Asashi Tanaka

Fibulin-1 and fibrinogen in human atherosclerotic lesions

Fibulin-1 is a fibrinogen-binding blood protein and a component of many extracellular matrices (ECM) including those of blood vessels. In this study, the deposition patterns of fibulin-1 and fibrinogen were examined in human coronary artery atherosclerotic lesions excised by atherectomy from 20 patients. Fibulin-1 deposition was found to be closely overlapping with fibrinogen located within the atherosclerotic lesions and in regions containing fresh thrombi. Pronounced intracellular fibulin-1 immunostaining was apparent in lesion areas rich in macrophages and foam cells, although THP-1 macrophages and foam cells were found not to express fibulin-1. Strong ECM deposition of fibulin-1 was observed in acellular atheromatous and myxomatous regions. By contrast, fibulin-1 was present at relatively low levels in the ECM associated with smooth muscle cells within and outside of lesions and was not detected in sclerotic regions. These results reveal the pattern of fibulin-1 within human atherosclerotic lesions and highlight the potential for fibulin-1, perhaps derived from the blood and acting in conjunction with fibrinogen, to play a role in the etiology and cardiovascular disease progression, particularly with respect to thrombotic aspects of atherosclerosis.

Successful management by recombinant activated factor VII in a case of disseminated intravascular coagulopathy caused by obstetric hemorrhage

Postpartum hemorrhage (PPH) is a life‐threatening emergency in obstetrics. Although recombinant activated factor VII (rFVIIa) has become used for the treatment of some cases of massive hemorrhage, its applications in the field of obstetrics are still limited. We describe a case of successful treatment with rFVIIa for PPH due to placenta accreta. The patient was a 33‐year‐old woman with placental previa. Cesarean section (CS) was performed at gestational week 35. During CS, there was massive hemorrhage due to placenta accreta. After CS, disseminated intravascular coagulopathy and hypovolemic shock were diagnosed. The PPH was not controlled by transfusion therapy. On the fourth day after CS, rFVIIa (90 µg/kg × 2) was given because of the persistent PPH. Bleeding decreased and no further transfusion was required from 2 days after administration. rFVIIa was useful in the treatment of this case of obstetric hemorrhage.

Fibrin monomer complex in normal pregnant women: a potential thrombotic marker in pregnancy.

Background: Pregnancy represents a major risk factor for deep vein thrombosis (DVT). Most coagulation/fibrinolysis markers currently utilized change during pregnancy, and therefore they cannot accurately evaluate thrombotic events in pregnancy because the rate of false positive results is high. Fibrin monomer complex (FMC) has recently become widely available for diagnosing DVT. The present study examined whether FMC is suitable for evaluating thrombotic status in pregnancy. Methods: Concentrations of FMC and other haemostatic markers were investigated in 87 pregnant women without major complications at early, mid- or late pregnancy. FMC concentrations were also measured in 127 normal non-pregnant women, and in one woman who developed DVT after delivery. Results: In normal pregnant women, FMC concentrations were unchanged during early or mid-pregnancy and slightly elevated during late pregnancy. Concentrations were within reference range in most cases, and none exceeded the cut-off value for DVT. In contrast, thrombin-antithrombin complex (TAT) and D-dimer (DD) concentrations were significantly elevated in late pregnancy, and median values exceeded reference ranges. The DVT case displayed significantly elevated FMC concentrations. Conclusions: Changes in FMC concentrations during normal pregnancy are minimal compared with other haemostatic markers. Because the rate of false positivity is lower, FMC could be a potential marker of thrombotic status in pregnancy rather than TAT and DD.

Molecular characterization of 3 factor V mutations, R2174L, V1813M, and a 5-bp deletion, that cause factor V deficiency

We identified 3 mutations in the factor V (FV) gene(F5) associated with FV deficiency in 3 unrelated Japanese patients. Patient 1 had severe bleeding symptoms (plasma FV activity, <1%; FV antigen, 9%) and was a compound heterozygote for a novel 5-bp deletion in exon 22 and the V1813M mutation. Patient 2 had moderate bleeding symptoms (plasma FV activity, <1%; FV antigen, 4%) and was homozygous for the V1813M mutation. Patient 3 had very mild symptoms (plasma FV activity, 1%; FV antigen, 5%) and was homozygous for the novel R2174L mutation. A study of recombinant protein expression revealed that the FV coagulant-specific activities in conditioned media for the FV-R2174L and FV-V1813M mutants were reduced to approximately 40% and 28% of wild-type FV, respectively. The amounts of FV-R2174L protein and messenger RNA in the platelets of patient 3 were similar to those of healthy subjects; however, the amount of FV-V1813M protein in patient 2 was decreased. Our data suggest that the severity of the bleeding tendency in patients with FV deficiency is correlated not only with plasma FV activity but also with the amount of FV protein in the platelets.

Online reporting system for transfusion-related adverse events to enhance recipient haemovigilance in Japan: A pilot study

BACKGROUND A surveillance system for transfusion-related adverse reactions and infectious diseases in Japan was started at a national level in 1993, but current reporting of events in recipients is performed on a voluntary basis. A reporting system which can collect information on all transfusion-related events in recipients is required in Japan. METHODS We have developed an online reporting system for transfusion-related events and performed a pilot study in 12 hospitals from 2007 to 2010. RESULTS The overall incidence of adverse events per transfusion bag was 1.47%. Platelet concentrates gave rise to statistically more adverse events (4.16%) than red blood cells (0.66%) and fresh-frozen plasma (0.93%). In addition, we found that the incidence of adverse events varied between hospitals according to their size and patient characteristics. CONCLUSION This online reporting system is useful for collection and analysis of actual adverse events in recipients of blood transfusions and may contribute to enhancement of the existing surveillance system for recipients in Japan.

A national survey of premedication for transfusion reactions in Japan

BACKGROUND Premedication before transfusion is commonly administered in clinical practice despite a lack of evidence for its efficacy. The aim of this study was to clarify the status of premedication and evaluate expert opinions regarding its use in Japanese medical institutions. METHOD Between May and July 2016, we conducted a questionnaire survey on premedication before transfusion in 252 medical institutes that were certified by an academic society or employed transfusion experts. RESULTS A total of 141 institutes (54.2%) responded, and hematologists (n=113) comprised the most frequent respondents. The purpose of premedication was to prevent urticaria, pruritus, and fever, and washed blood products were used for anaphylactic shock or refractory transfusion reactions before. Drugs for premedication were intravenously administered either just before or 30min before transfusion. Both inpatients and outpatients were premedicated in a similar manner, and institutional guidelines were not established. More than half of the experts recognized premedication as efficient and necessary, and premedication for previous transfusion reactions was frequently implemented, particularly for platelet transfusion or in patients with hematological diseases. Some institutions administered one or more drugs for premedication from the first transfusion. Antihistamines and hydrocortisone were the most frequently used as premedication. CONCLUSION Our study reports the current status of premedication for transfusion in Japan. Antihistamines and hydrocortisone were most commonly used for premedication despite a lack of evidence of their use. These findings may help clarify the indications for premedication and the use of washed blood products.