scholarly journals Advances in the Treatment of Hemophilia: Implications for Laboratory Testing

2019 ◽  
Vol 65 (2) ◽  
pp. 254-262 ◽  
Author(s):  
Armando Tripodi ◽  
Veena Chantarangkul ◽  
Cristina Novembrino ◽  
Flora Peyvandi
Keyword(s):  
Coagulation Factors ◽  
Alternative Methods ◽  
Laboratory Evaluation ◽  
One Stage ◽  
New Therapeutic Approaches ◽  
Novel Drugs ◽  
Coagulation Tests ◽  
Bypassing Agents ◽  
Long Acting ◽  
Near Future

Abstract BACKGROUND Until recently, clinical laboratories have monitored hemophilia treatment by measuring coagulation factors before/after infusion of human-derived or recombinant factors. Substantial changes are expected in the near future based on new therapeutic approaches that have been or are being developed. CONTENT Hemophilia treatment includes replacement therapy with human-derived/recombinant factors or treatment with bypassing agents for patients without or with inhibitors, respectively. Accordingly, laboratory methods for monitoring include one-stage clotting or chromogenic assays meant to measure either factor VIII/IX or global coagulation tests to measure the effect of bypassing agents. Recently, modified long-acting coagulation factors have been introduced for which discrepant results may be expected when measurement is performed with one-stage clotting or chromogenic assays. Currently, novel drugs not based on coagulation factors are under development and are being tested in clinical studies. These drugs do require new methods and therefore laboratory evaluation of hemophilia will undergo dramatic changes in the near future. SUMMARY From the analysis of the current practice and literature, we draw the following conclusions: (a) Thrombin generation or thromboelastometry are the logical candidate assays to monitor bypassing agents. (b) Considerable differences are expected when measuring modified long-acting coagulation factors, depending on whether one-stage or chromogenic assays are used. Although no definitive conclusions can presently be drawn, chromogenic assays are probably more suitable than one-stage clotting. (c) Novel drugs not based on coagulation factors such as emicizumab, fitusiran, or concizumab that are entering the market do require alternative methods that are not yet well established.

Classical and modern drug extraction techniques: facts and figures

2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Bharti Umrethia ◽  
Bharat Kalsariya ◽  
Prof. P. U. Vaishnav
Keyword(s):  
Solvent Extraction ◽  
Dosage Forms ◽  
Herbal Extract ◽  
Alternative Methods ◽  
Extraction Techniques ◽  
Modern Drug ◽  
Novel Drugs ◽  
Wide Range ◽  
In The Mists ◽  
Heating Pattern

In present era, herbal extract succeeds inimitable place in pharmaceutical science. In view back the earliest extraction techniques are lost in the mists of history. As time went the plants have been processed by grinding, boiling or immersing. The systemic presentation of Ayurvedic extraction system has been first time familiarized by Acharya Charaka as Panchavidha Kashaya Kalpana (five basic primary dosage forms) and based upon these primary dosage forms, secondary dosage forms are developed by using different heating pattern for extraction of pharmacological active ingredients. The administration of these dosage forms is mainly dependent on the Bala (strength) of Vyadhi (disease) and Atura (patient). Due to increased demand of Ayurvedic medicines and industrialization, the transformation of classical dosage forms takes place by implanting a wide range of technologies with different methods of extraction include conventional techniques such as maceration, percolation, infusion, decoction, hot continuous extraction etc. and recently, alternative methods like ultrasound assisted solvent extraction (UASE), microwave assisted solvent extraction (MASE) and supercritical fluid extractions (SFE). The extract obtained by these procedure uses as a large source of therapeutic phyto-chemicals that may lead to the development of novel drugs. Essentially, the purpose behind this changing face in both the extraction systems are different but can say that it is a new insight from ancient essence.

New insights of CRISPR technology in human pathogenic fungi

2019 ◽  
Vol 14 (14) ◽  
pp. 1243-1255 ◽  
Author(s):  
Elvira Román ◽  
Daniel Prieto ◽  
Rebeca Alonso-Monge ◽  
Jesús Pla
Keyword(s):  
Mammalian Cells ◽  
Genetic Manipulation ◽  
Pathogenic Fungi ◽  
Biological Research ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Short Palindromic Repeat ◽  
Future Outcomes ◽  
Near Future ◽  
Genome Manipulation

Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-Cas systems have emerged as a powerful tool for genome manipulation. Class 2 type II CRISPR/ CAS9 is so far the most studied system and has been implemented in many biological systems such as mammalian cells, plants, fungi and bacteria. Fungi are important causes of human diseases worldwide. Genetic manipulation of pathogenic fungi is critical to develop new therapeutic approaches and novel antifungals. We will review here the progress done with CRISPR/ CAS9 systems in human pathogenic fungi, with emphasis in Candida albicans and the main modifications that have improved their usefulness in biological research. We finally discuss possible future outcomes and applications to the developed in a near future.

Influence Of Elastase On Blood Coagulation Factors: Studies In Vitro, In Rats And In Göttinger Miniatur Pigs

1981 ◽  
Author(s):  
U Kasten ◽  
U Artmann ◽  
T Kaethner ◽  
H Burchardi ◽  
H Köstering
Keyword(s):  
Blood Coagulation ◽  
Coagulation Factors ◽  
Bleeding Complications ◽  
Thrombin Time ◽  
Normal Range ◽  
Blood Coagulation Factors ◽  
Acute Respiratory Insufficiency ◽  
Coagulation Tests ◽  
Antifibrinolytic Drugs

The influence of blood coagulation factors in pat. with acute respiratory insufficiency of adults, especially of the so called “pancreatitis lungs” is still unknown. In order to find out the effect of elastase, possibly activated by trypsin in pat. with acute pancreatitis, on blood coagulation factors, we performed some studies. In vitro elastase induces in plasma and blood in correlation to the dosages Enhancement of thrombingeneration in the TGT, a shortening of PTT, Thrombin time and of r- and k-time in the TEG, a loss of fibrinogen and an increase of fibrinmono-mercomplexes. In another study, elastase (960 U/ kg b.w.) was injected intravenously in rats. 30 min. later there was found a loss of fibrinogen, number of platelets, Prothrombin and a prolongation of PTT and Thrombin time and an increase of fibrinomonomercomplexes, especially in these rats, which received beside elastase Kalikreininhibitors or antifibrinolytic drugs. After repeated injections (3 times within 30 h) we found histomorpholgically thrombi as well as bleeding complications. In another study we performed (150 min) an infusion of elastase (333 U/kg b.w./h) to 9 pigs. We determined a loss of fibrinogen of platelets, of F. II, F. VII and F. XIII, a prolongation of PTT. F. VIII and F. V remained within the normal range But there was found an enhancement of Thrombin generation in the TGT, too. Compariening the results of blood coagulation tests and of histomorphological findings, elastase induced a DIC. We have to discuss their influence on ARIA and “Pancreatic lungs”.

scholarly journals Biological Rationale for New Drugs in the Bleeding Disorders Pipeline

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 397-404 ◽  
Author(s):  
Patrick F. Fogarty
Keyword(s):  
Coagulation Factor ◽  
Coagulation Factors ◽  
Developed Countries ◽  
Factor Ix ◽  
New Drugs ◽  
Joint Disease ◽  
Novel Agents ◽  
Clotting Factor ◽  
Alternative Pathways ◽  
Long Acting

AbstractSince the introduction of replacement coagulation factor infusions for the treatment of hemophilia in the 1970s and subsequent improvements in the safety profile of available factor VIII (FVIII) and factor IX (FIX) concentrates, mortality among patients with hemophilia has improved considerably and now parallels that of the noncoagulopathic population in developed countries. Substantial morbidity, however, continues from the development of inhibitory antibodies, a recognized complication of clotting factor replacement; from infections and thrombosis complicating placement of central venous catheters, which are required in children with hemophilia due to frequent prophylactic infusions of coagulation factors with defined half-lives; and from disabling joint disease in individuals without access to costly prophylaxis regimens. In response to the need for long-acting, more potent, less immunogenic, and more easily administered therapies, an impressive array of novel agents is nearly ready for use in the clinical setting. These therapeutics derive from rational bioengineering of recombinant coagulation factors or from the discovery of nonpeptide molecules that have the potential to support hemostasis through alternative pathways. The number of novel agents in clinical trials is increasing, and many of the initial results are promising. In addition to advancing treatment of bleeding episodes or enabling adherence to prophylactic infusions of clotting factor concentrate, newer therapeutics may also lead to improvements in joint health, quality of life, and tolerability of iatrogenic or comorbidity-associated bleeding challenges.

scholarly journals Stimulation of a non-functioning pituitary macroadenoma after administration of goserelin acetate for locally advanced prostate cancer causing a sustained elevation in PSA and testosterone

2013 ◽  
Vol 6 (2) ◽  
Author(s):  
Fady R. Youssef ◽  
Robert T. Robinson ◽  
Nigel R. Boucher
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Locally Advanced ◽  
Elevated Serum ◽  
Serum Testosterone ◽  
Androgen Deprivation ◽  
Alternative Methods ◽  
Pituitary Macroadenoma ◽  
Locally Advanced Prostate Cancer ◽  
Long Acting

Long-acting luteinizing hormone-releasing hormone (LHRH) agonists, such as goserelin, have been used for locally advanced and metastatic prostate cancer for many years and are the main forms of androgen deprivation therapy (ADT). Acting on pituitary LHRH receptors, they initially stimulate a transient rise in serum follicle stimulating hormone (FSH) and LH. Long-term administration of an LHRH analogue will eventually lead to down regulation of LHRH receptors, thus suppressing FSH and LH secretion. This in turn suppresses testosterone production hence achieving and maintaining androgen deprivation. This case highlights the potential anomaly of a sustained elevated serum testosterone in the context of newly diagnosed locally advanced prostate cancer with a co-existing pituitary macroadenoma after administration of LHRH analogues. Alternative methods of androgen deprivation must be considered in such patients.

LUPUS ANTICOAGULANT (LA) COEXISTENT WITH TRANSIENT PROTHROMBIN (FII) INHIBITOR: FTI DEFICIENCY DUE TO CLEARANCE OF THE B/MUNOCOMPLEX

1987 ◽  
Author(s):  
R Redaelli ◽  
F Baudo ◽  
B Busnach ◽  
T M Caimi ◽  
L Perrino ◽  
...  
Keyword(s):  
Survival Time ◽  
Replacement Therapy ◽  
Lupus Anticoagulant ◽  
Normal Tissue ◽  
Past History ◽  
Laboratory Data ◽  
Coagulation Factors ◽  
Precipitin Line ◽  
Coagulation Tests ◽  
Tissue Thromboplastin

23 y.o. man with acute nephritis and bleeding (epistaxis, ecchymosis) at presen-taticn. Family and personal past history negative for bleeding. Laboratory data consistent with SLE. Coagulation tests: FT Ratio (R) 1.8, aPTT R 2.4, FII:C <1%, FIIR:Ag 996, other coagulation factors normal. Tissue thromboplastin inhibition test (TTIT) R 2.8, congenital FII deficiency (696) R 1.6.1. FII survival time (Fll-ccncentrate infusion - 60 U/kg) t1/2: 9 hours.2. FII neutralizing activity (FTI:C normal plasma (NP) + buffer 5996; NP + patient plasna {PtP) 5096): absent.3. Irmunoccrplex formaticn4. FII inhibitor characterization (purified FII coupled to CNBr-activatedSepharose →PtP incubation with Fll-Sepharose→specific antiFII irrrrunoglobulins (Ig)* elution at acid pH→identification by double iimunodifftision): precipitin line with anti IgA, anti IgG2, anti k, anti 1.5. LA characterization (after FII inhibitor disappearance): TTTT on mixtures NP + PtP or N Ig in equal volumes.Diagnosis: SIE, LA (IgG); polyclonal (IgA, IgG2, k, 1) not neutralizing FII inhibitor; hypoprothrxmbinemia due to clearance of the irrrrunocorrplex.FII inhibitor was transient. Bleeding was rapidly controlled by replacement therapy. LA persits after FII inhibitor disappearance.

scholarly journals Defibrination Syndrome Developed after Replacement Therapy with PPSB in a Case of Hemophilia B.

1977 ◽  
Author(s):  
M. Kazama ◽  
H. Iwakura ◽  
M. Nakajima ◽  
M. Abe ◽  
T. Abe
Keyword(s):  
Bleeding Complication ◽  
Severe Pain ◽  
Coagulation Factors ◽  
Massive Bleeding ◽  
Hemophilia B ◽  
Valgus Osteotomy ◽  
The Third ◽  
Coagulation Tests ◽  
Fresh Plasma ◽  
Large Hematoma

A case of Hemophilia B, 20y., had valgus osteotomy of the left femoral neck. The preliminary replacement with PPSB was revealed not to introduce inhibitor and no other abnormal enzyme activity was found except for the slight disturbance of liver function. The operation was gotten ready with injection of 10 vials PPSB and performed smoothly in 2 hours with 340ml of blood loss. PPSB administration was scheduled in a daily dosis of 20 vials divided in twice. But at the third postoperative day, large hematoma concreted in the femoral region with severe pain and was followed by the massive bleeding from the wound. Coagulation tests revealed decreased platelet count, prolonged.PTT and prothrombin time, decreased fibrinogen and increased FDP. The concentration of F.IX was not lifted so high as expected after the injection of 10 vials of PPSB, which, together with the above mentioned changes of coagulation factors, suggested the developement of defibrination syndrome.The replacement of PPSB was continued together with 10,000 U of heparin and 800ml of fresh plasma per day. At the 7th postoperative day, the coagulation findings of defibrination syndrome were gradually improved, bleeding decreased and F. IX level elevated as could be calculated. The administration of PPSB was diminished and discontinued at 29th day and of heparin at 45th day without any bleeding complication thereafter.

scholarly journals The Effect of 3.2% and 3.8% Sodium Citrate on Specialized Coagulation Tests

2018 ◽  
Vol 142 (8) ◽  
pp. 992-997
Author(s):  
Franz Ratzinger ◽  
Mona Lang; ◽  
Sabine Belik; ◽  
Klaus G. Schmetterer ◽  
Helmuth Haslacher ◽  
...  
Keyword(s):  
Coagulation Factors ◽  
Reference Ranges ◽  
Buffer Concentration ◽  
Citrate Buffer ◽  
Citrate Concentration ◽  
Confirmation Test ◽  
Coagulation Testing ◽  
Significant Difference ◽  
Coagulation Tests ◽  
The Difference

Context.— Coagulation testing is challenging and depends on preanalytic factors, including the citrate buffer concentration used. Objective.— To better estimate preanalytic effects of the citrate buffer concentration in use, the difference between results obtained by samples with 3.2% and 3.8% citrate was evaluated. Design.— In a prospective observational study with 76 volunteers, differences related to the citrate concentration were evaluated. For both buffer concentrations, reference range intervals were established according to the recommendations of the C28-A3 guideline published by the Clinical and Laboratory Standards Institute. Results.— In our reagent-analyzer settings, most parameters evaluated presented good comparability between citrated samples taken with 3.2% and 3.8% trisodium buffer. The ellagic acid containing activated partial thromboplastin time reagent (aPTT-FS) indicated a systemic and proportional difference between both buffer concentrations, leading to an alteration in its reference ranges. Further, a confirmation test for lupus anticoagulant assessment (Staclot LA) showed only a moderate correlation (rρ = 0.511) with a proportional deviation between both citrate concentrations. Further, a statistically significant difference was found in the diluted Russell viper venom time confirmation testing, coagulation factors V and VIII, and the protein C activity, which was found to be of minor clinical relevance. Conclusions.— With caution regarding the potential impact of the reagent-analyzer combination, our findings demonstrate the comparability of data assessed with 3.2% and 3.8% buffered citrated plasma. As an exception, the aPTT-FS and the Staclot LA assay were considerably affected by the citrate concentration used. Further studies are required to confirm our finding using different reagent-analyzer combinations.

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