Immune-mediated Hemolytic Anemia Research Articles

A Case of Evanʼs Syndrome Triggered by Vedolizumab

Clinical trials have shown Vedolizumab to be a safe and highly effective therapy in treating inflammatory bowel disease. Its unique gut-specific mechanism of action has made it an attractive agent in recent years. However, Vedolizumab's side effect profile and long-term effects are not yet fully understood. We report a patient with ulcerative colitis (UC) presenting with epistaxis found to have a Vedolizumab-induced severe immune-mediated thrombocytopenia and hemolytic anemia, otherwise known as Evan's syndrome. Our patient is a 26 year-old man with a history of ulcerative pancolitis who presented with epistaxis and hematuria one week after his first Vedolizumab infusion. In terms of his UC history, he had been diagnosed with UC one year prior through colonoscopy and was initially managed with Mesalamine and Adalimumab with persistent symptoms of bloody diarrhea and abdominal pain. He was then switched to Vedolizumab and within five days, began experiencing severe epistaxis and scant hematuria. Physical exam was notable only for mild left lower quadrant tenderness. He was found to have a severe thrombocytopenia with a nadir of 7 K/μL. He had findings consistent with a hemolytic anemia with an indirect bilirubinemia, elevated LDH, and decreased haptoglobin. Direct Coomb's testing was positive and he was diagnosed with Evan's syndrome. He was treated with corticosteroids, intravenous immunoglobulin, and Rituximab. Both his UC symptoms and blood counts improved on treatment. He was eventually discharged on a Prednisone taper. All of his blood counts returned to normal four weeks after discharge. Evan's syndrome is a rare autoimmune disorder characterized by a Coomb's positive autoimmune hemolytic anemia and thrombocytopenia. It has been associated with several disorders and medications. However, to our knowledge, this is the first documented case of Vedolizumab-induced Evan's syndrome. This case highlights the potential for a paradoxical immunogenicity associated with the drug. Although there is excellent safety data on Vedolizumab, clinicians should be aware of this potentially rare but serious side effect. Rapid recognition and treatment of this uncommon disorder is essential. Ongoing post-market drug safety monitoring may help to fully understand all of the potential long and short term side effects of Vedolizumab.2099 Figure 1 No Caption available.

Phenylephrine use for blood sparing during splenectomy in a dog

A dog with immune-mediated haemolytic anaemia was presented for splenectomy. Phenylephrine administration immediately before the removal of the spleen induced splenic contraction and significantly elevated packed cell volume. This technique...

Resolution of iatrogenic calcinosis cutis in a dog through topical application of DMSO

A dog with calcinosis cutis was treated by topical dimethyl sulfoxide (DMSO) administration, reaching a complete involution of symptoms. DMSO is well-known for its transdermal penetration and anti-inflammatory capacity. For...

Pharmacokinetics of human recombinant C1-esterase inhibitor and development of anti-drug antibodies in healthy dogs

Complement-mediated intravascular hemolysis occurs in canine immune-mediated hemolytic anemia (IMHA). Complement inhibitors such as recombinant C1 esterase inhibitor (rC1-INH) might prevent this process and alter the disease course. This study aimed to characterize the pharmacokinetics of a single 500 IU IV dose of rC1-INH in 8 healthy beagle dogs, evaluate the dogs for any adverse effects of drug administration, and determine whether rC1-INH administration induces anti-drug antibody formation. Serum rC1-INH concentrations were measured using a commercial functional ELISA at baseline and at 10, 20, 40, 60, 80, 100, 120, 240, 360, 480, 600, 720, 960, and 1440 min post drug administration. Complete blood counts were conducted at baseline, 720 and 1440 min. Western blot analysis, using rC1-INH as the target antigen was used to detect anti-drug antibodies in 14-day serum samples. No adverse clinical reactions were noted following rC1-INH administration. Pharmacokinetic modelling suggested that the peak C1-INH concentration achieved is 0.21 IU/mL and that C1-INH concentration is significantly greater than baseline for 100 min following injection. A robust antibody response was detected which suggests that rC1-INH should not be re-administered after an initial course. Clinical trials of rC1-INH in dogs with intravascular IMHA are now warranted.

Primary Splenic Torsion in Dog as a Cause of Atypical Acute Abdomen

Background: A primary splenic torsion occurs when the organ rotates around its vascular pedicle in the absence of any other concomitant disease. The occurrence of primary splenic torsion is rare, with a prevalence lower than 1%. Splenic torsion is more often related to dilated gastric volvulus syndrome, and it has no clear etiology despite reports that associate it with congenital abnormalities or traumatic ruptures of the gastrosplenic or splenocolic ligaments. This study reports a case of splenic torsion in an American Pit Bull terrier dog, its related symptomatology, and the treatment adopted.Case: A 3-year-old male American Pit Bull terrier dog weighing 32 kg was admitted to the hospital with symptoms of acute abdomen, lethargy, increased abdominal volume, discomfort, restlessness, and with a history of collapse three days prior to admission. Clinical examination revealed lethargy, pale mucous membranes, reduced capillary refill time, moderate dehydration, and hyperthermia. Abdominal palpation revealed increased abdominal volume in the epigastric and mesogastric areas. CBC and serum biochemistry profile revealed hypochromic normocytic anemia, leukocytosis with absolute neutrophilia and eosinopenia, mild hypoalbuminemia, and thrombocytopenia. PCR for detection of Babesia sp. and Ehrlichia sp., which returned negative results, and measurement of clotting time, which was prolonged, were performed to exclude immune-mediated hemolytic anemia. Radiographic and ultrasonographic images showed a normal stomach, but revealed presence of splenomegaly. An exploratory laparotomy allowed direct observation of the spleen, which exhibited an increased volume, a blackened, cold, hyperemic appearance, and a complete torsion of the splenic vascular pedicle; the surgical team opted to perform total splenectomy rather than undoing the pedicle twist. The animal returned to the hospital after 10 days exhibiting an excellent clinical condition. Healing of the incisional wound was satisfactory, with formation of epithelial tissue throughout its extension. Thirty days after the surgery, the hematological parameters were within normal ranges. The animal was discharged, and its owner received information on adequate nutrition.Discussion: Clinical evaluation of symptoms of discomfort and increase in abdominal volume, especially on the left side, together with the information of the anamnesis, led to a suspicion of splenic torsion in this case. Splenic torsion can exhibit numerous clinical signs; here, ultrasound imaging allowed diagnosis of this condition. The anemia observed by means of the hematological tests could be explained by sequestration of red blood cells by the rotated spleen, with and inflammatory leukogram resulting from inflammation of the poorly perfused parenchyma, local peritonitis, and, possibly, increased release of neutrophils from the bone marrow. Thrombocytopenia and prolonged clotting time may be secondary to splenic torsion, as shown in this case. Splenectomy is the treatment of choice in cases of acute splenic torsion. This procedure is relatively easy to perform. Additionally, merely undoing the torsion does not prevent its recurrence, and may allow necrotic debris to reach the circulation. No intercurrences or involvement of adjacent organs were observed in this patient. This is due to factors such as early diagnosis, preoperative stabilization of the patient, and the short time between diagnosis and the surgical procedure, reiterating its importance in emergency conditions such as splenic torsion.

Factors associated with immune hemolytic anemia after pediatric liver transplantation.

Immune-mediated hemolytic anemia following SOT is a rare disorder, the risk factors for which are unknown. Our purpose was to analyze a seemingly increased incidence in our center with the aim to identify predisposing factors. This recipients single-center retrospective study reviewed the medical records of 96 pediatric LT between 2000 and 2013. IHA was defined as acute anemia with a positive direct antiglobulin test. Seven cases of immune-mediated hemolytic anemia were identified (incidence 8.5%). Three cases presented during the first 3months following LT (early IHA), and 4 presented later (late IHA). All patients with late IHA required rituximab. Using univariate analysis, the following factors were associated with IHA onset: BA (P=.04), younger age (P=.04), and the use of IGL-1 preservation solution (P=.05). Late IHA was associated with viral infections occurring beyond 3months following LT, younger age, and BA (P=.01). Overall, CMV infection was associated with the development of both early and late IHA: CMV-negative recipients who received an organ from a CMV-positive donor were more likely to develop IHA (P=.035), and de novo CMV infection during the first year post-LT was associated with late IHA (P=.03). IHA is a rare complication following pediatric LT, occurring more frequently in younger patients and patients with an initial diagnosis of BA. CMV-negative recipients and patients who experience a de novo CMV infection in the first year following LT seem particularly vulnerable. IGL-1 preservation solution may be associated with an increased likelihood of developing IHA, a novel finding which warrants further investigation.

Case-control study of plasma mean platelet component concentration and survival analysis for dogs with immune-mediated hemolytic anemia.

OBJECTIVE To determine whether dogs with immune-mediated hemolytic anemia (IMHA) had a low plasma mean platelet component (MPC) concentration and whether MPC was associated with outcome. DESIGN Retrospective case-control study and survival analysis. ANIMALS 95 dogs with IMHA (cases) as well as 95 healthy dogs and 95 sick dogs without IMHA (controls) matched to cases by age, reproductive status, and breed. PROCEDURES Plasma MPC concentration at initial examination was compared among groups. For dogs with IMHA only, sex, age, serum urea and bilirubin concentrations, Hct, platelet count, and plasma fibrinogen, D-dimer, and MPC concentrations were evaluated for associations with survival to 42 days after initial examination. RESULTS Plasma MPC concentration was significantly lower in dogs with IMHA than in the other 2 dog groups. In dogs with IMHA, plasma MPC concentration was the only factor significantly associated with outcome. The optimal plasma MPC concentration cutoff value for predicting nonsurvival of dogs with IMHA was 19.1 g/dL; values ≤ 19.1 g/dL were associated with nonsurvival. Likewise, the survival curve for dogs with plasma MPC concentrations ≤ 19.1 g/dL differed significantly from that for dogs with values > 19.1 g/dL. The mean estimated risk of death for dogs with IMHA decreased by 16% for every unit increase in plasma MPC concentration. CONCLUSIONS AND CLINICAL RELEVANCE In dogs with IMHA, platelets appeared to have been activated to a greater degree, as determined by lower plasma MPC concentrations, than in healthy dogs or sick dogs without IMHA. Plasma MPC concentration at initial examination may be useful for predicting prognosis in dogs with IMHA.

Influence of immune-mediated hemolytic anemia on flow velocities in the portal vein and caudal vena cava measured by use of pulsed-wave Doppler ultrasonography in dogs.

OBJECTIVE To compare blood flow velocities of the portal vein (PV) and caudal vena cava (CVC) measured by use of pulsed-wave Doppler ultrasonography in clinically normal dogs and dogs with primary immune-mediated hemolytic anemia (IMHA). ANIMALS 11 client-owned dogs admitted to a veterinary teaching hospital for management of primary IMHA and 21 staff- or student-owned clinically normal dogs. PROCEDURES Flow velocities in the PV and CVC at the porta hepatis were evaluated in conscious unsedated dogs with concurrent ECG monitoring; evaluations were performed before dogs with IMHA received heparin or blood transfusions. Three measurements of peak velocity at end expiration were obtained for each vessel, and the mean was calculated. Results were compared between IMHA and control groups. RESULTS Mean ± SD blood flow velocity in the CVC differed between control (63.0 ± 18.6 cm/s) and IMHA (104 ± 36.9 cm/s) groups. Variance in dogs with IMHA was significantly greater than that for the clinically normal dogs. No significant difference in blood flow velocity in the PV was detected between IMHA and control dogs. CONCLUSIONS AND CLINICAL RELEVANCE Higher blood flow velocities were detected by use of pulsed-wave Doppler ultrasonography in the CVC of dogs with naturally occurring IMHA and may be used to predict anemia in patients suspected of having IMHA.

Immunosuppressive therapy in dogs and cats. Properties of drugs and their use in various immune-mediated diseases

Veterinarians are regularly faced with the diagnosis and therapy of immune-mediated diseases. More frequently occurring immune-mediated diseases are immune-mediated hemolytic anemia, immunemediated thrombocytopenia and polyarthritis. Glucocorticoids are commonly used as first-line treatment because of their availability, efficacy and rapid action. Nevertheless, some patients do not respond to glucocorticoid therapy alone. Others require a rapid dose reduction because of severe side effects from glucocorticoid treatment. These patients benefit from adjuvant therapies. Ciclosporin preparations are licensed for use in veterinary medicine. The use of azathioprine, mycophenolate mofetil and human immunoglobulin therapy has also been documented. This article describes the mode of action of certain immunosuppressive agents and their use in selected diseases from recent literature.

Efficacy of the combination of glucocorticoids, mycophenolate-mofetil and human immunoglobulin for the therapy of immune mediated haemolytic anaemia in dogs

Idiopathic immune-mediated haemolytic anaemia (IMHA) is one of the most common immune-mediated diseases in dogs with a high mortality rate. In this retrospective study, we examined the effect of mycophenolate- mofetil (MMF) and human intravenous immunoglobulin (hIVIG) in combination with glucocorticoids on canine IMHA patients. Six dogs were treated with prednisolone and MMF (hIVIG-) and in 15 patients hIVIG was added (hIVIG+). There was no significant difference between the groups regarding age, weight, number of blood transfusions or hematocrit on the day of diagnosis. The hIVIG+ group showed a significantly faster recovery of the hematocrit, but this difference was only short-lived. The survival in the first year was similar in both groups and was with 71.5% somewhat higher than in other published studies. The addition of MMF to prednisolone for the treatment of dogs with acute IMHA was well tolerated and seemed to positively affect the course of the disease. Randomized studies are necessary to confirm this observation. Human immunoglobulin had only minimal clinical advantages and no effect on mortality.

How to…

This month Simon Tappin, Editor of Companion, discusses diagnosis and treatment of canine immune-mediated haemolytic anaemia.

In vivo effects of aspirin and cyclosporine on regulatory T cells and T-cell cytokine production in healthy dogs

Cyclosporine and aspirin are routinely used in combination to treat immune-mediated hemolytic anemia (IMHA) in dogs. Cyclosporine is a potent immunosuppressive agent that targets T cell production of the cytokines IL-2 and IFN-γ. Low-dose aspirin is often used to inhibit platelet function in dogs with IMHA, since these animals are prone to life-threatening thromboembolic disease. In rodents and humans, aspirin and cyclosporine have both been shown to variably affect T cell cytokine production, and also numbers of circulating regulatory T cells (Tregs). In dogs, it has not yet been determined if concurrent aspirin alters the effects of cyclosporine on T-cell cytokine expression, or if either drug influences Treg numbers.In a crossover study, seven healthy young adult dogs were given either oral high-dose cyclosporine (10 mg/kg Q12 h), oral low-dose aspirin (1 mg/kg Q24 h), oral high-dose aspirin (10 mg/kg Q12 h), or combined low-dose aspirin with cyclosporine, each for 8 days, with a washout of at least 2 weeks after each treatment. Activated T cell cytokine expression (IL-2 & IFN-γ) and percent CD4 + CD25 + FOXP3+ Tregs were evaluated using flow cytometry, both prior to and on the last day of treatment. The difference between pre- and post-treatment values for each group, as well as the difference between treatment groups, was evaluated.Cyclosporine significantly decreased IL-2 and IFN-γ expression when used alone or in combination with low-dose aspirin. High-dose aspirin, but not low-dose aspirin, also significantly decreased IL-2 expression, although the decrease was not as marked as that seen with cyclosporine alone or in combination with aspirin. Neither low-dose nor high-dose aspirin significantly affected IFN-γ expression. No drug or drug combination affected Treg numbers.Low-dose aspirin given with cyclosporine creates the same degree of T-cell cytokine suppression as does cyclosporine alone, suggesting that the two drugs can be used concurrently without significantly altering the immunosuppressive mechanism of action of cyclosporine.

Incidence of Idiopathic Immune Mediated Hemolytic Anaemia of Dogs in Chennai

Idiopathic Immune-mediated hemolytic anemia (IMHA) is the most common autoimmune disease in dogs. The aim of the study was to study the incidence and clinicopathological changes of idiopathic IMHA, which is not having any secondary underlying triggering causes. The suspected anaemic dogs brought with clinical signs such as pale or icteric mucous membranes were screened for IMHA by saline agglutination and spherocyte count and confirmed by flow cytometry. The positive cases were then subjected to PCR for ruling out secondary underlying causes like Babesia spp and Ehrlichia canis (secondary IMHA). Of the 75 suspected anemic dogs, 32 cases were confirmed by flow cytometry. Among thirty two cases, thirteen were primary (Idiopathic) IMHA (17.3 %) and remaining nineteen cases were diagnosed as secondary IMHA. The most common clinicopathological findings were anaemia with PCV less than 15 per cent with regenerative changes, leucocytosis, thrombocytopenia, elevated PT and APTT, elevated BUN, Creatinine, ALT, ALP, hypoalbuminemia and hyperbilirubinaemia.

Increased number of tissue factor protein expressing thrombocytes in canine idiopathic immune mediated hemolytic anemia

Dogs suffering from canine idiopathic immune mediated hemolytic anemia (cIIMHA) are at great risk of dying particularly in the first two weeks after the diagnosis is made. This high mortality risk may be associated with the development of thromboembolism (TE) and/or disseminated intravascular coagulation (DIC) resulting in organ failure. The exact mechanism of the development of TE and/or DIC in cIIMHA is still undetermined. Therefore, this study investigates the presence of tissue factor (TF) in thrombocytes of dogs suffering from cIIMHA, using OptiPrep™ for the isolation of blood cells and immunocytochemistry (ICC) to visualize TF on thrombocytes. The normalised TF quantity, acquired with ‘colour deconvolution’ (ImageJ plug in), revealed that in cIIMHA dogs the fraction TF positive thrombocytes was statistically significant higher (P < 0.001; mean 0.79; n = 7) compared to the fraction TF positive thrombocytes of the healthy dogs (mean 0.43; n = 9). We further have indications that the fraction of TF positive thrombocytes decreases with time and therapy, but that the progression rate differs individually. Since cIIMHA dogs have more thrombocytes that are TF-positive compared to healthy dogs, this may explain the increased risk to develop TE and DIC. Furthermore, it seems that the number of TF-positive thrombocytes in cIIMHA dogs remains high during the first two weeks of the disease, the time when the animals are at greatest health risk.

Neutrophil Extracellular Traps in Plasma from Dogs with Immune-mediated Hemolytic Anemia.

BackgroundNeutrophil extracellular traps (NETs) are part of the innate immune response and are essential in local pathogen control, but are associated with pathological inflammation, organ damage, autoimmunity, and thrombosis. Immune‐mediated hemolytic anemia (IMHA) is a pro‐inflammatory, prothrombotic disease associated with high mortality.Hypothesis/ObjectivesNeutrophil extracellular traps (NETs) are a feature of the inflammatory process in dogs with IMHA. The objective of the study was to evaluate plasma from dogs with IMHA for the presence of 2 indirect markers and 1 direct marker of NETs.AnimalsHealthy client‐owned dogs (56) and hospitalized dogs with IMHA (n = 35).MethodsProspective study. Plasma samples for all dogs were evaluated for cell‐free DNA using a fluorescence assay, histone‐DNA (hisDNA) complex using an ELISA, and citrullinated histone H3 (specific for NETosis) using Western blot. Reference intervals were generated using plasma from healthy dogs.ResultsIn dogs with IMHA, cell‐free DNA concentration was above the reference interval in 17% of samples with a median (range) of 1.0 μg/mL (0.1–17.3), and hisDNA concentration was above the reference interval in 94% of samples with a median (range) of 30.7 × pooled normal plasma (PNP; 0.6–372.1). Western blot for citrullinated histone H3 identified detectable bands in 84% samples from dogs with IMHA.Conclusions and Clinical ImportanceThe assay for cell‐free DNA detected evidence of NETs in fewer dogs than did the other approaches. Excessive NETs appears to be a feature of IMHA in dogs and contributions to the prothrombotic state deserve further study.

Granulocytic anaplasmosis in 63 dogs: clinical signs, laboratory results, therapy and course of disease.

To describe the clinical signs, laboratory results, therapy and course of disease in dogs with canine granulocytic anaplasmosis in which co-infections had been excluded. Medical records of dogs naturally infected with Anaplasma phagocytophilum were retrospectively evaluated with regard to clinical signs and laboratory abnormalities at the time of presentation, therapy and course of disease. Nine hundred and seventy-four dogs with clinical signs suspicious for canine granulocytic anaplasmosis were tested for A. phagocytophilum DNA by modified real-time PCR; 72 dogs had a positive result. Nine of the positive dogs were excluded from further evaluation due to other diseases or lack of data. The most common clinical signs in the 63 A. phagocytophilum-positive dogs included in the study were lethargy and reduced activity (83%), fever (67%) and inappetence (63%). Thrombocytopenia was the most common laboratory abnormality (86%), followed by increased liver enzyme activities and hyperbilirubinaemia (77%), anaemia (70%), hypoalbuminaemia (62%) and leucocytosis (27%). Of 36 thrombocytopenic dogs tested for platelet-bound antibodies, 44% were positive. Of the 63 infected dogs, 59 (97%) recovered, two dogs died (epileptic seizures and immune-mediated haemolytic anaemia) and two were lost to follow-up. In areas where it is endemic, canine granulocytic anaplasmosis should be considered as a potential cause of acute nonspecific clinical signs or immune-mediated disease if tick exposure cannot be excluded.

Staphyloccocus aureus‐associated infarctive purpura haemorrhagica, immune‐mediated haemolytic anaemia and myocarditis in a Quarter Horse mare

SummaryA 7‐year‐old Quarter Horse mare was presented for severe left hindlimb oedema and nonweightbearing lameness that was progressive over approximately 48 h. The mare subsequently developed marked and worsening oedema, immune‐mediated haemolytic anaemia (IMHA), myositis and myocarditis. The marked oedema, degree of pain and severity of myositis were consistent with infarctive purpura haemorrhagica. Fine needle aspiration of affected tissue resulted in positive bacterial culture of Staphylococcus aureus. Purpura haemorrhagica and associated complications are typically associated with Streptococcal sp. infection or exposure, and have not been previously reported in association with Staphylococcus aureus in the horse. The mare responded favourably to long‐term, high‐dose corticosteroid therapy, antimicrobials and supportive care.

Evaluation of the delta neutrophil index from an automated blood cell analyser in septic dogs

Immature granulocytes (IG) are a marker of severe inflammatory states in human beings and animals, and have been linked to a diagnosis of sepsis and poor prognosis. The delta neutrophil index (DNI), automatically calculated by a haematological analyser, provides an estimate of circulating IG. In particular, an increased DNI value has been associated with the severity of sepsis, and mortality, in critically ill human beings. The aims of this study were to determine the DNI reference interval (RI) in healthy dogs, and to evaluate its diagnostic and prognostic significance in dogs with sepsis. A total of 118 dogs with sepsis undergoing a complete blood cell count (CBC) at the time of hospital admission were included retrospectively. Dogs with sepsis were compared to 20 dogs with primary immune-mediated haemolytic anaemia (IMHA) and 99 healthy controls. The DNI RI was set from 0 to 9.2%. The DNI was significantly higher in dogs with sepsis compared to dogs with IMHA and healthy dogs (P<0.001), and significantly higher in dogs with septic shock compared to septic dogs without circulatory failure (P<0.03). No differences were detected between survivors (78/118) and non-survivors (40/118). Septic dogs with a DNI above the RI had significantly higher frequencies of IG and toxic neutrophil changes on manual blood smear evaluation (P=0.03 and P<0.001, respectively). The DNI had a fair performance in identifying dogs with sepsis in this population and predicted septic shock. Larger prospective studies are needed to validate DNI measurement in dogs and to test its clinical utility.

A Rare Case of Oxaliplatin-Induced ITP Causing Rapid Hematemesis

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by thrombocytopenia from accelerated platelet destruction and impaired production leading to bruising, petechiae, and rarely major GI or intracranial bleeding. Secondary causes of ITP include infection, medication, and autoimmune disease. We present the rarely seen case of a 56 year-old female with metastatic rectal adenocarcinoma presenting from an incomplete outpatient chemotherapy session containing Oxaliplatin due to hematemesis from drug-induced ITP. A 56 year-old female with metastatic rectal adenocarcinoma presented to the ED presenting with hematemesis. She came directly from an outpatient chemotherapy session receiving Oxaliplatin. The patient completed 75% of her chemotherapy when she developed nausea followed several hours later by hematemesis of 500 mL of bright red blood. CBC the morning of her chemo session revealed a platelet count of 204,000 dropping to a count of 5,000 on admission to the ED. She was started on dexamethasone for ITP with repeat counts the next morning of 31,000. She underwent an EGD, which showed several Mallory-Weiss tears (Fig. 1-2). She was discharged from the hospital asymptomatic on Protonix and a prednisone taper for Oxaliplatin-induced ITP. Drug-induced ITP (DITP) is a type of thrombocytopenic purpura defined as isolated thrombocytopenia with normal bone marrow and the absence of other causes of thrombocytopenia, incited by exposure to an offending drug. The pathogenesis of ITP involves loss of tolerance to glycoproteins expressed on platelets including: GP IIb/IIIa and GP Ib/IX complex-specific antibodies. There is also growing evidence that there may also be ‘drug-specific' antibodies that are not platelet reactive. Oxaliplatin is a platinum antineoplastic agent that commonly causes diarrhea, nausea, myelosuppression, and neuropathy. Rare adverse effects that have been reported include acute immune-mediated thrombocytopenia, hemolytic anemia, and pancytopenia. Our patient presented with acute hematemesis few hours after oxaliplatin infusion, despite having received this drug for 23 months in the past. Oxaliplatin induced DITP is a rare entity that can occur even after prior exposure to this drug. Physicians should be aware of this rare cause of GI bleeding and patients should not be rechallenged with this agent.Figure: Mallory-Weiss Year of the Lower Third of the Esophagus.Figure: Mallory-Weiss Tear of the Gastroesophageal Junction.

Urban environment: a risk factor for canine immune-mediated disease?

To investigate whether dogs living in urban areas are more likely to develop immune-mediated disease than those in rural areas. A case-control study comparing the prevalence of urban home location between dogs with immune-mediated disease and matched controls. Dogs diagnosed with immune-mediated haemolytic anaemia, immune-mediated thrombocytopenia, immune-mediated polyarthritis or meningoencephalomyelitis of unknown origin were identified by case record searches. Breed-matched dogs presenting to the same hospital during the same year as cases were randomly selected as controls. Home locations were classified as rural or urban using the population density of the relevant census tract and conditional logistic regression was used to examine association between home location and immune-mediated disease. In the 137 cases and 137 breed-matched controls, the odds ratio for any immune-mediated disease for dogs living in urban (versus rural) areas was 0·94 (95% confidence interval 0·58 to 1·55, P=0·80). Odds ratios for development of immune-mediated haematological diseases, immune-mediated polyarthritis or meningoencephalomyelitis of unknown origin were also not significantly different from the null value. Multivariable analysis including age, gender and season of presentation did not suggest confounding of effect of home location by these additional variables. This study does not support an association between urban environment and immune-mediated disease in dogs.