Challenges to Laboratory Monitoring of Direct Oral Anticoagulants.

Direct oral anticoagulants (DOACs) exert anticoagulation effect by directly inhibiting Factor Xa (rivaroxaban, apixaban, and edoxaban) or thrombin (dabigatran). Though DOACs are characterized by fixed-dose prescribing and generally do not require routine laboratory drug-level monitoring (DLM), circumstances may arise where the DLM may aid in clinical decision-making, including DOAC dose adjustment, anticoagulant class change, or decisions to withhold or administer reversal agents. We review the current literature that describes high-risk patient groups in which DLM may be beneficial for improved patient anticoagulation management and stewardship. The review also summarizes the limitations of conventional coagulation testing and discuss the emerging utility of quantitative methods for routine and rapid emergent evaluation of DOAC drug levels-in particular, the Anti-Xa activity to detect Factor Xa Inhibitors (rivaroxaban, apixaban, and edoxaban). Both technical and regulatory barriers to widespread DLM implementation are limiting factors to further clinical research that must be overcome, in order to propose universal DOAC DLM strategies and provide clinical-laboratory correlation to formally classify high-risk patient groups.

In vitro differential inhibition of the factor XI activity assay in the setting of a lupus anticoagulant.

Acquired factor XI deficiencies due to factor-specific inhibitors are rare and may be associated with lupus anticoagulant. We report a 63-year-old male with suspected postsurgical bleeding, prior surgical site infection, an isolated prolonged activated partial thromboplastin time, and a positive lupus anticoagulant. Although the factor II assay was normal, factor VIII and IX assays initially demonstrated nonparallelism with factor activity that consistently increased to normal reference ranges with serial dilutions. A discrepancy in factor XI activity results was discovered when the in-house method demonstrated undetectable activity (<3%); send-out testing using different instrument/reagent combinations revealed the presence of factor XI activity between 70% and 76%. The patient received surgical follow-up and was subsequently discharged home. Given the differential in vitro inhibition of factor XI activity on our initial in-house testing, this case highlights the importance of recognizing factor assay interference in the presence of a known lupus anticoagulant inhibitor, with strategies to mitigate potentially erroneous results.

A Masquerading Hematoma Resulting in the Delayed Diagnosis of a Soft Tissue Sarcoma: A Case Report.

A 27-year-old male with insidious right arm swelling was diagnosed with a hematoma secondary to a partial biceps tear, later identified as a rhabdomyosarcoma. Soft tissue sarcomas (STS) may present with misleading patient histories and nonspecific symptoms, resulting in misdiagnosis and delayed treatment. One of the classic masqueraders of soft tissue sarcomas is hematomas secondary to trauma. Obtaining a prudent history with careful scrutiny of appropriate imaging often helps establish the correct diagnosis. Ultimately, tissue biopsy can resolve any ambiguous cases and prevent delays in diagnosis and treatment.

Prostatic Leiomyoma: An Uncommon Diagnosis Found in Clinically Suspected Cases of Severe Benign Prostatic Hyperplasia Without Elevated Serum Total Prostate-Specific Antigen Levels.

Leiomyomas of the prostate are uncommon benign tumors. We report the case of a 67-year-old man who underwent an emergent, open prostatectomy for symptomatic relief of clinically severe benign prostatic hyperplasia (BPH). Ultrasound showed a severe prostatic enlargement with urinary tract obstruction. Gross pathology findings showed a 134-g prostate gland containing a 2.5-cm-long, well-circumscribed lesion. Histological findings showed a bland, smooth muscle neoplasm with positive staining for smooth muscle markers. No necrosis, nuclear atypia, or mitoses are identified. In such cases, gross and microscopic examination of adequately sampled lesions is necessary to assure a conclusive diagnosis and to exclude overt stromal malignancies, such as leiomyosarcoma.

Lessons learned from patient outcomes when lowering hemoglobin transfusion thresholds during COVID-19 blood shortages.

OBJECTIVES: This study examines whether patient outcomes were affected when the hemoglobin (Hb) transfusion threshold was lowered by 1 g/dL during COVID-19-related blood shortages. METHODS: Outcomes of lowered Hb thresholds (from <7 to <6 g/dL) were defined by 14-month intervals in 2 patient groups (prepandemic [January 2019-February 2020] and pandemic [April 2020-May 2021]). We evaluated patient admissions, pretransfusion (if transfused) or nadir admission (if not transfused) Hb levels between 5.0 and 8.0 g/dL, and total red blood cell (RBC) transfusions during admission (if transfused). Baseline variables and outcomes were selected from electronic health records. Primary COVID-19-related admissions were excluded. Regression analysis was conducted to determine outcomes. RESULTS: Those in the prepandemic group (1976) and pandemic group (1547) were transfused. Fewer RBCs (2186, vs 3337) were used in the prepandemic group than in the pandemic group, respectively. Those in the prepandemic group had significantly higher rates of hypertension and diabetes as well as more smokers. Significant differences were observed when comparing the number of procedures and incidence of sepsis between the patient groups. Similar patterns were observed for the not transfused and transfused subgroups. CONCLUSIONS: Patient outcomes were not affected after implementing lower Hb pretransfusion thresholds. Although confounding factors were mitigated, some may have been associated with procedures or sepsis. Proactive patient blood management strategies during COVID-19-related blood shortages may include adopting lower Hb thresholds.

Massive Transfusion Protocol in a 69 Year Old Woman with Alloantibodies.

Unlike routine blood transfusions that are managed by attending providers and rely on compatibility testing, massive transfusions are managed by the trauma team members, who usually do not have immediate access to compatibility testing. Incompatible C or E antigens, when present in uncrossmatched O positive blood, require transfusion support so that health care professionals can manage potential causes for extravascular hemolysis. Herein, we describe a massive transfusion situation in which immediate patient management was required to mitigate potentially fatal clinical consequences of transfused red blood cell antibodies. In addition, this case study shows how the utility of chemistry and hematology laboratory results can illustrate the complexities of massive transfusion management in the context of incompatible C or E antigens.

Transfusion management of trauma from the 2019 El Paso mass shooting incident.

BACKGROUND AND OBJECTIVES: Mortality rates, transfusion ratios, trauma management logistics, and assault characteristics from the El Paso mass shooting incident (MSI) are evaluated in comparison to other MSIs. In 2019, El Paso, TX experienced the eighth-deadliest MSIs in modern US history. In this 21st mass killing in the United States of 2019, 19 people died immediately, and four of 27 injured, later died from ballistic injuries. MATERIALS AND METHODS: We examined the victims' injuries, pre-hospital treatments, transfusions, rotational thromboelastometry (ROTEM) interpretation, tranexamic acid (TXA) use, and compared El Paso's outcomes with other MSIs. RESULTS: Fifteen casualties were treated for bullet injuries at University Medical Center (UMC). Three were in critical condition; one died during surgery. Of the remaining victims, two were guarded, and the remaining ten in stable condition. Anatomic trauma locations included chest, abdomen, hip, breast, thigh and arm. Haemostatic agents and TXA were administered to arriving patients. Seven casualties receiving blood products were administered 95 units at UMC (45 red blood cells [RBC], 38 fresh frozen plasma [FFP], 8 platelets and 4 cryoprecipitate). ROTEM guided mass transfusion decisions in three patients. Out of seven MSIs reviewed, El Paso had the highest mortality rate (50.0%) and lowest RBC:FFP:admission ratio (1.18 at UMC). CONCLUSION: We report the greatest proportion of transfusions per admission for an MSI and are first to discuss ROTEM roles to guide transfusion and manage coagulopathy during an MSI. This case highlights the severity and impact of MSIs on victims and requirements to follow established transfusion protocols with adjunct use of ROTEM, TXA and haemostatic agents.

Primary Urethral Malignant Peripheral Neural Sheath Tumor in a 58-Year-Old Female in the Absence of Neurofibromatosis Type 1.

A malignant peripheral neural sheath tumor (MPNST) is a malignant soft tissue neoplasm with cellular origin arising from the outer lining of peripheral nerves. Approximately 10 cases have been identified to date where the lower urinary tract was affected. We discuss the case of a female patient that presented with primary MPNST that arose in the urethral tract in the absence of neurofibromatosis type 1 (NF1) or prior malignancies. This patient presented with pain and acute urinary tract symptoms secondary to urethral obstruction by a protruding vaginal mass. The patient underwent an incomplete initial resection to alleviate symptoms and to obtain a tissue diagnosis. Three months after the first hospitalization, the patient was re-hospitalized due to the recurrence of symptoms and subsequently underwent a complete tumor excision. The initial resection showed a 7.0 x 4.5 x 4.5 cm aggregate of tan-red to gray tumor masses. Microscopic examination showed a spindle cell neoplasm with malignant cytological features (hypercellularity, atypical mitoses, nuclear pleomorphism, and indistinct borders). Tumor cells stained positive for SOX10, S-100 (10% of tumor), with a "mosaic pattern" of H3K27ME3 (50% of tumor nuclei positive). Other lineage-specific and keratin markers stained negative. In the absence of other patient known primaries, the findings were consistent with a primary MPNST of the urinary tract. Residual tumor was identified on MRI scans one month after the follow-up. The completely excised tumor specimen on the second admission showed identical morphology when compared to the first specimen. While MPNSTs typically carry a poor prognosis, knowledge of behavior and prognosis of primary MPNSTs in the bladder is limited, due to the few relative numbers of available case reports. Further research is needed to study the clinical behavior, morphology, immunophenotypes, and genetics of primary MPNSTs arising from the lower urinary tract.

Rare Distal Metastasis of Endometrial Adenocarcinoma Impersonating as Primary Colon Cancer.

An 89-year-old Caucasian female with a recent diagnosis of endometrial adenocarcinoma status post hysterectomy and acute deep vein thrombosis on anticoagulation presented with hematochezia. Colonoscopy revealed sigmoid colon stricture with the biopsy findings of metastatic endometrial adenocarcinoma based on positive immunohistochemistry staining for cytokeratin 7, paired box gene 8, and estrogen receptor. The oncologist referral was given to the patient for consideration of chemotherapy, but she decided to go with palliative care. Thus far, only 2 similar cases have been published in the literature. Our case exemplifies the potential for an unconventional pattern of metastasis of primary endometrial adenocarcinoma to the colon.

Adult-onset perianal Langerhans cell histiocytosis presenting as pruritus ani: a case report and review of the literature.

BACKGROUND: Langerhans cells belong to the histiocytic system and give rise to two tumors: Langerhans cell histiocytosis and Langerhans cell sarcoma. Clinical aggressiveness and degree of atypia distinguish the two neoplasms. Langerhans cell histiocytosis can infiltrate a single or multiple organ systems and particularly affects bone, skin, and lymph nodes. Perianal cutaneous Langerhans cell histiocytosis is a rare condition in adults, with 15 cases reported in the literature. CASE: We present the case of a 50-year-old hispanic man who presented with a 9-month history of pruritus ani and a personal history of diabetes insipidus. Punch biopsy confirmed a lesion of Langerhans cells origin but could not exclude Langerhans cell sarcoma because of limited sample size. An additional biopsy was planned as well as a positron emission tomography scan to determine the extent of disease spread. While the patient failed to follow up for repeat biopsy, the positron emission tomography scan was performed and was negative for metastatic disease. A stable perianal lesion of Langerhans cell histiocytosis with benign clinical features in a 50-year-old male despite lack of treatment is extremely rare and has not been described in the literature so far. Here, we review the presentation and workup of patients with Langerhans cell histiocytosis, review the relevant literature, and discuss treatment planning. CONCLUSION: Perianal Langerhans cell histiocytosis is rare, and there should be a high index of suspicion with chronic or new perianal lesions, especially in a patient with a history of diabetes insipidus. It is also important to consider the patient's full clinical course when it is not possible to reach a definitive pathological diagnosis before management.

Primary pancreatic diffuse large B-cell lymphoma, activated B-cell subtype, diagnosed by endoscopic ultrasound-guided fine needle aspiration-A case report and review of the literature.

Although primary pancreatic lymphoma is a rare cause of pancreatic mass, this diagnosis should be considered during work-up. Furthermore, when adequate diagnostic material is available from biopsy, complete workup of the lymphoma, including not only type but also subtype when applicable, should be performed.

A Flow Cytometric Study of Reagent Cells to Resolve ABO Typing Discrepancy.

OBJECTIVES: RBC alloantibodies can lead to ABO grouping discrepancies unrelated to A or B antigens or antibodies posing challenges in the blood bank testing. Routine blood bank testing and flow cytometry were used to immunophenotype reagent cells and elucidate the cause of ABO discrepancies in two patients. METHODS: ABO discrepancy was identified in two patients after transfusion with several units of RBCs. For both patients, the pretransfusion type and screen demonstrated blood group A. Eight and 16 days later, both patients showed an apparent antibody to reagent group A cells, which prompted additional study with patients' samples and flow cytometric testing of commercial reagent cells. RESULTS: In both patients' specimens, posttransfusion evaluation demonstrated an emerging antibody to the Kell antigen (K). The RBCs of both patients typed negative for K, and both were transfused with K-positive RBCs. Flow cytometric analysis of reagent RBCs demonstrated that five of seven lot numbers were positive for K. CONCLUSIONS: Emerging anti-K antibody led to agglutination of the K-positive reagent A1 cells, highlighting the importance of considering RBC alloantibodies and the composition of reagent cells when interpreting cases with an apparent ABO grouping discrepancy.