scholarly journals Coexistence of Antiphospholipid Syndrome and Heparin-Induced Thrombocytopenia in a Patient with Recurrent Venous Thromboembolism

2017 ◽  
Vol 2017 ◽  
pp. 1-4
Author(s):  
Samuel Adediran ◽  
Nicole Agostino
Keyword(s):  
Adverse Drug Reaction ◽  
Drug Reaction ◽  
Venous Thromboembolism ◽  
Antiphospholipid Syndrome ◽  
Platelet Factor 4 ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Recurrent Venous Thromboembolism

Heparin-induced thrombocytopenia (HIT) is a prothrombotic adverse drug reaction in which heparin forms complexes with platelet factor 4 forming neoantigens that are recognized by autoantibodies. Antiphospholipid syndrome (APS) is similar to HIT in that it is mediated by autoantibodies that are also prothrombotic. We present a case of rare coexistence of antiphospholipid antibody syndrome and heparin-induced thrombocytopenia.

scholarly journals Antigen and substrate withdrawal in the management of autoimmune thrombotic disorders

Blood ◽  
2012 ◽  
Vol 120 (20) ◽  
pp. 4134-4142 ◽  
Author(s):  
Douglas B. Cines ◽  
Keith R. McCrae ◽  
X. Long Zheng ◽  
Bruce S. Sachais ◽  
Eline T. Luning Prak ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Antiphospholipid Syndrome ◽  
Von Willebrand Factor ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Thrombocytopenic Purpura ◽  
Heparin Induced Thrombocytopenia ◽  
Systemic Anticoagulation ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractPrevailing approaches to manage autoimmune thrombotic disorders, such as heparin-induced thrombocytopenia, antiphospholipid syndrome and thrombotic thrombocytopenic purpura, include immunosuppression and systemic anticoagulation, though neither provides optimal outcome for many patients. A different approach is suggested by the concurrence of autoantibodies and their antigenic targets in the absence of clinical disease, such as platelet factor 4 in heparin-induced thrombocytopenia and β2-glycoprotein-I (β2GPI) in antiphospholipid syndrome. The presence of autoantibodies in the absence of disease suggests that conformational changes or other alterations in endogenous protein autoantigens are required for recognition by pathogenic autoantibodies. In thrombotic thrombocytopenic purpura, the clinical impact of ADAMTS13 deficiency caused by autoantibodies likely depends on the balance between residual antigen, that is, enzyme activity, and demand imposed by local genesis of ultralarge multimers of von Willebrand factor. A corollary of these concepts is that disrupting platelet factor 4 and β2GPI conformation (or ultralarge multimer of von Willebrand factor oligomerization or function) might provide a disease-targeted approach to prevent thrombosis without systemic anticoagulation or immunosuppression. Validation of this approach requires a deeper understanding of how seemingly normal host proteins become antigenic or undergo changes that increase antibody avidity, and how they can be altered to retain adaptive functions while shedding epitopes prone to elicit harmful autoimmunity.

Efficacy of Fondaparinux in the Treatment of Heparin-Induced Thrombocytopenia with Venous Thromboembolism: Reduction of Thromboembolic Burden, Normalization of Platelet Count and Disappearance of Anti-Platelet Factor 4/Heparin Antibodies.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 575-575 ◽  
Author(s):  
Franco Piovella ◽  
Marisa Barone ◽  
Chiara Beltrametti ◽  
Chiara Piovella ◽  
Andrea M. D’Armini ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Platelet Count ◽  
Venous Thromboembolism ◽  
Platelet Factor 4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Surgical Patient ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia

Abstract Heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia with thrombosis (HITT) may develop during anticoagulant treatment in patients submitted to various regimens of unfractionated or low-molecular weight heparins. Several molecules have been studied as alternative anticoagulants in patients with HIT or HITT, including danaparoid, argatroban, lepirudin. Lepirudin requires dosage adjustments in patients with renal insufficiency and has potential for antibody formation. Argatroban requires dosage adjustments in patients with hepatic insufficiency. Argatroban increases the International Normalized Ratio (INR) when co-administered with warfarin, leading to dosage difficulties when transitioning to warfarin therapy. Anticoagulation of patients with HIT or HITT may be limited by antibodies cross-reactivity with danaparoid and by new generation of antibodies with lepirudin. Fondaparinux is the first of a new class of synthetic antithrombotics: the selective inhibitors of coagulation factor Xa. It is the most advanced competitor of low molecular weight heparins, which are the reference drugs in prophylaxis and treatment of venous thromboembolism. Fondaparinux does not bind to platelet factor 4 (PF4) and does not react with anti-PF4/heparin antibodies in in vitro testing. We treated 20 patients who develop HIT (3 patients) or HITT (17 patients, of whom 4 had both DVT and PE). Nine patients were previously submitted to extracorporeal circulation with unfractionated heparin (UFH) followed by low-molecular weight heparin (LMWH) for major cardiac surgery. The remaining patients had been previously treated with either UHF or LMWH at therapeutic or prophylactic dosage in internal medicine or surgery wards. In the 17 patients who developed HITT, we applied therapeutic dosages of fondaparinux, i.e. 7.5 mg QD or lower, accordingly with their bleeding risk. To the remaining patients with HIT we gave prophylactic dosages of fondaparinux, i.e. 2.5 mg QD. Patients with HITT were treated for 4 to 25 days before starting warfarin. Fondaparinux was stopped when INR of 2.0 or more was reached. All patients showed a significant reduction of their thromboembolic burden. One episode of major bleeding was recorded in a post-surgical patient. All patients but one showed sustained normalization of the platelet number. In the remaining patient platelet count remained unchanged. Treatment was switched from fondaparinux to lepirudin and after few days her platelets reverted to close-to-normal levels. In seven patients, submitted to therapeutic dosages of fondaparinux, anti-PF4/heparin antibody titers were determined using a PF4/heparin enzyme-linked immunosorbent assay (ELISA): in all cases antibody levels progressively decreased close to disappearance by 30–45 days. This series of cases provides further evidence for the safety and efficacy of fondaparinux in the treatment of both HIT or HITT.

Thrombotic Disorders

2015 ◽  
Author(s):  
Lawrence L K Leung
Keyword(s):  
Venous Thromboembolism ◽  
Antiphospholipid Syndrome ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Screening Tests ◽  
Factor V ◽  
Antithrombin Deficiency ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Heparin Complexes

The three main elements in the pathophysiology of thrombosis are endothelial injury, a decrease in blood flow, and an imbalance between procoagulant and anticoagulant factors. The latter element can be either hereditary (e.g., antithrombin deficiency) or acquired (e.g., antiphospholipid syndrome). This review details the assessment of patients with thrombotic disorders, hereditary and acquired hypercoagulable states, and the management of venous thromboembolism. Figures show how the degradation of thrombin-activated factor V Leiden by activated protein C (APC) is significantly slower than that of normal activated factor V (factor Va), leading to enhanced thrombin generation; how normal factor V serves as a cofactor of APC in the inhibition of factor VIIIa, whereas factor V Leiden has a poor cofactor function; and how IgG antibodies recognize platelet factor 4–heparin complexes in heparin-induced thrombocytopenia. Tables list inherited and acquired hypercoagulable states, questions for assessing thrombosis, screening tests for patients with suspected hypercoagulable states, clinical features that suggest thrombophilia, frequency and relative risk of venous thrombosis in selected hypercoagulable states, proposed clinical and laboratory criteria for antiphospholipid syndrome, the classification of antiphospholipid antibodies, the 4Ts scoring system for heparin-induced thrombocytopenia, and general guidelines for the management of patients with venous thromboembolism. This review contains 2 highly rendered figures, 9 tables, and 168 references.

Thrombotic Disorders

2015 ◽  
Author(s):  
Lawrence L K Leung
Keyword(s):  
Venous Thromboembolism ◽  
Antiphospholipid Syndrome ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Screening Tests ◽  
Factor V ◽  
Antithrombin Deficiency ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Heparin Complexes

The three main elements in the pathophysiology of thrombosis are endothelial injury, a decrease in blood flow, and an imbalance between procoagulant and anticoagulant factors. The latter element can be either hereditary (e.g., antithrombin deficiency) or acquired (e.g., antiphospholipid syndrome). This review details the assessment of patients with thrombotic disorders, hereditary and acquired hypercoagulable states, and the management of venous thromboembolism. Figures show how the degradation of thrombin-activated factor V Leiden by activated protein C (APC) is significantly slower than that of normal activated factor V (factor Va), leading to enhanced thrombin generation; how normal factor V serves as a cofactor of APC in the inhibition of factor VIIIa, whereas factor V Leiden has a poor cofactor function; and how IgG antibodies recognize platelet factor 4–heparin complexes in heparin-induced thrombocytopenia. Tables list inherited and acquired hypercoagulable states, questions for assessing thrombosis, screening tests for patients with suspected hypercoagulable states, clinical features that suggest thrombophilia, frequency and relative risk of venous thrombosis in selected hypercoagulable states, proposed clinical and laboratory criteria for antiphospholipid syndrome, the classification of antiphospholipid antibodies, the 4Ts scoring system for heparin-induced thrombocytopenia, and general guidelines for the management of patients with venous thromboembolism. This review contains 2 highly rendered figures, 9 tables, and 168 references.

scholarly journals Thromboembolism after COVID-19 vaccine in patients with preexisting thrombocytopenia

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Alessandro Mauriello ◽  
Manuel Scimeca ◽  
Ivano Amelio ◽  
Renato Massoud ◽  
Antonio Novelli ◽  
...  
Keyword(s):  
Adverse Drug Reaction ◽  
Drug Reaction ◽  
Exome Sequencing ◽  
Clinical Case ◽  
Severe Disease ◽  
Low Frequency ◽  
Postmortem Examination ◽  
Capillary Leak ◽  
Platelet Factor ◽  
Whole Exome

AbstractWhile vaccination is the single most effective intervention to drastically reduce severe disease and death following SARS-CoV-2 infection, as shown in UK and Israel, some serious concerns have been raised for an unusual adverse drug reaction (ADR), including vaccine-induced immune thrombotic thrombocytopenia (VITT) with concurrent low platelets as well as capillary leak syndrome. In fact, the overall safety of the vaccine is highlighted by the low frequency of ADR considering that in UK, by the early June, 40 million first doses and 29 million second doses have been injected; nonetheless, 390 thrombotic events, including 71 fatal events have been reported. Interestingly, the cases reported low platelet counts with the presence of anti-platelet factor-4 (PF4) antibodies, indicating an abnormal clotting reaction. Here, out of three referred cases, we report a post-vaccine clinical case of fatal thrombosis with postmortem examination and whole exome sequencing (WES) analysis, whose pathogenesis appeared associated to a preexisting condition of thrombocytopenia due to myelodysplasia.

Prevalence, isotype, and functionality of antiheparin–platelet factor 4 antibodies in patients treated with heparin and clinically suspected for heparin-induced thrombocytopenia

2002 ◽  
Vol 105 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Brian Untch ◽  
Sarfraz Ahmad ◽  
Walter P. Jeske ◽  
Harry L. Messmore ◽  
Debra A. Hoppensteadt ◽  
...  
Keyword(s):  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia

scholarly journals Heparin-induced thrombocytopenia: in vitro studies on the interaction of dabigatran, rivaroxaban, and low-sulfated heparin, with platelet factor 4 and anti-PF4/heparin antibodies

Blood ◽  
2012 ◽  
Vol 119 (5) ◽  
pp. 1248-1255 ◽  
Author(s):  
Krystin Krauel ◽  
Christine Hackbarth ◽  
Birgitt Fürll ◽  
Andreas Greinacher
Keyword(s):  
Factor Xa ◽  
Platelet Factor 4 ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Alternative Anticoagulation ◽  
Heparin Complexes ◽  
History Of

Abstract Heparin is a widely used anticoagulant. Because of its negative charge, it forms complexes with positively charged platelet factor 4 (PF4). This can induce anti-PF4/heparin IgG Abs. Resulting immune complexes activate platelets, leading to the prothrombotic adverse drug reaction heparin-induced thrombocytopenia (HIT). HIT requires treatment with alternative anticoagulants. Approved for HIT are 2 direct thrombin inhibitors (DTI; lepirudin, argatroban) and danaparoid. They are niche products with limitations. We assessed the effects of the DTI dabigatran, the direct factor Xa-inhibitor rivaroxaban, and of 2-O, 3-O desulfated heparin (ODSH; a partially desulfated heparin with minimal anticoagulant effects) on PF4/heparin complexes and the interaction of anti-PF4/heparin Abs with platelets. Neither dabigatran nor rivaroxaban had any effect on the interaction of PF4 or anti-PF4/heparin Abs with platelets. In contrast, ODSH inhibited PF4 binding to gel-filtered platelets, displaced PF4 from a PF4-transfected cell line, displaced PF4/heparin complexes from platelet surfaces, and inhibited anti-PF4/heparin Ab binding to PF4/heparin complexes and subsequent platelet activation. Dabigatran and rivaroxaban seem to be options for alternative anticoagulation in patients with a history of HIT. ODSH prevents formation of immunogenic PF4/heparin complexes, and, when given together with heparin, may have the potential to reduce the risk for HIT during treatment with heparin.

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