Jo-Ann I Sheppard

McMaster University, Hamilton, Ontario, Canada

Are you Jo-Ann I Sheppard?

Claim your profile

Publications (18)114.22 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin utilization. An enzyme-linked immunosorbent assay (ELISA) is usually performed to assist in the diagnosis of HIT. ELISAs tend to be sensitive but lack specificity. We sought to utilize a new cut-off to define a positive HIT ELISA. We conducted a prospective observational study of hospitalized patients undergoing ELISA testing. All patients who underwent ELISA testing were eligible for inclusion (n=496). Irrespective of the results, all subjects had confirmatory testing with a serotonin release assay (SRA). We compared a threshold optical density (OD)>1.00 to the current definition of a positive ELISA (OD>0.40) as a screening test for a positive SRA. We used sensitivity, specificity, and area under the receiver operating curve to determine whether an OD>1.00 would improve diagnostic accuracy for HIT. The SRA was positive in 10 patients (prevalence: 2.0%). Adjusting the definition of a positive HIT ELISA to >1.00 maintained the sensitivity and negative predictive value at 100% in our cohort. The positive predictive value (PPV) of the higher cutoff OD was more than triple the PPV of an OD>0.40 (41.7% vs 13.3%). No patient with a positive SRA had an OD measurement <1.00. Increasing the OD threshold enhances specificity without noticeably compromising sensitivity. Altering the definition of the HIT ELISA could prevent unnecessary testing and/or treatment with non-heparin based anticoagulants in patients with possible HIT. (NCT 00946400).
    Chest 01/2015; 148(1). DOI:10.1378/chest.14-1417 · 7.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Repeated therapeutic plasma exchange (TPE) has been advocated to remove heparin-induced thrombocytopenia (HIT) IgG antibodies prior to cardiac/vascular surgery in patients who have serologically-confirmed acute or subacute HIT; for this situation, a negative platelet activation assay (e.g., platelet serotonin-release assay [SRA]) has been recommended as the target serological endpoint to permit safe surgery. We compared reactivities in the SRA and an anti-PF4/heparin IgG-specific enzyme-immunoassay (EIA), testing serial serum samples in a patient with recent (subacute) HIT who underwent serial TPE pre-cardiac surgery, as well as for 15 other serially-diluted HIT sera. We observed that post-TPE/diluted HIT sera-when first testing SRA-negative-continue to test strongly positive by EIA-IgG. This dissociation between the platelet activation assay and a PF4-dependent immunoassay for HIT antibodies indicates that patients with subacute HIT undergoing repeated TPE prior to heparin re-exposure should be tested by serial platelet activation assays even when their EIAs remain strongly positive. Copyright © 2014 American Society of Hematology.
    Blood 11/2014; 125(1). DOI:10.1182/blood-2014-07-590844 · 10.45 Impact Factor
  • Journal of cardiothoracic and vascular anesthesia 08/2014; 29(5). DOI:10.1053/j.jvca.2014.04.029 · 1.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thrombocytopenia occurs in 20% to 45% of critically ill medical-surgical patients. The 4Ts heparin-induced thrombocytopenia (HIT) score (with 4 domains: Thrombocytopenia, Timing of thrombocytopenia, Thrombosis and oTher reason[s] for thrombocytopenia) might reliably identify patients at low risk for HIT. Interobserver agreement on 4Ts scoring is uncertain in this setting. To evaluate whether a published clinical prediction rule (the "4Ts score") reliably rules out HIT in "low-risk" intensive care unit (ICU) patients as assessed by research coordinators (who prospectively scored) and 2 adjudicators (who scored retrospectively) during an international heparin thromboprophylaxis trial (PROTECT, NCT00182143). Of 3746 medical-surgical ICU patients in PROTECT, 794 met the enrollment criteria for this HIT substudy. Enrollment was predicated on one of the following occurring in ICU: platelets less than 50 × 10(9)/L, platelets decreased to 50% of ICU admission value (if admission value <100 × 10(9)/L), any venous thrombosis, or if HIT was otherwise clinically suspected. Independently, 4Ts scores were completed in real time by research coordinators blinded to study drug and laboratory HIT results, and retrospectively by 2 adjudicators blinded to study drug, laboratory HIT results, and research coordinators' scores; the adjudicators arrived at consensus in all cases. Of the 763 patients, 474 had a central or local laboratory HIT test performed and had 4Ts scoring by adjudicators; 432 were scored by trained research coordinators. Heparin-induced thrombocytopenia was defined by a centrally performed positive serotonin release assay (SRA). Of the 474 patients with central adjudication, 407 (85.9%) had a 4Ts score of 3 or lower, conferring a low pretest probability (PTP) of HIT; of these, 6 (1.5% [95% confidence interval, 0.7%-3.2%) had a positive SRA. Fifty-nine (12.4%) had a moderate PTP (4Ts score of 4-5); of these, 4 (6.8%) had a positive SRA. Eight patients had a high PTP (4Ts score of ≥6); of these, 1 (12.5%) had a positive SRA. Raw agreement between research coordinators and central adjudication on each domain of the 4Ts score and low, intermediate, and high PTP was good. However, chance-corrected agreement was variable between adjudicators (weighted κ values of 0.31-0.93) and between the adjudicator consensus and research coordinators (weighted κ values of 0.13 and 0.78). Post hoc review of the 6 SRA-positive cases with an adjudicated low PTP demonstrated that their scores would have been increased if the adjudicators had had additional information on heparin exposure prior to ICU admission. In general, the fourth domain of 4Ts (oTher causes of thrombocytopenia) generated the most disagreement. Real-time 4Ts scoring by research coordinators at the time of testing for HIT was not consistent with 4Ts scores obtained by central adjudicators. The results of this comprehensive HIT testing highlight the need for further research to improve the assessment of PTP scoring of HIT for critically ill patients.
    Journal of critical care 02/2014; 29(3). DOI:10.1016/j.jcrc.2014.02.004 · 2.00 Impact Factor
  • Theodore E Warkentin · Jo-Ann I Sheppard
    [Show abstract] [Hide abstract]
    ABSTRACT: Heparin re-exposure despite a history of previous heparin-induced thrombocytopenia (HIT) can be appropriate if platelet-activating antibodies are no longer detectable. We determined the frequency, timing, and magnitude of the anti-PF4/heparin immune response (by serotonin-release assay [SRA] and enzyme-immunoassay [EIA]), and the frequency of recurrent HIT, in 20 patients with previous HIT re-exposed to heparin 4.4 years (mean) post-HIT; 17 patients were given heparin intraoperatively (without postoperative heparin) for cardiac/vascular surgery. One patient developed recurrent HIT beginning 7 days post-cardiac surgery, with newly-regenerated HIT antibodies exhibiting strong heparin-independent platelet-activating properties. Intraoperative heparin induced EIA seroconversion in 11/17 (65%) patients (IgG>IgA>IgM) and SRA seroconversion in 8/17 (47%), whereas none of 3 medical patients re-exposed to heparin developed seroconversion. Anti-PF4/heparin IgG became detectable at day 7 (median), i.e., no sooner than observed in typical-onset HIT. The high proportion of SRA-positivity among EIA-seroconverting patients (8/11 [73%]) suggests that patients with previous HIT may be especially predisposed to forming recurrent antibodies with platelet-activating properties. We conclude that among patients with a previous history of HIT who are re-exposed to intraoperative (but not postoperative) heparin the risk of recurrent HIT appears to be low, but is possible if antibodies with strong heparin-independent platelet-activating properties are formed.
    Blood 02/2014; 123(16). DOI:10.1182/blood-2013-10-533083 · 10.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT BACKGROUND: In a recent multicenter randomized trial comparing unfractionated heparin (UFH) with low-molecular-weight heparin (dalteparin) for thromboprophylaxis in 3746 critically-ill patients, 17 (0.5%) patients developed heparin-induced thrombocytopenia (HIT) based on serotonin-release assay-positive (SRA+) status. A trend to lower frequency of HIT with dalteparin vs UFH was observed in the intention-to-treat analysis (5 vs 12 patients; P=0.14), which was statistically significant (3 vs 12 patients; P=0.046) in a prespecified per-protocol analysis which excluded patients with deep-vein thrombosis (DVT) at study entry. We sought to characterize HIT outcomes and to determine how dalteparin thromboprophylaxis might reduce HIT frequency in ICU patients. METHODS: In 17 patients with HIT, we analyzed platelet counts and thrombotic events in relation to study drug and other open-label heparin, to determine whether study drug plausibly explained seroconversion to SRA+ status and/or breakthrough of thrombocytopenia/thrombosis. We also compared antibody frequencies (dalteparin vs UFH) in 409 patients serologically investigated for HIT. RESULTS: HIT-associated thrombosis occurred in 10/17 (58.8%) patients (8:1:1 venous:arterial:both). Dalteparin was associated with fewer study drug-attributable HIT-related events (P=0.020), including less seroconversion (P=0.058) and less breakthrough of thrombocytopenia/thrombosis (P=0.032). Anti-PF4/heparin IgG antibodies by ELISA were less frequent among patients receiving dalteparin vs UFH (13.5% vs 27.3%; P<0.001). One patient with HIT-associated DVT died post-UFH bolus, whereas platelet counts recovered in two others with HIT-associated VTE despite continuation of therapeutic-dose UFH. CONCLUSIONS: The lower risk of HIT in ICU patients receiving dalteparin appears related to both decreased antibody formation and decreased clinical breakthrough of HIT among patients forming antibodies.
    Chest 05/2013; DOI:10.1378/chest.13-0057 · 7.48 Impact Factor
  • Thrombosis and Haemostasis 05/2012; 108(2):394-6. DOI:10.1160/TH12-03-0201 · 4.98 Impact Factor
  • Critical Care 03/2012; 16(1). DOI:10.1186/cc11030 · 4.48 Impact Factor
  • Thrombosis and Haemostasis 02/2012; 107(5):998-1000. DOI:10.1160/TH11-12-0839 · 4.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Acute ischaemic stroke patients sometimes receive heparin for treatment and/or prophylaxis of thromboembolic complications. This study was designed to elucidate the incidence and clinical features of heparin-induced thrombocytopenia (HIT) in acute stroke patients treated with heparin. We conducted a prospective multicentre cohort study of 267 patients who were admitted to three stroke centres within 7 d after stroke onset. We examined clinical data until discharge and collected blood samples on days 1 and 14 of hospitalization to test anti-platelet factor 4/heparin antibodies (anti-PF4/H Abs) using an enzyme-linked immunosorbent assay (ELISA); platelet-activating antibodies were identified by serotonin-release assay (SRA). Patients with a 4Ts score ≥4 points, positive-ELISA, and positive-SRA were diagnosed as definite HIT. Heparin was administered to 172 patients (64·4%: heparin group). Anti-PF4/H Abs were detected by ELISA in 22 cases (12·8%) in the heparin group. Seven patients had 4Ts ≥ 4 points. Among them, three patients (1·7% overall) were also positive by both ELISA and SRA. National Institutes of Health Stroke Scale score on admission was high (range, 16-23) and in-hospital mortality was very high (66·7%) in definite HIT patients. In this study, the incidence of definite HIT in acute ischaemic stroke patients treated with heparin was 1·7% (95% confidence interval: 0·4-5·0). The clinical severity and outcome of definite HIT were unfavourable.
    British Journal of Haematology 06/2011; 154(3):378-86. DOI:10.1111/j.1365-2141.2011.08775.x · 4.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Heparin-induced thrombocytopenia (HIT), which is caused by platelet (PLT)-activating immunoglobulin (Ig)G antibodies against platelet factor 4 (PF4)/heparin complexes, differs from other immune responses seen in immunohematology: IgG antibodies are formed as early as 5 days even without previous heparin exposure; antibodies are remarkably transient (<100 days); HIT is more frequent in postsurgery patients compared with medical patients despite administering the same type and dose of heparin; and increasing evidence implicates autoantibody-like reactivity of anti-PF4/heparin antibodies. We hypothesized that these unusual features could be caused by loss of regulatory anti-idiotype IgM antibodies due to disturbance (e.g., by surgery) of an idiotype-anti-idiotype network. Sera were obtained prospectively before heparin administration and during the immunization phase of HIT and also from patients with previous HIT after waning of antibodies to nondetectable levels. To detect inhibitory IgM anti-idiotype antibodies, we performed serum coincubation experiments and IgG purification by protein G and size filtration to exclude coprecipitating IgM. Sera (n = 3) containing known anti-PF4/heparin IgG or IgM antibodies and normal sera (n = 20) were processed as controls. Fifteen preimmune response sera (seroconverting in the PF4/heparin-IgG enzyme-linked immunosorbent assay only [n = 4] or additionally in a PLT activation assay [n = 5] or in both assays plus thrombosis [n = 6]) and four sera of previously immunized patients were included. Neither did the neat sera inhibit binding of anti-PF4/heparin antibodies nor did the purified IgG fractions show enhanced binding to PF4/heparin complexes. The atypical immunologic features of HIT do not appear to be caused by disruption of an idiotype (IgG)-anti-idiotype (IgM) network.
    Transfusion 06/2009; 49(9):1812-8. DOI:10.1111/j.1537-2995.2009.02205.x · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating antibodies that recognize PF4/heparin complexes. Uncertainties remain regarding HIT immunobiology, including the temporal relation of antibody formation to onset of thrombocytopenia, and whether immunoglobulin class switching occurs. Using serial plasma samples from 2 heparin thromboprophylaxis trials, we determined the time of onset, antibody levels, and immunoglobulin class distributions (IgG, IgA, IgM) for 12 patients with HIT and 36 patients who formed anti-PF4/heparin antibodies, but did not develop HIT ("seropositive non-HIT controls"). In patients with HIT, anti-PF4/heparin antibodies became detectable 4 days (median) after starting heparin; antibody detection preceded the platelet count decline by 2 days (median). Patients with HIT produced higher levels of IgG antibodies, but similar IgA and IgM levels, compared with seropositive non-HIT controls. Among all 48 seroconverting patients, the first day of a positive antibody test (median, day 6) did not differ among the immunoglobulin classes. Thus, the HIT immune response does not exhibit the classic paradigm of IgM class precedence/immunoglobulin class switching; rather, relatively rapid formation of IgG antibodies is observed, sometimes with concomitant IgA and IgM formation. Compared with seropositive non-HIT controls, HIT patients develop significantly higher anti-PF4/heparin IgG levels that are detectable before the onset of thrombocytopenia.
    Blood 02/2009; 113(20):4963-9. DOI:10.1182/blood-2008-10-186064 · 10.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The immune response in heparin-induced thrombocytopenia (HIT) is puzzling: heparin-naive patients can develop IgG antibodies and clinical HIT as early as day 5, and evidence for an anamnestic response on heparin reexposure is lacking. We assessed daily serum samples by anti-PF4/heparin enzyme-immunoassay (EIA) in patients receiving heparin thromboprophylaxis. Of 435 patients, 56.1% showed an increase in EIA optical density (OD) of more than or equal to 15%, with more than 90% starting between days 4 and 14. After reaching maximum reactivity by days 10 to 12, ODs declined despite heparin continuation, including in 2 patients with clinical HIT. Individual IgG/A/M classes showed identical time of onset (median, day 6). Most (58.7%) antibody-positive patients developed all 3 Ig classes; only 11.3% lacked IgG response. IgG/A/M increase usually occurred simultaneously (+/- 1 day) with no general tendency for IgM precedence. Consistent with the transient immune response, none of the IgG-EIA-positive (OD > 0.5) patients at discharge developed clinically evident thrombosis during extended low-molecular-weight heparin thromboprophylaxis. The rapid onset of the anti-PF4/heparin immune response, its transience, and the simultaneous appearance of antibodies of different classes with no IgM precedence suggest short-term activation of B cells that have previously undergone Ig-class switching even without previous pharmacologic heparin exposure.
    Blood 12/2008; 113(20):4970-6. DOI:10.1182/blood-2008-08-173062 · 10.45 Impact Factor
  • Theodore E Warkentin · Jo-Ann I Sheppard
    [Show abstract] [Hide abstract]
    ABSTRACT: Heparin-induced thrombocytopenia (HIT) has a distinct clinical profile and unique pathogenesis. It is caused by platelet-activating IgG antibodies that recognize multimolecular complexes of platelet factor 4 (PF4) bound to heparin or certain other polyanions. Although an immune response to PF4/heparin associated with heparin treatment is very common, clinical HIT occurs only among the minority of patients whose antibodies are capable of strongly activating platelets. This explains why certain platelet activation assays and anti-PF4/polyanion immunoassays have high sensitivity for HIT and why diagnostic specificity is highest for those assays that preferentially detect pathogenic antibodies, such as the washed platelet activation assays or immunoassays that detect only IgG antibodies. Negative results obtained in a solid-phase PF4/polyanion immunoassay generally exclude HIT (high negative predictive value), especially in a setting of a low pretest probability. In addition, because the magnitude of a positive test result correlates with greater likelihood of HIT, a Bayesian diagnostic approach that combines pretest probability and the magnitude of a positive test result is recommended. Recent studies suggest that presence of anti-PF4/polyanion antibodies in certain clinical settings confers an adverse prognosis, even without clinically evident HIT. Whether such antibodies impart "forme fruste" HIT or are simply a surrogate marker for a non-HIT adverse risk factor such as inflammation is unresolved.
    Transfusion Medicine Reviews 11/2006; 20(4):259-72. DOI:10.1016/j.tmrv.2006.05.001 · 2.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Heparin-induced thrombocytopenia (HIT) is caused by antibodies against a "self" protein-platelet factor 4-bound to heparin. We observed an overrepresentation of the female gender in 290 patients who developed HIT after cardiac or orthopedic surgery compared with the representation found in national databases (study 1). Therefore, we investigated gender imbalance in HIT by logistic regression analysis of a randomized controlled trial of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) (study 2), and we analyzed individual patient data from 7 prospective studies comparing HIT frequency between UFH and LMWH, evaluating effects of gender, heparin (UFH vs LMWH), and patient type (surgical vs medical) (study 3). All 3 studies showed female overrepresentation, which for study 3 was a common odds ratio (OR) of 2.37 (95% confidence interval [95% CI], 1.37-4.09; P = .0015). Study 3 also showed an interaction between gender, heparin, and patient type. Although UFH was more likely than LMWH to cause HIT (P < .0001), this effect was predominantly seen in women compared with men (common OR, 9.22 vs 1.83; P = .020) and in surgical patients compared with medical patients (common OR, 13.93 vs 1.75; P = .005). We conclude that females are at greater risk for HIT and that using LMWH to prevent HIT may have greatest absolute benefit in females undergoing surgical thromboprophylaxis.
    Blood 11/2006; 108(9):2937-41. DOI:10.1182/blood-2005-11-012450 · 10.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating IgG antibodies that recognize platelet factor 4 (PF4) bound to heparin. Immunogenicity of heparins differs in that unfractionated heparin (UFH) induces more anti-PF4/heparin antibodies than low-molecular-weight heparin (LMWH) and UFH also causes more HIT. Fondaparinux, a synthetic anticoagulant modeled after the antithrombin-binding pentasaccharide, is believed to be nonimmunogenic. We tested 2726 patients for anti-PF4/heparin antibodies after they were randomized to receive antithrombotic prophylaxis with fondaparinux or LMWH (enoxaparin) following hip or knee surgery. We also evaluated in vitro cross-reactivity of the IgG antibodies generated against PF4 in the presence of UFH, LMWH, danaparoid, or fondaparinux. We found that anti-PF4/heparin antibodies were generated at similar frequencies in patients treated with fondaparinux or enoxaparin. Although antibodies reacted equally well in vitro against PF4/UFH and PF4/LMWH, and sometimes weakly against PF4/danaparoid, none reacted against PF4/fondaparinux, including even those sera obtained from patients who formed antibodies during fondaparinux treatment. At high concentrations, however, fondaparinux inhibited binding of HIT antibodies to PF4/polysaccharide, indicating that PF4/fondaparinux interactions occur. No patient developed HIT. We conclude that despite similar immunogenicity of fondaparinux and LMWH, PF4/fondaparinux, but not PF4/LMWH, is recognized poorly by the antibodies generated, suggesting that the risk of HIT with fondaparinux likely is very low.
    Blood 01/2006; 106(12):3791-6. DOI:10.1182/blood-2005-05-1938 · 10.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Four direct thrombin inhibitors (DTIs), lepirudin, bivalirudin, argatroban, and melagatran, differ in their ability to prolong the prothrombin time (PT). Paradoxically, the DTI in clinical use with the lowest affinity for thrombin (argatroban) causes the greatest PT prolongation. We compared the effects of these DTIs on various clotting assays and on inhibition of human and bovine factor Xa (FXa). On a mole-for-mole basis, lepirudin was most able to prolong the PT, activated partial thromboplastin time (APTT), and thrombin clotting time (TCT), whereas argatroban had the least effect. At concentrations that doubled the APTT (argatroban, 1 micromol/l; melagatran, 0.5 micromol/l; bivalirudin, 0.25 micromol/l; lepirudin, 0.06 micromol/l), the rank order for PT prolongation was: argatroban > melagatran > bivalirudin > lepirudin. Although the Ki's associated with inhibition of human FXa by melagatran (1.4 micromol/l) and argatroban (3.2 micromol/l) approach their therapeutic concentrations, inhibition of FXa did not appear to be a major contributor to PT prolongation, since argatroban also prolonged the PT of bovine plasma (despite a Ki for bovine FXa of 2,600 micromol/l). Only melagatran inhibited prothrombinase-bound FXa. We conclude that the differing effects of the DTIs on PT prolongation are primarily driven by their respective molar plasma concentrations required for clinical effect. DTIs with a relatively low affinity for thrombin require high plasma concentrations to double the APTT; these higher plasma concentrations, in turn, quench more of the thrombin generated in the PT, thereby more greatly prolonging the PT.
    Thrombosis and Haemostasis 12/2005; 94(5):958-64. DOI:10.1160/TH05-03-0154 · 4.98 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Heparin-induced thrombocytopenia (HIT) is usually caused by platelet-activating antibodies of immunoglobulin G class that recognize platelet factor-4 (PF4) bound to heparin or certain other polyanions. Commercial enzyme immunoassays (EIAs) for PF4/polyanion-reactive antibodies detect two immunoglobulin classes (IgA and IgM) besides IgG. To investigate whether the additional detection of these antibody classes improves or worsens assay operating characteristics, we compared the sensitivity and specificity of EIAs that detect these 3 immunoglobulin classes individually with that of a commercial EIA (Genetic Testing Institute, GTI), as well as a platelet-activation assay, the serotonin-release assay (SRA). We compared the operating characteristics of these 5 assays by evaluating 448 patients, in 14 of whom clinical HIT developed, who received either unfractionated or low molecular weight heparin in prospective studies that included systematic platelet-count monitoring and serologic evaluation for anti-PF4/polyanion antibodies. We found that the SRA and IgG and commercial EIAs had similar high sensitivity for HIT; however, diagnostic specificity (for unfractionated and low molecular weight heparin, respectively) varied considerably, as follows: SRA (95.1%, 97.2%) > IgG EIA (89.0%, 93.7%) > GTI EIA (74.2%, 87.6%). Additional detection of IgA and IgM antibodies by the GTI EIA worsened test specificity by detecting numerous nonpathogenic antibodies. Moreover, the frequency and magnitude of IgA and IgM antibody formation in non-HIT immune responses did not differ from that exhibited by patients in whom clinical HIT developed. We conclude that an EIA that detects anti-PF4/polyanion antibodies of only the IgG class has greater diagnostic usefulness in revealing clinical HIT than does an assay that also detects IgA and IgM class antibodies.
    Journal of Laboratory and Clinical Medicine 12/2005; 146(6):341-6. DOI:10.1016/j.lab.2005.08.003 · 2.80 Impact Factor

Publication Stats

669 Citations
114.22 Total Impact Points


  • 2005–2014
    • McMaster University
      • Department of Pathology and Molecular Medicine
      Hamilton, Ontario, Canada
  • 2009
    • University of Greifswald
      • Institute of Immunology and Transfusion Medicine
      Griefswald, Mecklenburg-Vorpommern, Germany