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.

Parvovirus infection and thrombotic thrombocytopenic purpura (TTP) are rare manifestations in adults with sickle cell beta-thalassemia. Due to the lack of a clear demarcation between the complications related to sickle cell disease (SCD) and TTP, the diagnosis is often challenging. The treatment requirements for both these entities are divergent and complicated, thus necessitating a careful plan of action during atypical presentations. Here we present a case of a 22-year-old woman during the peripartum period with fever, generalized body aches, and large joint pains that soon evolved into labor. The patient\'s history was suggestive of an undiagnosed and inherited blood disorder. The presentation of aplastic crisis-splenic sequestration during early adulthood is atypical for the SCD course in general populations. Moreover, as the patient\'s clinical status deteriorated with blood transfusion, the diagnosis and management of a sickle cell crisis event and TTP added to the dilemma in the presence of non-classic parvovirus infection. Though the causation of TTP due to SCD-parvovirus infection is questionable, the treatment of the baseline sickle cell crisis with the novel supportive measures resolved the underlying complications in our patient, suggesting the causal effect. As a result of this, we emphasize the importance of being vigilant about such atypical presentations to avoid delays in diagnosis and treatment of such life-threatening emergencies like TTP.

Thrombotic thrombocytopenic purpura (TTP) is typically characterized by the symptomatic pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, and renal failure. Atypical TTP is the diagnosis used to describe the subset of patients with TTP who present with symptoms that deviate from the classic pentad. We report a case an 86-year-old woman who presented to the emergency department complaining of chest pain for one day. She was reportedly on antibiotics for sinus infection. Physical examination revealed multiple bilateral superficial hematomas, predominantly on her extremities. On admission, her lab values were as follows: platelet count of 6,000/cubic millimeter, hemoglobin of 10.4 grams/deciliter, leukocyte count of 5100 cells/cubic millimeter, total bilirubin of 2.3 milligrams/deciliter, and troponin-I of 5.190 nanograms/milliliter. Peripheral blood smear was normal and did not reveal any schistocytes. The patient was admitted to the intensive care unit with a diagnosis of a non-ST-elevation myocardial infarction and a presumed diagnosis of immune thrombocytopenic purpura from antibiotic use. She was treated with intravenous solumedrol and a high-intensity statin. On the third day of her admission, the patient\'s mental functioning deteriorated and was intubated to protect her airway. A second peripheral smear revealed schistocytes, and subsequent laboratory studies supported the diagnosis of TTP. Plasma exchange therapy was planned. However, the patient succumbed to cardiac arrest before it could be initiated. The diagnosis was later confirmed with an ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) assay.  This case serves as an example of one of the many ways in which TTP can present, and emphasizes the importance of considering TTP as a differential diagnosis.