How Should Complicated Cases of Thrombotic Thrombocytopenic Purpura With Positive Coombs Test Be Treated?

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.

Streptococcus intermedius: From a Normal Oral Commensal to a Life-Threatening Organism.

Subdural empyema is a collection of pus in the subdural space between the dura mater and the arachnoid. It carries very high morbidity and mortality as it can spread anywhere in the brain; however, the risk can be mitigated with appropriate surgical and medical intervention. Being protected by the skull, cranial infections are usually preceded by a significant risk factor, either an external invader such as skull fractures secondary to trauma, penetrating injury, prior surgery, or, more commonly, in more than 50% of cases, due to spread of an internal infection such as ear or sinus infections. Anaerobic and aerobic bacteria can cause subdural empyema. Both gram-positive and gram-negative bacteria are notorious for developing this kind of infection; for example, different groups of gram-positive streptococci and staphylococci, gram-negative Haemophilus influenza, and other gram-negative bacilli can cause subdural empyema. While streptococci are more frequent with sinus infection causing subdural empyema, staphylococci are associated with skin invasion secondary to either head trauma or cranial surgery. Streptococcus intermedius is a gram-positive alpha-hemolytic pathogen belonging to the larger Streptococcus anginosus group that itself is a subgroup from viridans streptococci, aka Streptococcus milleri. Streptococcus intermedius is an oral commensal flora and is considered to be a low-virulence bacteria in immunocompetent patients but can be associated with significant morbidity and mortality. Subdural empyema tends to occur more often in immunocompromised patients such as diabetic patients, those with human immunodeficiency virus infection, and those using immunosuppressive medications. The clinical course ranges from indolent to fulminant. The size and location of the abscess play a role in clinical presentation. Headache is the most common presenting symptom, but patients can also present with fever, nausea, seizure, or altered mental status. Diagnosis can be obtained with CT and MRI scans of the brain. Prompt drainage of the abscess and lengthy antibiotics improve the prognosis significantly. Our case highlights a rare origin of subdural empyema from the direct spread of a skin abscess.

Primary Dural Diffuse Large B-cell Lymphoma: A Comprehensive Review of Survival and Treatment Outcomes.

Primary dural diffuse large B-cell lymphoma (PD-DLBCL) is a rare and aggressive B-cell non-Hodgkin lymphoma that can present in intracranial or intraspinal locations. Although the optimal management is unknown, PD-DLBCL therapy is often mirrored after primary central nervous system lymphoma therapy and aggressive treatment with a high dose methotrexate-based regimen is frequently used. Our comprehensive, retrospective study of 24 reported cases of PD-DLBCL provide the most complete analysis of this rare disease including data on biology, treatment outcomes, and survival. Our findings demonstrate good outcomes following induction treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), suggesting that these cases can be treated as DLBCL rather than primary central nervous system lymphoma, obviating the need for more aggressive and toxic approaches. The durable responses following R-CHOP also confirm that PD-DLBCL is not protected by the blood brain barrier.