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Research and Practice in Thrombosis and... May 2024Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disease characterized by complement-mediated hemolysis and thrombosis. Complement component 5...
BACKGROUND
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disease characterized by complement-mediated hemolysis and thrombosis. Complement component 5 (C5) inhibitors have decreased PNH-related thrombosis rates and reduced mortality compared with those of age-matched controls. A small but significantly increased risk of life-threatening infections, especially , represents a long-term safety risk of complement inhibition.
OBJECTIVES
To evaluate the rates of thrombosis and meningococcal infections in patients with PNH treated with the complement component 3-targeted therapy pegcetacoplan.
METHODS
Cumulative patient-year exposure to pegcetacoplan was calculated, and thrombotic events and meningococcal infections were reviewed in 7 clinical trials and in the postmarketing setting. The clinical trial protocols and pegcetacoplan labeling required vaccination against , , and before pegcetacoplan use; the label allowed for prophylactic antibiotic use if pegcetacoplan must be administered before vaccination.
RESULTS
As of November 13, 2022, 464 patients with PNH had 619.4 patient-years of pegcetacoplan exposure in completed/ongoing clinical trials and the postmarketing setting. Seven thrombotic events were reported: 5 in clinical trials (2 in the same patient) and 2 in the postmarketing setting. The overall thrombosis rate was 1.13 events per 100 patient-years (clinical trials: 1.22 events/100 patient-years in 409.4 years; postmarketing: 0.95 events/100 patient-years in 210.0 years). No infections with meningococcal bacteria were reported.
CONCLUSION
Event rates for thrombosis were comparable between pegcetacoplan and previously reported rates of C5 inhibitors in patients with PNH, and no cases of meningococcal infection were reported with pegcetacoplan. Continued follow-up is required.
PubMed: 38812989
DOI: 10.1016/j.rpth.2024.102416 -
Open Veterinary Journal Apr 2024Bloody urine is classified in farm animals as hematuria, hemoglobinuria, and myoglobinuria. In small ruminants, discolored urine is reported due to several etiologies...
BACKGROUND
Bloody urine is classified in farm animals as hematuria, hemoglobinuria, and myoglobinuria. In small ruminants, discolored urine is reported due to several etiologies which is sometimes fatal. Of these causes are babesiosis, bacillary hemoglobinuria, copper toxicity, and hypophosphatemia.
AIM
This study was designed to investigate the clinical, etiological, hematobiochemical, ultrasonographic, and pathological findings in rams and bucks with red urine syndrome.
METHODS
Eighteen male animals (nine rams and nine bucks) of 6 months to 3 years were examined. Parallel, 10 healthy controls were used. They were admitted due to red urine, voiding of only urine drops, straining during the act of urination, grunting during urination, ventral abdominal edema, and abdominal distension. The duration of the disease ranged from 2 to 30 days. A history of chronic copper toxicosis was informed in two bucks and a ram. Two blood samples were collected from diseased as well as from controls in EDTA tubes (for complete blood count testing) and in plain tubes (for serum collection).
RESULTS
Hematuria was found in 11 animals (seven bucks and four rams) while hemoglobinuria was detected in seven animals (five bucks and two rams). Sonographic findings in diseased animals included ruptured urinary bladder in 3, ruptured urethra in 5, penile calculi, uroperitoneum in 6, distended urinary bladder in 7, hydronephrosis in 5, echogenic deposits in the bladder in 3, and ventral urine accumulation in four animals. Laboratory evaluation of a Geimsa-stained blood smear confirmed the infection with Babesia in three bucks and a ram. Hemolytic anemia was marked in two bucks and a ram due to chronic copper toxicity. Biochemical abnormalities included hypoalbuminemia, hyperglobulinemia, increased blood urea nitrogen and creatinine concentration, and hyperglycemia. Postmortem examination was carried out on six animals (four rams and two bucks).
CONCLUSION
Discolored urine in rams and bucks in this study resulted from hematuria due to urinary calculi and pelvic abscessation or from hemoglobinuria due to Babesia infection or due to copper toxicity. Hemolytic anemia was the outstanding hematological finding and hypoalbuminemia, hyperglobulinemia, increased blood urea nitrogen (BUN) and creatinine, and hyperglycemia were the characteristic biochemical findings. Sonography of the urinary tract was very helpful in assessing the renal parenchyma, urinary bladder, and abdominal cavity for the verification of urolithiasis, hydronephrosis, intact or ruptured urinary bladder, uroperitoneum, and perforated urethra.
Topics: Animals; Male; Goat Diseases; Sheep Diseases; Sheep; Goats; Ultrasonography; Hematuria; Hemoglobinuria
PubMed: 38808288
DOI: 10.5455/OVJ.2024.v14.i4.13 -
Cureus May 2024Thrombopoietin receptor agonist (TPO-RA) is effective for aplastic anemia (AA) and idiopathic thrombocytopenic purpura (ITP). However, the risk of thrombosis during ITP...
Thrombopoietin receptor agonist (TPO-RA) is effective for aplastic anemia (AA) and idiopathic thrombocytopenic purpura (ITP). However, the risk of thrombosis during ITP treatment with TPO-RA is higher than without TPO-RA. It is unclear whether TPO-RA increases the risk of thrombosis in patients with AA. We report a case of a 66-year-old female with severe AA having paroxysmal nocturnal hemoglobinuria (PNH) clones in the peripheral blood who developed ischemic colitis after three days of starting eltrombopag. Contrast-enhanced computed tomography showed ischemic colitis and contrast enhancement defect in the left atrial appendage, which indicated a thrombus in the heart. Stopping eltrombopag and providing supportive care improved her symptoms, and her blood cell counts gradually increased. Thrombosis should be considered when TPO-RA is administered during the immunosuppressive treatment of AA.
PubMed: 38800784
DOI: 10.7759/cureus.61135 -
Kidney International Reports Apr 2024
PubMed: 38765558
DOI: 10.1016/j.ekir.2024.01.048 -
Frontiers in Immunology 2024Drug-induced immune hemolytic anemia (DIIHA) is a rare but serious condition, with an estimated incidence of one in 100,000 cases, associated with various antibiotics....
BACKGROUND
Drug-induced immune hemolytic anemia (DIIHA) is a rare but serious condition, with an estimated incidence of one in 100,000 cases, associated with various antibiotics. This study reports on a case of ceftizoxime-induced hemolysis observed in a patient in China.
CASE DESCRIPTION
A Chinese patient diagnosed with malignant rectal cancer underwent antimicrobial therapy after laparoscopic partial recto-sigmoid resection (L-Dixon). After receiving four doses of ceftizoxime, the patient developed symptoms including rash, itchy skin, and chest distress, followed by a rapid decline in hemoglobin levels, the presence of hemoglobin in the urine (hemoglobinuria), renal failure, and disseminated intravascular coagulation. Laboratory analysis revealed high-titer antibodies against ceftizoxime and red blood cells (RBCs) in the patient's serum, including immunoglobulin M (IgM) (1:128) antibodies and immunoglobulin G (IgG) (1:8) antibodies, with noted crossreactivity to ceftriaxone. Significant improvement in the patient's hemolytic symptoms was observed following immediate discontinuation of the drug, two plasma exchanges, and extensive RBC transfusion.
CONCLUSION
This case, together with previous reports, underscores the importance of considering DIIHA in patients who exhibit unexplained decreases in hemoglobin levels following antibiotic therapy. A thorough examination of the patient's medical history can provide crucial insights for diagnosing DIIHA. The effective management of DIIHA includes immediate cessation of the implicated drug, plasma exchange, and transfusion support based on the identification of specific drug-dependent antibodies through serological testing.
Topics: Humans; Rectal Neoplasms; Hemoglobins; Anti-Bacterial Agents; Male; Ceftizoxime; Multiple Organ Failure; Middle Aged; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; China; East Asian People
PubMed: 38756782
DOI: 10.3389/fimmu.2024.1390082 -
International Journal of Molecular... May 2024Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low... (Review)
Review
Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low platelet counts are referred to as thrombosis with thrombocytopenia syndrome, including heparin-induced thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia, paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, thrombotic microangiopathy (TMA), and disseminated intravascular coagulation. TMA includes thrombotic thrombocytopenic purpura, Shiga toxin-producing -associated hemolytic uremic syndrome (HUS), and atypical HUS. Patients with these pathologies present with thrombosis and consumptive thrombocytopenia associated with the activation of platelets and the coagulation system. Treatment varies from disease to disease, and many diseases have direct impacts on mortality and organ prognosis if therapeutic interventions are not promptly implemented. Underlying diseases and the results of physical examinations and general laboratory tests as part of a thorough workup for patients should promptly lead to therapeutic intervention before definitive diagnosis. For some diseases, the diagnosis and initial treatment must proceed in parallel. Utilization of not only laboratory tests but also various scoring systems is important for validating therapeutic interventions based on clinical information.
Topics: Humans; Thrombocytopenia; Thrombosis; Blood Platelets; Platelet Count; Heparin; Thrombotic Microangiopathies
PubMed: 38732176
DOI: 10.3390/ijms25094956 -
Indian Journal of Pathology &... May 2024Autoimmune hemolytic anemia (AIHA) is a rare immune disorder which occurs when antibodies are directed against self red blood cells (RBCs) leading to hemolysis. AIHA is...
BACKGROUND
Autoimmune hemolytic anemia (AIHA) is a rare immune disorder which occurs when antibodies are directed against self red blood cells (RBCs) leading to hemolysis. AIHA is widely classified as warm autoimmune hemolytic anemia, cold agglutinin syndrome, mixed AIHA, paroxysmal cold hemoglobinuria and rarely drug induced AIHA. The pathogenesis of AIHA is complex interplay between genetic predisposition, immune dysregulation and enviornmental triggers. A direct antiglobulin test can be used to assess the immunological origin of the hemolysis in order to diagnose AIHA after identifying laboratory and clinical symptoms of hemolysis.
OBJECTIVE
The objective is to understand underlying mechanism in AIHAs, and usage of targeted therapies to modulate specific components of the immune response.
MATERIALS AND METHODS
We are hereby presenting a case series of 11 clinically suspected cases of AIHA in collaboration with their clinical features, immuno-hematological and other laboratory parameters, Flow cytometric analysis of lymphocyte subset in relevant cases, underlying etiology as well as serological subtype are also included.
RESULTS
Majority of the patients were categorized as secondary AIHA (7/11, 63.63%). Out of 11 cases 7 were serologically subtyped as warm AIHA (7/11, 63.63%) ,2 cases were DaaT negative AIHA (2/11;18.18%), 2 cases were characterized as mixed AIHA subtype (2/11, 18.18%).
CONCLUSION
Accurate subtyping of AIHA requires a systematic immunohematological approach coupled with comprehensive evaluations of clinical, hematological, and biochemical parameters.
PubMed: 38727423
DOI: 10.4103/ijpm.ijpm_896_23 -
Clinical Case Reports May 2024Paroxysmal nocturnal hemoglobinuria is a rare disease with the incidence ranging from 0.08 to 0.57 per 100,000 person-years. Up to 25% of cases in women are detected...
Paroxysmal nocturnal hemoglobinuria is a rare disease with the incidence ranging from 0.08 to 0.57 per 100,000 person-years. Up to 25% of cases in women are detected during pregnancy. We report two cases of successful pregnancy outcomes in patients treated with eculizumab, pointing out the importance of interdisciplinary approach in these high-risk pregnancies.
PubMed: 38725930
DOI: 10.1002/ccr3.8900 -
Acute Necrotizing Pancreatitis Complicated with Paroxysmal Nocturnal Haemoglobinuria: A Case Report.Clinical and Experimental... 2024This report presents a unique case of acute necrotizing pancreatitis(ANP) concomitant with paroxysmal nocturnal hemoglobinuria(PNH), a combination that has not been...
This report presents a unique case of acute necrotizing pancreatitis(ANP) concomitant with paroxysmal nocturnal hemoglobinuria(PNH), a combination that has not been documented in existing literature. The impact of PNH on ANP and its treatment remains uncertain due to the lack of consensus. The case described herein involves a patient who exhibited both ANP and PNH, subsequently experiencing splanchnic vein thrombosis (SVT), resulting in substantial intra-abdominal and gastrointestinal hemorrhaging. We attempted to analyze the role of PNH in the formation of SVT in ANP and propose some new insights and hypotheses for the treatment of such patients.
PubMed: 38708059
DOI: 10.2147/CEG.S449594