Scholars@Duke
Sanjay Khandelwal

Sanjay Khandelwal

Assistant Professor in Medicine
Medicine, Hematology
sanjay.khandelwal@duke.edu
Room 371, Alex H Sands Building, Research Drive, Durham, NC 27710

Selected Publications

Platelet and red cell responses to three North American pit vipers.

Journal Article Toxicon · August 28, 2024 We investigated the hemotoxic effects of three North American pit vipers in healthy human donor blood. Using experiments focusing on platelet and red blood cell activity, we found differential effects of these venoms on these cellular components. Platelet ... Full text Link to item Cite

Inhibition of the C1s Protease and the Classical Complement Pathway by 6-(4-Phenylpiperazin-1-yl)Pyridine-3-Carboximidamide and Chemical Analogs.

Journal Article J Immunol · February 15, 2024 The classical pathway (CP) is a potent mechanism for initiating complement activity and is a driver of pathology in many complement-mediated diseases. The CP is initiated via activation of complement component C1, which consists of the pattern recognition ... Full text Link to item Cite

Deciphering and disrupting PIEZO1-TMEM16F interplay in hereditary xerocytosis.

Journal Article Blood · January 25, 2024 Cell-surface exposure of phosphatidylserine (PS) is essential for phagocytic clearance and blood clotting. Although a calcium-activated phospholipid scramblase (CaPLSase) has long been proposed to mediate PS exposure in red blood cells (RBCs), its identity ... Full text Link to item Cite

Treatment of thrombocytopenia and thrombosis in HIT in mice using deglycosylated KKO: a novel therapeutic?

Journal Article Blood Adv · August 8, 2023 Heparin-induced thrombocytopenia (HIT) is characterized by thrombocytopenia associated with a highly prothrombotic state due to the development of pathogenic antibodies that recognize human platelet factor 4 (hPF4) complexed with various polyanions. Althou ... Full text Link to item Cite

Modulation of ultralarge immune complexes in heparin-induced thrombocytopenia.

Journal Article J Thromb Haemost · March 2023 BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a serious thrombotic disorder caused by ultralarge immune complexes (ULICs) containing platelet factor 4 (PF4) and heparin that form the HIT antigen, together with a subset of anti-PF4 antibodies. ULICs ... Full text Link to item Cite

Neutrophil functional heterogeneity is a fixed phenotype and is associated with distinct gene expression profiles.

Journal Article J Leukoc Biol · December 2022 Differences in the ability of neutrophils to perform relevant effector functions has been identified in a variety of disease states. Although neutrophil functional heterogeneity is increasingly recognized during disease, few studies have examined neutrophi ... Full text Link to item Cite

Minimal role for the alternative pathway in complement activation by HIT immune complexes.

Journal Article J Thromb Haemost · November 2022 BACKGROUND: Anti-platelet factor 4 (PF4)/heparin immune complexes that cause heparin-induced thrombocytopenia (HIT) activate complement via the classical pathway. Previous studies have shown that the alternative pathway of complement substantially amplifie ... Full text Link to item Cite

Complement mediates binding and procoagulant effects of ultralarge HIT immune complexes.

Journal Article Blood · November 25, 2021 Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder mediated by ultra-large immune complexes (ULICs) containing immunoglobulin G (IgG) antibodies to a multivalent antigen composed of platelet factor 4 and heparin. The limitations of current ... Full text Link to item Cite

C3 complement inhibition prevents antibody-mediated rejection and prolongs renal allograft survival in sensitized non-human primates.

Journal Article Nat Commun · September 15, 2021 Sensitized kidney transplant recipients experience high rates of antibody-mediated rejection due to the presence of donor-specific antibodies and immunologic memory. Here we show that transient peri-transplant treatment with the central complement componen ... Full text Link to item Cite

Heterogeneity in neutrophil responses to immune complexes.

Journal Article Blood Adv · October 8, 2019 Immune complexes (ICs) can trigger inflammation and thrombosis, in part, by activating neutrophils. Much attention has focused on the serologic characteristics of ICs and Fc receptors associated with cellular activation, but few studies have examined host ... Full text Link to item Cite

Polyreactive IgM initiates complement activation by PF4/heparin complexes through the classical pathway.

Journal Article Blood · December 6, 2018 The mechanisms by which exposure to heparin initiates antibody responses in many, if not most, recipients are poorly understood. We recently demonstrated that antigenic platelet factor 4 (PF4)/heparin complexes activate complement in plasma and bind to B c ... Full text Link to item Cite

Serologic characterization of anti-protamine/heparin and anti-PF4/heparin antibodies.

Journal Article Blood Adv · April 25, 2017 Anti-protamine (PRT)/heparin antibodies are a newly described class of heparin-dependent antibodies occurring in patients exposed to PRT and heparin during cardiac surgery. To understand the biologic significance of anti-PRT/heparin antibodies, we develope ... Full text Link to item Cite

Polyphosphate/platelet factor 4 complexes can mediate heparin-independent platelet activation in heparin-induced thrombocytopenia.

Journal Article Blood Adv · November 29, 2016 Heparin-induced thrombocytopenia (HIT) is a thrombotic disorder initiated by antibodies to complexes between platelet factor 4 (PF4) and heparin. The risk of recurrent thromboembolism persists after heparin is cleared and platelet activation leading to rel ... Full text Link to item Cite

Immune pathogenesis of heparin-induced thrombocytopenia.

Journal Article Thromb Haemost · October 28, 2016 The immune response to heparin is one of the most common drug-induced allergies, and yet, atypical for a drug hypersensitivity reaction. Whereas most drug-induced allergies are rare, idiosyncratic and life-long, the allergic response to heparin is common, ... Full text Link to item Cite

The antigenic complex in HIT binds to B cells via complement and complement receptor 2 (CD21).

Journal Article Blood · October 6, 2016 Heparin-induced thrombocytopenia is a prothrombotic disorder caused by antibodies to platelet factor 4 (PF4)/heparin complexes. The mechanism that incites such prevalent anti-PF4/heparin antibody production in more than 50% of patients exposed to heparin i ... Full text Link to item Cite

Heparin enhances uptake of platelet factor 4/heparin complexes by monocytes and macrophages.

Journal Article J Thromb Haemost · August 2015 BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an iatrogenic complication of heparin therapy caused by antibodies to a self-antigen, platelet factor (4) and heparin. The reasons why antibodies form to PF4/heparin, but not to PF4 bound to other cellu ... Full text Link to item Cite

CD47 regulates the phagocytic clearance and replication of the Plasmodium yoelii malaria parasite.

Journal Article Proc Natl Acad Sci U S A · March 10, 2015 Several Plasmodium species exhibit a strong age-based preference for the red blood cells (RBC) they infect, which in turn is a major determinant of disease severity and pathogenesis. The molecular basis underlying this age constraint on the use of RBC and ... Full text Link to item Cite

Reduced expression of CD47 during murine red blood cell (RBC) senescence and its role in RBC clearance from the circulation

Journal Article Transfusion · September 2007 BACKGROUND: Almost 2 percent of murine blood red blood cells (RBCs) are destroyed each day and are replaced by fresh RBCs generated through the process of erythropoiesis. RBCs to be destroyed are phagocytosed by macrophages i ... Full text Cite