The infused autograft lymphocyte to monocyte ratio (A-LMR) as a surrogate marker of host immunity (ie, absolute lymphocyte count) and CD14+ HLA-DRlow/neg immunosuppressive monocytes (ie, absolute monocyte count) is a prognostic factor for patients with diffuse large B-cell lymphoma after autologous peripheral hematopoietic stem cell transplantation (APHSCT). Thus, we set out to investigate if A-LMR can also affect survival post-APHSCT in classical Hodgkin lymphoma. From 1994 to 2012, 183 patients with classical Hodgkin lymphoma who underwent APHSCT were studied. The patients were randomly divided into a training set (n=122) and a validation set (n=61). The receiver operating characteristic and area under the curve identified an A-LMR ≥1 as the best cut-off value and validated by the k-fold cross-validation in the training set. Multivariate analysis showed A-LMR to be an independent prognostic factor for survival in the training set. Patients with an A-LMR ≥1.0 experienced a superior overall survival (OS) versus patients with an A-LMR <1.0 (median OS not reached versus 40.4 months, 5-year OS rates of 86% [95% CI 72–93] versus 43% [95% CI 28–58], P<0.0001, respectively) in the training set. In the validation set, an A-LMR ≥1 showed a median OS of not reached versus 41.4 months for an A-LMR <1, 5-year OS rates of 90% (95% CI 73–97) versus 48% (95% CI 28–68; P<0.0001). A-LMR provides a platform to engineer an autograft versus tumor effect to improve clinical outcomes in patients with classical Hodgkin lymphoma undergoing APHSCT.
autograft absolute lymphocyte to monocyte count ratio; survival; autologous peripheral hematopoietic stem cell transplantation; classical Hodgkin lymphoma
“Immune thrombocytopenia” (ITP) is an autoimmune disorder that leads to peripheral destruction, as well as a decreased production of platelets. ITP most commonly presents as mild mucocutaneous bleeding. Though it is rare, the leading cause of mortality in persons with ITP is intracranial hemorrhage and those that do not respond to therapy are at increased risk. Our understanding of the pathophysiology of ITP has evolved immensely, especially over the last 60 years. The discovery of the platelet-production stimulator, thrombopoietin (TPO), lent clarity to an earlier hypothesis that inhibition of platelet production at the level of the megakaryocyte, at least in part, accounts for thrombocytopenia in adults with ITP. This facilitated the development of TPO-based therapies to treat ITP. Thrombopoietin receptor agonists are one of the most recent treatments to enter the landscape. Original production of a recombinant human TPO was halted after clinical trials revealed the untoward effect of autoantibodies to the recombinant human TPO with cross-reactivity to endogenous TPO. Next-step development focused on stimulation of the TPO receptor with fewer immunogenic agents. Currently, two such thrombopoietin receptor agonists, romiplostim and eltrombopag, are licensed in the USA to treat thrombocytopenia in adults with persistent or chronic ITP. Ongoing research will assess their efficacy in other immune-mediated and nonimmune-mediated primary and secondary thrombocytopenias.
thrombopoietin; thrombopoietin receptor agonist; megakaryocyte; peptibody
Human T-cell lymphotrophic/leukemia virus (HTLV-1) is a retrovirus implicated in transfusion-transmitted infection.
The objective of this study was to determine the seroprevalence of HTLV-1 antibodies among blood donors at the University of Nigeria Teaching Hospital, Enugu, Eastern Nigeria.
A cross-sectional study was carried out on consented participants over 4 months. A total of 300 blood donors were recruited consecutively from the blood bank. The serum of the collected 5 mL of blood obtained from each participant was stored at −20°C until required for analysis. The serum samples were then analyzed for antibodies to HTLV-1 using a one-step incubation double-antigen sandwich ELISA (enzyme-linked immunosorbent assay) kit. Participants’ demographic characteristics and degree of exposure to the risk factors associated with HTLV-1 infection were captured using a questionnaire. Statistical analysis of results was done using SPSS version 17.
Of the 300 blood donors, 288 (96%) were male, while 12 (4%) were female. The average age of the blood donors was 26.85±8.52 years. The age group with the highest representation among the blood donors were those aged between 21 and 25 years. Only 22.3% of the blood donors were above 30 years. None of the 300 screened blood donors tested positive to HTLV-1 antibodies. Hence, the seroprevalence of HTLV-1 infection among blood donors was 0%. Of the blood donors, 5% had history of previous sexually transmitted disease, while 34.7% used condoms during sexual intercourse.
The seroprevalence obtained in this study cannot statistically support the justification of routine screening of blood donors for HTLV-1 infection. More prospective and multicentered studies are required to determine the infectivity of HTLV-1 in blood donors in Nigeria.
retrovirus; transfusion; blood-borne infection; screening; Africa
In a Phase III trial, 485 patients (≥65 years) with newly diagnosed acute myeloid leukemia received decitabine 20 mg/m2 intravenously for 5 days every 4 weeks or a treatment choice (supportive care or cytarabine 20 mg/m2 subcutaneously for 10 days every 4 weeks).
Materials and methods
We summarized overall and progression-free survival by baseline white blood cell count using two analyses: <1, 1–5, >5×109/L; ≤10 or >10×109/L.
There were 446 deaths (treatment choice, n=227; decitabine, n=219). Median overall survival was 5.0 (treatment choice) versus 7.7 months (decitabine; nominal P=0.037). Overall survival differences between white blood cell groups were not significant; hazard ratios (HRs) favored decitabine. Significant progression-free survival differences favored decitabine for groups 1–5×109/L (P=0.005, HR =0.67), greater than 5×109/L (P=0.027, HR =0.71), and up to 10×109/L (P=0.003, HR =0.72).
There was a trend toward improved outcome with decitabine, regardless of baseline white blood cell count.
decitabine; acute myeloid leukemia; prognosis; leukemia; adult
To review the responses of advance directives signed by Jehovah’s Witness patients prior to undergoing surgery at a gynecologic oncology service.
A retrospective chart review of gynecologic oncology patients undergoing surgery at a bloodless surgery center from 1998–2007 was conducted. Demographic, pathologic, and clinical data were recorded. The proportion of patients who accepted and refused various blood-derived products was determined and was compared to previously published results from a similar study of labor and delivery unit patients.
No gynecologic oncology patients agreed to accept transfusions of whole blood, red cells, white cells, platelets, or plasma under any circumstance, whereas 9.8% of pregnant patients accepted transfusion (P=0.0385). However, 98% of gynecologic oncology patients agreed to accept some blood products, including fractions such as albumin, immunoglobulins, and clotting factors, while only 39% of pregnant patients agreed (P<0.0001). In addition, all gynecologic oncology patients (100%) accepted intraoperative hemodilution, compared to 55% of pregnant patients (P<0.0001).
Our results confirm the commonly held belief that the majority of Jehovah’s Witness patients refuse to accept major blood components. However, Jehovah’s Witness patients at a gynecologic oncology service will accept a variety of blood-derived products (minor fractions) and interventions designed to optimize outcomes when undergoing transfusion-free surgery. Patients presenting to a gynecologic oncology service respond differently to advanced directives related to bloodless surgery, as compared to patients from an obstetrical service.
Jehovah’s Witness; bloodless surgery; advanced directives
Myelodysplastic syndromes (MDS) represent a heterogeneous group of acquired clonal hematopoietic disorders characterized by peripheral blood cytopenias, paradoxical BM hypercellularity, ineffective hematopoiesis, and increased risk of leukemic transformation. Risk stratification, using different prognostic scores and markers, is at the core of MDS management. Deletion 5q [del(5q)] MDS is a distinct class of MDS characterized by the haploinsufficiency of specific genes, microRNAs, and proteins, which has been linked to increased sensitivity to the drug lenalidomide. Phase II and III clinical trials have demonstrated the efficacy of lenalidomide in improving clinical outcomes of patients with del(5q) MDS, including reduction in red blood cell transfusion requirements and improvements in quality of life. Lenalidomide has also demonstrated some activity in non-del(5q) lower-risk MDS as well as higher-risk MDS, especially in combination with other agents. In this paper, we review the pathogenesis of del(5q) MDS, the proposed mechanisms of action of lenalidomide, the major clinical trials that documented the activity of lenalidomide in different MDS populations, potential predictors of benefit from the drug and suggested mechanisms of resistance, and the use of combination strategies to expand the clinical utility of lenalidomide in MDS.
deletion 5q; lenalidomide; myelodysplastic syndromes; 5q-syndrome
Iron overload causes iron deposition and accumulation in the liver, heart, skin, and other tissues resulting in serious tissue damages. Significant blood clearance from iron and ferritin using wet cupping therapy (WCT) has been reported. WCT is an excretory form of treatment that needs more research efforts. WCT is an available, safe, simple, economic, and time-saving outpatient modality of treatment that has no serious side effects. There are no serious limitations or precautions to discontinue WCT. Interestingly, WCT has solid scientific and medical bases (Taibah mechanism) that explain its effectiveness in treating many disease conditions differing in etiology and pathogenesis. WCT utilizes an excretory physiological principle (pressure-dependent excretion) that resembles excretion through renal glomerular filtration and abscess evacuation. WCT exhibits a percutaneous excretory function that clears blood (through fenestrated skin capillaries) and interstitial fluids from pathological substances without adding a metabolic or detoxification burden on the liver and the kidneys. Interestingly, WCT was reported to decrease serum ferritin (circulating iron stores) significantly by about 22.25% in healthy subjects (in one session) and to decrease serum iron significantly to the level of causing iron deficiency (in multiple sessions). WCT was reported to clear blood significantly of triglycerides, low-density lipoprotein (LDL) cholesterol, total cholesterol, uric acid, inflammatory mediators, and immunoglobulin antibodies (rheumatoid factor). Moreover, WCT was reported to enhance the natural immunity, potentiate pharmacological treatments, and to treat many different disease conditions. There are two distinct methods of WCT: traditional WCT and Al-hijamah (WCT of prophetic medicine). Both start and end with skin sterilization. In traditional WCT, there are two steps, skin scarification followed by suction using plastic cups (double S technique); Al-hijamah is a three-step procedure that includes skin suction using cups, scarification (shartat mihjam in Arabic), and second skin suction (triple S technique). Al-hijamah is a more comprehensive technique and does better than traditional WCT, as Al-hijamah includes two pressure-dependent filtration steps versus one step in traditional WCT. Whenever blood plasma is to be cleared of an excess pathological substance, Al-hijamah is indicated. We will discuss here some reported hematological and therapeutic benefits of Al-hijamah, its medical bases, methodologies, precautions, side effects, contraindications, quantitative evaluation, malpractice, combination with oral honey treatment, and to what extent it may be helpful when treating thalassemia and other conditions of iron overload and hyperferremia.
Al-hijamah; prophetic medicine; cupping therapy; phlebotomy; iron chelation therapy; oral honey
Hemophilia is a hematological disorder characterized by a partial or complete deficiency of clotting factor VIII or IX. Its bleeding complications primarily affect the musculoskeletal system. Hemarthrosis is a major hemophilia-related complication, responsible for a particularly debilitating chronic arthropathy, in the long term. In addition to clotting factor concentrates, usually prescribed by the hematologist, managing acute hemarthrosis and chronic arthropathy requires a close collaboration between the orthopedic surgeon and physiotherapist. This collaboration, comprising a coagulation and musculoskeletal specialist, is key to effectively preventing hemarthrosis, managing acute joint bleeding episodes, assessing joint function, and actively treating chronic arthropathy. This paper reviews, from a practical point of view, the pathophysiology, clinical manifestations, and treatment of hemarthrosis and chronic hemophilia-induced arthropathy for hematologists, orthopedic surgeons, and physiotherapists.
hemophilia; arthropathy; hemarthrosis; hematoma; physiotherapy; target joint
Hereditary hemorrhagic telangiectasia (HHT), also known by the eponym Osler–Weber–Rendu syndrome, is a group of related disorders inherited in an autosomal dominant fashion and characterized by the development of arteriovenous malformations (AVM) in the skin, mucous membranes, and/or internal organs such as brain, lungs, and liver. Its prevalence is currently estimated at one in 5,000 to 8,000. Most cases are due to mutations in the endoglin (HHT1) or ACVRLK1 (HHT2) genes. Telangiectasias in nasal and gastrointestinal mucosa generally present with recurrent/chronic bleeding and iron deficiency anemia. Larger AVMs occur in lungs (~40%–60% of affected individuals), liver (~40%–70%), brain (~10%), and spine (~1%). Due to the devastating and potentially fatal complications of some of these lesions (for example, strokes and brain abscesses with pulmonary AVMs), presymptomatic screening and treatment are of utmost importance. However, due to the rarity of this condition, many providers lack an appreciation for the whole gamut of its manifestations and complications, age-dependent penetrance, and marked intrafamilial variation. As a result, HHT remains frequently underdiagnosed and many families do not receive the appropriate screening and treatments. This article provides an overview of the clinical features of HHT, discusses the clinical and genetic diagnostic strategies, and presents an up-to-date review of literature and detailed considerations regarding screening for visceral AVMs, preventive modalities, and treatment options.
arteriovenous malformations; epistaxis; bevacizumab; embolization; guidelines; screening; review
Hemophilia A is an inherited disorder characterized by deficiency of coagulation factor VIII, which predisposes patients to bleeding events. Treatment is based on replacement of the deficient factor, in a therapeutic or prophylactic manner. Brazil is the country with the third largest population of people with hemophilia, for which the public health system provides free comprehensive care. Maintaining an updated registry of patients, documenting the prevalence of complications, and assessing the effectiveness of resource use are indispensable elements in the design of a well-coordinated national program. According to sociodemographic, clinical, and laboratory data collected by the computerized Brazilian system on coagulopathies, in June 2013, there were 9,122 registered patients with hemophilia A in Brazil, of which 36.1% had a severe form of the disease. Clotting factor inhibitors were present in 7.5%, but 25.7% of records did not provide this type of data. Around 70% of the patients belonged to the economically active population, being between 15 and 59 years old. Infection by the human immunodeficiency virus was present in 23.4% of the patients tested and infection by hepatitis C virus antibodies in 59.3%. Infection by the hepatitis B virus and human T-lymphotropic virus was also reported. The high percentage of incomplete records regarding serological data shows the fragility of the information system to date. There was also no information available on the prevalence of permanent or disabling joint damage. Although few hemophiliacs receive adequate care in developing countries, and despite Brazil exhibiting great social inequalities, the Ministry of Health has made significant advances in the treatment of hemophilia A. The gradual increase in importation of factor VIII concentrate enabled the implementation of primary and secondary modalities of prophylaxis, in addition to the induction of immune tolerance. There are also plans to set up a factory in the country, to ensure Brazilian self-sufficiency in the production of blood products.
cryoprecipitate; factor VIII; prophylaxis; comprehensive health care; health information system
High red blood cell distribution width (RDW) is related to impairment of erythropoiesis, reflecting chronic inflammation and increased levels of oxidative stress, both of which are telltale signs of type 2 diabetics. The aim of this study was to evaluate the relationship between the RDW and fasting blood sugar/blood pressure, and compare the results from diabetics with nondiabetic controls.
This was an unmatched case-control study involving 200 participants consisting of 100 diabetics and 100 nondiabetic controls. Blood (4.5 mL) was collected from all of the diabetics and nondiabetic controls, and placed into EDTA anticoagulant tubes. A full blood count was performed using the Sysmex KX-21N, a three-part auto analyzer able to run 19 parameters per sample, including RDW. Blood pressure was measured during sample collection and in a sitting position.
The mean fasting blood sugar level was 95.20±30.10 mg/dL in the controls, and 147.85±72.54 mg/dL in the diabetics. The mean blood pressures for diabetics was 138/90 mmHg and for non-diabetics 120/80 mmHg. The mean RDW-SD (RDW standard deviation) was 46.44±4.64 fl in the controls, and 46.84±3.18 in the diabetics. The mean RDW-CV (RDW coefficient of variation) was 14.74%±1.94% in controls, and 14.80±0.71 for diabetics. No statistically significant correlation was found between the RDW-SD and fasting blood sugar/blood pressure in the diabetics. A statistically significant positive correlation was found between the RDW-CV and blood pressure in the diabetics.
A positive correlation between the RDW-CV and blood pressure was established in the diabetics in this study.
RDW; fasting blood sugar; type 2 DM
There is a significant association of human T-lymphotropic viruses (HTLV) with lymphoid malignancies. HTLV causes a lymphoproliferative malignancy of CD4-activated cells called adult T-cell leukemia/lymphoma (ATL) and a chronic myelopathy called tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). This study aims to determine the prevalence of HTLV among patients with lymphoid malignancies at a tertiary center in Lagos.
A cross-sectional study was carried out at the hematology clinic of the Lagos State University Teaching Hospital. After obtaining consent, approximately 5 mL of venous blood was collected from each subject. The serum was separated and stored at −20°C. Sera were assayed for HTLV by an enzyme-linked immunoassay (ELISA) for the determination of antibodies to HTLV-1 and -2. Western blot confirmatory testing was done on reactive samples. All patients were also screened for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) by rapid kits.
A total of 39 patients with lymphoid malignancies were enrolled, consisting of 24 (61.5%) with solid malignancies, while 15 (38.5%) had leukemia. Only two patients (5.1%) with lymphoid malignancies were reactive on the ELISA test. On confirmatory testing with Western blot, two patients (5.1%) with lymphoid malignancies were also positive for HTLV. All patients were HIV negative, but four were positive to HBsAg and HCV. There was no association between history of previous blood transfusion and positivity to HTLV (P=0.544).
A prevalence of 5.1% of HTLV among patients with lymphoid malignancies was found in this study, and previous history of blood transfusion was not found to be a significant cause of HTLV infection.
HTLV; lymphoid malignancies; ATL; ELISA; TSP/HAM
Dyskeratosis congenita (DC) is an inherited bone marrow failure (BMF) syndrome characterized by the classic triad of abnormal skin pigmentation, nail dystrophy, and oral leukoplakia. However, patients usually develop BMF and are predisposed to cancer, with increased risk for squamous cell carcinoma and hematolymphoid neoplasms. DC is a disease of defective telomere maintenance and is heterogeneous at the genetic level. It can be inherited in X-linked, autosomal dominant, or autosomal recessive patterns. Mutations in at least ten telomere- and telomerase-associated genes have been described in DC. There are no targeted therapies for DC and patients usually die of BMF due to a deficient renewing capability of hematopoietic stem cells. Allogeneic hematopoietic stem cell transplantation is the only curative treatment for BMF.
dyskeratosis congenita; diagnosis; genetics; clinical; treatment
DOSE (Dosing Observational Study in Hemophilia) was a prospective, observational diary study designed to evaluate the use of bypassing agents in patients prescribed recombinant activated factor VII (rFVIIa) as first-line treatment in the home setting. Patients with congenital hemophilia with inhibitors and caregivers participated, and as part of the study, the time spent preparing and administering product was recorded for bypassing agent (BPA) infusions. The aim of this manuscript is to present the results of the analysis of the time spent preparing and administering a single dose of either rFVIIa or plasma-derived activated prothrombin complex concentrate (pd-aPCC). Diaries were completed for 18 adult patients and 19 caregivers of 21 children with 176 BPA-treated bleeding episodes and 1,350 BPA infusions (1,270 rFVIIa, 80 pd-aPCC). The median preparation and administration times were 5.0 minutes and 5.0 minutes for rFVIIa and 29.0 minutes and 24.5 minutes for pd-aPCC, respectively. Preparation and administration times were significantly shorter with rFVIIa than pd-aPCC (P<0.0001). The significantly shorter combined preparation and administration time of rFVIIa, taking into consideration the faster-than-recommended aPCC infusion rates, suggests that rFVIIa permits a rapid and safe initiation of treatment once a bleeding episode is identified and a decision is made to treat at home.
congenital hemophilia; inhibitors; bypassing agent; recombinant-activated factor VIIa; home treatment
Pacritinib (previously known as SB-1518) is an innovative selective inhibitor of Janus kinase 2 and FMS-related tyrosine kinase 3 providing potential in the treatment of hematological malignancies such as myeloproliferative neoplasias, acute myeloid leukemia, and various lymphomas. Pacritinib has potent antiproliferative activity in Janus kinase 2 and/or FMS-related tyrosine kinase 3 activity-dependent cell lines and an ability to promote apoptosis and inhibit the signal transducers and activators of transcription (STAT) pathway. Pharmacokinetic studies have indicated a good per os bioavailability and favorable kinetic parameters. To date, promising results have been produced in five completed early-phase clinical trials in which pacritinib has been studied. Pacritinib displayed interesting activity and an acceptable safety profile, with mild to moderate gastrointestinal disorders being its most common adverse effects.
pacritinib; SB-1518; JAK inhibitors; myeloproliferative neoplasms; acute myeloid leukemia; lymphoma; treatment
Heparin-induced thrombocytopenia (HIT) is a rare but potentially severe complication of heparin therapy that is strongly associated with venous and arterial thrombosis (HIT and thrombosis syndrome, HITTS), which requires urgent detection and treatment with a nonheparin anticoagulant. Argatroban, a synthetic direct thrombin inhibitor, is indicated for the treatment and prophylaxis of thrombosis in patients with HIT, including those undergoing percutaneous coronary intervention. Argatroban has a relatively short elimination half-life of approximately 45 minutes, which is predominantly performed via hepatic metabolism. It is derived from L-arginine that selectively and reversibly inhibits thrombin, both clot-bound and free, at the catalytic site. Argatroban anticoagulation has been systematically studied in patients with HIT and HITTS and proved to be a safe and effective agent for this indication. The current review presents the pharmacology of argatroban, data regarding monitoring of the agent, and an overview of the results of the major clinical trials assessing argatroban anticoagulation in HIT patients. Additionally, data from recent clinical trials with argatroban use in more special indications such as in percutaneous coronary intervention, liver dysfunction, renal replacement therapy, and intensive care medicine, are reviewed. The approved initial dosage of argatroban for adults with HIT or HITTS is 2 μg/kg/minute for patients with normal hepatic function and 0.5 μg/kg/minute for patients with hepatic dysfunction. There is evidence that a reduced initial dose may also be advisable for patients with heart failure, multiple organ dysfunction, severe anasarca, or after cardiac surgery. Given this information, argatroban can be effectively used in treating HIT with monitoring of activated partial thromboplastin time.
argatroban; HIT; direct thrombin inhibitor
Essential thrombocythemia (ET) is a neoplastic proliferation of mature myeloid cells – in particular, megakaryocytes – leading to persistently elevated platelet count. Usual clinical presentation is related to an increase in the risk of hemorrhage and/or thrombosis. Management of ET consists of antiplatelet therapies – mainly aspirin and cytoreductive therapies. Coronary involvement in patients with ET is rare. The optimal treatment strategies for ET patients presenting with acute myocardial infarction remains unclear. Acute interventions like intracoronary thrombolytic therapy, angioplasty, and coronary-artery bypass grafting have been reported in such patients. However, several questions remain unanswered about the acute and long-term management of these patients. Herein, we report the case of a 47-year-old female who presented with acute myocardial infarction as the first clinical sign of ET, and also present the long-term follow-up of this patient.
STEMI; platelets; hypercoagulability; thrombosis; antiplatelets
Numerous challenges confront adult hemophilia patients with inhibitors, including difficulty in controlling bleeding episodes, deterioration of joints, arthritic pain, physical disability, emotional turmoil, and social issues. High-intensity treatment regimens often used in the treatment of patients with inhibitors also impose significant scheduling, economic, and emotional demands on patients and their families or primary caregivers. A comprehensive multidisciplinary assessment of the physical, emotional, and social status of adult hemophilia patients with inhibitors is essential for the development of treatment strategies that can be individualized to address the complex needs of these patients.
adult hemophilia patients with inhibitors; adherence; physical challenges; psychosocial challenges; health-related quality of life
Circulating factor XIII (FXIII) consists of two active (A) and two carrier (B) subunits in tetrameric form. Congenital FXIII deficiency is a rare autosomal-recessive trait that mostly results from an FXIII A-subunit deficiency. Classic coagulation assays, such as prothrombin time or activated partial thromboplastin time, are not sensitive to FXIII; therefore, specific FXIII assays are necessary to detect the deficiency. The clinical picture of congenital FXIII deficiency comprises abortions, umbilical cord bleeding, increased surgical bleeding, intracerebral hemorrhage (which can, unfortunately, be the very first sign of severe FXIII deficiency), menorrhagia, and wound-healing disorders. Given the risk of intracranial hemorrhage, continued prophylaxis is to be recommended in severe deficiency, even in the actual absence of bleeding symptoms. Functional FXIII half-life decreases in consumptive processes (eg, surgery), explaining why increased dosing is needed in such situations. A recombinant FXIII (rFXIII) subunit-A molecule, which is expressed in Saccharomyces cerevisiae, has been evaluated for replacement therapy in congenital FXIII deficiency. The bleeding frequency under continued rFXIII prophylaxis during a year-long treatment period was significantly lower compared to on-demand treatment. Importantly, no severe spontaneous bleedings occurred, and bleeding requiring additional intervention only occurred after relevant trauma. Treatment with rFXIII proved to be safe: antibodies against rFXIII detected in four patients were not considered clinically relevant. No allergic reactions were observed. These data show that rFXIII can be used safely and effectively for continued prophylaxis in congenital FXIII deficiency; it is conceivable that this also holds true for treatment of acute bleeding, but clinical proof of this is pending.
FXIII; transglutaminase; bleeding; clot firmness
Blood samples are extensively used for the molecular diagnosis of many hematological diseases. The daily practice in a clinical laboratory of molecular diagnosis in hematology involves using a variety of techniques, based on the amplification of nucleic acids. Current methods for polymerase chain reaction (PCR) use purified genomic DNA, mostly isolated from total peripheral blood cells or white blood cells (WBC). In this paper we describe a real-time fluorescence resonance energy transfer-based method for genotyping directly from blood cells. Our strategy is based on an initial isolation of the WBCs, allowing the removal of PCR inhibitors, such as the heme group, present in the erythrocytes. Once the erythrocytes have been lysed, in the LightCycler® 2.0 Instrument, we perform a real-time PCR followed by a melting curve analysis for different genes (Factors 2, 5, 12, MTHFR, and HFE). After testing 34 samples comparing the real-time crossing point (CP) values between WBC (5×106 WBC/mL) and purified DNA (20 ng/μL), the results for F5 Leiden were as follows: CP mean value for WBC was 29.26±0.566 versus purified DNA 24.79±0.56. Thus, when PCR was performed from WBC (5×106 WBC/mL) instead of DNA (20 ng/μL), we observed a delay of about 4 cycles. These small differences in CP values were similar for all genes tested and did not significantly affect the subsequent analysis by melting curves. In both cases the fluorescence values were high enough, allowing a robust genotyping of all these genes without a previous DNA purification/extraction.
real-time PCR; LightCycler® 2.0 Instrument; melting peak; FRET; white blood cells; lysis; erythrocytes
The procedures for collecting voluntarily and freely donated umbilical cord blood (UCB) units and processing them for use in transplants are extremely costly, and the capital flows thus generated form part of an increasingly pervasive global bioeconomy. To place the issue in perspective, this article first examines the different types of UCB biobank, the organization of international registries of public UCB biobanks, the optimal size of national inventories, and the possibility of obtaining commercial products from donated units. The fees generally applied for the acquisition of UCB units for transplantation are then discussed, and some considerations are proposed regarding the social and ethical implications raised by the international network for the importation and exportation of UCB, with a particular emphasis on the globalized bioeconomy of UCB and its commerciality or lack thereof.
cord blood banking; economy; ethics; stem cells; transplantation
Hemophagocytic lymphohistiocytosis (HLH) covers a wide array of related life-threatening conditions featuring ineffective immunity characterized by an uncontrolled hyperinflammatory response. HLH is often triggered by infection. Familial forms result from genetic defects in natural killer cells and cytotoxic T-cells, typically affecting perforin and intracellular vesicles. HLH is likely under-recognized, which contributes to its high morbidity and mortality. Early recognition is crucial for any reasonable attempt at curative therapy to be made. Current treatment regimens include immunosuppression, immune modulation, chemotherapy, and biological response modification, followed by hematopoietic stem-cell transplant (bone marrow transplant). A number of recent studies have contributed to the understanding of HLH pathophysiology, leading to alternate treatment options; however, much work remains to raise awareness and improve the high morbidity and mortality of these complex conditions.
macrophage activation syndrome; hyperinflammatory response
While platelet activation is essential to maintain blood vessel patency and minimize loss of blood upon injury, untimely or excessive activity can lead to unwanted platelet activation and aggregation. Resultant thrombosis has the potential to block blood vessels, causing myocardial infarction or stroke. To tackle this major cause of mortality, clinical therapies that target platelet responsiveness (antiplatelet therapy) can successfully reduce cardiovascular events, especially in people at higher risk; however, all current antiplatelet therapies carry an increased probability of bleeding. This review will evaluate new and emerging targets for antithrombotics, focusing particularly on platelet glycoprotein VI, as blockade or depletion of this platelet-specific receptor conveys benefits in experimental models of thrombosis and thromboinflammation without causing major bleeding complications.
platelet; bleeding; antithrombotic; hemostasis; glycoprotein; vessel; thrombosis
Drug-induced immune hemolytic anemia (DIIHA) is an uncommon side effect of pharmacologic intervention. A rare mediator of DIIHA, carboplatin is an agent used to treat many pediatric cancers. We describe here, the first case of fatal carboplatin induced DIIHA in a pediatric patient and a brief review of the literature. Our patient developed acute onset of multi-organ failure with evidence of complement activation, secondary to a drug induced red cell antibody. Early recognition of the systemic insult associated with carboplatin induced hemolytic anemia may allow for future affected patients to receive plasmapheresis, a potentially effective therapy.
hemolytic anemia; carboplatin; glioma; complement fixation; drug-induced hemolysis