A comparison between erythrocytapheresis and venesection for the treatment of JAK2-mutated polycythaemia.

BACKGROUND: JAK2-mutated polycythaemia vera (PV) is associated with reduced survival because of thrombotic events and haematological disease transformation. Therapeutic venesection has traditionally been used to lower haematocrit, but the technique of erythrocytapheresis has emerged over the last decade. AIM: To compare erythrocytapheresis with venesection as treatment for PV by assessing medical efficacy and financial viability. METHODS: One hundred sixteen patients with PV who received red cell depletion therapy at Barwon Health between 2014 and 2021 were identified. The haematocrit drop after each session, interval between treatment times and number of sessions required to achieve a haematocrit <0.45 were compared with an independent t test. Thrombosis rates were compared with Pearson's chi-squared test. Cost-funding analysis was done by assessing the Weighted Inlier Equivalent Separation and National Weighted Activity Unit funding models. RESULTS: Patients treated with erythrocytapheresis achieved a greater haematocrit drop each treatment session (0.075 vs 0.03, P < 0.01), required fewer sessions to achieve a haematocrit <0.45 (1 vs 4, P < 0.01) and experienced fewer thrombotic complications (8.7% vs 32.1%, P = 0.02) than those treated with venesection. Cost-funding analysis demonstrated that erythrocytapheresis was more financially viable with a surplus of AU$297 per session compared to a deficit of AU$176 with venesection. Even if funding for venesection is increased, the cost of erythrocytapheresis may be mitigated by a lower number of procedures required per year (3.8 vs 5.3, P < 0.01). CONCLUSIONS: Erythrocytapheresis is more efficacious than venesection for the treatment of PV and is accompanied by rapid reductions in haematocrit and reduced thrombotic complications.

EASL Clinical Practice Guidelines on haemochromatosis.

Haemochromatosis is characterised by elevated transferrin saturation (TSAT) and progressive iron loading that mainly affects the liver. Early diagnosis and treatment by phlebotomy can prevent cirrhosis, hepatocellular carcinoma, diabetes, arthropathy and other complications. In patients homozygous for p.Cys282Tyr in HFE, provisional iron overload based on serum iron parameters (TSAT >45% and ferritin >200 µg/L in females and TSAT >50% and ferritin >300 µg/L in males and postmenopausal women) is sufficient to diagnose haemochromatosis. In patients with high TSAT and elevated ferritin but other HFE genotypes, diagnosis requires the presence of hepatic iron overload on MRI or liver biopsy. The stage of liver fibrosis and other end-organ damage should be carefully assessed at diagnosis because they determine disease management. Patients with advanced fibrosis should be included in a screening programme for hepatocellular carcinoma. Treatment targets for phlebotomy are ferritin <50 µg/L during the induction phase and <100 µg/L during the maintenance phase.

A critical evaluation of the role of iron overload in fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) has been associated with a condition known as the dysmetabolic iron overload syndrome, but the frequency and severity of iron overload in NAFLD is not well described. There is emerging evidence that mild to moderate excess hepatic iron can aggravate the risk of progression of NAFLD to nonalcoholic steatohepatitis and eventually cirrhosis. Mechanisms are postulated to be via reactive oxygen species, inflammatory cytokines, lipid oxidation, and oxidative stress. The aim of this review is to assess the evidence for true hepatic iron overload in NAFLD, to discuss the pathogenesis by which excess iron may be toxic, and to critically evaluate the studies designed to deplete iron by regular venesection. In brief, the studies are inconclusive due to heterogeneity in eligibility criteria, sample size, randomization, hepatic iron measurement, serial histological endpoints, target ferritin levels, length of venesection, and degree of confounding lifestyle intervention. We propose a trial designed to overcome the limitations of these studies.

The effect of therapeutic phlebotomy for hemochromatosis on non-suicidal self-injury: A case report.

BACKGROUND: Self-phlebotomy has been described as a form of non-suicidal self-injury. However, a relationship between non-suicidal self-injury and therapeutic phlebotomy for hemochromatosis has not previously been described. Case presentation: We present a case of a 52-year-old man in whom the frequency of his therapeutic phlebotomy and non-suicidal self-injury were inversely linked, leading to adverse outcomes when his phlebotomy was suspended. CONCLUSIONS: This is the first report describing the relationship between non-suicidal self-injury and therapeutic phlebotomy. This case highlights the need for risk assessment and monitoring of self-harm in patients who are undergoing therapeutic phlebotomy in order to prevent adverse outcomes.

A cohort study assessing the impact of small volume blood tubes on diagnostic test quality and iatrogenic blood loss in a cohort of adult haematology patients.

BACKGROUND/AIM: To estimate the reduction in blood volume loss and impact on diagnostic test quality associated with introduction of small volume blood tubes in a cohort of haematology inpatients compared to a historical comparator group. METHODS: Prospective cohort study of haematology inpatients admitted to a tertiary referral hospital in Adelaide. Small volume blood tubes were used in an intervention cohort admitted between 2012 and 2013 and compared to a control cohort admitted between 2009 and 2010 where standard volume blood tubes had been used. The diagnostic test quality, specimen integrity and total reduction in blood loss associated with small volume blood tubes were estimated. RESULTS: Small volume blood tubes demonstrated acceptable collinearity on commonly assayed haematological and biochemical parameters. Small volume tubes were associated with a 42% reduction in blood volume loss equating to a saving of 8.5 mL per patient per day or 180 mL of blood loss over a 3-week admission. Small volume blood tubes were associated with a slight but significantly increased rate of fibrin contamination of ethylenediaminetetraacetic acid samples (0.2-0.5% of specimens). CONCLUSION: Small volume blood tubes are associated with a substantial reduction in total blood volume collected per day in haematology inpatients. They have similar diagnostic validity and sample integrity to that of standard volume containers.

A retrospective analysis of the impact of treatments and blood counts on survival and the risk of vascular events during the course of polycythaemia vera.

Vascular and non-vascular complications are common in patients with polycythaemia vera. This retrospective study of 217 patients with polycythaemia vera aimed to determine whether blood counts with respect to different treatments influenced the complication rate and survival. We found that 78 (36%) patients suffered from at least one complication during follow-up. Older age and elevated lactate dehydrogenase at diagnosis were found to be risk factors for vascular complications. When the vascular complication occurred, 41% of the patients with a complication had elevated white blood cells (WBC) compared with 20% of patients without a complication (P = 0·042). Patients treated with hydroxycarbamide (HC; also termed hydroxyurea) experienced significantly fewer vascular complications (11%) than patients treated with phlebotomy only (27%) (P = 0·013). We also found a survival advantage for patients treated with HC, when adjusted for age, gender and time period of diagnosis (Hazard ratio for phlebotomy-treated patients compared to HC-treated patients at 5 years was 2·42, 95% confidence interval 1·03-5·72, P = 0·043). Concerning survival and vascular complications, HC-treated patients who needed at least one phlebotomy per year were not significantly different from HC-treated patients with a low phlebotomy requirement. We conclude that complementary phlebotomy in HC-treated patients in order to maintain the haematocrit, is safe.

Controlled moderate hypovolaemia in healthy volunteers is not associated with the development of oxidative stress assessed by plasma F2-isoprostanes and isofurans.

Hypovolaemia can be associated with substantial morbidity, particularly when it occurs in the setting of trauma and in patients with comorbid diseases. Hypovolaemia and inflammation such as occur in the setting of trauma and surgery, are associated with systemic oxidative stress and free-radical injury. Free-radical injury that results from hypovolaemia-induced organ reperfusion may further augment inflammatory processes. It is unknown exactly what proportion of free-radical injury is associated with isolated hypovolaemia as opposed to the contribution from inflammation from surgery or trauma. In the first human study of its kind, we exposed 8 adult male volunteers to venesection-induced hypovolaemia in progressive aliquots of 5% of total blood volume until 20% had been removed. This blood was subsequently reinfused. Plasma F2-isoprostanes and isofurans, markers of in vivo lipid oxidation, were measured by gas chromatography-mass spectrometry at each 5% aliquot venesected and at each 5% reinfused. Between baseline and maximal blood loss there was a minor fall in haemoglobin concentration from 143.9g/l to 138.8g/l (p=0.004, 95% CI 2.2, 8.0g/L). No significant change from baseline occurred in the concentrations of either plasma F2-isoprostanes or isofurans during venesection (p=0.116 and p=0.152, respectively) or blood reinfusion (p=0.553 and p=0.736, respectively). We can conclude that in healthy adult volunteers, isolated hypovolaemia to 20% total blood volume loss is not associated with detectable systemic oxidative stress. The free-radical injury identified in surgical and trauma patients may represent the effects of tissue damage and inflammation, with an uncertain contribution from tissue ischemia as may occur with hypovolaemia.

Difficult venesections: An easy solution.

Venesection is common procedure performed in day to day life of every doctor. Conventional vein finders available are costly and not easily available. The present paper highlights the use of makeshift vein finder.

Crohn's Disease, Hemochromatosis, Hepatocellular Carcinoma, and Liver Cirrhosis: A Case Study.

Hemochromatosis, an inherited disorder characterized by excessive iron absorption and accumulation, can lead to organ damage and is a known contributor to liver cirrhosis. This case report discusses a 57-year-old man with a history of Crohn's disease, whose general practitioner identified elevated ferritin levels, cirrhotic liver features, and abnormal liver function tests. Further investigation revealed non-hereditary hemochromatosis, hepatic cirrhosis, and hepatocellular carcinoma (HCC). This case highlights the rare coexistence of hemochromatosis and Crohn's disease, underscoring the diagnostic and therapeutic challenges of managing these concurrent conditions. It also emphasizes the importance of prompt and effective treatment to prevent severe complications.

Comparative efficacy of acupuncture, venesection, and physical therapy on chronic low back pain outcomes: a randomized clinical trial.

Objective: Chronic low back pain (CLBP) imposes considerable financial and social burden with poor response to medical and surgical treatments. Alternatively, acupuncture and venesection(Fasd) are traditionally used to alleviate nociceptive and musculoskeletal pains. This study aimed to evaluate the effectiveness and the safety of acupuncture and venesection on CLBP and patient functionality. Methods: The current study was a single-blinded, randomized clinical trial with balanced allocation, conducted in the Department of Physical Medicine & Rehabilitation Medicine, in 2022. One hundred five CLBP patients who had no back pain-attributable structural or major diseases were randomly allocated into three parallel arms and received either physical therapy (PTG), acupuncture (APG), or venesection (VSG). Pain severity and functional aspects were evaluated using the visual analogue scale (VAS) and Oswestry disability index (ODI) during the study. VAS and ODI scores were defined as the primary outcomes. Results: Ninety-five patients were reviewed in the final analysis (PTG=33, APG=30, VSG=31). Demographic data showed equal group distribution. Statistical analysis showed all procedures had reduced VAS score immediately after the first session, after the last session, and after follow-up; however, APG and VSG values were significantly lower (P<0.05). Pain reduction results in follow-up period were more sustainable in APG and VSG as compared to PTG (P<0.01). ODI results revealed global improvement after the last session of the treatment in all groups, while APG had more significant results (P<0.05). During the follow-up period, ODI still tended to decrease in VSG, non-significantly increased in APG, and significantly increased in PTG. Only two patients reported fainting after receiving venesection. Conclusion: Considering the pain and functional scores, both acupuncture and venesection can reproduce reliable results. Acupuncture and venesection both have sustained effects on pain and daily function of the patients even after treatment termination, while physical therapy had more relapse in pain and functional limitations.

The effectiveness of wet cupping vs. venesection on arterial O2 saturation level of cigarette smokers: A randomized controlled clinical trial.

OBJECTIVE: Wet cupping is a traditional bloodletting method recommended for controlling of respiratory disease complications. This study aimed to compare the efficacy of wet cupping vs. venesection on arterial O2 saturation level of smokers. METHODS: This is a randomized controlled clinical trial which started with simple sampling of smokers. After administering spirometery, participants (N = 110 male smokers) with positive pulmonary function test (PFT), who manifested Chronic Obstructive Pulmonary Disease (COPD), were randomly assigned to intervention and control groups. The two groups were assessed in terms of demographic data, rate of hemoglobin (Hb), hematocrit (Hct), and arterial O2 saturation. Then, the intervention participants underwent wet cupping whereas venesection was performed on the control participants. At four stages after the two treatments, pulse oximetery was performed. Data was analyzed using SPSS (Version 17). RESULTS: Result shows that mean arterial O2 sat level increased at three stages, namely before, immediately after, and 6 and 12 hrs after these two treatments (p ≤ 0.001). This indicates that wet cupping and venesection alike were effective on O2 sat level in the two groups, but the increasing pattern was maintained 12 hrs afterward only in those participants who had received wet cupping (p ≤ 0.001). Moreover, the results of repeated measure ANOVA between the two groups at the four stages showed that there were significant differences between the means of O2 saturation level at the 6- and 12-hrs stages (F = 66.92, p ≤ 0.001). CONCLUSION: Wet cupping caused a continued O2 saturation in the intervention group even up to 12 hrs afterward. Participants expressed liveliness and improved respiration after wet cupping. Therefore, wet cupping is recommended for promoting the health of cigarette smokers.

Lights Off, Lights On: Amaurosis Fugax in Polycythemia.

There are many causes of amaurosis fugax, including polycythemia. Polycythemia is associated with elevated hematocrit levels and hyperviscosity, which can lead to ocular manifestations. We report a polycythemia patient with amaurosis fugax, who had resolution of ocular symptoms following venesection. A 29-year-old gentleman presented with a six-month history of episodic bilateral transient loss of vision (amaurosis fugax), followed by slow recovery back to normal after 15-20 minutes. The symptoms worsened with fatigue. He also had an unsteady gait for the preceding one year. Ocular examination was unremarkable. His visual acuity was 20/20 OU. Neurological examination revealed gait ataxia and dysdiadochokinesia. Computed tomography (CT) angiogram showed an old cerebellar infarct. Blood investigations showed persistent elevated hemoglobin and hematocrit with positive JAK-2 V617F mutation. Infective and connective tissue workups were all negative. A diagnosis of polycythemia was made by the haematology team. In addition to oral aspirin given by the neurology team, he underwent venesection with improvement in ocular symptoms following each episode of venesection. The frequency of amaurosis fugax reduced from 2-3 episodes a week to once a month, then resolved completely after five venesections. Systemically, his cerebellar symptoms also resolved and there were no neurological deficits. Polycythemia is a rare disease that can cause amaurosis fugax and thrombotic events in young patients. Better knowledge and accurate diagnosis are important, as early treatment may improve the symptoms and long-term morbidity.

A New Treatment Approach for Acute Propanil Poisoning: A Case Report.

Propanil is a widely used herbicide in agriculture and is also an important cause of poisoning in Sri Lanka. Incidence is around 2% and is commonly reported as self-poisoning. Although it is classified as an agent with low to medium toxicity, severe poisoning can cause lethal outcome and death especially when there is a limited medical facility. We describe a case of severe Propanil poisoning who was successfully treated in a peripheral hospital with available facilities.

Evaluation of the Effectiveness of Modified Pectoral Nerve Blocks Type II (PECS II) for Vascular Access Port Implantation Using Cephalic Vein Venesection.

The vascular access port implantation procedure can be performed using the venesection method by inserting a catheter into the cephalic vein in the region of the deltopectoral groove. This method eliminates the need for catheter tunneling. An alternative method to infiltration anaesthesia for port implantation may be a modified pectoral nerve block type II (PECS II). This study aimed to evaluate the effectiveness of modified PECS II for vascular access port implantation using cephalic vein venesection. This retrospective observational study was conducted at the 4th Military Clinical Hospital in Wroclaw, Poland. A group of 114 patients underwent the modified PECS II block and additional cutaneous infiltration anesthesia at the incision line. Pain intensity was assessed on the NRS scale measured intraoperatively at four points. The QoR-15 questionnaire was used to assess patient satisfaction during the first 24 h after surgery. The operator's condition assessment score was used to assess surgical conditions and operator comfort. The analysis showed that the median pain intensity during vascular port implantation was 0. A statistically significant difference in pain intensity was demonstrated between the specialist's group and the resident's group at the second and third measurement points (p < 0.008; p < 0.012). The mean value on the QoR-15 scale was 132. There was a significant difference between the pain scores of the groups. The mean score in the pain position in the specialist's group was 18 points and in the resident's group, it was 19 points (p < 0.029). In conclusion, the present study revealed that the modified PECS II block is an effective and safe method of anesthesia for Port-A-Cath implantation.

Transient elevation of serum ferritin in a Sri Lankan with homozygosity for H63D mutation in the HFE gene: a case report.

INTRODUCTION: Hereditary hemochromatosis is an inherited disorder of iron metabolism, characterized by excessive iron deposition in major organs of the body, leading to multi-organ dysfunction. It is a genetically heterogeneous disease caused by mutations in one or more different genes, the most common being mutations in the HFE gene. HFE hereditary hemochromatosis is mostly found in Europeans and is almost always a result of two mutations: C282Y and H63D. The H63D mutation is not as penetrant as the C282Y mutation, but there are rare reported cases of hereditary hemochromatosis with homozygous H63D genotype. While the C282Y mutation is primarily confined to persons of Northern European origin, the H63D mutation is spread worldwide. Other types of hereditary hemochromatosis are rare and broadly defined as non-HFE hereditary hemochromatosis and include mutations in the hemojuvelin gene, hepcidin (HAMP gene), transferrin receptor 2 gene, and ferroportin gene. Hereditary hemochromatosis is commonly found in populations of European origin; in contrast, it is rare and less well understood in Asia. It can be masked by the presence of concurrent iron deficiency or secondary iron overload in thalassemias. CASE PRESENTATION: We report the case of a 42-year-old Sri Lankan man investigated for fatigue during a brief upper respiratory tract infection and found to have high liver transaminases and high serum ferritin, which persisted even after complete resolution of the infection. Homozygosity for H63D mutation in the HFE gene was detected. Liver enzymes, serum ferritin, and transferrin saturation normalized following venesections. CONCLUSION: This case adds to the literature on the importance of being vigilant and investigating patients suspected for iron overload, including genetic studies for hereditary hemochromatosis, even though it is a rare clinical entity in Asians.

Systemic iron reduction by venesection alters the gut microbiome in patients with haemochromatosis.

BACKGROUND & AIMS: Iron reduction by venesection has been the cornerstone of treatment for haemochromatosis for decades, and its reported health benefits are many. Repeated phlebotomy can lead to a compensatory increase in intestinal iron absorption, reducing intestinal iron availability. Given that most gut bacteria are highly dependent on iron for survival, we postulated that, by reducing gut iron levels, venesection could alter the gut microbiota. METHODS: Clinical parameters, faecal bacterial composition and metabolomes were assessed before and during treatment in a group of patients with haemochromatosis undergoing iron reduction therapy. RESULTS: Systemic iron reduction was associated with an alteration of the gut microbiome, with changes evident in those who experienced reduced faecal iron availability with venesection. For example, levels of Faecalibacterium prausnitzii, a bacterium associated with improved colonic health, were increased in response to faecal iron reduction. Similarly, metabolomic changes were seen in association with reduced faecal iron levels. CONCLUSION: These findings highlight a significant shift in the gut microbiome of patients who experience reduced colonic iron during venesection. Targeted depletion of faecal iron could represent a novel therapy for metabolic and inflammatory diseases, meriting further investigation. LAY SUMMARY: Iron depletion by repeated venesection is the mainstay of treatment for haemochromatosis, an iron-overload disorder. Venesection has been associated with several health benefits, including improvements in liver function tests, reversal of liver scarring, and reduced risk of liver cancer. During iron depletion, iron absorption from the gastrointestinal (GI) tract increases to compensate for iron lost with treatment. Iron availability is limited in the GI tract and is crucial to the growth and function of many gut bacteria. In this study we show that reduced iron availability in the colon following venesection treatment leads to a change in the composition of the gut bacteria, a finding that, to date, has not been studied in patients with haemochromatosis.

Cotton Mather's medicine, with particular reference to measles.

While the vocation of Cotton Mather (1663-1728) was his ministry in Boston, he made important contributions to medicine, most famously in helping to introduce variolation to New England in 1721-22 and in writing The Angel of Bethesda (1724), the first medical treatise produced in Colonial North America. This article, however, focuses on an earlier initiative, Mather's efforts to quell the epidemic of measles that struck Boston in 1713, killing among many others his wife and three children. Historians have devoted little attention to this episode or to measles in general, even though the disease was highly mortal during the colonial period. To help victims, Mather published a 'letter' on treating measles. Such a specific discussion of treatment would have been rare in Europe and it was unprecedented in America. The therapy that Mather proposed not only reflected popular medicine but also incorporated newer practices, notably those associated with Thomas Sydenham. In contrast to heroic therapies for measles, which were often dangerous but became more popular across the eighteenth century, Mather's recommendations were moderate.

Investigating the ability of non-invasive measures of cardiac output to detect a reduction in blood volume resulting from venesection in spontaneously breathing subjects.

BACKGROUND: Monitoring cardiac output (CO) in shocked patients provides key etiological information and can be used to guide fluid resuscitation to improve patient outcomes. Previously this relied on invasive monitoring, restricting its use in the Emergency Department (ED) setting. The development of non-invasive devices (such as LiDCOrapidv2 with CNAP™ and USCOM 1A), and ultrasound based measurements (Transthoracic echocardiography, inferior vena cava collapsibility index (IVCCI), carotid artery blood flow (CABF) and carotid artery corrected flow time (FTc)) enables stroke volume (SV) and CO to be measured non-invasively in the ED. We investigated the ability of these techniques to detect a change in CO resulting from a 500 ml reduction in circulating blood volume (CBV) following venesection in spontaneously breathing subjects. Additionally, we investigated if using incentive spirometry to standardise inspiratory effort improved the accuracy of IVC based measurements in spontaneously breathing subjects. METHODS: We recorded blood pressure, heart rate, IVCCI, CABF, FTc, transthoracic echocardiographic (TTE) SV and CO, USCOM 1A SV and CO, LIDCOrapidv2 SV, CO, Stroke volume variation (SVV) and pulse pressure variation (PPV) in 40 subjects immediately before and after venesection. The Log-Odds and coefficient of variation of the difference between pre- and post-venesection values for each technique were used to compare their ability to consistently detect CO changes resulting from a reduction in CBV resulting from venesection. RESULTS: TTE consistently detected a reduction in CO associated with venesection with an average decrease in measured CO of 0.86 L/min (95% CI 0.61 to 1.12) across subjects. None of the other investigated techniques changed in a consistent manner following venesection. The use of incentive spirometry improved the consistency with which IVC ultrasound was able to detect a reduction in CBV. CONCLUSIONS: In a population of spontaneously breathing patients, TTE is able to consistency detect a reduction in CO associated with venesection.

Hemochromatosis: a model of metal-related human toxicosis.

Many environmental agents, such as excessive alcohol intake, xenobiotics, and virus, are able to damage the human body, targeting especially the liver. Metal excess may also assault the liver. Thus, chronic iron overload may cause, especially when associated with cofactors, diffuse organ damage that is a source of significant morbidity and mortality. Iron excess can be either of acquired (mostly transfusional) or of genetic origin. Hemochromatosis is the archetype of genetic iron overload diseases and represents a serious health problem. A better understanding of iron metabolism has deeply modified the hemochromatosis field which today benefits from much more efficient diagnostic and therapeutic approaches.