[Prevalence of Elevated Lipoprotein (a) Levels in Patients < 60 Years of Age with Retinal Vein Occlusion]. / Prävalenz erhöhter Lipoprotein(a)-Spiegel bei unter 60-jährigen Patienten mit venösen retinalen Gefäßverschlüssen.

BACKGROUND: The potential impact of elevated Lipoprotein (a) [Lp(a)] levels on retinal venous occlusive (RVO) diseases with regard to age and various risk factors has not been studied extensively. PATIENTS AND METHODS: In a retrospective case-control study, thrombophilia data of 106 young patients (< 60 years at the time of the RVO or a previous thromboembolic event) with RVO and 76 healthy subjects were evaluated. RESULTS: Elevated Lp(a) plasma levels were significantly more prevalent among RVO patients (29.2 %) than among controls (9.2 %; p = 0.0009). Lp(a) levels were found to be significantly (p = 0.012) different between patients and controls. Moreover, we found that an unusual personal or family history of thromboembolism was a strong predictor of elevated Lp(a) (p = 0.03). We observed a significant correlation between elevated Lp(a) and other coagulation disorders (p = 0.005). Multivariate analysis showed that elevated lipoprotein(a) levels (OR: 3.5; p = 0.003) were an independent risk factor for the development of RVO. CONCLUSIONS: Elevated plasma levels of Lp(a) are associated with the development of RVO. Selective screening of young patients and subjects with a personal or family history of thromboembolism may be helpful in identifying RVO patients with elevated Lp(a).

[Multiple thrombophilic risk markers in patients ≺65 years of age with retinal vein occlusion]. / Multiple thrombophile Risikomarker bei Patienten ≺65 Jahre mit venösen retinalen Gefäßverschlüssen.

BACKGROUND: The potential impact of multiple thrombophilic defects on retinal venous occlusive (RVO) diseases with regard to age and various risk factors has not been studied extensively. MATERIALS AND METHODS: In a retrospective, multicenter study, thrombophilia data of 128 patients <65 years of age with RVO and 110 healthy subjects were evaluated. The main measure outcome was the prevalence of multiple thrombophilic disorders. RESULTS: Multiple thrombophilic defects were significantly more prevalent among RVO patients (18.0%) than among controls (1.8%; P < 0.0001). We identified factor VIII elevation, elevated lipoprotein(a) plasma levels and resistance to activated protein C as the most prevalent combined disorders. Factor XII deficiency and prothrombin mutation G20210A were found to be isolated thrombophilic risk factors. Multiple thrombophilic defects were significantly associated with RVO recurrence (P = 0.008). CONCLUSION: Multiple thrombophilic disorders are associated with the development of RVO among patients younger than 65 years of age. Moreover, our results suggest that patients with RVO associated with underlying combined thrombophilic defects are at increased risk for RVO recurrence. Further studies are required to analyze whether the diagnosis of combined thrombophilic defects among RVO patients could be a predictor for RVO recurrence.

[Prophylaxis of venous thromboembolism and anticoagulation bridging. Strategies in otorhinolaryngology]. / Thromboembolieprophylaxe und überbrückende Antikoagulation. Strategien in der HNO-Heilkunde.

Various interdisciplinary guidelines recommend that in-patients at risk of venous thromboembolism should receive pharmacologic prophylaxis. Among the anticoagulants low-molecular-weight heparins (LMWH) and fondaparinux can be considered the medications of choice because of the favorable pharmacokinetic properties when compared with unfractionated heparin. Treatment with vitamin K antagonists has to be interrupted in patients undergoing major surgery or invasive procedures. Oral anticoagulation has to be temporarily replaced by short-acting anticoagulants such as LMWH in order to prevent thromboembolic complications (anticoagulation bridging). Although LMWHs have not been approved for this clinical setting their efficacy and safety has been demonstrated in several recent studies. Detailed recommendations for prophylaxis of venous thromboembolism in otorhinolaryngology are lacking although numerous surgical procedures are considered to be associated with a significant risk of thromboembolism. A strategy for pharmacologic prophylaxis of venous thromboembolism and anticoagulation bridging in otorhinolaryngology is proposed.

[New cross-sectional guidelines of the German Medical Association for hemotherapy with fresh frozen plasma. Evidence-based recommendations for risk-benefit assessment]. / Neue (Querschnitt-)Leitlinien der Bundesärztekammer für die Hämotherapie mit gefrorenem Frischplasma. Evidenzbasierte Empfehlungen für die Risiko-Nutzen-Abwägung.

Some new blood products and plasma derivatives have extended the possibilities in hemotherapy to such an extent that the therapeutic and evidence-based therapy options can only really be managed with the aid of guidelines. Four approved plasma preparations are available in Germany: fresh frozen plasma, lyophilized plasma, solvent-detergent (SD) pool plasma and methylene blue-light-treated plasma. Evidence of the clinical efficacy of plasma is mainly based on uncontrolled observational studies, case reports or expert opinion. Plasma is indicated for complex coagulopathy associated with manifest or imminent bleeding, particularly with massive transfusion, disseminated intravascular coagulation and liver disease. With the exception of emergency situations when clotting assay results are not available in time, a clinically relevant coagulopathy must be verified before plasma is administered. The rapid infusion of at least 10 ml of plasma per kg body weight is required to significantly increase the respective clotting factor or inhibitor levels. Prothrombin complex concentrates (PPSB) should be preferred to plasma for the rapid reversal of oral anticoagulation. Side effects of plasma are rare but have to be considered.

Leukocyte-platelet aggregates in acute and subacute ischemic stroke.

BACKGROUND: Leukocyte-platelet aggregates appear to be a stable and sensitive marker of platelet activation as suggested by studies in coronary heart disease. We tested the hypothesis that leukocyte-platelet aggregates are increased after ischemic stroke and investigated the contribution of different leukocyte subtypes to such increase. METHODS: We serially determined granulocyte-, lymphocyte- and monocyte-platelet aggregates, using flow cytometry at days 1, 2, 3, 5, 7, 10, and 90 in patients with ischemic stroke (n = 45) and in age- and sex-matched healthy control subjects (n = 30). RESULTS: Granulocyte-platelet aggregates (granulocytes with > or =1 platelet/microl) were more common in patients than control subjects from day 1 through day 10 (p < 0.04, respectively), but not on day 90 after stroke. The percentage of granulocytes forming aggregates was increased on days 1-3 after stroke but not at other time points. Lymphocyte-platelet aggregates were not more common at any time point after stroke. Total numbers and percentages of monocytes forming platelet aggregates were significantly increased on day 2 (p = 0.003), but not at other time points after stroke. CONCLUSION: The 3 leukocyte subtypes showed different kinetics regarding aggregate formation with platelets after ischemic stroke. Increase of monocyte-platelet aggregates is short-lived and may reflect an acute reaction to cerebral ischemia, whereas granulocyte-platelet aggregate formation persists into the subacute phase, suggesting that they are a particularly sensitive parameter reflecting both prothrombotic and inflammatory processes after stroke.

[Haemostatic testing prior to elective surgery? Yes!]. / Laboranalytischer Ausschluss einer hämorrhagischen Diathese vor elektiven Eingriffen? Ja!

Haemorrhagic disorders must be excluded prior to any operation or other invasive procedure that has the potential to involve serious bleeding. When assessing the individual risk of bleeding, screening tests of hemostasis must be combined with the patient's clinical history and symptoms, and any history of bleeding must be explored under direct medical supervision using a standardized questionnaire. However, this bleeding history is neither very specific, nor is it particularly sensitive. Screening tests that have been found to be useful include platelet count, activated partial thrombo plastin time (aPTT), prothrombin time (PT) and clottable fibrinogen. No reliable, sensitive and specific screening test is however available today to screen for platelet dysfunction or von Willebrand disease. A specialized coagulation laboratory should be involved when the bleeding history or laboratory screening indicate a potential haemorrhagic disorder.

Coagulation factor XII (FXII) activity, activated FXII, distribution of FXII C46T gene polymorphism and coronary risk.

BACKGROUND: Whether factor XII (FXII) activity, its 46C>T polymorphism and activated FXII (FXIIa) are associated with coronary heart disease (CHD) remains to be determined. METHODS: FXII, FXIIa and the FXII 46C>T polymorphism were determined in a hospital-based cohort of 2615 patients undergoing coronary angiography. RESULTS: Fifty-seven per cent of the participants were identified as wild-type (46CC), 38% as heterozygous (46CT) and 5% as homozygous (46TT) for FXII 46C>T. FXII and FXIIa levels were significantly lower in carriers of the T-allele: 132 (97-151) U dL(-1) FXII in 46CC, 87 (77-99) U dL(-1) FXII in 46CT and 53 (42-67) U dL(-1) FXII in 46TT carriers (P < 0.001), and 2.8 (2.3-3.5) microg L(-1) FXIIa in CC, 2.1 (1.6-2.6) microg L(-1) FXIIa in CT and 1.2 (0.9-1.5) microg L(-1) FXIIa in TT carriers (P < 0.001; medians, lower and upper quartiles). Patients with stable CHD (n = 935), a history of myocardial infarction (n = 785) or who were suffering from acute coronary syndromes (ACS; n = 323) had significantly lower FXII levels than controls (n = 572). The differences remained statistically significant after adjustments for age, sex, diabetes mellitus, smoking, hypercholesterolemia and hypertension. Significantly reduced FXIIa levels in ACS patients lost significance once adjusted for covariates. FXII genotype was not associated with any clinical phenotype. CONCLUSION: Lower FXII activity represents an independent risk for CHD and ACS. This is not the case for FXIIa levels or the FXII 46C>T variation.

Preservation of in vitro function of platelets stored in the presence of a synthetic dual inhibitor of factor Xa and thrombin.

BACKGROUND: The use of citrate anticoagulant limits the clinical significance of platelet function tests. Thrombin inhibitors cannot prevent thrombin-induced platelet activation completely. We examined the influence of benzylsulfonyl-d-Arg-Pro-4-amidinobenzylamide (BAPA), a dual inhibitor of Factor Xa (FXa) and thrombin, on platelet responsiveness to agonists when measured between 2 and 24 h after venipuncture. METHODS: Blood samples from 36 individuals were anticoagulated with citrate and BAPA, respectively. Turbidimetric platelet aggregometry (TPA) and impedance platelet aggregometry (IPA), a whole blood platelet counting assay for measuring platelet aggregation (PCA), and Platelet Function Anlayzer-100 (PFA-100 closure times (CTs) were determined after whole blood storage between 2 and 24 h after venipuncture. Native whole blood was studied over 48 h to determine the inhibition of thrombin generation by BAPA, hirudin and melagatran. RESULTS: BAPA inhibited thrombin generation completely for 48 h, while hirudin and melagatran did not. The use of citrate resulted in significantly reduced TPA induced by arachidonic acid (AA) or adenosine 5'-diphosphate (ADP), and significantly reduced IPA regardless of agonist when measured 10 and 24 h after blood collection. PCA ratios in citrated blood also dropped significantly 10 and 24 h after venipuncture. The length of storage of BAPA-anticoagulated blood samples over 24 h had no significant influence on any platelet response. The reproducibility of platelet function assay results obtained from BAPA-anticoagulated samples was significantly better than corresponding data from citrated blood. CONCLUSION: TPA, IPA, PCA or PFA-100 CTs remain stable for 24 h when whole blood is anticoagulated with a dual inhibitor of FXa and thrombin. This would greatly simplify the shipment of samples for platelet function testing.

The impact of a medium molecular weight, low molar substitution hydroxyethyl starch dissolved in a physiologically balanced electrolyte solution on blood coagulation and platelet function in vitro.

BACKGROUND AND OBJECTIVES: Hydroxyethyl starches (HES) may have the potential to impact negatively on haemostasis. Recent findings suggest that side-effects on haemostasis stem not only from the physicochemical differences between HES, but also from the composition of the solvent. We compared the effects of a newly developed medium molecular weight (MW) and low molar substitution (MS) HES dissolved in a physiologically balanced electrolyte solution (MW 130, MS 0.42; B-HES) with a commercially available non-balanced HES (MW 130, MS 0.4; NB-HES), and with Ringer's lactate (RL) solution in vitro. MATERIALS AND METHODS: Activated partial thromboplastin time (APTT), factor VIII clotting activity (F VIII:C) and von Willebrand factor (vWF) activity were investigated in 48 healthy individuals. Platelet function as measured by turbidimetric platelet aggregometry and whole blood impedance aggregometry induced by adenosine diphosphate (ADP), collagen and thrombin receptor activating peptide (TRAP), and by ADP and TRAP-induced expression of activated platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa was determined in 24 participants. Haemodilution (25% and 50%, v/v for blood coagulation analyses and 20% and 40%, v/v for platelet function studies) was performed using the two HES preparations and RL. RESULTS: APTT was significantly longer and F VIII and vWF significantly lower at 25% and 50% dilutions with NB-HES compared to B-HES and RL. At 20% and 40% dilutions, ADP and TRAP-induced expression of activated platelet surface GP IIb/IIIa was significantly increased by B-HES compared to NB-HES and RL. Percentages of platelet GP IIb/IIIa expression were also significantly greater in samples diluted with B-HES than in undiluted blood. Neither the diluent (B-HES, NB-HES and RL) nor the degree of dilution (undiluted, 20% and 40% dilution) had any significant influence on ADP, collagen or TRAP-induced turbidimetric platelet aggregation or impedance platelet aggregation. CONCLUSIONS: In contrast to a non-balanced 130 kDa, MS 0.4 HES (NB-HES), a 130 kDa, MS 0.42 HES preparation dissolved in a physiologically balanced electrolyte solution (B-HES) does not affect APTT, F VIII:C and vWF in vitro. Both types of HES do not affect platelet aggregation induced by ADP, collagen or TRAP. B-HES but not NB-HES increases the expression of activated platelet GP IIb/IIIa induced by ADP or TRAP.

A prospective multicentre study on the safety of long-term intensive plasmapheresis in donors (SIPLA).

BACKGROUND AND OBJECTIVES: The safety of chronic intensive donor plasmapheresis has not been determined in large prospective studies examining dropout rates, dropout reasons and predictors of withdrawals. MATERIALS AND METHODS: Twenty-one plasma centres recruited 3783 donors who were switched from a moderate to an intensive plasmapheresis programme and observed over a 3-year period. Individuals weighing < 70 kg and > or = 70 kg donated 750 ml and 850 ml of plasma per session, respectively. The maximum of annual donations was limited to 60. Total serum protein (TSP) and haemoglobin (Hb) or haematocrit (Hct) were determined at each donation, and immunoglobulin G (IgG) at every fifth donation. Dropout rates, dropout reasons and potential predictors of withdrawal were analysed. RESULTS: Dropouts were predominantly due to socioeconomic (49.2% of all donors) or medical reasons not related to plasma donations (10.4% of all donors). Sixteen per cent of donors dropped out when IgG, TSP or Hb levels fell below threshold values. Severe clinical adverse events related to plasmapheresis were observed in five subjects. The incidence in severe cardiovascular diseases was lower in donors than in the general population. The risk factors that led to dropping out as a result of low IgG, TSP or Hb levels included younger age, female gender, low initial IgG levels and a high donation frequency. Neither body weight nor the amounts of plasma donated per kilogram of body weight per session were associated with ceasing due to medical reasons, whether related or unrelated to plasma donations. Females and males within the respective lowest body weight category were not at higher risk of dropping out. CONCLUSION: Long-term intensive donor plasmapheresis under conditions investigated in this study is safe. All donors weighing > or = 70 kg are safely able to donate 850 ml of plasma in each session up to 60 times per year, provided that they are carefully monitored.

A prospective trial on the safety of long-term intensive plasmapheresis in donors.

BACKGROUND AND OBJECTIVES: There are still concerns about the safety of long-term intensive donor plasmapheresis, because the reasons that donors drop out of plasmapheresis programmes have not been determined in prospective studies. MATERIALS AND METHODS: Seventy-two donors were switched from a moderate plasmapheresis programme to an intensive plasmapheresis programme and observed over a 3-year period. In addition to measuring total serum protein (TSP), albumin, immunoglobulin G (IgG) and haemoglobin (Hb) levels, parameters of iron metabolism and blood coagulation, and biochemical cardiovascular risk markers, were determined at baseline and at every 15th donation. We also collected statements from donors who dropped out of the plasmapheresis programme about their reasons for withdrawal. RESULTS: Dropouts were predominantly related to socioeconomic (n = 34) or medical reasons not related to plasma donations (n = 8). Three donors had to drop out when their TSP levels fell below threshold for the third time within a 5-week period. At baseline, donors had significantly lower TSP, albumin, IgG, Hb and ferritin levels than gender-matched and age-matched non-donor controls. However, subsequent intensive plasmapheresis over 3 years did not impair the individuals' ability to donate plasma. TSP, IgG, Hb, ferritin, transferrin, cardiovascular risk markers and parameters of blood coagulation did not change significantly during the observation period. CONCLUSIONS: The reasons why donors cease to participate in intensive plasmapheresis programmes are predominantly not directly related to the plasma donation itself.

The impact of two whole blood inline filters on markers of coagulation, complement and cell activation.

BACKGROUND AND OBJECTIVES: There exists a current lack of information about the impact of different inline filters, used for the leucoreduction of whole blood (WB), on the levels of clotting factors and markers of coagulation, complement and cell activation in plasma. Only a few small comparisons of different types of WB inline filters have been published to date. MATERIALS AND METHODS: This study compared two plasma types of 200 units each. Both study groups were derived from WB, inline-filtered and held for 2 h at 20 degrees between donation and filtration. Then, 200 units (Group A) were filtered using a positively charged polyester filter (Baxter RZ2000) and the other 200 units (Group B) were filtered using an uncharged polyester filter (Fresenius). After filtration, both groups were analysed for fibrinogen, factors V and VIII:C (FV and FVIII:C, respectively), immunoglobulin G (IgG), residual leucocytes and platelets, and markers of coagulation, complement and cell activation. Predonation plasma samples from CPDA1-anticoagulated blood were obtained from 100 different individuals and served as controls. RESULTS: WB inline filtration did not influence fibrinogen, FV, FVIII:C or IgG levels. Neither filter induced thrombin or fibrin formation. The charged filter caused substantial complement activation and neutrophil elastase and platelet factor 4 release. In contrast, the plasma filtered through the uncharged filter showed markedly lower levels of C3a-desArg, C5a, neutrophil elastase and platelet factor 4, and moderately reduced levels of prothrombin fragments 1+2 and D-dimer, compared with controls. CONCLUSIONS: Filter type has a significant impact on the quality of plasma derived from WB filtered through inline filtration systems. Some filters produce substantial coagulation and complement activation and cell release, while others appear to reduce the plasma levels of activation markers. The clinical significance of these findings remains to be determined.

[Platelet function tests for monitoring of acetylsalicylic acid: clinical significance in antiplatelet treatment]. / Plättchenfunktionstests zum Monitoring der Azetylsalizylsäuretherapie acid: Klinische Wertigkeit bei plättchenfunktionshemmender Behandlung.

Several studies have demonstrated with the use platelet function tests (PFT) that subgroups of patients under acetylsalicylic acid (ASA) fail to produce the anticipated antiplatelet effect. This phenomenon as well as the clinical failure of ASA to protect patients from thromboembolic complications has been termed ASA resistance (AR) or ASA nonresponsiveness. Several subtypes of AR can be distinguished by PFT. The following PFT were used to characterize AR: optical aggregometry, platelet aggregation in whole blood, platelet function analyzer (PFA-100), platelet reactivity test or platelet aggregate ratio, flow cytometry and thromboxane B(2) generation. All PFT have in common that their widespread clinical use is substantially limited due to complex preanalytic factors, reduced specificity and poor reproducibility. PFT are not interchangeable for monitoring antiplatelet treatment. Three prospective clinical trials revealed a possible relationship between AR and subsequent cardiovascular events. There is a need for a simple and reliable assay for predicting the clinical efficacy of antiplatelet therapy. Recent data demonstrate that none of the currently available assays including the PFA-100 system are capable to accomplish these objectives.

The impact of different intensities of regular donor plasmapheresis on humoral and cellular immunity, red cell and iron metabolism, and cardiovascular risk markers.

BACKGROUND AND OBJECTIVES: Major studies are still lacking on the impact of differing intensities of long-term donor plasmapheresis, not only on total serum protein, albumin and immunoglobulin G (IgG), but also on humoral and cellular immunity, red cell and iron metabolism, and biochemical cardiovascular risk markers. MATERIALS AND METHODS: Three groups of donors, comprising 483 individuals undergoing differing intensities of long-term serial plasmapheresis, were entered into a cross-sectional study. A fourth control group consisted of 100 non-donors. In addition to measuring total protein, albumin and IgG levels, we determined parameters of humoral and cellular immunity, red cell and iron metabolism and recognized biochemical cardiovascular risk factors. RESULTS: The median annual net amount of plasma donated by the three donor groups was 37, 16 and 10 l, respectively (P < 0.0001). Donors had significantly lower total serum protein, albumin and IgG levels than non-donors (P < 0.0001), but the intensity of plasmapheresis had no influence on those parameters. Like non-donors, all plasma donors had normal humoral and cellular immunity. No increased rates of iron store depletion were observed in the three groups of plasma donors. Plasma donors were not at increased cardiovascular risk. CONCLUSIONS: Regular donor plasmapheresis of up to 45 l of plasma per year appears to be as safe as more moderate plasmapheresis programmes, with respect to the parameters analysed in this study. Individuals donating under these conditions did not develop impaired humoral and cellular immunity, iron store depletion, or increased cardiovascular risk with regard to established biochemical risk markers. Prospective studies are required to determine more exactly than in retrospective analyses the reasons why donors withdraw from plasmapheresis programmes.

Gamma-irradiation of blood products following autologous stem cell transplantation: surveillance of the policy of 35 centers.

Blood products should be irradiated during allogeneic stem cell transplantation and before performing autologous stem cell harvest for prevention of acute transfusion-associated graft-versus-host disease (TA-GVHD). Usually, irradiation of all blood products is continued lifelong in the allogeneic setting. Up to now, no broadly accepted rules exist concerning autologous stem cell transplantation. We present here the results of an inquiry sent to 47 German transplantation centers regarding the transfusion policy following autologous stem cell transplantation. The results of 35 answering centers are included. Ten out of 35 centers offer irradiated blood products lifelong to their patients, mainly for the prevention of mistransfusion of non-irradiated blood components to allogeneic recipients. Twenty-two out of 35 centers administer irradiated blood products for a special time span after autologous stem cell transplantation. In most centers, this time span is from 3 to 6 months. Only few centers (4/35) expand this time span to 1-2 years after transplantation. A minority of centers (3/35) gave non-irradiated blood products to all of their patients or to patients not suffering from acute leukemia or after total body irradiation (TBI) containing preparative regimens. Most centers (19/35) deliver irradiated blood products irrespective of the conditioning regimen. Fifty-three percent of the centers decide to donate irradiated blood products not depending on immunological reconstitution. But in most centers some kind of hematological reconstitution is a major criterion for termination of irradiated blood products. Sixty-four percent of the centers made no difference in transfusion policy in regard to the underlying disease. No center experienced cases of proofed TA-GVHD. Guidelines should be worked out concerning transfusion policy after autologous stem cell transplantation.

Prevalence of illicit drug use in plasmapheresis donors.

BACKGROUND AND OBJECTIVES: No data are presently available concerning the frequency of illicit drug use in plasmapheresis donors. We therefore examined source plasma units produced in the United States (US) and in Germany for evidence of illicit drug use among donors. MATERIALS AND METHODS: Seventy-five US plasma units from 10 different US states and 75 German plasma units that had been analysed principally for their protein composition were screened for drugs. Determinations were made, using automated immunoassays, of the presence of cannabis, cocaine, amphetamine, methamphetamine, methylenedioxymethamphetamine (MDMA), methylenedioxyethylamphetamine (MDE) and opiates. Positive results were confirmed by gas chromatography-mass spectrometry. RESULTS: Eleven US plasma units were found to be positive for cocaine (14.6%), whereas all German samples were cocaine negative (P = 0.0007). Fifteen US plasma units (20%) and one German unit (1.3%) were confirmed as positive for cannabis (P = 0.0003). Three out of 75 US plasma units were positive for both cannabis and cocaine. In none of the 150 samples were amphetamine, methamphetamine, MDMA, MDE or opiates detected. CONCLUSIONS: Our results strongly suggest differences in cocaine and cannabis consumption between US and German plasmapheresis donors. If these results are confirmed by larger-scale studies, random drug screening (including cocaine) of donors should be implemented in order to reduce the number of drug-containing plasma units, especially in the USA.

Prospective cross-sectional study of haemostatic factors in patients with and without coronary artery disease.

The role of haemostatic factors for arterial thrombosis, especially the prevalence of activated protein C (APC) resistance in patients with coronary artery disease (CAD), is controversial. Between November 1996 and August 1997, 665 patients were analyzed. Diagnosis of CAD was confirmed by coronary angiography, exclusion of CAD was accepted in the presence of negative stress testing or a negative coronary angiography. CAD was present in 370 (56%) and excluded in 295 (44%) patients. Patients with CAD were older (64 +/- 9.2 versus 57.7 +/- 16 years; P

Effects of solvent/detergent-treated plasma and fresh-frozen plasma on haemostasis and fibrinolysis in complex coagulopathy following open-heart surgery.

BACKGROUND AND OBJECTIVES: Solvent/detergent-treated plasma (SDP) contains markedly lower protein S (PS) and plasmin inhibitor (PI) activity than standard fresh-frozen plasma (FFP). It has also been reported that SDP contains no alpha(1)-antitrypsin. Despite the lack of clinical data, it is suspected that SDP may be less effective than FFP in the treatment of complex coagulopathies. We therefore conducted a prospective trial to study the impact of SDP and FFP on haemostasis and fibrinolysis in complex coagulopathy after open-heart surgery. MATERIALS AND METHODS: Patients received either 600 ml of SDP (n = 36) or 600 ml of FFP (n = 31) at an infusion rate of 30 ml/min. The following parameters were measured before treatment and 60 min after termination of plasma infusion: prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, factor VIII, antithrombin, protein C (PC), free PS and PS activity, prothrombin fragments F1+2 (F1+2), D-dimers (DD), fibrinogen degradation products (FDP), plasmin-plasmin inhibitor complexes (PPI), plasminogen, PI and alpha(1)-antitrypsin. RESULTS: The rise in fibrinogen, factor VIII, antithrombin, PC, free PS, alpha(1)-antitrypsin and plasminogen, and the decrease in PT and APTT, did not significantly differ between the two study arms. However, PS activity did not increase after SDP infusion but did show a significant elevation after infusion with FFP. PI declined significantly after SDP and remained uninfluenced by FFP. Neither SDP nor FFP had any significant influence on F1+2, DD or FDP. However, a significant decrease in PPI levels caused by both types of plasma indicated a reduction in hyperfibrinolysis. Clinical haemostasis evaluation revealed no significant difference between the two treatment regimens. No adverse reactions were observed. CONCLUSION: With the exception of PS and PI, SDP and FFP improved haemostasis and fibrinolysis to a similar degree. The clinical significance of these findings has to be determined in patients with severe acquired PS and PI deficiency requiring plasma transfusions.

[Complications after high dose therapy and autologous stem cell transplantation. Retrospective study of an unselected patient sample]. / Komplikationen nach Hochdosistherapie und autologer Stammzelltransplantation. Retrospektive Untersuchung an einem nicht selektionierten Patientenkollektiv.

BACKGROUND: High-dose therapy (HDT) with autologous blood stem cell transplantation (ASCT) has become the therapy of choice for patients with specific hematologic neoplasms. Although pancytopenia after HDT with stem cell support is of relatively short duration, complications may be severe and life-threatening. In unselected patients with hematologic and solid tumor malignancies, only few data have been published regarding complications. We therefore analyzed the rate of infection and toxicity in patients with different neoplasms undergoing HDT and ASCT. PATIENTS AND METHODS: From 6/96 to 12/99 42 patients received 54 HDT and ASCT (nine tandem transplants and one triple transplant). The median age was 55 years (range 25-74 years) with equal sex distribution. 30 patients suffered from hematologic malignancies and twelve from solid tumors. RESULTS: Infections were the major cause for complications followed by mucositis, pain and diarrhea. In four patients a positive cytomegalovirus polymerase chain reaction (CMV-PCR) was detected. In two patients this positive test result was accompanied by clinical symptoms of CMV infection. One patient developed lung fibrosis due to busulfan (WHO 4 degrees) and additionally a veno-occlusive disease (VOD) of the liver (WHO 4 degrees). Two patients (4%) died due to CMV pneumonia and multiple organ failure after idiopathic pneumonia, respectively. Four patients developed secondary neoplasms (two patients myelodysplastic syndromes, two patients solid tumors). Three of them had been heavily pretreated. We further analyzed whether the following parameters had an influence on the rate of complications: tumor diagnosis (hematologic vs. solid), number of pretreatment protocols (< 2 vs. > or = 2), CD34+ cell count (< median CD34+ cell count vs. > or = median CD34+ cell count), age (< or = 55 years vs. > 55 years), mucositis (WHO 1-2 degrees vs. 3-4 degrees) and conditioning regimen (myeloablative vs. myelosuppressive). The infection rate was higher in patients receiving myeloablative therapy compared to patients with myelosuppressive conditioning and the platelet count recovery was slower. In patients receiving a higher CD34+ cell count, time until platelets reached > 50/nl was shorter than in patients with a lower CD34+ cell count. Patients with > or = 2 pretreatment protocols had a higher infection rate than patients with < 2 pretreatments. Patients suffering from severe mucositis (WHO 3-4 degrees) exhibited a slower platelet recovery and a higher infection rate. No difference was noted in the complication rate for the other parameters (tumor diagnosis, age). CONCLUSION: Complication rate and mortality in this heterogeneous patient group were not different from the data of other authors describing selected patients receiving a uniform conditioning regimen or having a distinct disease. The complication rate is influenced by the number of pretreatment protocols, conditioning regimens and the number of transplanted CD34+ cells.

[Gene polymorphisms of hemostasis and coronary risk]. / Genpolymorphismen der Hämostase und Koronarrisiko.

Hemostatic disorders are substantially involved in the pathogenesis of coronary heart disease and acute coronary syndromes. In addition to biochemical markers, gene polymorphisms of hemostasis have been intensively studied in terms of their association with coronary risk. These include polymorphisms of the genes of platelet glycoproteins, fibrinogen, prothrombin, factors V, VIII and XIII, plasminogen activator inhibitor-1 and tissue-type plasminogen activator. An association of a certain gene polymorphism with an increased coronary risk has usually been demonstrated in retrospective case-control studies. However, numerous clinical studies have not yet been able to identify any of these polymorphisms as unequivocal risk factors of coronary heart disease or acute coronary syndromes. These inconsistencies are mainly due to the complexity of the pathogenesis of coronary heart disease and the minor contribution of a single polymorphism to total coronary risk. This review reports on essential requirements of future studies as a prerequisite to improve our understanding of the genetic basis of coronary heart disease.