Monitoring Of Full Blood Count Research Articles

Peculiar Paliperidone – A Case of Neutropenia Despite Previous Uneventful Use of a Similar Antipsychotic

Schizophrenia is commonly treated with antipsychotic medications. Among the atypical antipsychotics, routine full blood count investigations are only recommended with the use of clozapine, due to a known risk of agranulocytosis. The objective of this index case is to present a patient who experienced leukopenia and neutropenia with the use of injectable paliperidone, despite previous successful treatment with risperidone. Paliperidone is the metabolite of risperidone and similar in structure. A patient with schizophrenia was treated with oral risperidone for 5 years, without adverse events. He was then given depot paliperidone for better compliance. In the subsequent months of follow-up, he was observed to have leukopenia and neutropenia despite only switching from oral to injectable therapy. Lithium carbonate was used to treat his hematological side effects. Treatment with antipsychotic medications can potentially lead to adverse outcomes, such as leukopenia and neutropenia. Apart from clozapine, routine screening of hematological profiles is not performed. Although hematological side effects from other antipsychotics are rare, they represent serious consequences. As such, there may be value in full blood count monitoring when switching to a new oral antipsychotic, or when switching from oral to injectable antipsychotic therapy. [ Psychiatr Ann . 2022;52(7):302–304.]

Haematological Monitoring in Clozapine Use: Blood Best Sampled in the Afternoon?

AimsClozapine is an atypical antipsychotic used in the management of Treatment-Resistant Schizophrenia (TRS). Despite its efficacy, Clozapine is associated with rare but clinically important haematological side effects of neutropenia and agranulocytosis, thus warranting regular monitoring of full blood count (FBC) white blood count (WBC) and neutrophil count (NC).Clozaril Patient Monitoring service (CPMS) supervises the prescribing of Clozapine and haematological testing for patients. Amber and Red alerts are issued by the CPMS when WBC and NC values fall below specified levels, Clozapine treatment is either suspended or discontinued completely.MethodsWe present a case of 35-year-old Caucasian lady with a history of schizophrenia who was maintained on Clozapine treatment for 10 years and whose Clozapine was necessarily stopped because of red alerts. This lead to a significant deterioration in her mental state and level of functioning necessitating a prolonged hospital admission.Results•Detailed retrospective review of this patient's CPMS results over a 2-year period identified consistently higher levels of WBC and NC, when the blood tests were conducted in the afternoon compared to mornings.•Literature review supported the phenomenon of a diurnal variation of WBC and NC levels in a proportion of patients prescribed Clozapine.•With clear knowledge of this patient's diurnal trends in WBC and NC count, it was possible to liaise with CPMS and restart her Clozapine treatment, leading to a significant improvement in her mental state and level of functioning.Conclusion•We recommend that clinicians consider this phenomenon of diurnal variation in blood parameters in patients with frequent amber and red alert results who are at risk of having their Clozapine medication discontinued.•Close collaboration with CPMS and haematological advice may lead to a more nuanced approach to blood sampling, whereby afternoon samples are used in certain at-risk patients.

Mind and body: physical health monitoring in clozapine treatment

AimsTo evaluate physical health monitoring standards in patients on Clozapine in the community.StandardsNICE and BNF guidelines for patients on established clozapine treatment advise annual monitoring of weight, waist circumference, pulse, blood pressure, fasting blood glucose, HbA1c, blood lipids and overall physical health assessment. Full blood count is monitored 1-4 weekly.BackgroundIn the management of schizophrenia, antipsychotic medication remains the cornerstone of treatment. Patients affected carry a significant physical health burden with a reduced life expectancy of 10-25 years. Factors that contribute include sedentary lifestyles, consequent obesity and cardiovascular disease, disengagement from health services, a higher incidence of suicide and the physical side effects of antipsychotic medication. For these reasons, comprehensive routine physical assessment of patients on antipsychotic treatment is of central importance.MethodThis audit is a retrospective study of patients known to South Kensington & Chelsea Community Mental Health Team (CMHT). Patients (n = 48) were audited from the Clozapine clinic SystemOne database over a one year period (October 2018-2019) to assess annual monitoring of full blood count (FBC), urea and electrolytes (U&Es), lipid profile, liver function tests (LFTs), HbA1C, thyroid function tests (TFTs), clozapine levels, ECG, and general physical and mental health review.ResultOf the 48 patients, one was transferred to a different service so was excluded (n = 47 total).All (100.0%) of the patients had annual FBC tests. All but one (97.9%) of the patients had a physical health review including blood pressure, pulse, weight and BMI measurement. Three quarters (74.5%) received annual U&Es and LFTs. Almost two thirds of patients had annual lipid and HBA1c screening (63.8%) and over half the cohort had annual TFTs (61.7%). Regarding annual multidisciplinary mental health review, this was performed for the majority of the patients (70.2%).Contrastingly, only a quarter of the patients received annual screening of glucose and Clozapine levels (27.7% for both). Only 12 patients had annual ECG (25.5%).ConclusionFollowing review it is clear that most parameters were monitored annually in a majority of patients. However, shortcomings were detected, specifically annual ECG and waist circumference monitoring.In order to ensure comprehensive monitoring of mental and physical health of patients on Clozapine, flow charts of tests and reviews needed for each patient were written up clearly and will be included in the management pathway for every patient on Clozapine. This was agreed to minimise missing any step, particularly annual ECGs.

Prescribing and monitoring high dose and combined antipsychotics in community mental health team

AimsThe aim was to establish the prevalence of prescription of combined and high dose antipsychotics in the community mental health team and to see if such patients were being offered regular monitoring as advised by NICE guidelines.BackgroundThe use of high dose antipsychotic treatment (HDAT) should be in line with the recommendations of the Royal College of Psychiatrists Consensus statement on high dose antipsychotic Treatment. Such treatment should be initiated only when standard treatments have failed. As high dose prescribing of antipsychotic medications can potentially harm than benefit causing serious side effects and sudden death. Close monitoring and documentation are required. Also, reviewing these patients at regular intervals is recommended.MethodA retrospective audit of 50 case notes of patients currently on antipsychotics was done. Case notes were selected randomly from a pool of 300 plus patients under the care of Isle of Wight NHS Trust in the HoNos Cluster 11 and 12 care pathways. Data were gathered on patients` demographics, diagnosis, medication monitoring. Data were analysed and discussed with consultant psychiatrist and senior mental health pharmacist. Patients who were not on any antipsychotic medications were not included in the audit.Result90% of the patients were on single antipsychotic (45 out of 50), 4.45% (2 out of 45)were above BNF recommended dose. 10% (5) patients were prescribed combined antipsychotics. 40% (2)of them were above BNF recommended maximum dose. A total of 8% (4 out of 50) patients were on above BNF recommended maximum dose. All the patients on high dose antipsychotics had a clear plan documented in the system. Documented monitoring of Full blood count was found in 75%, blood glucose in 50%, lipid in 75%, cardiac monitoring (Electrocardiogram or ECG) in 0%, physical health monitoring in 0%ConclusionAs far as we know, this is the first time an audit has been done on the patients under the Community Mental Health Team on high dose antipsychotic treatment. The data showed areas of good practice as the majority of the patients were on monotherapy, and all the patients on a high dose or combined antipsychotics had clear management plans outlined in their notes. However, the audit also highlighted areas that currently need improvements such as regular monitoring of the patients on high dose and combined antipsychotics. It should also be clearly documented, recorded, and reviewed at six-monthly intervals.

Routine blood monitoring in maintenance immunoglobulin treatment of inflammatory neuropathy: Is it clinically relevant?

BackgroundPre-treatment screening for IgA deficiency and close monitoring of full blood count(FBC) and renal function is recommended with intravenous immunoglobulin(IVIg) therapy in neurological diseases. AimsTo examine the frequency of biochemically defined and clinically significant episodes of treatment associated haemolysis, neutropenia, thrombocytopenia and acute kidney injury(AKI) in a cohort of patients on maintenance Immunoglobulin(Ig) therapy for inflammatory neuropathy. MethodsA retrospective review of routine blood monitoring in patients from two UK specialist peripheral nerve centres. Accepted definitions for clinically and biochemically significant haemolysis, neutropenia, thrombocytopenia and AKI were used. Results1919 infusion episodes in 90 patients were analysed. Age(mean(S.D)) = 58.09(14.4)years, 63% male, 72% CIDP(28% MMN), 97% IVIg(3% SCIg). Dose = 1.57(0.79)g/kg/month or 97.1(37.3)g/infusion, frequency:3.9(1.4) weeks.Relative IgA deficiency was noted in 2 individuals (prevalence:2.2%, 95%C.I.:0–5.2) who received a combined total of 38 infusions(3800 g IVIg) without adverse event. No clinically significant episodes of haemolysis, neutropenia, thrombocytopenia or AKI occurred in relation to treatment. An asymptomatic drop>10 g/L haemoglobin(Hb) occurred in 3.5%(95%CI:2.7–4.3) of treatment episodes in 38 individuals, mean reduction:17.7(7.4)g/L; lowest Hb:86 g/L. Lower pre-treatment haemoglobin correlated with risk of recurrent Ig-related drop(p:0.007). Two patients with chronic renal failure(stage 1 and 3) received 28(IV) and 104(SC) infusions respectively(6416 g) without impact on estimated glomerular filtration rate(eGFR). ConclusionsNo clinically significant Ig-related episodes of haemolysis or AKI were identified in this representative cohort. This suggests that routine monitoring is not essential in long-term Ig use but should be considered when clinically indicated.

How do paediatricians use and monitor antithyroid drugs in the UK? A clinician survey.

We aimed to document current practice in the medical management of paediatric hyperthyroidism in the UK and compare to international recommendations. A 27-question online survey distributed via an electronic newsletter in August 2018. Responses from 48 members (11%) of the British Society for Paediatric Endocrinology and Diabetes. Information about antithyroid drug (ATD) preference, treatment duration, monitoring of full blood count (FBC), management of neutropaenia, agranulocytosis screening and patient education. Carbimazole is favoured by 98% of respondents and a "dose titration" regimen preferred over "block and replace" (65% vs 29%). TRAbs (thyroid-stimulating hormone receptor antibodies) are used for diagnostic purposes by 85% and by 33% to look for evidence of disease remission. The majority (81%) treat for a minimum of 2years before considering a trial off ATD. All respondents reported that they "always/usually" warn their patients about the risk of agranulocytosis before starting ATD, but written information is "rarely/never" provided by 63%. Sore throat (98%) and fever (92%) are the most commonly cited symptoms used to alert a patient to possible agranulocytosis. FBC is measured prior to treatment by 65% and measured periodically during treatment by 70%. The management of paediatric hyperthyroidism with ATDs in the UK is not consistent with all international recommendations because a block and replace ATD regimen remains widely used. TRAbs are utilized at presentation, but underused for detecting disease remission. National consensus guidelines and written patient information may refine the management of paediatric patients on ATDs.

The Implications of Recent Recommendations for Managing Patients with Psoriasis Treated with Fumaric Acid Esters

Background/Aims: Fumaric acid esters (FAEs) are a well-established efficacious systemic treatment for psoriasis. Recent recommendations from the European Medicines Agency suggest monitoring of full blood count every 4 weeks for the duration of therapy for psoriasis. The aim of our study was to assess the incidence of lymphopenia in patients taking FAEs and the impact of recent recommendations for our practice. Methods: We reviewed 151 patients treated with FAEs for psoriasis between December 2013 and 2015. Results: Lymphopenia <700 × 10⁹/L was detected within the last 12 months in 36/151 (24%) and lymphopenia <500 × 10⁹/L in 10/151 (7%). Of 39 patients no longer on treatment, 7 (18%) stopped because of persistent lymphopenia. Conclusion: The implementation of these recommendations would have significant resource implications and also likely influence the acceptability of FAEs to patients. Cessation of FAEs necessitates the need for alternative therapy, commonly biologic therapy.

Sa1272 Thiopurine Prescribing and Monitoring Behavior, Including Metabolites Testing and Allopurinol Co-Therapy: An Australian Perspective From 2008 to 2013

Background: Thiopurines (TP) are a mainstay of inflammatory bowel disease (IBD) therapy. Thiopurine methyltransferase (TPMT) and TP metabolites testing have been suggested to predict variation in metabolism and response to therapy. However, prospective data to confirm clinical benefits of metabolites guided dosing is still limited, as are guidelines for TP monitoring. We aimed to evaluate current Australian gastroenterologists' (GEs) practice in TP use for IBD, including TPMT testing, full blood count (FBC) monitoring, metabolites testing, allopurinol co-therapy, effects on clinical outcomes, and how practices have changed over time. Methods: An anonymous survey was distributed to GEs by email and at meetings across Australia over 6 months in 2013. The results were compared with a similar survey conducted in 2008. The Chi-squared test was used to calculate statistical significance. Results: Most GEs started TP at escalating rather than full doses (76.6%). FBC monitoring intervals varied most in the first 3 months. Compared to 2008, TPMT had become more frequently tested (79.1% vs 44.5%, p 1 week for the majority (87.6%), and >2 weeks for a large minority (41.1%). The majority of GEs perceived that TP metabolites had improved clinical outcomes: improved response rates (80.6%), reduced complication rates (60.4%) and altered clinical practice (79.2%). Allopurinol co-therapy was used by the majority (71%), although not all for the same indications [82.8% for shunters with abnormal liver function tests (LFTs), 24.7% for shunters irrespective of LFTs, and 36.6% for side effects irrespective of LFTs]. Conclusions: Over the past 5 years, the practices of TPMT and TP metabolites testing have increased markedly and have altered TP prescribing practice amongst Australian GEs. However, variability exists in FBC monitoring and TP dosing, especially in context of reduced TPMT levels, as well as indications for TP metabolites testing and allopurinol cotherapy. Despite these, the subjective appraisals of the majority of Australian GEs were that TP metabolites testing had improved clinical outcomes. Further studies to objectively confirm these, and evidence to inform standardization of TP prescribing and monitoring practices are keenly awaited.

P442 Infliximab versus combination infliximab and immunosuppressant therapy for patients with active ulcerative colitis: a meta-analysis

Background: Thiopurines (TP) are a mainstay of inflammatory bowel disease (IBD) therapy. Thiopurine methyltransferase (TPMT) and TP metabolites testing have been suggested to predict variation in metabolism and response to therapy. However, prospective data to confirm clinical benefits of metabolites guided dosing is still limited, as are guidelines for TP monitoring. We aimed to evaluate current Australian gastroenterologists' (GEs) practice in TP use for IBD, including TPMT testing, full blood count (FBC) monitoring, metabolites testing, allopurinol co-therapy, effects on clinical outcomes, and how practices have changed over time. Methods: An anonymous survey was distributed to GEs by email and at meetings across Australia over 6 months in 2013. The results were compared with a similar survey conducted in 2008. The Chi-squared test was used to calculate statistical significance. Results: Most GEs started TP at escalating rather than full doses (76.6%). FBC monitoring intervals varied most in the first 3 months. Compared to 2008, TPMT had become more frequently tested (79.1% vs 44.5%, p 1 week for the majority (87.6%), and >2 weeks for a large minority (41.1%). The majority of GEs perceived that TP metabolites had improved clinical outcomes: improved response rates (80.6%), reduced complication rates (60.4%) and altered clinical practice (79.2%). Allopurinol co-therapy was used by the majority (71%), although not all for the same indications [82.8% for shunters with abnormal liver function tests (LFTs), 24.7% for shunters irrespective of LFTs, and 36.6% for side effects irrespective of LFTs]. Conclusions: Over the past 5 years, the practices of TPMT and TP metabolites testing have increased markedly and have altered TP prescribing practice amongst Australian GEs. However, variability exists in FBC monitoring and TP dosing, especially in context of reduced TPMT levels, as well as indications for TP metabolites testing and allopurinol cotherapy. Despite these, the subjective appraisals of the majority of Australian GEs were that TP metabolites testing had improved clinical outcomes. Further studies to objectively confirm these, and evidence to inform standardization of TP prescribing and monitoring practices are keenly awaited.

Current perspectives on tocilizumab for the treatment of rheumatoid arthritis: a review

Rheumatoid arthritis (RA) remains a major clinical problem with many patients having continuing systemic inflammatory disease resulting in progressive erosive damage and high levels of disability. A range of pro-inflammatory cytokines including tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6 are involved in RA pathogenesis; these cytokines can be specifically inhibited by biological agents. Tocilizumab (TCZ) is a recombinant humanized anti-IL-6 receptor monoclonal antibody, administered monthly by intravenous infusion that prevents IL-6 signal transduction. There is strong evidence that it is both clinically efficacious and cost-effective. There have been several key clinical trials evaluating the safety and efficacy of TCZ in RA patients. We review five Phase II trials and seven Phase III trials enrolling a total of 626 and 5268 RA patients respectively. The American College of Rheumatology (ACR) response criteria were used as the primary or secondary outcome measure in all trials. Overall these trials demonstrated that TCZ was effective in the treatment of RA in a number of patient groups, including those with an inadequate response to methotrexate (MTX) or TNF inhibition. TCZ use, both as monotherapy and in combination with MTX, improved the signs and symptoms of RA within several weeks of commencing treatment. Additionally, TCZ was shown to reduce radiological disease progression and improve physical function, both as monotherapy and in combination with MTX. A 5-year extension study demonstrated that TCZ sustained good long-term efficacy and safety profiles. TCZ was generally well tolerated. Although its use increased the risk of an adverse event, these were usually mild to moderate in severity and treatment did not increase the risk of a serious adverse event in comparison to controls. Due to moderate increases in serum levels of total cholesterol, triglycerides, high-density lipoproteins and serum transaminases seen in those patients treated with TCZ, as well as severe neutropenia in some, regular blood monitoring of full blood count, liver function and lipids is recommended. Given its clinical efficacy in the treatment of RA, TCZ may be beneficial in the treatment of other autoimmune diseases where IL-6 plays a role in the inflammatory cascade.

Hematological Effects of Valproate in Psychiatric Patients

Sodium valproate is an anticonvulsant that is also one of the common treatments used for bipolar disorder. The present study was conducted in psychiatric patients with the aim of examining the effects of valproate on hematological parameters and to explore any association with sex and age. A list of all psychiatric patients who underwent valproate level estimation in the years 2004-2008 in Newcastle upon Tyne was drawn from the biochemistry database of the local hospital. The names and date of births of these patients were used to draw corresponding hematological data, including hemoglobin, white blood cell count, mean corpuscular volume (MCV), and platelet count, conducted on the same day or within a week of the valproate level measurement. : The data from 126 patients were analyzed. The prevalence of thrombocytopenia (platelet count, <150,000/microL) was found to be approximately 5%. In female subjects, a significant negative correlation was found between serum valproate level and platelet count; also, a positive correlation between valproate level and MCV was found. Neither correlation was found in male subjects. The risk of a low platelet count was found to be significantly increased at serum valproate level above 80 microg/mL in female subjects. The regression analysis in female patients showed a trend toward fall in platelet count and an increase in MCV with increasing age. In psychiatric patients on valproate therapy, close monitoring of full blood count is required in women particularly at valproate serum level above 80 microg/mL. This may be particularly important in older patients.

Haematological management of obstetric haemorrhage

Obstetric haemorrhage (OH) remains the leading cause of maternal morbidity and mortality worldwide, 140 000–160 000 women die annually. Uterine atony (70%), and retained and invasive placentae remain the commonest causes. Rarely OH is due to an inherited bleeding disorder. Although risk factors and preventive strategies are documented, not all cases are expected or avoidable. Haematological management includes regular monitoring of full blood count and coagulation screen, with the appropriate use of blood products: red cells to maintain a Hb>8 g/dl; if APPT ratio and/or INR>1.5 then 15 ml/kg of fresh frozen plasma; if fibrinogen<1 g/L, then cryoprecipitate with 10 bags, increasing fibrinogen by approximately 1 g; if platelets<50 × 10 9 then one single donor pool. As fibrinolytic activation occurs with blood loss, 1–2 g tranexamic acid is suggested as it is safe, but as yet no studies of its use in OH have been undertaken. The use of rFVIIa is also reviewed. Women with OH are at high risk of venous thromboembolism post delivery and thromboprophylaxis is recommended for these women once bleeding has ceased.

Failure to monitor ticlopidine: the case for clopidogrel.

AIM: Ticlopidine remains unlicensed for use in coronary artery stenting. Haematological monitoring at two-weekly intervals of all patients taking ticlopidine is recommended because of the risk of neutropaenia. The authors assessed their ability to monitor a two-week course of ticlopidine given to patients undergoing coronary stenting procedures. METHODS AND RESULTS: One hundred and forty-one unselected consecutive patients undergoing coronary stenting procedures were prescribed ticlopidine 250 mg twice daily for two weeks, in addition to aspirin. Prior to discharge home they and their GPs were given written information outlining the side-effects of ticlopidine and the monitoring procedures required. One hundred and thirty-three patients (94%) completed the full two-week course of ticlopidine; three (2.4%) developed significant neutropaenia (neutrophil count <0.5 x 10(9)/mm(3)). Patient compliance with full blood count monitoring was 85% at two weeks and 80% at four weeks. Two patients (1.4%) suffered subacute stent thrombosis. At six months, there were no deaths, one (0.7%) myocardial infarction and nine patients (6%) requiring target vessel revascularization. CONCLUSION: A two-week course of ticlopidine is well tolerated and does not appear to be associated with an increase in adverse cardiac events. However, even with a dedicated monitoring team, adequate haematological follow-up was achieved in only 80% of patients. The need for a licensed antiplatelet agent which has a lower side-effect profile and does not require haematological monitoring is obvious.

Audit of full blood count monitoring in patients on longterm gold therapy for rheumatoid arthritis

The use of injectable gold in the treatment of rheumatoid arthritis (RA) is hampered by the high incidence of adverse reactions of which myelotoxicity is potentially the most serious. Regular full blood count (FBC) monitoring prior to each injection, a practice which requires much time and effort, has never been fully evaluated. Of 154 patients who were started on gold and followed by the lifetable method for up to 10 years, five patients were withdrawn from treatment because of myelotoxicity, thrombocytopenia in all cases: the two most serious cases occurred early at 3 and 7 months after starting treatment; three mild cases occurred at 17, 37 and 60 months, were of slow onset and reversed spontaneously. Clearly, FBC monitoring is justifiable in the first two years of treatment when the incidence of adverse reaction is highest. Further investigation is required to justify this practice after two years of uncomplicated treatment.