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Biomedical subjects

C E Dempfle

Publications and source records attributed to C E Dempfle.

At least 19 recordsLinked to original sources
PubMed2005

[Avoiding emergency situations under anticoagulant therapy with vitamin K antagonists].

Despite 50 years of clinical experience with vitamin K antagonists such as phenprocoumon or warfarin, many clinicians are uncertain how to start treatment, deal with overdose or bleeding complications, and how to bridge anticoagulation when treatment with vitamin K antagonists is interrupted. Patients with overdose of vitamin K antagonists or bleeding complications are treated with vitamin K, prothrombin complex concentrates (PCC), or recombinant factor VIIa. Rapid reversal of anticoagulation is only achieved by using PCC or recombinant factor VIIa. Both should be combined with vitamin K for a sustained effect. For elective surgery, treatment with vitamin K antagonists is paused and vitamin K given either orally or intravenously. Unfractionated or low molecular weight heparin is given when INR levels are below therapeutic range. Patients with contraindications to heparin may be treated with alternative anticoagulants such as danaparoid, lepirudin or fondaparinux.

Anticoagulants↗
PubMed2004

Fibrinogen Mannheim II: a novel gamma307 His-->Tyr substitution in the gammaD domain causes hypofibrinogenemia.

BACKGROUND: In recent years it has become clear that the molecular investigation of hypofibrinogenemia provides unique insight into regions of the fibrinogen molecule that are important in molecular assembly, secretion and stability. OBJECTIVES: To investigate a case of hypofibrinogenemia at the molecular level. PATIENTS AND METHODS: The study was conducted on a 37-year-old woman from Mannheim, Germany, who had an antigenic plasma fibrinogen concentration of 0.86 g L(-1). Mutation screening was performed by DNA sequencing and the effect of the identified mutation was investigated at the protein level. RESULTS: Analysis of exon 8 of the fibrinogen gamma gene identified a heterozygous CAT-->TAT transition at codon 307. This novel His-->Tyr substitution was not detected when plasma fibrinogen was analyzed by electrospray ionization mass spectrometry. The mutation predicts a mass increase of 26 Da in the gamma chain, but purified gamma chains had a normal mass, indicating non-expression of the gamma(Tyr307) chain in plasma fibrinogen. CONCLUSIONS: This work reports a novel gamma307 His-->Tyr mutation (fibrinogen Mannheim II) that causes hypofibrinogenemia. Crystal structures show that His307 is located immediately adjacent to three residues that have been implicated in fibrin polymerization at the D:D interface. However, the histidine residue appears critical in maintaining structure of the fibrinogen gammaD domain, rather than in determining function.

Adult↗
PubMed2003

[Heparin during acute ischemic stroke. Present data and clinical situation].

Therapy with low- or high-dose heparin in acute stroke is changing. Despite several clinical studies (>20), some with quite large numbers of patients, no statistically significant benefit was found for the clinical endpoints of death and functional outcome. This negative result remains even when considering the preventive effect of high-dose heparin on secondary acute embolic events (e.g., cardiac emboli-arrhythmia) and low-dose heparin on venous thrombosis. Based on study results, most reviews and therapy recommendations for the treatment of acute stroke generally decline the use of high-dose heparins and heparinoids with full anticoagulation for improving outcome or preventing secondary embolic events as well as low-dose applications for venous thrombosis prophylaxis. This paper reviews the literature and presents the data of a standardised survey on coagulation therapy in acute stroke patients from all university and major stroke units in Germany (n=33). Contrary to the restrictive recommendations, therapy with heparin is firmly established in most stroke units. Full anticoagulation with heparin ("full dose") is performed on selected patients in 32/33 stroke units (97%). The selection criteria and thus the frequency of high-dose heparin use varies widely among the different centers. Almost all German stroke units (97%) routinely use low-dose heparin to prevent venous thrombosis and pulmonary embolism.The heparin agents and dosage, however, vary. These data correspond to those from the USA and Canada,where daily routine also departs from evidence-based treatment recommendations. That may be due to individual pathophysiological and aetiological considerations and of course the low acceptance of treatment recommendations based on classic, randomised trials. This underlines the need for new concepts (e.g.observational trials, continuous registers, etc.) addressing the adaptation of study-related conditions to the much more complex situation of daily routine (with risk/benefit, safety, and economic variables).

Acute Disease↗
PubMed2003

Valproate induces reversible factor XIII deficiency with risk of perioperative bleeding.

The antiepileptic drug valproic acid (VPA) induces subclinical changes in both the intrinsic and extrinsic coagulation system. However, fatal bleeding is very rare. This study reports a 39-year-old patient who underwent selective amygdalohippocampectomy because of drug-resistant temporal lobe epilepsy. Preoperatively, the patient was on a combined therapy with VPA and topiramate, and routine coagulation laboratory parameters were entirely normal. Epilepsy surgery was immediately followed by severe intracranial bleeding events which promped repeated craniectomy. Extensive laboratory analyses revealed a factor XIII activity level of 17%, indicating factor XIII deficiency confirmed by a reduced XIIIA-antigen. After termination of treatment with VPA, factor XIII levels returned to normal. Control examinations after 9 and 24 months showed normal range values for all coagulation parameters, including factor XIII, platelet function, and von Willebrand factor. To our knowledge, this case is the first description of a well-documented, clinically relevant transient factor XIII-deficiency syndrome related to VPA treatment.

Adult↗
PubMed2003

Changes in coagulation and markers of fibrinolysis in horses undergoing colic surgery.

Activation of coagulation can be frequently found in horses with colic. However, it has also been demonstrated as a sequela of surgical trauma alone in humans. The purpose of the present study was to determine changes in coagulation and fibrinolysis in horses that underwent colic surgery and to evaluate whether these changes were secondary to the colic or the surgery and wound healing. Thirty horses that underwent colic surgery with uncomplicated recovery were included. Ten horses with a Forssell's procedure served as control group with a standardized surgical trauma. Besides daily physical examinations during the observation period of 10 days, activated partial thromboplastin time (aPTT), prothrombin time and thrombin time as well as fibrin monomer (FM), D-Dimer (DD) and antithrombin (AT) III were determined. Compared with the control group the aPTT was the only standard coagulation test that was significantly prolonged before and after the event of colic surgery. After surgery, hyperfibrinogenaemia occurred in all groups. In colic groups FM and DD concentrations were within reference range at admission,and were significantly greater than in control horses after surgery. AT III activity decreased after colic surgery, but did not change in the control group. It was concluded that an activated coagulation state after colic surgery has to be expected, resulting not only from the colic disease, but also from the event of surgery.

Animals↗
PubMed2002

Alterations in platelet function during the ovarian cycle.

Steroid hormones may profoundly influence hemostasis; for example, as discussed for hormone replacement therapy, pregnancy and, being less obvious, for the ovarian cycle. We investigated primary hemostasis parameters using a platelet function analyzer (PFA-100) during the follicular and luteal phases in 18 healthy young women without oral contraceptives. During the follicular phase, the mean closure time (CT) was 164.7 +/- 56.7 s, and it decreased to 130.2 +/- 30.6 s in collagen/epinephrine cartridges in the luteal phase (P = 0.0095). No significant difference could be found for CT values in collagen/adenosine diphosphate cartridges during the follicular phase as compared with the luteal phase (97.2 +/- 24.2 s versus 89.6 +/- 18.4 s, P = 0.174). Negative correlations between the CT values in collagen/epinephrine cartridges and von Willebrand factor from both phases of the cycle were found (follicular phase: r = -0.53; luteal phase: r = -0.54). Fibrinogen and fibrinogen degradation products were significantly increased in the luteal phase (2.49 +/- 0.62 g/l versus 2.05 +/- 0.59 g/l and 0.12 +/- 014 versus 0.04 +/- 0.04, P = 0.02 for both parameters) as compared with the follicular phase. No significant differences could be detected for plasminogen, plasmin-antiplasmin complex, prothrombin fragment 1 + 2 and D-dimer between the groups. This study indicates that platelet function is periodically altered during the ovarian cycle due to the influence of progesterone and estrogen on von Willebrand factor concentrations.

Adult↗
PubMed2001

Plasminogen activation without changes in tPA and PAI-1 in response to subcutaneous administration of ancrod.

Ancrod is a purified fraction of venom from the Malayan pit viper, Calloselasma rhodostoma, currently under investigation for treatment of ischemic stroke. The therapeutic effect is ascribed to a lowering of plasma fibrinogen. Thirty-two healthy volunteers received subcutaneous ancrod at doses of 1.0, 1.5 and 2.0 IU/kg body weight or placebo. Blood samples were drawn before the injection and at various time points until 96 h after the injection. Ancrod leads to the formation of desAA-fibrin, which serves as cofactor in tissue plasminogen activator activity (tPA)-induced plasminogen activation. Unchanged concentrations of prothrombin fragment F1.2 and thrombin-antithrombin complex (TAT) indicate that fibrin formation occurs independent of thrombin. Plasmin generation is independent of an increase in tPA activity or changes in plasminogen activator inhibitor-1 (PAI-1) concentration in plasma. Subcutaneous injection of ancrod leads to a generalized fibrino(geno)lytic response caused solely by providing tPA with soluble fibrin as its cofactor in plasminogen activation. Maximal plasmin activity is present 12 h after subcutaneous injection.

Adult↗
PubMed2001

Transcranial ultrasound-improved thrombolysis: diagnostic vs. therapeutic ultrasound.

Success of stroke treatment with rt-PA depends on rapid vessel recanalization. Enzymatic thrombolysis may be enhanced by additional transcranial application of ultrasound (US). We investigated this novel technique using a 185-kHz probe and compared it to standard diagnostic US. In vitro studies were performed in a continuous pressure tubing system. Clots were placed in a postmortem skull and treated with rt-PA together with or without transtemporal 185-kHz US insonation (2W/cm(2)) and in comparison to 1-MHz diagnostic US (0.5 W/cm(2)). Recanalization time was significantly (p < 0.01) shorter in the 185-kHz (14.1 min) and 1-MHz (17.1 min) US rt-PA treatment group compared to rt-PA treatment alone (29.3 min.). Flow rate was significantly higher (p < 0.025) and increased faster in the combined treatment group with rt-PA + 185-kHz US compared to rt-PA + 1-MHz US. We investigated the blood-brain barrier in rats after 90-min exposure time of the brain with 185-kHz US, but no damage was observed. Results suggest efficacy and safety of the 185-kHz transducer, which is superior to diagnostic US. Such a novel US probe may be able to optimize thrombolytic stroke treatment.

Analysis of Variance↗
PubMed2001

A novel perfusion catheter for hybrid procedures in minimally invasive bypass surgery.

BACKGROUND: Combined off-pump bypass grafting and percutaneous coronary intervention (hybrid procedures) is supposed to be beneficial for high-risk patients. We developed a novel perfusion catheter to facilitate these hybrid interventions. METHODS: First, we tested coagulatory activation in vitro. Afterwards, 6 landrace pigs underwent active coronary perfusion of the LAD. In a second study, 15 pigs underwent off-pump bypass surgery (LIMA to LAD grafting) and the catheter was used to provide myocardial perfusion and prevent bleeding at the site of the coronary anastomosis. RESULTS: In the in vitro perfusion studies, no activation of coagulation or clotting occurred. Active coronary perfusion was feasible without signs of regional myocardial ischemia or coagulation over a 50-minute period. During off-pump bypass surgery, the catheter prevented bleeding in the operation field and facilitated the surgical procedure. CONCLUSION: The new perfusion catheter can optimize the conditions of off-pump bypass surgery by preventing bleeding in the operation field, maintaining myocardial perfusion and allowing direct angiographic control of the anastomosis. Therefore, this new technique could be an important tool to facilitate hybrid interventions.

Anastomosis, Surgical↗
PubMed2001

Impact of plasmapheresis on platelet hemostatic capacity in healthy voluntary blood donors detected by the platelet function analyzer PFA-100.

Previous flow cytometry studies showed that platelet activation may occur during cytapheresis, cardiopulmonary bypass and hemodialysis. The aim of this pilot study was to determine if the impact of plasmapheresis leads to alterations in platelet hemostatic capacity. Plasmapheresis was carried out in 30 volunteers using an Autopherese C (Baxter) and an MCS3p (Haemonetics). Blood samples were collected and analyzed immediately before and after plasmapheresis. As a result of the plasmapheresis on the Autopherese C, the mean closure time (CT) for collagen/epinephrine (Col/Epi) increased from 118.2 +/- 25.1 to 149.9 +/- 35.0 s and from 88.7 +/- 16.9 to 98.5 +/- 26.3 s for collagen/ADP (Col/ADP), respectively. Seven subjects showed impaired CTs after plasmapheresis for Col/Epi. For Col/ADP, five subjects showed impaired CTs after apheresis. Statistical analysis (McNemar test) showed a significant difference before and after apheresis for Col/Epi (P = 0.024) but not for Col/ADP (P = 0.088). Similar results were shown for plasmapheresis carried out with the MCS3p. These findings show that plasmapheresis can cause an impairment of platelet function in healthy volunteers as measured by the PFA-100, an effect of so far unknown clinical significance.

Adult↗
PubMed2001

The Fibrin Assay Comparison Trial (FACT): evaluation of 23 quantitative D-dimer assays as basis for the development of D-dimer calibrators. FACT study group.

Although D-dimer has gained widespread clinical use as a parameter for detection of in vivo fibrin formation, the issue of standardization of D-dimer assays remains to be resolved. The FACT study was performed to generate basic data for development of calibrators and standard preparations. A set of 86 samples, including plasma samples from patients with DIC, DVT. and other clinical conditions, serial dilutions of pooled plasma samples, and plasma samples containing fibrinogen- and fibrin derivatives, were distributed to 12 manufacturers of D-dimer assays. D-dimer assays differ concerning specificity for crosslinked fibrin, and preference for either high molecular weight fibrin complexes, or low molecular weight fibrin degradation products. Terminal plasmin digests of fibrin clots for calibration produce aberrant results in some assays, especially those with preference for high molecular weight crosslinked fibrin derivatives. The best conformity is achieved by the use of pooled plasma samples from patients with high levels of D-dimer antigen in plasma. In vitro preparations containing a comparable composition of fibrin derivatives to clinical plasma samples may also serve as reference material.

Adult↗
PubMed2001

Fibrin formation and proteolysis during ancrod treatment. Evidence for des-A-profibrin formation and thrombin independent factor XIII activity.

Ancrod is a purified fraction of venom from the Malayan pit viper Calloselasma rhodostoma, containing a serine protease that cleaves fibrinopeptides A from fibrinogen. We report on a study that involved intravenous and subcutaneous application of ancrod in healthy subjects in which it was shown that ancrod induces the formation of desAA-fibrin complexes that are partially crosslinked by factor XIII proenzyme, and act as cofactor in tPA induced plasminogen activation. The plasmin generated degrades fibrin, as well as fibrinogen, leading to the appearance of large amounts of fibrinogen and fibrin degradation products in the circulation, including fragment D-dimer. At low concentrations of ancrod, formation of desAA-fibrin is preceded by production of desA-profibrin, lacking only one fibrinopeptide A.

Ancrod↗
PubMed2001

The fibrin assay comparison trial (FACT): correlation of soluble fibrin assays with D-dimer.

Soluble fibrin (SF) is regarded as an indicator of acute fibrin formation and a precursor of fibrin thrombi. Using a set of clinical plasma samples, and fibrin derivatives, five assays for measurement of SF, including two chromogenic assays, two ELISA systems, and one latex-enhanced photometric immunoassay were compared. Correlation between SF assays was moderate (Spearman's rho values between 0.344 and 0.805). Re-calibration with serial dilutions of desAABB-fibrin monomer resulted in adjustment of the numerical scale of the assays without improving correlation. All SF assays reacted with purified crosslinked fibrin derivatives. Using clinical plasma samples, Spearman's rho of SF assays with D-dimer consensus values based upon results of 23 quantitative D-dimer assays were between 0.491 and 0.911. Although all SF assays react with desAABB-fibrin monomer complexes, SF assays are heterogeneous concerning reactivity with fibrin compounds observed in clinical plasma samples. The prospect of a common calibrator for SF assays therefore seems to be remote. Since SF assays react with crosslinked fibrin derivatives, it is not possible to clearly distinguish between acute fibrin formation, and fibrin dissolution on the basis of the results of current SF assays.

Calibration↗
PubMed2000

Analysis of fibrin formation and proteolysis during intravenous administration of ancrod.

Ancrod is a purified fraction of venom from the Malayan pit viper, Calloselasma rhodostoma, currently under investigation for treatment of acute ischemic stroke. Treatment with ancrod leads to fibrinogen depletion. The present study investigated the mechanisms leading to the reduction of plasma fibrinogen concentration. Twelve healthy volunteers received an intravenous infusion of 0.17 U/kg body weight of ancrod for 6 hours. Blood samples were drawn and analyzed before and at various time points until 72 hours after start of infusion. Ancrod releases fibrinopeptide A from fibrinogen, leading to the formation of desAA-fibrin monomer. In addition, a considerable proportion of desA-profibrin is formed. Production of desA-profibrin is highest at low concentrations of ancrod, whereas desA-profibrin is rapidly converted to desAA-fibrin at higher concentrations of ancrod. Both desA-profibrin and desAA-fibrin monomers form fibrin complexes. A certain proportion of complexes carries exposed fibrin polymerization sites E(A), indicating that the terminal component of the protofibril is a desAA-fibrin monomer unit. Soluble fibrin complexes potentiate tissue-type plasminogen activator-induced plasminogen activation. Significant amounts of plasmin are formed when soluble fibrin in plasma reaches a threshold concentration, leading to the proteolytic degradation of fibrinogen and fibrin. In the present setting, high concentrations of soluble fibrin are detected after 1 hour of ancrod infusion, whereas a rise in fibrinogen and fibrin degradation products, and plasmin-alpha(2)-plasmin inhibitor complex levels is first detected after 2 hours of ancrod infusion. Ancrod treatment also results in the appearance of cross-inked fibrin degradation product D-dimer in plasma. (Blood. 2000;96:2793-2802)

Adult↗
PubMed2000

Acceleration of thrombolysis with ultrasound through the cranium in a flow model.

Thrombolysis is an efficient therapy for hyperacute stroke within a limited time window. Neurological outcome depends on the recanalization time of the occluded vessel. Nonthermal effects of low-frequency ultrasound (US) accelerate enzymatic fibrinolysis in vitro. We examined the effects of transcranially applied US on recombinant tissue plasminogen activator (rt-PA)-mediated thrombolysis in a flow model in vitro. Pure fibrin clots were placed in a continuous-pressure flow model and treated with rt-PA during 1-MHz US exposure (0.5 W/cm(2); spatial peak, temporal peak intensity). Transcranial and direct US application in combination with rt-PA significantly (p<0.001) shortened recanalization time, increased perfusion flow and reperfusion rate in comparison with rt-PA-mediated thrombolysis alone. Recanalization rate within 30 min was 90-100% in the US-exposed clots vs. 30% in the clots treated only with rt-PA. Our results suggest that transcranial application of 1-MHz US may accelerate reperfusion and recanalization rate of occluded intracerebral vessels by enhancing rt-PA-mediated thrombolysis. Shortening of recanalization time could contribute to optimizing effects of acute thrombolytic stroke therapy.

Blood Flow Velocity↗
PubMed2000

Use of D-dimer assays in the diagnosis of venous thrombosis.

In the course of fibrin formation, the D-domains of adjacent fibrin molecules within the fibrin polymer are covalently linked by factor XIIIa, leading to the formation of a D-domain dimer. Proteolysis of this cross-linked fibrin generates fibrin fragments D-dimer and E as terminal products. Fragment D-dimer therefore is an indicator for the proteolysis of cross-linked fibrin, whereas the monomeric fragment D can stem from fibrinogen and non-cross-linked fibrin. Various monoclonal antibodies have been prepared that distinguish between fragments D-dimer and D and allow the detection of fibrin derivatives in the presence of fibrinogen. These anti-D-dimer-antibodies have been shown to react with fragment D-dimer, but also detect dimeric D-domains within larger fibrin compounds, including cross-linked fibrin complexes generated in an early phase of coagulation activation. Assay systems for D-dimer antigen therefore may uncover intravascular clot formation early, by detection of fibrin complexes, and after completion of clot formation, by the detection of proteolytic fragments released from the particulate clot. Various trials have shown that low concentrations of D-dimer antigen in the blood exclude recent venous thrombosis or pulmonary embolism. Elevated levels may be caused by venous thrombotic disease, but also by a variety of other conditions, leading to intra- or extravascular fibrin formation. Assay systems include manual immunoagglutination assays, immunofiltration assays, microtiter plate enzyme-linked immunosorbent assay (ELISA) systems, automated ELISA systems, and latex-enhanced photometric immunoassays. According to clinical studies, D-dimer assays may be the "first line" of technical screening in symptomatic outpatients with suspected venous thrombosis or pulmonary embolism, but further prospective management trials, and improved standardization of assay systems, are needed for the validation of this approach.

Antifibrinolytic Agents↗