Novel diagnostic assays for heparin-induced thrombocytopenia.

Blood. 2013 Feb 27;

Authors: Cuker A, Rux AH, Hinds JL, Dela Cruz M, Yarovoi SV, Brown IA, Yang W, Konkle BA, Arepally GM, Watson SP, Cines DB, Sachais BS

Abstract

Laboratory testing for heparin-induced thrombocytopenia (HIT) has important shortcomings. Immunoassays fail to discriminate platelet-activating from non-pathogenic antibodies. Specific functional assays are often impracticable due to the need for platelets and radioisotope. We describe two assays that may overcome these limitations. The KKO-inhibition test (KKO-I) measures the effect of plasma on binding of the HIT-like monoclonal antibody KKO to PF4/heparin. DT40-luciferase (DT40-luc) is a functional test comprised of a B-cell line expressing Fc?RIIa coupled to a luciferase reporter. We compared these assays to polyspecific and IgG-specific PF4/heparin ELISAs in samples from 58 patients with suspected HIT and circulating anti-PF4/heparin antibodies. HIT was defined as a 4Ts score ?4 and positive 14C-serotonin release assay. HIT-positive plasma demonstrated greater mean inhibition of KKO binding than HIT-negative plasma (78.9% vs. 26.0%, p<0.0001) and induced greater luciferase activity (3.14-fold basal vs. 0.96-fold basal, p<0.0001). The area under the ROC curve (AUC) was greater for KKO-I (0.93) than for the polyspecific (0.82, p=0.020) and IgG-specific ELISA (0.76, p=0.0044) and for DT40-luc (0.89) than for the IgG-specific ELISA (p=0.046). KKO-I and DT40-luc showed better discrimination than two commercially available immunoassays, are simple to perform, and hold promise for improving the specificity and feasibility of HIT laboratory testing.

PMID: 23446735 [PubMed - as supplied by publisher]

How I diagnose amyloidosis.

Blood. 2012 Sep 4;

Authors: Leung N, Nasr SH, Sethi S

Abstract

Amyloidosis is a rare group of diseases characterized by deposition of amyloid fibrils in soft tissues. More than 28 types of amyloid have been identified. They all share common ultrastructural and chemical characteristics. Treatments are available for many types but are type specific. Therefore, confirmation and typing of amyloid is essential before initiating treatment. Monoclonal protein studies should be performed on suspected cases but the diagnosis requires a tissue biopsy. Congo red stain and electron microscopy are helpful to discriminate between amyloid and other pathologic fibrils. Once amyloid is confirmed, typing should be performed. Immunofluorescence and immunohistochemistry are frequently used and are helpful but this approach has limitations such as availability specificity and sensitivity of commercial antibodies. Genetic mutational analysis is vital for ruling in and out hereditary amyloidoses but is unhelpful in non-mutated forms. The most advanced technique of amyloid typing is laser microdissection followed by mass spectrometry (LMD-MS). Using proteomics, LMD -MS can directly identify proteins with or without mutations. Finally, imaging studies such as cardiac MRI with gadolinium and I-123 labeled SAP scintigraphy not only assist in evaluation of patients with known amyloidosis but cardiac MRI has detected amyloid in patients previously unsuspected of the disease.

PMID: 22948045 [PubMed - as supplied by publisher]

Perioperative management of patients on chronic antithrombotic therapy.

Blood. 2012 Aug 1;

Authors: Ortel TL

Abstract

Perioperative management of antithrombotic therapy is a situation that occurs frequently and requires consideration of the patient, the procedure, and an expanding array of anticoagulant and antiplatelet agents. Preoperative assessment must address the individual patient's risk for thromboembolic events, balanced against the risk for perioperative bleeding. Procedures can be separated into those with a low bleeding risk, which generally do not require complete reversal of the antithrombotic therapy, and those associated with an intermediate or high bleeding risk. For patients who are receiving warfarin who need interruption of the anticoagulant, consideration must be given to whether simply withholding the anticoagulant is the optimal approach, or whether a perioperative 'bridge' with an alternative agent, typically a low-molecular weight heparin, should be used. The new oral anticoagulants dabigatran and rivaroxaban have shorter effective half-lives, but they introduce other concerns for perioperative management, including prolonged drug effect in patients with renal insufficiency, limited experience with clinical laboratory testing to confirm lack of residual anticoagulant effect, and lack of a reversal agent. Antiplatelet agents must also be considered in the perioperative setting, with particular consideration given to the potential risk for thrombotic complications in patients with coronary artery stents who have antiplatelet therapy withheld.

PMID: 22855600 [PubMed - as supplied by publisher]