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P Eichler

Publications and source records attributed to P Eichler.

At least 19 recordsLinked to original sources
PubMed2006

IgG classification of anti-PF4/heparin antibodies to identify patients with heparin-induced thrombocytopenia during mechanical circulatory support.

Commercial immunoassays frequently detect anti-PF4/heparin antibodies during mechanical circulatory support (MCS), but only a small minority of patients develops heparin-induced thrombocytopenia (HIT). Whereas platelet functional tests can distinguish between platelet-activating and non-platelet-activating antibodies, commercial PF4-dependent immunoassays do not. Between 2003 and 2004, 113 patients were placed on MCS. Blood samples were obtained on postimplant day 5-7 for analyses by antibody assays and the functional heparin-induced platelet activation (HIPA) assay. Three distinct groups of patient sera were identified: platelet-activating anti-PF4/heparin antibodies (n = 10), non-platelet-activating anti-PF4/heparin antibodies (n = 53), and anti-PF4/heparin antibody negative (n = 50). Patients with platelet-activating antibodies had the highest risk for thromboembolic events (P < 0.005), whereas those with non-platelet-activating antibodies did not differ from antibody negative patients (P = 0.369). The enzyme-immunoassay and column agglutination assays, which cover all immunoglobulin classes, demonstrated adequate sensitivity and negative predictive value; yet, both lacked specificity with respect to the platelet-activating antibodies. If all antibody positive patients were further classified by an IgG-specific anti-PF4/heparin enzyme-immuno assay, specificity for platelet-activating antibodies increased. Whereas IgG-specific optical density (OD) values below 1.0 were likely for non-platelet-activating anti-PF4/heparin antibodies, higher values were progressively predictive for pathogenic platelet activation. The probability of the development of clinical HIT also increased steeply. In conclusion, platelet-activating anti-PF4/heparin antibodies are relatively common (about 9%) in patients on MCS and are associated with significantly higher thrombotic event rates. Low IgG-specific OD values (< 1.0) in the enzyme-immunoassay indicate low likelihood for the presence of platelet-activating antibodies. These results justify further validation so that anticoagulation during MCS becomes safer and adequate.

Assisted Circulation↗
PubMed2006

Avoiding misclassification bias with the traditional Charnley classification: rationale for a fourth Charnley class BB.

Long-term follow up of patients with total hip arthroplasty (THA) revealed a marked deterioration of walking capacities in Charnley class B after postoperative year 4. We hypothesized that a specific group of patients, namely those with unilateral hip arthroplasty and an untreated but affected contralateral hip was responsible for this observation. Therefore, we conducted a study taking into consideration the two subclasses that make up Charnley class B: patients with unilateral THA and contralateral hip disease and patients with bilateral THA. A sample of 15,160 patients with 35,773 follow ups that were prospectively collected over 10 years was evaluated. The sample was categorized into four classes according to a new modified Charnley classification. Annual analyses of the proportion of patients with ambulation longer than 60 min were conducted. The traditionally labeled Charnley class B consists of two very different patient groups with respect to their walking capacities. Those with unilateral THA and contralateral hip disease have underaverage walking capacities and a deterioration of ambulation beginning 3 to 4 years after surgery. Those with bilateral THA have stable overaverage walking capacities similar to Charnley class A. An extension of the traditional Charnley classification is proposed, taking into account the two different patient groups in Charnley class B. The new fourth Charnley class consists of patients with bilateral THA and was labeled BB in order to express the presence of two artificial hip joints and to preserve the traditional classification A through C.

Adult↗
PubMed2006

Post-transfusion purpura in a patient with HPA-1a and GPIa/IIa antibodies.

Post-transfusion purpura is a rare bleeding disorder characterized by severe and sudden thrombocytopenia within 3-12 days after blood transfusion. Typically, preformed antibodies directed against human platelet antigens, especially HPA-1a, are associated with the clinical symptoms. A 46-year-old female presenting to the hospital with acute progressive kidney insufficiency and anaemia received two units of packed red blood cells (RBC) within 2 days. On day 7, platelet count felt from 414 to 189 x 10(9) L(-1) and 1 day later dropped to 4 x 10(9) L(-1). Four platelet concentrates were applied without success. After serological confirmation of an HPA-1a antibody, the patient was treated with intravenous gamma immunoglobulin (ivIgG), and the platelet count increased to normal values on day 17. In addition to the persisting HPA-1a alloantibody, an antibody reactive with GPIa/IIa of HPA-5a- and HPA-5b-positive platelets was detected during the acute phase of thrombocytopenia. After complete remission, the patient was transfused with four units of packed RBC from HPA-1a-negative donors, and platelet counts remained normal.

Anemia↗
PubMed2006

Evaluation of pretest clinical score (4 T's) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a prothrombotic adverse drug reaction caused by heparin. As thrombocytopenia is common in hospitalized patients receiving heparin, it would be useful to have a clinical scoring system that could differentiate patients with HIT from those with other reasons for thrombocytopenia. AIM: To compare prospectively the diagnostic utility of a clinical score for HIT in two different clinical settings. METHODS: The pretest clinical scoring system, the '4 T's', was used to classify 100 consecutive patients referred for possible HIT in one hospital (Hamilton General Hospital, HGH) into high, intermediate, and low probability groups. This system was also used to classify likewise 236 patients by clinicians in Germany referring blood for diagnostic testing for HIT in Greifswald (GW). The clinical scores were correlated with the results of laboratory testing for HIT antibodies using the serologic criteria for HIT with high diagnostic specificity. RESULTS: In both centers, patients with low scores were unlikely to test positive for HIT antibodies [HGH: 1/64 (1.6%), GW: 0/55 (0%)]. Patients with intermediate [HGH: 8/28 (28.6%), GW: 11/139 (7.9%)] or high scores [HGH: 8/8 (100%), GW: 9/42 (21.4%)] were more likely to test positive for clinically significant HIT antibodies. The positive predictive value of an intermediate or high clinical score for clinically significant HIT antibodies was higher at one center (HGH). CONCLUSIONS: A low pretest clinical score for HIT seems to be suitable for ruling out HIT in most situations (high-negative predictive value). The implications of an intermediate or high score vary in different clinical settings.

Adult↗
PubMed2005

Lepirudin in patients with heparin-induced thrombocytopenia - results of the third prospective study (HAT-3) and a combined analysis of HAT-1, HAT-2, and HAT-3.

OBJECTIVES: To assess efficacy and safety of lepirudin in patients with heparin-induced thrombocytopenia (HIT) in a prospective study (HAT-3) as well as in a combined analysis of all HAT study data. PATIENTS/METHODS: Patients with laboratory-confirmed HIT were treated with lepirudin in three different aPTT-adjusted dose regimen and during cardiopulmonary bypass (CPB). Endpoints were new thromboembolic complications (TEC), limb amputations, and death and major bleeding. A historical control group (n = 120) was used for comparison. RESULTS: After start of lepirudin in 205 patients treated in HAT-3, the combined endpoint occurred in 43 (21.0%). Thirty (14.6%) patients died, 10 (4.9%) underwent limb amputation, and 11 (5.4%) new TECs occurred. Major bleeding occurred in 40 patients (19.5%) (seven during CPB surgery). Combining all prospective HAT trials (n = 403), after start of lepirudin treatment, the combined endpoint occurred in 82 patients (20.3%), with 47 deaths (11.7%), 22 limb amputations (5.5%), 30 new TECs (7.4%), and 71 (17.6%) major bleedings. Compared with the historical control group (log-rank test), the combined endpoint after start of treatment was reduced (29.7% vs. 52.1%, P = 0.0473), primarily because of reduction in new thromboses (11.9% vs. 32.1%, P = 0.0008). Mean lepirudin maintenance doses ranged from 0.07 to 0.11 mg kg(-1) h(-1). Major bleeding was more frequent in the lepirudin-treated patients (29.4% vs. 9.1%, P = 0.0148). CONCLUSIONS: The rate of new TECs in HIT patients is low after start of lepirudin treatment. The rate of major bleeding of 17.6% might be reduced by reducing the starting dose to 0.1 mg kg(-1) h(-1).

Adult↗
PubMed2003

Anaphylactic and anaphylactoid reactions associated with lepirudin in patients with heparin-induced thrombocytopenia.

BACKGROUND: Lepirudin (Refludan) is a hirudin derivative. It is a direct thrombin inhibitor obtained by recombinant technology from the medicinal leech and is approved for treatment of heparin-induced thrombocytopenia complicated by thrombosis. Because 3 cases of fatal anaphylaxis possibly associated with use of lepirudin have been reported, we initiated an investigation of putative lepirudin-associated anaphylaxis. METHODS AND RESULTS: Aided by the manufacturer (Schering AG, Berlin, Germany), we used the lepirudin study databases to identify all patients in whom possible anaphylaxis/severe allergy was recorded from 1994 to September 2002. The 26 possible cases identified were reviewed independently by 2 investigators. After excluding patients with mild skin reactions, reactions likely caused by concomitant medications, poorly documented cases, and reactions that did not correspond temporally with lepirudin use, there remained 9 patients judged to have had severe anaphylaxis in close temporal association with lepirudin. All reactions occurred within minutes of intravenous lepirudin administration, with 4 fatal outcomes (3 acute cardiorespiratory arrests, 1 hypotension-induced myocardial infarction). In these 4 cases, a previous uneventful treatment course with lepirudin was identified (1 to 12 weeks earlier). We recorded high-titer IgG-anti-lepirudin antibodies in an additional patient with anaphylaxis. Because lepirudin has been used in approximately 35 000 patients, the risk of anaphylaxis is approximately 0.015% (5 of 32 500) on first exposure and 0.16% (4 of 2500) in reexposed patients (7.5% estimated reexposures). CONCLUSIONS: Lepirudin can cause fatal anaphylaxis, particularly in patients who are treated within 3 months of a previous exposure. The overall risk/benefit assessment of lepirudin as a treatment for heparin-induced thrombocytopenia remains favorable.

Aged↗
PubMed2001

Glucosamine sulfate does not crossreact with the antibodies of patients with heparin-induced thrombocytopenia.

OBJECTIVE: To assess the crossreactivity of glucosamine sulfate, used for treatment of degenerative joint disease with antibodies induced in heparin-induced thrombocytopenia (HIT). BACKGROUND: HIT is a severe adverse effect of heparin therapy induced by an immunological mechanism. The antibodies in HIT are induced by a complex of heparin and, in most cases, platelet factor 4. Hereby generation of the antigen is not strictly dependent on heparin. Heparin can be substituted by a variety of polysulfated carbohydrates. In vitro and in vivo crossreactivity of HIT antibodies has been demonstrated for a chemically polysulfated chondroitin-like substance (Arteparon, Luitpoldwerke, Munich, Germany), formerly used for chondroprotection. Another drug widely used in the treatment of degenerative joint disease is glucosamine sulfate. Glucosamine is a building block of glycosaminoglycans, of which heparin is the clinically most important. Many patients with degenerative joint disease use glucosamine sulfate. This group is also at the highest risk to develop HIT following joint replacement surgery. METHODS: We examined the interactions of glucosamine sulfate (DONA 200-S, Opfermann, Wiehl, Germany) with platelets and antibodies of patients with HIT in and without the presence of heparin. Sera of 5 HIT patients and platelets of 4 healthy donors were used. The binding of HIT antibodies to PF4/glucosamine sulfate complexes was assessed by an ELISA. RESULTS: HIT antibodies did not activate platelets in the presence of glucosamine sulfate in a serotonin-release assay. Preincubation with glucosamine sulfate did not inhibit platelet activation by HIT antibodies in the presence of heparin (0.2 IU/ml). Antibodies bonded to PF4/heparin but not to PF4/glucosamine sulfate complexes. CONCLUSIONS: In contrast to sulfated glycosaminoglycans, there is no evidence for an immunological crossreactivity of HIT antibodies between heparin and glucosamine sulfate.

Antibody Specificity↗
PubMed2001

Drug-induced and drug-dependent immune thrombocytopenias.

Thrombocytopenia is a frequent comorbid condition in many in hospital patients. In some patients, drugs are the cause of low platelet counts. While cytotoxic effects of anti-tumor therapy are the most frequent cause, immune mechanisms should also be considered. This review addresses thrombocytopenias in four groups. Heparin-dependent thrombocytopenia (HIT), by far the most frequent drug-induced immune-mediated type of thrombocytopenia, has a unique pathogenesis and clinical consequences. HIT is a clinicopathological syndrome in which antibodies mostly directed against a multimolecular complex of platelet factor 4 and heparin cause paradoxical thromboembolic complications. The mechanisms through which heparin can enhance thrombin generation are discussed and treatment alternatives for affected patients are presented in detail. It is of primary importance to recognize these patients as early as possible and to substitute heparin with a compatible anticoagulatory drug, such as hirudin, danaparoid or argatroban. Patients seem to benefit from therapeutic doses of alternative treatment rather than from low-dose prophylactic doses. With the increasing use of glycoprotein (GP) IIb/IIIa inhibitors in patients with acute coronary syndromes, thrombocytopenias are increasingly recognized as an adverse effect of these drugs. Up to 4% of treated patients are affected. Most important, pseudothrombocytopenia, a laboratory artefact, is as frequent as real drug-induced thrombocytopenia and must be excluded before changes in treatment are considered. The pathogenesis of these thrombocytopenias is still debated; an immune mechanism involving preformed antibodies is likely. However, since these antibodies are also detectable in a high percentage of normal controls and of patients not developing thrombocytopenia, their impact is still unclear. Patients with real thrombocytopenia are at an increased risk of bleeding; treatment consists of cessation of the GP IIb/IIIa inhibitor and platelet transfusions in cases of severe hemorrhage. Classic immune thrombocytopenia can be induced by some drugs, e.g. gold, which trigger anti-platelet antibodies indistinguishable from platelet autoantibodies found in autoimmune thrombocytopenia. Drug-induced and drug-dependent immune thrombocytopenia is induced by antibodies recognizing an epitope on platelet GP formed after binding of a drug to a platelet glycoprotein. Still unresolved is whether antibody binding is the consequence of a conformational change of the antigen, the antibody, or both. These antibodies typically react with monomorphic epitopes on platelet GP, but only in the presence of the drug or a metabolite. Although several platelet GP have been identified as antibody target (GPIb/IX, GPV, GP IIb/IIIa), antibodies in an individual patient are highly specific for a single GP. Clinically, these patients present with very low platelet counts and acute, sometimes severe, hemorrhage. Treatment is restricted to withdrawal of the drug and symptomatic treatment of bleeding.

Anticoagulants↗
PubMed2001

A comparison of danaparoid and lepirudin in heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a hypercoagulable syndrome strongly associated with thrombosis that is usually treated with drugs that inhibit factor Xa (danaparoid) or thrombin (lepirudin). In the present study the outcome of HIT-patients treated with danaparoid or lepirudin was compared using the single or combined endpoints of new thromboembolic complications (new TECs), amputations and/or death, and major bleeding. HIT-patients treated with lepirudin were enrolled in two prospective trials and patients, who were identified in the same two laboratories during the same time period, who were not enrolled into these studies but treated with danaparoid, were assessed retrospectively according to a standardized questionnaire. 126 danaparoid (60.3% female) and 175 lepirudin treated patients (58.3% female) fulfilled the same inclusion and exclusion criteria. In a time-to-event-analysis the cumulative risk of combined endpoint was higher in HIT-patients without thromboembolic complication at baseline treated with danaparoid (usually in prophylactic dose 750 anti-factor Xa units b.i.d. or t.i.d.s.c.) as compared to lepirudin (aPTT adjusted) (P = 0.020). Whereas HIT-patients with TEC at baseline who were usually treated with therapeutic dose had a similar outcome in both treatment groups (P = 0.913). Major bleeding occurred in 2.5% (95% CI 0.5-7.0%) of danaparoid treated patients as compared to 10.4% (95% CI 6.3-15.9%) of lepirudin treated patients until day 42 (P = 0.009). This indicates that the efficacies of therapeutic doses of danaparoid or lepirudin in preventing death, amputation or new TEC in HIT-patients do not differ largely, but the risk of bleeding seems to be higher in lepirudin treated patients. The prophylactic dose of danaparoid approved in the European Union for HIT without TEC at baseline seems suboptimal. A prospective comparative trial is required to verify these preliminary conclusions.

Age Factors↗
PubMed2000

Very low platelet counts in post-transfusion purpura falsely diagnosed as heparin-induced thrombocytopenia. Report of four cases and review of literature.

Differential diagnosis between post-transfusion purpura (PTP) and heparin-induced thrombocytopenia (HIT) can be difficult in the initial stages of thrombocytopenia, as the early clinical presentations are often similar. Four patients are described who were suspected clinically of suffering from HIT. All four patients had recent blood transfusions and platelet alloantibodies, thus the diagnosis of PTP was made. One lethal gastrointestinal and one retroperitoneal hemorrhage developed in two of the four patients. Unusually, one patient was male and two different platelet alloantibodies were present in his serum; in another patient platelet alloantibodies and HIT-antibodies were detectable. To arrive at the right diagnosis as quickly as possible is vitally important since treatment, which has to be initiated promptly, is very different for the two syndromes. Thus, we suggest that in patients where HIT is suspected, additional information should be sought. If features consistent with PTP (such as a recent blood transfusion or a marked drop in platelet count to below 15 Gpt/L) are present, we recommend parallel testing for platelet alloantibodies to rule out PTP.

Acute Disease↗
PubMed2000

Antihirudin antibodies in patients with heparin-induced thrombocytopenia treated with lepirudin: incidence, effects on aPTT, and clinical relevance.

Hirudin, a potent and specific thrombin inhibitor, is a protein of nonhuman origin and therefore potentially immunogenic. The primary objectives of this investigation were to determine the incidence of antihirudin antibodies (ahir-ab) in patients with heparin-induced thrombocytopenia (HIT) who received lepirudin as parenteral anticoagulation and to determine the incidence of death, limb amputation, new thromboembolic complications (TECs), and major hemorrhage in patients who had ahir-ab, compared with patients who were ahir-ab negative. The investigation used data from 2 prospective multicenter studies with the same study protocol, in which HIT patients received 1 of 4 intravenous lepirudin dosage regimens. The treatment duration was 2 to 10 days. Ahir-ab were determined by a newly developed enzyme-linked immunosorbent assay (ELISA). Eighty-seven of 196 evaluable patients (44.4%) had ahir-ab of the IgG class. Development of ahir-ab was dependent on the duration of treatment (ahir-ab-positive patients 18.6 days vs ahir-ab-negative patients 11.8 days; P =.0001). Fewer ahir-ab-positive than ahir-ab-negative patients died (P =.001). Ahir-ab did not cause an increase in limb amputation (P =.765), new TECs (P >.99), or major bleedings (P =.549). In 23 of 51 (45.1%) evaluable patients in whom ahir-ab developed during treatment with lepirudin ( = 12% of all lepirudin treated patients), the ahir-ab enhanced the anticoagulatory effect of lepirudin. Ahir-ab are frequent in patients treated with lepirudin for more than 5 days. Ahir-ab are the first example for a drug-induced immune response causing enhanced activity of a drug. Therefore, during prolonged treatment with lepirudin, anticoagulatory activity should be monitored daily to avoid bleeding complications.

Amputation, Surgical↗
PubMed2000

Heparin-induced thrombocytopenia with thromboembolic complications: meta-analysis of 2 prospective trials to assess the value of parenteral treatment with lepirudin and its therapeutic aPTT range.

This meta-analysis focuses on 2 prospective studies in patients with heparin-induced thrombocytopenia (HIT) and thromboembolic complication (TEC) who were treated with lepirudin (n = 113). Data were compared with those of a historical control group (n = 91). The primary endpoint (combined incidence of death, new TEC, and limb amputation) occurred in 25 lepirudin-treated patients (22.1%; 95% CI, 14.5%-29.8%): 11 died (9.7%; 95% CI, 4.9%-16.8%), 7 underwent limb amputation (6.2%; 95% CI, 2.5%-12.3%), and 12 experienced new TEC (10.6%; 95% CI, 5.8%-18.3%). The risk was highest in the period between diagnosis of HIT and the start of lepirudin therapy (combined event rate per patient day 6.1%). It markedly decreased to 1.3% during lepirudin treatment and to 0.7% in the posttreatment period. From the start of lepirudin therapy to the end of follow-up, lepirudin-treated patients had consistently lower incidences of the combined endpoint than the historical control group (P =.004, log-rank test), primarily because of a reduced risk for new TEC (P =. 005). Thrombin-antithrombin levels in the pretreatment period (median, 43.9 microg/L) decreased after the initiation of lepirudin (at 24 hours +/- 6 hours; median, 9.18 microg/L.) During treatment with lepirudin, aPTT ratios of 1.5 to 2.5 produced optimal clinical efficacy with a moderate risk for bleeding, aPTT ratios lower than 1. 5 were subtherapeutic, and aPTT levels greater than 2.5 were associated with high bleeding risk. Bleeding events requiring transfusion were significantly more frequent in patients taking lepirudin than in historical control patients (P =.02). In conclusion, this meta-analysis provides further evidence that lepirudin is an effective and acceptably safe treatment for patients with HIT.

Aged↗
PubMed2000

A prospective study on the incidence and clinical relevance of heparin-induced antibodies in patients after vascular surgery.

The heparin-platelet factor 4-antibody assay, polyanion-platelet factor 4-antibody assay and heparin-induced platelet activation test are used for laboratory diagnosis of the immune form of heparin-induced thrombocytopenia. Fifty consecutive patients receiving heparin treatment for more than 5 days after vascular surgery were prospectively screened for heparin-induced thrombocytopenia antibodies, thrombocytopenia (daily platelet counts), deep-vein thrombosis (color-coded duplex sonography), and arterial reocclusion (clinical assessment). None of the patients developed thrombocytopenia or thrombosis in association with formation of heparin-induced thrombocytopenia antibodies. Despite the absence of clinical evidence of heparin-induced thrombocytopenia, many patients formed heparin-induced thrombocytopenia antibodies: 34% of the patients were positive in the heparin-platelet factor 4-antibody assay, 28% in the polyanion-platelet factor 4-antibody assay, 14% in the heparin-induced platelet activation test, and 54% with any of these tests. Patients predominantly developed IgM (24%) and IgA antibodies (16%), whereas IgG antibodies were found in 12% of patients. Whereas the majority of patients with positive ELISA assays had IgM and IgA antibodies, patients with a positive functional assay (heparin-induced platelet activation test) predominantly had IgG antibodies. We conclude that a high percentage of patients develop heparin-induced antibodies after vascular surgery without any clinical symptoms of heparin-induced thrombocytopenia. None of the assays therefore is predictive of the clinical manifestation of heparin-induced thrombocytopenia in asymptomatic patients. Therefore, the diagnostic specificity of both antigen and activation assays for heparin-induced thrombocytopenia appears to be relatively low in the vascular surgery patient population.

Aged↗
PubMed1999

Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia. Heparin-Associated Thrombocytopenia Study (HAT) investigators.

BACKGROUND: We prospectively investigated lepirudin for further parenteral anticoagulation in patients with heparin-induced thrombocytopenia (HIT). METHODS AND RESULTS: Patients with confirmed HIT (n=112) received lepirudin according to need for 2 to 10 days (longer if necessary): A1, treatment: 0.4 mg/kg IV bolus, followed by 0.15 mg. kg(-1). h(-1) intravenous infusion, n=65; A2, treatment in conjunction with thrombolysis: 0.2 mg/kg, followed by 0.10 mg. kg(-1). h(-1), n=4; and B, prophylaxis: 0.10 mg. kg(-1). h(-1), n=43. Outcomes from 95 eligible lepirudin-treated patients were compared with those of historical control patients (n=120). Complete laboratory response (activated partial thromboplastin time ratio >1.5 with </=2 dose increases and platelet count normalization by day 10) was achieved in 65 lepirudin-treated patients (69.1%; 95% CI, 59. 3% to 78.3%). At 2 weeks after cessation of lepirudin, 11 patients died (9.8%), 10 underwent limb amputation (8.9%), and 20 suffered a new thromboembolic complication (17.9%). The average combined event rate per patient-day decreased from 5.1% in the pretreatment period to 1.5% in the treatment period. Thirty-five days after HIT confirmation, fewer lepirudin-treated patients than historical control patients had experienced >/=1 outcome (cumulative incidence 30.9% versus 52.1%; relative risk [RR] 0.71; P=0.12, log-rank test). Bleeding events were more frequent in the lepirudin group than the historical control group (cumulative incidence at 35 days, 44.6% versus 27.2%; RR 2.57; P=0.0001, log-rank test). No difference was observed in bleeding events requiring transfusion (cumulative incidence at 35 days, 12.9% versus 9.1%; RR 1.66; P=0.23, log-rank test); no intracranial bleeding was observed in the lepirudin group. CONCLUSIONS: Lepirudin effectively prevents death, limb amputations, and new thromboembolic complications and has an acceptable safety profile in HIT patients. Treatment should be initiated as soon as possible if HIT is suspected.

Aged↗
PubMed1999

[Difficulties of fungus detection in corneal culture medium].

UNLABELLED: It is not always possible to prevent the growth of microorganisms in organ culture for cornea preservation, despite many prophylactic measures. It is especially difficult to prove the presence of fungi in the cultural medium. MATERIALS AND METHODS: A culture medium was examined for sterility after 8 days' storage of cornea in organ culture. To prove the presence of fungi a culture of Sabouraud 2% glucose-agar was prepared and its growth examined by light microscopy. RESULTS: After 8 days of preservation we noticed a color change in the cultural medium and suspected contamination with fungi. Coagulase-negative Staphylococci could be cultivated from the conjunctival smear obtained before preparation of the cornea only. Routine screening of microbiological contamination did not show any results. We were able to identify an Aspergillus species only after preparing a special culture. The conjunctival smear as well as the cultural medium of the other eye of the same donor showed no contamination. CONCLUSIONS: In spite of the fact that microbiological contamination can be seen macroscopically, it is difficult to prove the presence of a specific microorganism and even more so when dealing with fungus. Especially in these cases the incubation of the cornea in media might have an advantage because contamination can be suspected by just looking at the medium. By excluding these preparations from transplantation we can possibly prevent infections, even when routine examinations show negative results.

Aspergillus↗
PubMed1999

First workshop for detection of heparin-induced antibodies: validation of the heparin-induced platelet-activation test (HIPA) in comparison with a PF4/heparin ELISA.

BACKGROUND: No data exist regarding the inter-laboratory reproducibility of the heparin-induced-platelet-activation (HIPA) test, the most widely used functional assay in Germany for the detection of heparin-induced thrombocytopenia (HIT) antibodies. METHODS: Nine laboratories used an identical protocol to test eight different sera with the HIPA test. Five laboratories also tested the sera with a platelet factor 4 (PF4)/heparin-complex ELISA. Cross-reactivity with danaparoid-sodium was assessed using 0.2 aFXa units instead of heparin in the HIPA test. RESULTS: Two of nine laboratories had no discrepant HIPA test results. Four laboratories differed in one sample, one reported two discrepant results, and two laboratories reported more than two discrepant results. Cross-reactivity with danaparoid-sodium test results differed among laboratories. PF4/heparin ELISA results were identical in all five laboratories. CONCLUSION: The HIPA test requires strict quality control measures. Using both a sensitive functional assay (HIPA test) and a PF4/heparin ELISA will allow detection of antibodies directed to antigens other than PF4/heparin complexes as well as detection of IgM and IgA antibodies with PF4/heparin specificity.

Antibodies↗