Thrombocytopenia with concomitant anemia is a serious condition with a high mortality risk. Destruction of platelets, i.e., thrombocytopenia, can be secondary to either auto-antibodies (immune-mediated) or mechanical destruction (non-immune-mediated). The Coombs test is a widespread tool to differentiate between the two categories, resulting in different specific treatment approaches for each diagnosis. A peripheral blood smear can also help make the diagnosis; for instance, in cases of mechanical destruction such as thrombotic thrombocytopenic purpura (TTP), the red blood cell (RBC) shape looks fragmented, forming schistocytes. In rare instances, TTP can present with both schistocytes and a positive Coombs test, challenging the diagnosis of TTP. TTP is a hematological emergency requiring appropriate anticipation and the initiation of treatment prior to the confirmatory ADAMTS-13 test results. Mild forms of TTP can be managed with glucocorticoids and therapeutic plasma exchange. Refractory cases need more aggressive additional treatment with caplacizumab and rituximab. Caplacizumab is an expensive medication that is usually reserved for use after confirmation of a TTP diagnosis. The advantage of caplacizumab lies in its targeted mechanism of action against the A1 domain of the von Willebrand multimers that are normally destructed by the ADAMTS-13 enzyme. Here, we present a young female patient with confirmed TTP, and the initial diagnosis was challenged by the presence of antibodies with the Coombs test. Very little research has studied this rare instance and the appropriate treatment. Our case will save many future lives, as clinicians should be more aggressive in treating refractory TTP with a positive Coombs test.

Loxoscelism-associated hemolytic anemia is a rare but critical complication of brown recluse spider bites. It may lead to various systemic manifestations, including jaundice, dark urine, and anemia-related symptoms, in addition to general loxoscelism symptoms such as skin lesions, fever, myalgia, nausea, and vomiting. Prompt diagnosis is crucial and requires recognizing typical laboratory findings such as low hemoglobin, elevated lactate dehydrogenase, reduced haptoglobin levels, and possibly a positive direct antiglobulin test. There is no definitive guideline for the treatment of loxoscelism-associated hemolytic anemia. we report a case of a 32-year-old female who developed severe Coombs-positive autoimmune hemolytic anemia following a brown recluse spider bite, with an improvement in hemoglobin levels and hemolysis indices after the administration of systemic corticosteroids.

BACKGROUND: Molecular multitargeted small tyrosine kinase inhibitory (TKI) agents such as axitinib, sunitinib and pazopanib are commonly used in several types of solid tumors. Anemia is not a rare effect of these drugs which may occur at all grades. However, drug-induced immune hemolytic anemia (IHA), a very rare condition is distinctive from other types of anemia with its specific mechanism and management strategy.
METHODS: We reported three different TKI-induced IHA cases that occurred due to axitinib, sunitinib, and pazopanib, respectively. The first two cases were diagnosed with renal cell carcinoma and the last one was diagnosed with soft tissue sarcoma. They all presented with the characteristic symptoms of anemia and hemolysis. All the cases were detected positive for the complement C3d direct antiglobulin (direct coombs) test.
METHODS: Discontinuation of the causative drug and 1 mg/kg/day dose of corticosteroid treatment were able to control IHA in all three cases. Excluding the other factors of IHA and an evident laboratory and clinical benefit after withholding the TKI led to the diagnosis of TKI-related IHA in each case.
CONCLUSIONS: TKIs are relatively new in clinical practice and are being used for more indications and in more patients. To our knowledge#these three cases are unique in terms of axitinib#sunitinib#and pazopanib-related IHA.

Cold agglutinin syndrome (CAS) is a rare subset of autoimmune hemolytic anemia (AIHA) and can be classified as either primary or secondary. Secondary cold agglutinin disease has been associated with both viral and bacterial pathogens with the most common bacterial pathogen being Mycoplasma pneumoniae. Legionella pneumonia is a well-known causative agent for community-acquired pneumonia that can lead to a severe disease requiring hospitalization that is rarely associated with AIHA. We highlight the importance of recognizing Legionella pneumonia as a causative pathogen for CAS.

Cold agglutinin hemolytic anemia (cAHA) is a rare autoimmune disorder characterized by the production of cold agglutinins. We present a case of secondary cAHA in a 23-year-old female with severe anemia and unexplained hemolysis. The patient exhibited findings indicative of hemolysis and a positive direct antiglobulin test (DAT) with complement alone. Additional investigations revealed incidental lung infiltrates, negative serology for infections and autoimmune diseases, and a low cold agglutinin titer. The patient showed a favorable response to doxycycline and supportive therapy, including multiple packed red blood cell transfusions. At the two-week follow-up, the patient had a stable hemoglobin level with no evidence of ongoing hemolysis. This case highlights the importance of considering secondary cAHA in patients with cold symptoms or unexplained hemolysis. Primary cAHA patients may require more aggressive treatment, including rituximab and sutilumab.

Drugs can have a wide array of effects on hematological cells, including red blood cells (RBCs), white blood cells (WBCs), and platelets. Drug-induced hemolytic anemia (DIHA) can be explained by three different pathophysiological mechanisms. We present a case of a premature neonate born at 34 weeks gestation who was admitted to the neonatal intensive care unit (NICU). He developed respiratory difficulty with mottled skin and was suspected to have bacterial sepsis due to necrotizing enterocolitis (NEC). The patient was eventually started on a broad-spectrum antibiotic, piperacillin-tazobactam. On day eight, the patient started developing jaundice and his hemoglobin level dropped from 12.1 to 8.2 mg/dL. His direct antiglobulin test (DAT) was strongly positive. The patient was suspected to have DIHA. Piperacillin-tazobactam is a commonly used antibiotic for neonatal sepsis, but its potential to cause DIHA in neonates is not well-established. Our case highlights the importance of considering piperacillin-tazobactam as an unrecognized contributor to neonatal jaundice and a potential cause of DIHA in neonates. Further research is needed to explore the extent of its involvement in this condition. Physicians should be cautious when administering this drug to neonates and be aware of the possibility of hemolysis and jaundice.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired X-linked, clonal hematopoietic stem cell disease. Patients with PNH may complain of vague symptomatology that contributes to the challenge of its diagnosis. This is especially true in the clinical context of a coinciding hematologic disorder. Aplastic anemia (AA) is an additional immune-mediated illness that results in the destruction of hematopoietic precursors and pancytopenia. The authors encourage screening for PNH clones in patients initially diagnosed with AA, treating underlying hematologic disease to prevent clonal expansion, and further research to investigate the effectiveness of eculizumab in an unusual \"classical\" PNH secondary to AA with hypercellular bone marrow.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune inflammatory disease that usually affects the small-sized vasculature, most notably of the lungs and kidneys. One of the challenges of suspecting and diagnosing the condition lies in the insidious and unclear symptoms of presentation. In this case report, we discuss the case of a patient who initially presented with solely unclear pulmonary symptoms, without other organ system dysfunction.

The association between malignancies and autoimmunity had been well-established. The proposed pathophysiology and causality can be bidirectional. For example, a paraneoplastic syndrome can be triggered by an underlying malignancy or vice versa, where chronic inflammation of organs affected by autoimmunity can induce malignant transformation such as the case with inflammatory bowel disease and colorectal cancer or primary sclerosing cholangitis and hepatobiliary cancer. This report presents a case of autoimmune phenomena, namely, autoimmune hemolytic anemia, pernicious anemia, and Graves disease associated with newly diagnosed breast cancer. We also highlight the postulated pathophysiologic mechanisms in an attempt to answer the question of whether the occurrence of these autoimmune phenomena in our patient is a result of the law of parsimony (Occam\'s razor), where clinical variables are pathogenically related, or the counterargument, where random events and diseases can take place simultaneously (Hickam\'s dictum).

Cold agglutinin disease (CAD) is a type of hemolytic anemia in which cold agglutinins can cause agglutination of red blood cells in cold parts of the body and hemolytic anemia. Cold agglutinin-mediated hemolytic anemia can occur in the setting of an underlying viral infection, autoimmune disorder, or lymphoid malignancy, referred to as a secondary cold agglutinin syndrome, or without one of these underlying disorders, referred to as primary CAD (also known as idiopathic CAD). We present a case of a 71-year-old female with hemolytic anemia due to primary CAD. The secondary causes of CAD, including infections, autoimmune disorders, and malignancy, were ruled out. She was successfully treated with prednisone.