Acute Acquired Hemophilia A Following Snake Bite: A Case Report and Clinical Insights.

BACKGROUND Coagulopathies can manifest on a spectrum, from minor mucosal bleeding to life-threatening hemorrhage. Minor cases can be discovered in the setting of known risk factors, such as malignancy, old age, immunosuppression. However, acquired hemophilia A diagnosed after a snake bite is of lesser-known incidence and can present in a more acute, potentially life- or limb-threatening fashion. To properly diagnose this coagulopathy, one must be familiar with the related signs, symptoms, and laboratory findings so that swift diagnosis can follow. Diagnosis is key for early proper management, as displayed in the following case. CASE REPORT Our case report details a male patient presenting with diffuse bruising after a snake bite. Initially, on presentation to outside facilities, the diagnosis of acquired hemophilia A was not found. However, upon worsening of bruising in the setting of previous treatments initiated for the patient, he presented to our facility, where he subsequently received a diagnosis with acquired hemophilia A. He developed compartment syndrome due to excessive bleeding, requiring surgical intervention. With proper diagnosis, his bleeding diathesis was corrected with multiple rounds of repletion of factors and immunosuppression. His follow-up laboratory test results and examinations have shown continued resolution of his symptoms. CONCLUSIONS As acquired hemophilia A is less often linked with snake bites, this case highlights the importance of considering this disease process as a differential in patients with bleeding diathesis after a snake bite. The coagulation dysfunction can be severe, and, as such, early identification of this diagnosis leads to more targeted and effective therapy.

Risk factors for Non-Hodgkin's lymphoma in autoimmune disease: a large database analysis.

Immune dysregulation in autoimmune diseases (ADs) is a risk factor for the development of Non-Hodgkin's lymphoma (NHL). However, the underlying mechanisms are not well understood. Hence, this retrospective study aims to describe the clinical and demographic factors that increase the risk of NHL development in patients with ADs. Our study utilised data from National Inpatient Sample (NIS) for the duration of 2016-2020 on all adult patients aged > 18 years who had NHL. We divided them into two cohorts: one with underlying ADs and one without underlying ADs. We then compared the adjusted odds ratios (aOR) of various risk factors. It was found that 0.9% of autoimmune cases had NHL, while 0.7% of non-autoimmune cases had NHL. Among those with autoimmune conditions, various factors influenced the presence of lymphoma, such as personal history of chemotherapy or radiation, family history of lymphoid malignancy, HIV infection, advanced age of 60-69 years, Asian and Pacific Islander ethnicity and viral hepatitis. The increased risk of NHL with autoimmune conditions is well established. Studies have also shown that these patients can overall have a poor prognosis from their NHL when compared to patients without autoimmune diseases. However, there is limited literature regarding the interplay of traditional NHL risk factors with underlying autoimmunity. Hence, our study sheds light on the lesser studied risk factors, such as patient characteristics and comorbidities.

Detecting Multiple Driver Mutations in a Patient with Essential Thrombocythemia.

BACKGROUND Three driver mutations have been identified in patients with essential thrombocythemia - JAK2 V617F, CALR, and MPL. Out of these, JAK2 V617F is mostly common. These mutations are thought to be mutually exclusive; therefore, the initial workup may not include the identification of all mutations separately. CASE REPORT We present a case of a 55-year-old woman who was referred to the hematology clinic for an elevated platelet count noted when she was hospitalized for a renal stone. The patient was asymptomatic. A workup was initiated for essential thrombocythemia, and she was tested for JAK2 V617F mutation using an allele-specific polymerase chain reaction (AS-PCR) test in peripheral blood, which came back positive. The variant allele frequency was 2%. She underwent a bone marrow biopsy, and next-generation sequencing (NGS) showed a CALR mutation. A 52 bp deletion-type mutation was detected in the CALR gene on exon 9, with a variant allele frequency of 7%. The NGS did not detect JAK2 mutation due to its low sensitivity. She was started on aspirin alone as she was less than 60 years old and had no history of thrombotic events. The patient has been following up with the hematology clinic for the last 2 years and has not had any thrombotic events. CONCLUSIONS We propose that in patients with a low JAK2 V617 allele variant, testing for other driver mutations should be performed. In our patient, JAK2 mutation could be clonal hematopoiesis of indeterminate potential; therefore, the dominant mutation (CALR) would determine the disease phenotype.

Adult-onset Still's disease with concurrent thrombotic microangiopathy: Observations from pooled analysis for an uncommon finding.

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder that is characterized by quotidian fevers, arthritis, and an evanescent rash. Occurrence of concurrent thrombotic microangiopathy (TMA) in AOSD is rare. The treatment aspects of TMA in AOSD are actively being debated. METHODS: Medline search using MeSH terms and snowballing yielded a total of 29 articles with co-occurrence of AOSD and thrombotic thrombocytopenic purpura (TTP) including our own. Pooled data were synthesized for descriptive analysis. RESULTS: Median age was 35 years with a majority of females (68.96%). A majority of these studies/patients were either Asian (34.48%) or Caucasian (31.03%). Concurrent TMA at the time of AOSD diagnosis was seen in 65.51% patients. Only 3/29 patients had ADAMTS13 level less than 10%, consistent with TTP and 3/29 were diagnosed with hemolytic uremic syndrome (HUS). The remainder were diagnosed clinically. Complication rate was high, and 15/29 (51.72%) patients died or had permanent neurological/renal/vision/gangrenous complications. Median and mean ferritin peak was observed to be higher (7458 and 12 349, respectively) in patients who either died/had partial remission, compared to those who had complete response (3257 and 10 899, respectively), p = .829. CONCLUSIONS: A majority of patients with AOSD-associated TMA either died or had permanent complications. TMA was diagnosed alongside AOSD in 65% patients, while the rest developed TMA during the course of their disease. Blurred vision may precede TMA and could help risk-stratify high-risk AOSD patients clinically. Glycosylated ferritin remains low several weeks to months after disease remission and may be used to monitor severity of disease process. Further studies are necessary to confirm the existing vascular endothelial growth factor hypothesis in AOSD-associated TMA.

Co­existence of triple­negative essential thrombocythemia and double transcript chronic myeloid leukemia: A case report.

Chronic myeloproliferative neoplasms (MPN) include polycythemia vera (PV), primary myelofibrosis, essential thrombocythemia (ET) and chronic myeloid leukemia (CML). Overlapping MPNs are rare; however, they can occur in the same individual. The present case report describes a patient with both triple-negative ET and CML. A 64-year-old woman was followed-up at our hematology clinic at Feist Weiller Cancer Center, Louisiana State University Health Shreveport (Shreveport, LA, USA) since 2000 after she was diagnosed with JAK2V617F-negative ET. The patient remained stable on hydroxyurea until 2012, when they underwent a bone marrow biopsy for progressively increasing white blood cell counts, and the pathology was consistent with CML; PCR for BCR-ABL was positive for both P210 and P190 transcripts. The patient was then initiated on dasatinib. After dasatinib, they were given a trial of imatinib, and were later transitioned to nilotinib and finally to bosutinib (2019) due to unchanged thrombocytosis. Next-generation sequencing from a bone marrow biopsy in 2019 demonstrated an EZH2 mutation that may be associated with triple-negative ET. CML was in major molecular response at that time. The patient was continued on bosutinib with hydroxyurea, after which hydroxyurea was changed to anagrelide due to worsening anemia and persistent thrombocytosis. However, bosutinib and anagrelide were discontinued due to worsening pulmonary hypertension. The patient was noted to have peripheral blasts of 14% by flow cytometry, after which they underwent a repeat bone marrow biopsy in 2022, which showed extensive myelofibrosis. BCR-ABL transcripts were undetectable. Given their accelerated myelofibrosis, the patient was started on a hypomethylating agent, decitabine/cedazuridine, along with darbepoetin for anemia in June 2022. Given their persistent thrombocytosis, the patient was also started on peginterferon α. Most studies reporting two clonal processes in the same patient have been for PV and CML. To the best of our knowledge, this is the first reported case of triple-negative ET with double transcript CML in the same individual.

A rare synchrony of adenocarcinoma of the ampulla with an ileal gastrointestinal stromal tumor: A case report.

BACKGROUND: This is a unique case of a patient who was found to have two extremely rare primary malignancies synchronously, i.e., an ampullary adenocarcinoma arising from a high-grade dysplastic tubulovillous adenoma of the ampulla of Vater (TVAoA) with a high-grade ileal gastrointestinal stromal tumor (GIST). Based on a literature review and to the best of our knowledge, this is the first report of this synchronicity. Primary ampullary tumors are extremely rare, with an incidence of four cases per million population, which is approximately 0.0004%. Distal duodenal polyps are uncommon and have a preponderance of occurring around the ampulla of Vater. An adenoma of the ampulla ( AoA) may occur sporadically or with a familial inheritance pattern, as in hereditary genetic polyposis syndrome such as familial adenomatous polyposis syndrome (FAPS). We report a case of a 77-year-old male who was admitted for painless obstructive jaundice with a 40-pound weight loss over a two-month period and who was subsequently diagnosed with two extremely rare primary malignancies, i.e., an adenocarcinoma of the ampulla arising from a high-grade TVAoA and a high-grade ileal GIST found synchronously. CASE SUMMARY: A 77-year-old male was admitted for generalized weakness with an associated weight loss of 40 pounds in the previous two months and was noted to have painless obstructive jaundice. The physical examination was benign except for bilateral scleral and palmar icterus. Lab results were significant for an obstructive pattern on liver enzymes. Serum lipase and carbohydrate antigen-19-9 levels were elevated. Computed tomography (CT) of the abdomen and pelvis and magnetic resonance cholangiopancreatography were consistent with a polypoid mass at the level of the common bile duct (CBD) and the ampulla of Vater with CBD dilatation. The same lesions were visualized with endoscopic retrograde cholangiopancreatography. Histopathology of endoscopic forceps biopsy showed TVAoA. Histopathology of the surgical specimen of the resected ampulla showed an adenocarcinoma arising from the TVAoA. Abdominal and pelvic CT also showed a coexisting heterogeneously enhancing, lobulated mass in the posterior pelvis originating from the ileum. The patient underwent ampullectomy and resection of the mass and ileo-ileal side-to-side anastomosis followed by chemoradiation. Histopathology of the resected mass confirmed it as a high-grade, spindle cell GIST. The patient is currently on imatinib, and a recent follow-up positron emission tomography (PET) scan showed a complete metabolic response. CONCLUSION: This case is distinctive because the patient was diagnosed with two synchronous and extremely rare high-grade primary malignancies, i.e., an ampullary adenocarcinoma arising from a high-grade dysplastic TVAoA with a high-grade ileal GIST. An AoA can occur sporadically and in a familial inheritance pattern in the setting of FAPS. We emphasize screening and surveillance colonoscopy when one encounters an AoA in upper endoscopy to check for FAPS. An AoA is a premalignant lesion, particularly in the setting of FAPS that carries a high risk of metamorphism to an ampullary adenocarcinoma. Final diagnosis should be based on a histopathologic study of the surgically resected ampullary specimen and not on endoscopic forceps biopsy. The diagnosis of AoA is usually incidental on upper endoscopy. However, patients can present with constitutional symptoms such as significant weight loss and obstructive symptoms such as painless jaundice, both of which occurred in our patient. Patient underwent ampullectomy with clear margins and ileal GIST resection. Patient is currently on imatinib adjuvant therapy and showed complete metabolic response on follow up PET scan.

Plasmablastic Lymphoma or Plasmablastic Myeloma: A Case of Post-Transplant Lymphoproliferative Disorder.

Plasmablastic lymphomas and plasmablastic myelomas are malignancies with overlapping clinical and pathological features which pose a diagnostic dilemma and are known to be aggressive with a poor outcome. CD38 is a common immunophenotypic maker for both these malignancies and provides a rationale for using daratumumab-based regimes. We describe a 57-year-old male with a history of end-stage renal disease who underwent a deceased-donor renal transplant maintained on chronic immunosuppression who presented with ascites and was found to have abdominal adenopathy and a lytic lesion in the humerus and diagnosed with a post-transplant lymphoproliferative disorder with features intermediate between plasmablastic lymphoma and plasmablastic myeloma. The patient was subsequently treated with a daratumumab-based regime with an excellent response. This case highlights a rare scenario that poses a diagnostic and therapeutic challenge. As there is no standard of care for the treatment of both these malignancies, this case report also describes the use of daratumumab with a good long-term outcome, especially when the pathological distinction between the two entities is difficult.

Pulmonary sarcomatoid carcinoma presenting as subcutaneous nodules.

Subcutaneous nodules secondary to metastasis can be a presenting symptom of lung cancer. Underlying cancer must be ruled out in patients presenting with multiple subcutaneous nodules with suspicious history, physical, and radiological findings. Prognosis is extremely poor with limited treatment options.

Melanoma and mantle cell lymphoma in a single collision tumor.

The simultaneous occurrence of two different neoplasms is uncommon, and collision tumors are even rarer. We describe a cutaneous collision tumor of melanoma and mantle cell lymphoma presenting synchronously in a previously healthy individual.

Bariatric Surgery Causing Hyperammonemia.

Bariatric surgery is recognized as a highly effective therapy for obesity but it does carry a risk of short term and long term complications since it results in a permanent alteration of the patient's anatomy. We present a case of 45-year-old female presented with a macular rash on extremities and facial rash from a rehabilitation center after having been discharged a month earlier from a revision surgery on her gastric bypass for anastomotic bleeding. She progressively became lethargic with Magnetic Resonance Imaging (MRI) of the brain showed symmetrically restricted diffusion concerning for hypoxic injury. Her ammonia levels were at 142 micromoles per liter (mmol/L) at the initial check which worsened to 432 mmol/L over a few days, despite treatment. Laboratory investigation later revealed her to be deficient in zinc along with many essential and nonessential amino acids. Supplemental nutrition was initiated, specifically fortifying her parenteral feeds with the essential amino acid combinations that were found deficient on testing. This lead to a slow but progressive improvement in encephalopathy. This case highlights the importance of understanding the short and long term complications of bariatric surgery. Although neurological complications are rare with peripheral neuropathy being the most common one, hyperammonemic encephalopathy is a very severe complication, with incompletely understood mechanisms and predispositions, frequently resulting in failure of recognition and subsequent delays in intervention.

Differential expression of miRNAs in acute myeloid leukemia quantified by Nextgen sequencing of whole blood samples.

New approaches are needed for understanding and treating acute myeloid leukemia (AML). MicroRNAs (miRs) are important regulators of gene expression in all cells and disruption of their normal expression can lead to changes in phenotype of a cell, in particular the emergence of a leukemic clone. We collected peripheral blood samples from 10 adult patients with newly diagnosed AML, prior to induction chemotherapy, and 9 controls. Two and a half ml of whole blood was collected in Paxgene RNA tubes. MiRNA was purified using RNeasy mini column (Qiagen). We sequenced approximately 1000 miRs from each of 10 AML patients and 9 controls. In subset analysis, patients with NPM1 and FLT3 mutations showed the greatest number of miRNAs (63) with expression levels that differed from control with adjusted p-value of 0.05 or less. Some of these miRs have been described previously in association with leukemia, but many are new. Our approach of global sequencing of miRs as opposed to microarray analysis removes the bias regarding which miRs to assay and has demonstrated discovery of new associations of miRs with AML. Another strength of our approach is that sequencing miRs is specific for the 5p or 3p strand of the gene, greatly narrowing the proposed target genes to study further. Our study provides new information about the molecular changes that lead to evolution of the leukemic clone and offers new possibilities for monitoring relapse and developing new treatment strategies.

Dangers of flying high and diving low! An unusual case of dyspnea.

Giant bullae are bullae that occupy at least 30 percent of a hemi thorax. This condition can rarely be idiopathic and not usually suspected in young patients with no risk factors. We describe a case of a giant solitary pulmonary bulla in a healthy young female with no known risk factors. 23-year-old female presented to the Emergency department with dyspnea and pleuritic right sided chest pain. She started experiencing these symptoms when she was on a 7-h flight and later experienced similar symptoms when she went scuba diving. Lung exam revealed decreased breath sounds on the right and she was saturating well on room air. Chest X-ray done showed a large bleb at the right lung apex. CT angiogram done was negative for pulmonary embolism, but confirmed a large bulla involving the right upper lobe. She had no history of lung diseases, marfanoid features, cigarette smoking, drug use or family history of similar condition. She underwent VAT assisted mini thoracotomy with resection of the right apical bulla and tube thoracostomy. Surgical pathology showed a pulmonary bleb with pleural fibrosis and prominent adhesions with parietal pleura and no evidence of malignancy. She was advised to avoid air travel and diving for 3 months and is doing well. Idiopathic giant pulmonary bullae have rarely been reported. It is a rare cause of dyspnea and chest pain in young adults. This may be suspected when patients develop symptoms with air travel and deep sea diving.

Recipient Criteria Predictive of Graft Failure in Kidney Transplantation.

Several classifications systems have been developed to predict outcomes of kidney transplantation based on donor variables. This study aims to identify kidney transplant recipient variables that would predict graft outcome irrespective of donor characteristics. All U.S. kidney transplant recipients between October 25,1999 and January 1, 2007 were reviewed. Cox proportional hazards regression was used to model time until graft failure. Death-censored and nondeath-censored graft survival models were generated for recipients of live and deceased donor organs. Recipient age, gender, body mass index (BMI), presence of cardiac risk factors, peripheral vascular disease, pulmonary disease, diabetes, cerebrovascular disease, history of malignancy, hepatitis B core antibody, hepatitis C infection, dialysis status, panel-reactive antibodies (PRA), geographic region, educational level, and prior kidney transplant were evaluated in all kidney transplant recipients. Among the 88,284 adult transplant recipients the following groups had increased risk of graft failure: younger and older recipients, increasing PRA (hazard ratio [HR],1.03-1.06], increasing BMI (HR, 1.04-1.62), previous kidney transplant (HR, 1.17-1.26), dialysis at the time of transplantation (HR, 1.39-1.51), hepatitis C infection (HR, 1.41-1.63), and educational level (HR, 1.05-1.42). Predictive criteria based on recipient characteristics could guide organ allocation, risk stratification, and patient expectations in planning kidney transplantation.