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Medicine Jun 2024Immune thrombocytopenic purpura (ITP) comprises ~1% to 4% of thrombocytopenia cases during pregnancy. Factors predicting neonatal thrombocytopenia and associated... (Observational Study)
Observational Study
Immune thrombocytopenic purpura (ITP) comprises ~1% to 4% of thrombocytopenia cases during pregnancy. Factors predicting neonatal thrombocytopenia and associated morbidities due to maternal ITP are unclear. The present study aimed to assess the neonatal outcomes of pregnant women with ITP. Fifty-five pregnant women with ITP and their babies, born between January/2013 and April/2021, were retrospectively reviewed. Maternal and neonatal thrombocytopenia cases other than ITP were excluded from the study. Physical examination, blood count, and cranial/abdominal ultrasonography findings of the newborns were recorded. Neonatal thrombocytopenia was defined as a platelet count < 150 × 109/L. Relationship between neonatal thrombocytopenia and maternal factors was investigated. Thrombocytopenia was detected in 17/55 babies (30.9%), and 8/17 (47.1%) had symptoms of bleeding, all but one being mild bleeding. There was a significant correlation between neonatal platelet counts of < 100 × 109/L and maternal splenectomy history. Incidence of moderate and severe thrombocytopenia was higher (statistically insignificant) in neonates of mothers with ITP. No significant correlation was determined between maternal and neonatal platelet counts. There was a weak insignificant correlation between platelet counts of neonates of mothers with or without thrombocytopenia. A significant correlation was found between the presence of splenectomy before delivery in the mother and a platelet count of < 100 × 109/L in the neonate. Moderate and severe thrombocytopenia was higher in neonates of mothers diagnosed with ITP before pregnancy and needed treatment during pregnancy and/or delivery, but the difference was insignificant. Close follow-up of babies born to mothers with ITP after birth is crucial since there is no significant prediction criterion for developing neonatal thrombocytopenia and associated morbidities.
Topics: Humans; Female; Retrospective Studies; Infant, Newborn; Pregnancy; Purpura, Thrombocytopenic, Idiopathic; Cross-Sectional Studies; Adult; Platelet Count; Pregnancy Complications, Hematologic; Thrombocytopenia, Neonatal Alloimmune; Splenectomy
PubMed: 38905433
DOI: 10.1097/MD.0000000000038587 -
Retrograde adenosine/A receptor signaling facilitates excitatory synaptic transmission and seizures.Cell Reports Jun 2024Retrograde signaling at the synapse is a fundamental way by which neurons communicate and neuronal circuit function is fine-tuned upon activity. While long-term changes...
Retrograde signaling at the synapse is a fundamental way by which neurons communicate and neuronal circuit function is fine-tuned upon activity. While long-term changes in neurotransmitter release commonly rely on retrograde signaling, the mechanisms remain poorly understood. Here, we identified adenosine/A receptor (AR) as a retrograde signaling pathway underlying presynaptic long-term potentiation (LTP) at a hippocampal excitatory circuit critically involved in memory and epilepsy. Transient burst activity of a single dentate granule cell induced LTP of mossy cell synaptic inputs, a BDNF/TrkB-dependent form of plasticity that facilitates seizures. Postsynaptic TrkB activation released adenosine from granule cells, uncovering a non-conventional BDNF/TrkB signaling mechanism. Moreover, presynaptic ARs were necessary and sufficient for LTP. Lastly, seizure induction released adenosine in a TrkB-dependent manner, while removing ARs or TrkB from the dentate gyrus had anti-convulsant effects. By mediating presynaptic LTP, adenosine/AR retrograde signaling may modulate dentate gyrus-dependent learning and promote epileptic activity.
PubMed: 38905101
DOI: 10.1016/j.celrep.2024.114382 -
Cureus Jun 2024A 65-year-old male with multiple comorbidities and recently diagnosed with diabetic kidney disease developed upper and lower extremity rash following escitalopram...
A 65-year-old male with multiple comorbidities and recently diagnosed with diabetic kidney disease developed upper and lower extremity rash following escitalopram initiation for his depressive mood. Clinical assessment and skin biopsy confirmed cutaneous small-vessel vasculitis (CSVV), prompting drug discontinuation and oral methylprednisolone therapy. The resolution of the rash was achieved within a week. This rare case of CSVV induced by escitalopram highlights the importance of timely recognition and management of drug-induced CSVV and adds to the limited literature on selective serotonin reuptake inhibitor-associated CSVV.
PubMed: 38903979
DOI: 10.7759/cureus.62776 -
Frontiers in Immunology 2024Drug-induced immune thrombocytopenia is an adverse reaction marked by accelerated destruction of blood platelets. In cancer therapy, thrombocytopenia has many other... (Review)
Review
Drug-induced immune thrombocytopenia is an adverse reaction marked by accelerated destruction of blood platelets. In cancer therapy, thrombocytopenia has many other causes including bone marrow suppression induced by chemotherapeutic agents, infection, and progression of cancer; drug-induced thrombocytopenia can easily be misdiagnosed or overlooked. Here, we present a case of an ovarian cancer patient with a history of mixed connective tissue disease who underwent surgery followed by treatment with paclitaxel, cisplatin, and bevacizumab. The patient developed acute isolated thrombocytopenia after the sixth cycle. Serum antiplatelet antibody testing revealed antibodies against glycoprotein IIb. After we analyzed the whole therapeutic process of this patient, drug-induced immune thrombocytopenia was assumed, and bevacizumab was conjectured as the most probable drug. Thrombocytopenia was ultimately successfully managed using recombinant human thrombopoietin, prednisone, and recombinant human interleukin-11. We provide a summary of existing literature on immune thrombocytopenia induced by bevacizumab and discuss related mechanisms and triggers for drug-induced immune thrombocytopenia. The present case underscores the potential of bevacizumab to induce immune-mediated thrombocytopenia, emphasizing the need for heightened vigilance towards autoimmune diseases or an autoimmune-activated state as plausible triggers for rare drug-induced immune thrombocytopenia in cancer therapy.
Topics: Humans; Female; Bevacizumab; Ovarian Neoplasms; Purpura, Thrombocytopenic, Idiopathic; Mixed Connective Tissue Disease; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Antineoplastic Agents, Immunological
PubMed: 38903494
DOI: 10.3389/fimmu.2024.1382964 -
EJHaem Jun 2024Bleeding and thrombosis are common complications during immune thrombocytopenic purpura (ITP) treatment. There is a strong need to predict bleeding and thrombosis risks...
Bleeding and thrombosis are common complications during immune thrombocytopenic purpura (ITP) treatment. There is a strong need to predict bleeding and thrombosis risks before ITP treatment to optimize therapy and appropriately manage these complications. We performed a retrospective cohort study of 120 patients with primary ITP to identify a biomarker to predict bleeding and thrombosis. We compared blood test results at diagnosis between patients with and without bleeding or thrombosis episodes. The standard deviation of red blood cell distribution width (RDW-SD) differed significantly between those with and without bleeding and between those with and without thrombosis, leading us to identify it as a variable representative of risk. RDW-SD was significantly associated with patient age and with histories of several vascular diseases. Multivariate regression analyses showed that RDW integrated several variables associated with vascular risks. RDW-SD was significantly associated with difficulty with corticosteroid discontinuation (hazard ratio [HR], 2.22, = 0.01), incidence of bleeding (HR, 2.75, < 0.01), incidence of thrombosis (HR, 2.67, < 0.01) and incidence of infection (HR, 1.78, = 0.04). The RDW-SD value at the time of ITP diagnosis is a useful biomarker to predict the risks of bleeding, thrombosis, and other complications.
PubMed: 38895062
DOI: 10.1002/jha2.897 -
Healthcare (Basel, Switzerland) May 2024During the COVID-19 pandemic, there have been multiple reports about an unforeseen surge in adolescents and young adults exhibiting sudden onset functional tic-like... (Review)
Review
During the COVID-19 pandemic, there have been multiple reports about an unforeseen surge in adolescents and young adults exhibiting sudden onset functional tic-like behaviors. This phenomenon has been mainly associated with the female gender and occasionally after exposure to social media content featuring similar patterns of functional tic-like behaviors. A significant portion of these individuals have been directed to specialist clinics for movement disorders with initial misdiagnoses of late-onset refractory Tourette syndrome. Distinguishing between rapid onset functional tic-like behaviors and neurodevelopmental tics as part of Tourette syndrome can be challenging; however, the differential diagnosis is facilitated by focusing on specific clinical and demographic factors, which we have explored in a systematic literature review. Compared to neurodevelopmental tics, functional tic-like behaviors typically present with a more abrupt and intense manifestation of symptoms, onset at a later age, higher prevalence among females, inability to suppress tics, coexisting anxiety and depression, and sometimes a history of exposure to social media content portraying tic-like behaviors of a similar nature. This novel manifestation of a functional neurological disorder may thus be viewed as an emerging neuropsychiatric condition potentially triggered/exacerbated by the psychosocial repercussions of the COVID-19 crisis.
PubMed: 38891181
DOI: 10.3390/healthcare12111106 -
Clinical Case Reports Jun 2024Vincristine therapy can be effective in refractory Immune thrombocytopenia (ITP) following COVID-19 vaccination. Our case report highlights the need for further research...
KEY CLINICAL MESSAGE
Vincristine therapy can be effective in refractory Immune thrombocytopenia (ITP) following COVID-19 vaccination. Our case report highlights the need for further research to establish standard management guidelines for COVID-19-vaccine-associated ITP.
ABSTRACT
Adult immune thrombocytopenia (ITP) can occur as a rare complication following several viral infections or a rare adverse event or complication of vaccination. In this paper, we report a case of a 39-year-old male patient with severe refractory ITP that began 4-weeks after receiving his third (booster) dose of the COVID-19 vaccine (BNT162b2, Pfizer-BioNTech). He was given oral dexamethasone 40 mg daily for 4 days followed by prednisone at 1 mg/kg (85 mg daily) for 10 days. In the following weeks, we attempted several other lines of therapy to treat his ITP, including anti-RhD immunoglobulin, which, unfortunately, caused moderate hemolysis requiring packed red blood cell transfusion, intravenous immunoglobulin (given at a subtherapeutic dose of 0.4 g/kg for only 1 day since it was not available), rituximab, and eltrombopag. The patient, unfortunately, showed no response to any of these treatments. This was an indicator to initiate salvage therapy with vincristine 2 mg weekly for 3 weeks. The patient's platelet count started to increase remarkably during the third week of vincristine and normalized after 4 weeks. We review the findings, clinical characteristics, and management approaches that were reported in the literature regarding COVID-19-vaccine-induced ITP. More in-depth research is needed to delineate standard guidelines for the management of such cases. This report underscores the importance of resorting to vincristine and eltrombopag as great options for severe and refractory ITP related to the COVID-19 vaccine.
PubMed: 38883219
DOI: 10.1002/ccr3.9070 -
Neurobiology of Disease Jun 2024Biallelic variants in the SPG11 gene account for the most common form of autosomal recessive hereditary spastic paraplegia characterized by motor and cognitive...
Biallelic variants in the SPG11 gene account for the most common form of autosomal recessive hereditary spastic paraplegia characterized by motor and cognitive impairment, with currently no therapeutic option. We previously observed in a Spg11 knockout mouse that neurodegeneration is associated with accumulation of gangliosides in lysosomes. To test whether a substrate reduction therapy could be a therapeutic option, we downregulated the key enzyme involved in ganglioside biosynthesis using an AAV-PHP.eB viral vector expressing a miRNA targeting St3gal5. Downregulation of St3gal5 in Spg11 knockout mice prevented the accumulation of gangliosides, delayed the onset of motor and cognitive symptoms, and prevented the upregulation of serum levels of neurofilament light chain, a biomarker widely used in neurodegenerative diseases. Importantly, similar results were observed when Spg11 knockout mice were administrated venglustat, a pharmacological inhibitor of glucosylceramide synthase expected to decrease ganglioside synthesis. Downregulation of St3gal5 or venglustat administration in Spg11 knockout mice strongly decreased the formation of axonal spheroids, previously associated with impaired trafficking. Venglustat had similar effect on cultured human SPG11 neurons. In conclusion, this work identifies the first disease-modifying therapeutic strategy in SPG11, and provides data supporting its relevance for therapeutic testing in SPG11 patients.
PubMed: 38876323
DOI: 10.1016/j.nbd.2024.106564 -
Cureus May 2024Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially life-threatening condition characterized by fever, acute hemolysis, thrombocytopenia, renal...
Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially life-threatening condition characterized by fever, acute hemolysis, thrombocytopenia, renal dysfunction, and CNS dysfunction. A peripheral smear shows schistocytes because of microangiopathy. It is extremely rare for TTP and systemic lupus erythematosus (SLE) to coexist. This report details an Indian female patient's uncommon clinical presentation of TTP linked to SLE. A 52-year-old woman presented to the emergency department with complaints of altered sensorium and weakness of the right side of the body. She was initially evaluated as a case of a cerebrovascular accident. CT brain imaging revealed multiple ischemic infarcts involving both cerebral hemispheres. MRI brain confirmed the same. During further evaluation, she was found to have hemolytic anemia, thrombocytopenia, and nephrotic range proteinuria. Immunological investigations confirmed SLE. A peripheral smear revealed schistocytes, and the PLASMIC score confirmed a high risk of TTP. The patient was treated with immunosuppressants, plasma exchange, and hemodialysis, along with other supportive measures. The patient showed a positive response to the therapy mentioned, with improved power and renal function. The patient denied a renal biopsy and was discharged after two weeks. This case report emphasizes the importance of the association between TTP and SLE.
PubMed: 38872677
DOI: 10.7759/cureus.60238