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Biomedical subjects

W Korte

Publications and source records attributed to W Korte.

At least 19 recordsLinked to original sources
PubMed2006

[Paroxysmal nocturnal hemoglobinuria--consequences of a missing anchor].

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematological disorder characterized by the clonal expansion and differentiation of a multi-potent hematopoietic stem cell carrying a somatic mutation in the X-linked PIG-A gene. As a consequence of this mutation, glycosylphosphatidylinositol (GPI)-anchored proteins are lacking on the surface of blood cells derived from the mutated stem cell. This may result clinically in hemolytic anemia and a tendency for venous thrombosis and serious infection. Bone marrow failure is a frequently observed phenomenon associated with PNH. Reliable diagnosis of PNH is currently best achieved by flow cytometric analysis of GPI-anchored proteins on peripheral blood cells. Both the clinically relevant size of the PNH clone and type of GPI deficiency (complete or partial) can be reproducibly determined by this method. Most patients will benefit from supportive measures, albeit that allogeneic hematopoietic stem cell transplantation is currently considered the only potentially curative therapy. The development of a new therapeutic monoclonal antibody that reduces intravascular hemolysis and progress in diagnostic flow cytometry using a new GPI-specific marker may provide further benefit for PNH patients in the future.

Clinical Trials as Topic↗
PubMed2006

[Treatment of bleeding due to anticoagulants].

The increased incidence in cardiovascular diseases has initiated research that finally led to improvements in prophylactic therapies that aim to prevent the occurrence of occlusive thromboses. Nowadays, the post interventional prophylaxis in the arterial system is mainly achieved by using antiplatelet drugs; in this setting, the combination of drugs with different mechanisms allow to achieve a maximum effect. This is important since patients with cardiovascular diseases often use multiple medications which by themselves can already induce a platelet dysfunction, increasing the potential for bleeding due to side effects. Prophylaxis for venous thromboembolism or in patients with heart valve replacements is still performed with coumarin derivatives in most instances. It is crucial to target an INR of 2.5 as close and as stable as possible, since INRs below 2.0 are associated with increased incidences of thromboses and those above 3.0 show an increased bleeding tendency. In cancer patients, prophylaxis of thromboembolism with low molecular weight heprin seems more efficient than with coumarin derivatives; this might be due to the fact that low molecular weight heparin not only seems to have an antithrombotic but also an anti-tumor effect. From a pharmacokinetic point of view, renal insufficiency is always to be considered and looked for in (especially elderly) patients undergoing LMWH therapy in order to avoid cumulation. In patients suffering from a thrombotic event during heparin therapy or in patients with a significant drop in platelet count during heparin therapy, heparin-induced thrombocytopenia should be considered as a differential diagnosis; in his case, vitally important diagnostic or therapeutic steps might have to follow. This review discusses the most frequent indications for anticoagulant therapy, potential side effects of this therapy and the management of these side effects.

Anticoagulants↗
PubMed2006

An audit of red cell and blood product use after the institution of thromboelastometry in a cardiac intensive care unit.

Cardiac surgery is estimated to use 20% of the UK blood supply. However, there has been much interest recently in decreasing red cell and blood product use not only to ease strain on blood stocks or avoid potential transmission of infection but also to decrease post-operative transfusion-related complications. Coagulopathies are not uncommon in cardiac surgical patients, but the time lapse for reporting conventional laboratory results has been highlighted as an obstacle to the appropriate use of blood products. Accordingly, much interest has arisen in rapid near-patient testing of coagulation and, in January 2002, a thromboelastometer (ROTEM, Pentapharm, Germany) was purchased for our unit. This audit sought to assess its impact by retrospective analysis of 990 sequential patients' demographic data and transfusion details covering 6 months prior to its introduction and 6 months after. In the 6 months prior to its introduction, red cells were used in 60% of patients and fresh frozen plasma (FFP) and platelets used in 17 and 16% of patients, respectively. In the following 6 months, red cell use had fallen to 53% and FFP and platelets to 12 and 11%, respectively (P < 0.05). Introduction of thromboelastometry has significantly decreased our use of red cells and blood products.

Aged↗
PubMed2006

[Fibrin monomer and factor XIII: a new concept for unexplained intraoperative coagulopathy].

Unexplained intraoperative coagulopathies continue to be a diagnostic and therapeutic dilemma. The pathophysiology behind unexplained intraoperative coagulopathies is of great variety and complexity (preexisting coagulopathies, dilutional coagulopathy, interactions of medications etc.). We have shown in prospective studies that patients undergoing elective surgery who develop "unexplained" intraoperative coagulopathies have significantly less FXIII per unit thrombin available at any point in time (i.e. already preoperatively) than patients without such coagulopathies. The consequence is a significant loss of clot firmness associated with an increase in intraoperative blood loss. Thus, these patients have less cross-linking capacity to begin with, which explains their preoperatively increased fibrin monomer concentration. The association of increased preoperative fibrin monomer and increased intraoperative blood loss was prospectively evaluated and confirmed in a separate clinical study. It is important to note that the acquired or (compared to the amount of thrombin generated) relative F. XIII deficiency in situations with surgical stress shows early clinical relevance (even if only mild to moderate changes are present); this differs from the experiences with patients with inborn FXIII deficiency, where a pronounced deficiency must be present to have clinically significant spontaneous bleeding. Patients undergoing elective surgery, without clinically obvious coagulopathy but increased preoperative fibrin monomer concentration (as a marker of decreased crosslinking capacity) are at risk for increased intraoperative blood loss. This new concept helps to explain the pathophysiology behind unexplained intraoperative coagulopathies and thus allows for corresponding treatment strategies. Further clinical studies for early detection and interventions in patients with such coagulopathies are necessary.

Blood Coagulation↗
PubMed2004

[Chronic lymphocytic leukemia--the old and the new].

Chronic Lymphocytic Leukemia (CLL) is the most frequent lymphoproliferative disease and leukaemia in western countries. CLL occurs more frequently in men than women, the median age at diagnosis is 65 years. CLL is defined as a persisting chronic lymphocytosis > 5 G/l with classical morphological features (small lymphocytic cells with round nuclei, dense chromatin and small cytoplasmic rim) and a classical immunophenotype (CD5+, CD19+, CD20+, CD23+); however, deviations from classical morphology are frequent. In cases with classical diagnostic features in the peripheral blood, a bone marrow biopsy is not necessary for diagnosis. Prognostic features comprise the stage of the disease according to the Rai or Binet systems, laboratory markers such as LDH, beta-2-microglobulin, lymphocyte doubling time and CD38 expression by flow cytometry (and ZAP-70 expression if available) as well as the status on IgV(H) hypermutations and cytogenetic analysis. Up to 2/3 of patients do not need treatment at the time of diagnosis and can initially be followed using a watch and wait strategy. If therapy becomes necessary, initial standard treatment still is chlorambucil. Later, purine analogues and Alemtuzumab are treatment options for refractory or relapsing disease. Therapies with antibodies such as Alemtuzumab and Rituximab in combination with purine analogues are currently under clinical investigation. With recurrent or atypical infections, hypogammaglobulinemia should be searched for and immunoglobulins should be substituted if necessary. However, their prophylactic use is not recommended.

Aged↗
PubMed2004

[Differential diagnosis of absolute lymphocytosis].

The differential diagnosis of absolute lymphocytosis is variegated. In general, reactive (secondary) lymphocytosis can be well differentiated from a lymphoproliferative disease (primary lymphocytosis). Together with correspondent clinical characteristics, an absolute lymphocytosis often suggests a potential diagnosis and the further diagnostic process. Reactive lymphocytosis is usually self limiting and normalizes after cessation of the inflammatory stimulus. If a lymphoproliferative disorder is suspected further diagnostic procedures (i.e. cytometry, bone marrow examinations, biopsies of other organs if needed and molecular analyses) should be performed. If the distinction between malignant lymphoproliferation and reactive lymphocytosis cannot be done immediately, a watch and wait strategy may be implemented. In case of persistent lymphocytosis for longer than six months or occurrence of additional symptoms earlier on, diagnosis should be forced.

Adolescent↗
PubMed2002

Short-term effects of atorvastatin on C-reactive protein.

AIM: To study the short-term effect of atorvastatin on C-reactive protein (CRP) in patients with or at risk for coronary heart disease. METHODS AND RESULTS: One hundred and fifty-five randomly selected patients from the SWiss Intervention Trial for lowering CHolesterol (SWITCH) were assessed for high sensitivity CRP, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides at baseline, and after 1 and 3 months of treatment with atorvastatin at various doses to reach pre-defined lipid target values. The median decrease of cholesterol was 28% after 1 month and 35% after 3 months. LDL-cholesterol was decreased by 37% and 45%, HDL-cholesterol was increased by 7% and 8%, respectively. Patients with a low CRP baseline concentration (lowest quartile <1.34 mg. l(-1)) displayed no significant change, whereas patients in the other quartiles showed a significant decrease, of 22% to 40% (P -value <0.05 to <0.001) at 1 month and of 32% to 36% after 3 months compared to baseline. The decrease in CRP lowering was thus fully established by 1 month and this response was independent of lipid and lipoprotein changes as well as atorvastatin doses. CONCLUSION: Atorvastatin significantly decreases CRP concentrations after 4 weeks of therapy. These results may be important with respect to the early benefit of statin therapy.

Anticholesteremic Agents↗
PubMed2001

Repetitive intraoperative use of recombinant hirudin (Lepirudin) in peripheral vascular surgery with HITT.

Heparin induced thrombocytopenia with thrombosis (HITT) is a rare but dangerous complication related to the application of unfractionated heparin or low molecular weight heparin. Due to an antibody dependent in vivo platelet activation, severe thromboembolic episodes may occur. We present the case of a patient with HITT following implantation of an aortobifemoral graft secondary to bilateral common iliac artery stenoses. An arterial clot developed and led to a partial occlusion of the graft to the right external iliac artery. Heparin was replaced by Lepirudin, a recombinant hirudin. A bolus of 0.4 mg/kg body weight was given, thereafter 0.15 mg/kg body weight per hour was administered continuously i.v. to maintain the aPTT 2- to 2.5-fold above the baseline value. The platelet count (minimum 47 G/l) normalised within two days. During thrombectomy of the right common femoral artery we used Lepirudin intraoperatively (bolus injection of 0.2 mg/kg body weight) to prevent any further platelet and coagulation activation during the clamping phase. Six months later the patient underwent two further bypass operations due to severe stenoses of both superficial femoral arteries. Due to the high risk of thromboembolism if HITT recurred, a bolus of 0.2 mg/kg body weight of Lepirudin was given during each intervention. No bleeding complications occurred. In addition Lepirudin appeared to decrease platelet consumption in the absence of active thrombosis. Direct thrombin inhibitors such as Lepirudin possess no heparin-like immunological properties and seem to have become the therapeutic "gold-standard" in patients with HITT. Our experience suggests that the repetitive intraoperative use of Lepirudin is safe and effective.

Anticoagulants↗
PubMed2001

Multicentre evaluation of a new point-of-care test for the quantitative determination of D-dimer.

Imprecision studies, interference testing and multicentre method comparisons using patient samples were carried out with of a new point-of-care test for D-dimer (CARDIAC D-Dimer). The CV of the within-series and the day-to-day imprecision with blood samples and control materials were between 7% and 13%. Compared with Tina-quant D-Dimer, CARDIAC D-Dimer showed a good correlation and accuracy (n=353; r=0.91; y=1.06x-0.03), compared with STA LIATEST D-Dimer some poorer accuracy (n=304; r=0.91; y=1.12x-0.03). No interference was detected for different hematocrit values (16% to 51%) and in investigations with hemoglobin (up to 0.13 mmol/l), biotin (up to 30 microg/l), bilirubin (up to 340 micromol/l), intralipid (up to 31.1 mmol/l) and rheumatic factor (up to 79 IU/ml). Overdosing or underdosing by 10 microl did not affect the test result. The diagnostic sensitivity of CARDIAC D-Dimer for the detection of acute venous thromboembolic diseases was 100% in our study. With CARDIAC D-Dimer reliable quantitative D-dimer results can be easily obtained. Because of the good analytical and clinical agreement with Tina-quant D-Dimer, it should be suitable for ruling out venous thromboembolic diseases.

Clinical Chemistry Tests↗
PubMed2001

[Postoperative heparin-induced thrombopenia with thromboembolism (HITT)--a rare complication of heparin therapy?].

Many surgical patients receive either unfractionated or low-molecular weight heparin in a prophylactic or therapeutic intention. Feared upon the administration of heparin is the heparin-induced thrombopenia (HIT). In HIT type 1, the heparin directly interacts with the platelets. The platelet count rarely falls below 100,000/microliter and normalizes again despite continuous administration of heparin. In HIT type 2 or HIT with thrombosis (HITT) the platelet count usually falls more than 50% and due to an antibody-dependent platelet activation, thromboembolic episodes may occur. Compared to non-surgical patients, the incidence of HITT in the postoperative phase is markedly increased. In suspicion of a HITT, heparins should immediately be stopped and replaced by an alternative coagulant because of a high risk of further thromboembolic complications. Direct thrombin-inhibitors such as the recombinant hirudins are considered to be safe and effective. They have no heparin-like immunological properties and therefore, they seem to become the therapeutic and prophylactic "gold-standard" in patients with HITT.

Heparin↗
PubMed2001

Rapid D-dimer testing and pre-test clinical probability in the exclusion of deep venous thrombosis in symptomatic outpatients.

We assessed the performance of three rapid D-dimer tests (Auto Dimertest, VIDAS and Tinaquant) in combination with a pretest clinical probability model for deep venous thrombosis (DVT) in 106 consecutive outpatients with suspected DVT. Contrast venography or colour-coded duplex ultrasonography demonstrated the presence of DVT in 47 patients (14 distal DVT and 33 proximal DVT). First, we assessed the accuracy indices for different cut-off levels of the rapid D-dimer tests. Sensitivity was found to be 97.9-100%, negative predictive value (NPV) was 96.3-100%, and the exclusion rate was 24.5-31.1%. Next, the patients were grouped according to the pre-test clinical probability model in categories with low, moderate or high probability. In patients with a low pre-test probability, DVT would have been directly ruled out and the patients would not have undergone further investigations. In patients with a moderate probability, D-dimer testing and, in the case of a positive result, objective testing would have been performed and, in the case of a negative result, they would have been ruled out of having DVT. Patients with high probability would directly have undergone objective tests for DVT. The combination with the pre-test clinical probability model improved the exclusion rate (43.5-44.6%), whereas sensitivity (97.5-100%) and NPV (97.6-100%) remained roughly unchanged. The combination of rapid D-dimer tests with a pre-test clinical probability model may help to reduce unnecessary work-up in patients with suspected DVT.

Adolescent↗
PubMed2001

Comparability of serum and plasma concentrations of haemostasis activation markers.

Since serum and plasma D-dimer concentrations correlate very well, we evaluated the comparability of other haemostasis activation markers in plasma and serum. Prothrombin fragment F1+2, fibrin monomer and D-dimer concentrations were measured with commercially available immunoassays in serum and plasma. Serum to plasma ratios were evaluated to determine the direct (prothrombin fragment F1+2) and indirect (fibrin monomer, D-dimer) downstream influence of prothrombinase on the serum to plasma comparability. Prothrombin fragment F1+2 serum and plasma concentrations did not correlate (R2 = 0.09, ns), while an unexpected high degree of correlation was found for fibrin monomer (R2 = 0.66, p < 0.001), and, as expected, a very good correlation was found for D-dimer (R2 = 0.94, p < 0.001). Median serum to plasma ratios decreased from prothrombin fragment F1+2 (16.26) to fibrin monomer (2.24, p < 0.001) and D-dimer (1.00, p < 0.001), following a highly linear relationship (R2 = 0.93) Plasma and serum concentrations of the evaluated markers correlate the better the farther from prothrombinase activity the respective marker is generated. Serum is not suitable for prothrombin fragment F1+2 measurements, whereas fibrin monomer serum concentrations seem of value for research applications. With the used assay, serum seems an appropriate matrix for clinical D-dimer measurements. This would considerably simplify testing strategies. Validation in further clinical trials is needed.

Blood↗
PubMed2000

Mild renal dysfunction is sufficient to induce erythropoietin deficiency in patients with unexplained anaemia.

Current guidelines suggest that anaemia due to erythropoietin deficiency almost exclusively occurs with creatinine concentrations of at least 177 micromol/l or above. The aim of this prospective case control pilot study was to evaluate whether borderline renal function or mild renal dysfunction with creatinine concentrations well below 177 micromol/l is sufficient to induce inadequate erythropoietin secretion. Patients referred for work-up of otherwise unexplained anaemia with mildly abnormal creatinine concentrations (104-129 micromol/l; study group: eight patients) and patients referred for work-up or therapy of other diseases who also presented with anaemia but normal creatinine levels (<100 micromol/l; control group: nine patients matched for gender, age and degree of anaemia) were included. All but two patients in the control group had bone marrow biopsies to exclude other pathologies. Mild renal dysfunction (as evidenced by creatinine concentrations between 100 and 140 micromol/l, median concentration 112 micromol/l) was found to be sufficient to induce inadequate erythropoietin secretion. The physiologic hemoglobin-dependent erythropoietin regulation demonstrated in the control group was abolished in the study group. Patients with mild renal dysfunction and unexplained anaemia should be investigated for erythropoietin concentration. If the erythropoietin concentration is found to be inadequate for the degree of anaemia, substitution therapy should be considered.

Adult↗
PubMed2000

Short activated partial thromboplastin times are related to increased thrombin generation and an increased risk for thromboembolism.

This prospective study was designed to investigate whether patients with short activated partial thromboplastin times (aPTTs) have increased thrombin generation and are at increased risk for thromboembolism. During a 4-month period, routine coagulation specimens were screened for the presence of a short or normal aPTT, and, accordingly, 250 specimens were collected. Prothrombin fragment F1 + 2 (F1 + 2) was measured to evaluate thrombin activation, and a second aPTT was performed with a different reagent. Diagnoses were obtained from medical records after conclusion of sample collection. Five to 9 months later, patients were questioned on thromboembolic events during the previous 18 months by questionnaire and telephone interview. F1 + 2 and the incidence of venous thromboses were elevated significantly in the short aPTT group. Unexpectedly, patients with acute bleeding had short aPTTs, but 36% of these also had thromboembolic events during the 18 months proximal to blood collection. These findings were confirmed with the second aPTT reagent. Patients with short aPTTs have increased thrombin generation and are at increased risk for thromboembolism, mainly venous thromboses, despite the fact that a short aPTT can occur in the acute setting of bleeding.

Female↗
PubMed2000

Changes of the coagulation and fibrinolysis system in malignancy: their possible impact on future diagnostic and therapeutic procedures.

The interaction between malignant cell growth and the coagulation and fibrinolysis system has been a well known phenomenon for decades. During recent years, this area of research has received new attention. Experimental data suggest a role for the coagulation and fibrinolysis system in tumor development, progression and metastasis. Also, clinical research suggests that targeting the coagulation system or fibrinolysis system might influence the course of malignant disease beneficially. This paper reviews data on various hemostatic and fibrinolytic parameters in malignancy; the possible use of such parameters as risk markers in oncology patients; and possible targets of anti-neoplastic therapies using anticoagulant and/or antifibrinolytic strategies. Current evidence suggests that the tissue factor/factor VIIa pathway mediates the most abundant procoagulant stimulus in malignancy via the increase in thrombin generation. Tissue factor has been suggested to mediate pro-metastatic properties via coagulation-dependent and coagulation-independent pathways; tissue factor has also been implicated in tumor neo-angiogenesis. However, so far no model has been validated that would allow the use of tissue factor in its soluble or insoluble form as a marker for risk stratification in tumor patients. On the other hand, there is now good evidence that parts of the fibrinolytic system, such as urokinase-type plasminogen activator and its receptor ("uPAR"), can be used as strong predictors of outcome in several types of cancer, specifically breast cancer. Observation of various treatment options in patients with thromboembolic disease and cancer as well as attempts to use anticoagulants and/or therapies modulating the fibrinolytic system as anti-neoplastic treatment strategies have yielded exciting results. These data indicate that anticoagulant therapy, and specifically low molecular weight heparin therapy, is likely to have anti-neoplastic effects; and that their use in addition to chemotherapy will probably improve outcome of tumor treatment in certain types of cancer. However, the body of clinical data is still relatively small and the question whether or not we should routinely consider the coagulation and/or fibrinolysis system as therapeutic targets in cancer patients is yet to be answered.

Antineoplastic Agents↗