Treatment Of Sickle Cell Crisis Research Articles

SAFETY OF UVARIA CHAMAE P. BEAUV ROOTS AQUEOUS EXTRACTS IN WISTAR RATS

Uvaria chamae is used in the treatment of sickle cell crisis in Benin. The aim of this work is to determine the safety of Uvaria chamae roots aqueous extract in wistar rats. The aqueous extract was obtained by maceration. The tests for Acute Oral Toxicity (AOT) and of Sub-Chronic Oral Toxicity (SCT) respectively by forced gavage in a single dose of 2000 mg / Kg and 200 mg / Kg of body weight for 28 days were performed on female Wistar rats. The weight of the animals, serum creatinine, transaminases and the number of white blood cells were determined on day 0 and then on day 14 and day 28 respectively for AOT and SCT. Histologic analysis of the liver, kidneys and spleen was performed for both tests. There were no deaths in toxicity testing and organ histology did not show atypia. Weight, serum AST and ALT transaminases, and mean white blood cell count did not change significantly between the start and end of the experiment for both AOT and SCT. Only creatinine decreased significantly for SCT, indicating more protection of kidney function. Uvaria chamae roots did not show hepatic, renal and immune toxicity in the acute or sub-chronic state.

New Prescriptions After Hospitalization: A Bitter Pill or Just What the Doctor Ordered?

New Prescriptions After Hospitalization: A Bitter Pill or Just What the Doctor Ordered?

Manual Partial Exchange Transfusion a Cost Effective Life Saving Intervention in Sickle Cell Crisis: Single Centre Retrospective Data Analysis

Introduction: Sickle cell disease (SCD) poses a considerable health burden in lower middle income country (LMIC) like India. One ICMR survey reported about 20% of children with SCD died by the age of two years and 30% of children with SCD amongst the tribal community in India died before they reached adulthood. Data on mortality rate in the adult population with SCD is sparse. Our centre data shows that despite the availability of Hydroxyurea and supportive care, almost one-third of hospitalized Sickle Cell Crisis patients develop life threatening complications. Manual Partial Exchange Transfusion is a cost-effective intervention to decrease mortality in Sickle Cell Crisis. But perhaps, it is an underutilized therapy. In India, the cost incurred for each session of exchange transfusion, if done by the RBC apheresis machine, is $420. Whereas Manual Exchange Transfusion costs only $70(including the cost of the central venous catheter) for the first session followed by $15 for each subsequent session. Aim: A single centre retrospective data analysis to evaluate the outcome of Sickle Cell Crisis patients undergoing Manual Partial Exchange Transfusion during hospitalization. Material and Method: A total of 553 SCD patients on regular follow up at the Haemato Oncology Care Centre (HOCC) from July 2012 to July 2020 were evaluated.169 patients were hospitalized for treatment of Sickle Cell Crisis at the Bhailal Amin General Hospital and Sterling Hospital Vadodara. The data was retrieved after the IRB/Apex committee approvals for retrospective analysis. The indication for exchange transfusion was Acute Chest Syndrome 19(35%), Hepatic cell crisis 11(20%), Vaso Occlusive Crisis not responding to the conservative line of therapy in 48 hours of treatment 11(20%), Cerebrovascular Accident (CVA) 5 (9%), Avascular Necrosis of Femur with excruciating pain 3 (6%), Complicated Dengue with Multi-organ failure 3 (6 %), Priapism 1 (2%) and Splenic Sequestration 1 (2%). Central venous access was secured with a central venous catheter or dialysis catheter. Simple packed cell volume was transfused to 11(20%) patients and 5(9%) patients received platelet transfusion. The cut-off values for HB and Platelet count were 8 gm% and 50000/cumm, respectively at the time of the Manual Partial Exchange Transfusion procedure. Blood volume withdrawn was 5 to 10 ml /kg, followed by an equal volume of packed cell volume transfusion at every session. The procedure was repeated every 12 hr or 24 hr depending on the clinical condition of the patient. HbS value was reassessed post 4 sessions with repeat testing done after 2 to 4 sessions if the observed HbS value was more than 30% or more than 10% (for CVA) after 4 sessions. The endpoint was clinical recovery with HbS less than 30% or no clinical recovery despite the achievement of HbS less than 10%. In CVA the endpoint was HBS less than 10%. Results: Manual Partial Exchange Transfusion was carried out in 54/169 (32 %) hospitalized patients. The median age was 25yrs (range 5 yrs to 69 yrs), with male predominance [Males 42(77%) and females 12(23%)].Pre procedure HbF value was <10% in 13(24%), 10 to 20% in 23 (43%) and >20% in 18(33%). A total of 50 out of 54 (93%) patients recovered completely. 28 (52%) patients were hemodynamically stable with normal SPO2 on room air at the time of Manual Partial Exchange Transfusion with an average of 7 days of hospitalization. All of these patients recovered completely with less than 5 sessions of Manual Partial Exchange Transfusion. 26(49%) patients were critically ill and had an average of 12 days of hospitalization. They were on Ventilator and Inotrope support at the time of Manual Partial Exchange Transfusion. 14/26(54%) critically ill patients recovered completely with an average of 6 sessions of Manual Partial Exchange Transfusion. 12/26(46%) critically ill patients succumbed even though post exchange HBS value decreased to less than 10%. The overall mortality rate of SCD patients in this analysis was 12/553 (2.1%), significantly lower than what was historically reported as 30% in the ICMR survey. Underlying Dengue viral infection associated with Multi-organ dysfunction and Fulminant hepatic failure were risk factors for mortality observed in our study. Conclusion: Manual Partial Exchange Transfusion is highly effective in reducing mortality in Sickle Cell Crisis. It is feasible and cost-effective in small centres lacking apheresis machine facility. Disclosures No relevant conflicts of interest to declare.

Update in Hematology and Oncology: Evidence Published in 2016.

Articles about advances in the treatment of sickle cell crisis, the use of agents to reverse anticoagulation, and targeted treatment of immune thrombocytopenia are highlighted. A study on how long ...

Agonists of the A2A adenosine receptor reduce inflammation and hypoxia‐induced pulmonary damage in transgenic sickle cell mice

Polymerization of deoxygenated HbS is the primary event in the molecular pathogenesis of sickle cell disease (SCD). Recently it has been proposed that chronic inflammation plays an important role in the etiology of vaso-occlusive crisis (VOC) and long-term pathologic manifestations of SCD. SCD patients and transgenic mice (NY-S) expressing human betaS globin exhibit increased plasma levels of pro-inflammatory cytokines, increased numbers of circulating endothelial cells, leukocytosis, and elevated expression of cell-surface activation markers on leukocytes and endothelial cells. Adenosine acts through the A2A adenosine receptor (A2AAR) found on bone marrow-derived cells to inhibit inflammation. We used hypoxia/reoxygenation to trigger VOC in NY-S mice and assessed plasma cytokine levels, hypoxia-induced lung inflammation and pulmonary function following the subcutaneous administration of the highly selective adenosine A2A receptor agonist, ATL146e (10 ng/kg/min). Compared to vehicle treated NY-S mice, ATL146e-treated mice displayed: 1) decreased plasma IL-6 levels; 2) reduced severity of hypoxia-induced vascular congestion as evidenced by pulmonary histology; 3) decreased pulmonary hypoxia based on 2-nitroimidazole hypoxia staining in lung tissue sections and in vivo pulmonary accumulation of BRU59-21, a 99mTc-labeled 2-nitroimidazole; and 4) improved pulmonary function (decreased breathing frequency and minute volume, increased expiratory time) as measured using whole-body plethysmography. These data suggest that A2A adenosine agonists may be clinically useful for the treatment of sickle cell crisis. NIH grant #PO1 HL073361.

Changing practice of emergency department pain management in sickle cell crisis: Past, present, and future

Study objectives: I assess the impact of continuous quality improvement (CQI) approach used in the treatment of sickle cell crisis. Methods: This was a retrospective study undertaken in the Accident and Emergency Department (ED) of Queen Elizabeth Hospital, Barbados. A new protocol devised for the treatment of patients with sickle cell crisis was introduced for use in this department in September 2001. Data were collected on patients who presented to this department before and after the introduction of the new protocol to assess the impact of this new protocol. Outcomes measured were waiting time, time to analgesia, total time spent in the ED, interval between subsequent doses of analgesics, and admission rate. Results: Mean waiting time in a cubicle before being treated by emergency physicians in the pre-CQI period was 1 hour 49 minutes and in the post-CQI period was 4 hours 8 minutes. Mean waiting time before the patient received analgesics in the pre-CQI period was 2 hours 30 minutes (men) and 2 hours 45 minutes (women). In the post-CQI period, it was 2 hours 33 minutes (men) and 2 hours 13 minutes (women). Total time spent in the ED in the pre-CQI period was 9 hours 26 minutes (men) and 10 hours 59 minutes (women). In the post-CQI period, these times were 12 hours and 10 minutes (men) and 12 hours 54 minutes (women). In the pre-CQI period, 16% of patients needed to be admitted to the inpatient facility, but in the post-CQI period, it was 44.7%. Conclusion: After the introduction of the CQI, there was an overall increase in the waiting time and in total time spent in the ED, along with an increase in the overall admission rate to the inpatient facility. No significant change has been noted in the time to receive analgesics. The introduction of the CQI in the management of sickle cell crisis pain has not been as effective as expected.

Intra-operative use of inhaled vasodilators: are there indications?

The US Food and Drug Administration and European authorities have recently approved inhaled nitric oxide for the treatment of neonates with hypoxic respiratory failure associated with pulmonary hypertension. In addition to this highly specific condition, there is an increasing 'off-label' use of inhaled nitric oxide and other inhaled vasodilators in the perioperative setting. Potential indications include right heart failure as a result of acute pulmonary hypertension in cardiac and non-cardiac surgery, the prevention of reperfusion injury in lung transplantation, the treatment of hypoxaemia during single-lung ventilation, and more recently, the treatment of sickle cell crisis.

Isoxsuprine in the Treatment of Sickle Cell Painful Crises: A Double-Blind Comparative Study with Narcotic Analgesic

Isoxsuprine is a tocolytic agent which improves erythrocyte deformability. It was accidentally found to be effective in the management of sickle cell disease (SCD) painful crises. The experience with the drug in the treatment of sickle cell disease is limited. This double-blind randomized comparative study was undertaken to test its efficacy and safety in the treatment of SCD painful crises. Forty-three SCD patients (33 males and 10 females) with 44 episodes of pain were included in the study (i.e., one patient was included twice). Only those with painful crises requiring hospital admission were included. Patients were randomized to receive either isoxsuprine 5-10 mg, or meperidine 50100 mg intramuscularly, according to body weight, every four hours. A random selection of 23 patients received isoxsuprine, and 21 received meperidine. Pain score, duration of crisis, hospital stay, and side effects were monitored. No significant difference was found in any parameter except for pain score at 30 and 60 minutes. We conclude that isoxsuprine appears to be effective in the treatment of sickle cell painful crises. Confirmation of its efficacy in studies involving a larger number of patients is warranted.

Fluosol in the treatment of sickle cell crisis

Fluosol in the treatment of sickle cell crisis

Fluosol in the treatment of sickle cell crisis

The enhancement of oxygen delivery to ischemic tissue has long been a goal of sickle cell treatment. Fluosol, a member of the family of compounds known as perfluorocarbons, solubilizes large volumes of oxygen which should be beneficial in vaso-occlusive crises. A clinical trial using Fluosol in the management of sickle cell crisis was undertaken in seven patients, three men and four women, aged 18–37 y, with homozygous S-S disease. Patients were randomized within 12 h of hospital admission to standard supportive care, with or without Fluosol, 20 mL/kg, given intravenously over 4–10 h. Presenting symptoms in most patients were leg and back pain. A crossover design allowed both methods of treatment to be tested in each patient. Parameters evaluated included subjective pain intensity, rapidity of pain relief, cumulative narcotic use, and duration of crisis. At 48 h, pain intensity and narcotic use were not measurably different between Fluosoltreated crises and those treated with standard supportive care. Acute toxicity, in the form of hypertension and vomiting, prompted the withdrawal of one patient, and two others experienced hematuria and worsening of back pain, respectively, following Fluosol administration. In summary, this study was not able to demonstrate that Fluosol improved treatment. Variables including the timing of drug administration, dose, and stage of crisis may need to be assessed in a larger trial before concluding that Fluosol has no role in sickle cell disease.

Experience with isoxsuprine in the treatment of sickle cell crisis: a proposed mechanism of action.

An accidental clinical observation triggered this investigation into the possible beneficial effects of isoxsuprine in the treatment of painful sickle cell crisis. Twenty-four patients were studied with a total of 34 episodes of painful crisis. As they had all been previously treated by us we knew the duration of their crisis under conventional treatment, so that the two regimens with and without isoxsuprine could be compared. Isoxsuprine was administered in 3 successive steps: (1) as an IM injection (5-10 mg), (2) as a rapid IV infusion (1 mg/minute), and (3) as a slow, continuous IV infusion, (0.1-0.3 mg/minute). The results from this study suggest that isoxsuprine exerts in fact a remarkable action in sickle cell crisis by bringing about prompt relief in approximately 80% of the cases within 5 hours, and in 40% of the cases within 2 hours. There were only 2 cases of absolute failure. The hospitalization time was remarkably reduced and the use of narcotics was minimized. Side effects (tachycardia, palpitations, somnolence) have been observed mainly in cases where relatively high doses of isoxsuprine had to be administered IV.

Treatment of sickle cell crisis with urea in invert sugar. A controlled trial. Cooperative urea trials group

Treatment of sickle cell crisis with urea in invert sugar. A controlled trial. Cooperative urea trials group

The Molecular Basis for the Treatment of Sickle Cell Crisis by Intravenous Urea.

Excerpt We show that the molecular basis for the use of intravenous urea in the treatment of sickle cell crisis is supported by molecular pathology and in vitro experiments. We have been able to in...