrombin time measurement (Quick and Owren PT) measuring the sum of coagulation activity and inhibition. The narrow therapeutic range here involves a danger of serious complications and the risk of bleeding or thrombosis. The new-generation PT method can measure coagulation activity and inhibition separately. This new technique promotes patient care and anticoagulant medication (warfarin, dicoumarol) based on coagulation activity in vivo. Both therapy and laboratory controls should be unquestionably accurate and based solely on in vivo coagulation activity. Inactive coagulation factors (inhibition) render measurement, calibration, and harmonization. The use of the new-generation PT method based on measurement of coagulation activity in vivo could develop vitamin K antagonist (VKA) therapy for the marked benefit of patients. Full article

Thirty-four blood samples of neonates in Dubai, UAE, with an MCV below 90 fL were checked by high performance liquid chromatography (HPLC) for hemoglobin variants to confirm a previous study carried out in Western Province of Saudi Arabia which showed a very high predictive index of such MCV for alpha (α-) thalassemia minor (ATM). MCH below 30 pg was an additional factor which supported such a prediction. The Dubai study confirmed the original finding with 100% of such neonates showing Hb Barts band. A control group of 26 neonates with an MCV between 90 and 95 fl showed Hb Barts in only 11 cases (42.3%). Of these, 6 (23.1%) were preterm babies, expected to have higher MCV. Five cases (19.2%) had an MCH below 30 pg, though MCV was 90 or higher. Three of the preterm babies also had MCH below 30. The study confirmed the Saudi results in neonates. It seems very highly probable that a term neonate with MCV below 90 and MCH below 30 has ATM. Full article

Pleural effusion directly attributable to multiple myeloma is exceedingly uncommon and is said to occur in only 1–2% of cases. Of these around 80% occur in IgA disease. We report a case of myelomatous pleural effusion (proven on cytological and immunohistochemical analysis) in a patient with the IgG-k subtype. We describe the diagnosis, pathogenesis and management of this condition and show the radiological and cytological evidence of the case. Full article

Mesenteric panniculitis (MP) is a rare disease occasionally complicated with lymphoma. A 55-year old female presented with MP accompanied by malignant lymphoma. This patient was first treated for follicular lymphoma and subsequently for panniculitis. After 6 courses of R-CHOP chemotherapy, the treatment response was partial. An additional course of salvage chemotherapy led to a complete response. Since the mesenteric mass progressed simultaneously with the regression of other lymphoma lesions, we performed a biopsy of the mesenteric mass and pathologically confirmed an MP lesion without lymphoma. Subsequent high-dose chemotherapy led to CR and the MP lesion remained stable. In the present case, MP progressed with chemotherapy. We concluded that mesenteric lesions suspected of progressing or recurring should be diagnosed pathologically even if asymptomatic. Full article

There are very few cases of clear cell renal cell carcinoma with metastases to the vagina and brain reported in the literature. Our case study highlights this rare clinical occurrence and its associated complications including pulmonary embolism. In addition we discuss current management guidelines for treating and diagnosing the disease, and how this management improves prognosis.
Full article

Prothrombin time (PT) is the leading test for monitoring oral anticoagulation therapy (OAT). According to the World Health Organization recommendation, International Normalized Ratio (INR) results obtained from the same patient samples with the major PT methods (Quick and Owren) should be the same when the therapeutic range is the same. In our study blood samples were obtained from 207 OAT patients. We analyzed the samples using two Quick and two Owren PT (combined thromboplastin) reagents for INR and assessed the sensitivity and true coagulation activity using a new-generation PT method. The INR values with the Quick PT and Owren PT methods were very similar around the normal range, while unacceptable differences were seen within the therapeutic range and at higher INR values. The Quick PT results as INR are clearly lower than those given by Owren PT and the difference increases toward higher INR. The new PT method functions well with both Owren PT reagents, and we can calculate the true active INR. The Quick PT methods show no sensitivity to coagulation inhibition measurement. The harmonization of the INR is an important goal for the safety of OAT patients. More accurate INR results reduce morbidity and mortality, and the therapeutic ranges should be similar worldwide. In this study we found unacceptable differences in INR results produced by the two PT methods. The new method showed a lack of sensitivity to Quick PT. For the global harmonization of OAT therapy and for INR accuracy only the more sensitive Owren PT method should be used. Full article

Hematopoietic stem cell (HSC) chemotaxis, adhesion, proliferation, quiescence and differentiation are regulated by interactions with bone marrow (BM) niches. Two niches have been identified in the adult BM: the endosteal (close to the bone) and the perivascular niche (close to blood vessels). A vast body of literature has revealed the molecular basis for the interaction of HSCs with the two niches. However, the signals that regulate the communication between the two niches have not been well defined. Taking in consideration several clinical and experimental arguments this review highlights the molecular cues, involved in the communication between the BM niches, which regulate the basic properties of HSCs in physiological and malignant conditions. As such, it aims at clarifying the most important advances in basic and clinical research focusing on the role of different factors in the regulation of the BM microenvironment. Full article

The impact of chemotherapy resistant B cells in multiple myeloma (MM) needs to be evaluated by in vivo targeted therapy. Here we report the conclusions from a phase II randomized, placebo controlled trial adding fludarabine to the induction with cyclophosphamide-dexamethasone. Based on an interim toxicity and safety analysis, the trial was stopped following inclusion of 34 of a planned 80 patients due to a reduced number of patients (4/17) actually harvested in the experimental arm compared to the control arm (11/17; p < 0.05). In conclusion, the scheduled fludarabine dosage in 2 cycles combined with alkylating therapy impairs stem cell mobilization and standard therapy in young MM patients and should not be administrated up-front. Full article

The homeoprotein TLX1, which is essential to spleen organogenesis and oncogenic when aberrantly expressed in immature T cells, functions as a bifunctional transcriptional regulator, being capable of activation or repression depending on cell type and/or promoter context. However, the detailed mechanisms by which it regulates the transcription of target genes such as ALDH1A1 remains to be elucidated. We therefore functionally assessed the ability of TLX1 to regulate ALDH1A1 expression in two hematopoietic cell lines, PER-117 T-leukemic cells and human erythroleukemic (HEL) cells, by use of luciferase reporter and mobility shift assays. We showed that TLX1 physically interacts with the general transcription factor TFIIB via its homeodomain, and identified two activities in respect to TLX1-mediated regulation of the CCAAT box-containing ALDH1A1 promoter. The first involved CCAAT-dependent transcriptional repression via perturbation of GATA factor-containing protein complexes assembled at a non-canonical TATA (GATA) box. A structurally intact homeodomain was essential for repression by TLX1 although direct DNA binding was not required. The second activity, which involved CCAAT-independent transcriptional activation did not require an intact homeodomain, indicating that the activation and repression functions of TLX1 are distinct. These findings confirm ALDH1A1 gene regulation by TLX1 and support an indirect model for TLX1 function, in which protein-protein interactions, rather than DNA binding at specific sites, are crucial for its transcriptional activity. Full article