Search

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Background: Data are lacking on the impact that the intensity of serial donor plasmapheresis has on the quality of source plasma. A study was conducted to examine the quality of source plasma produced by intensive plasmapheresis and slow deep-freezing and to compare it to source plasma manufactured by moderate plasmapheresis and rapid freezing.Study Design and Methods: Seventy-five plasma samples from intensive plasmapheresis programs (Group 1) and 75 plasma units from moderate plasmapheresis programs (Group 2) were examined. The plasma had been deep-frozen either slowly at -30 degrees C in walk-in freezers (Group 1) or rapidly within 1 hour to a core temperature below -30 degrees C (Group 2). Determinations were made of the plasma levels of citrate; total protein; albumin; IgG; fibrinogen; factors II, V, VII, VIII, and IX; vWF; antithrombin; protein C; D-dimers; and prothrombin fragments 1+ 2.Results: Plasma units of Group 2 contained substantially greater levels of citrate, IgG, FVIII, and FV than samples of Group 1 (p<0.0001). Plasma levels of total protein, albumin, and fibrinogen also were higher in Group 2 (p<0.0001, p = 0.007, and p = 0.006, respectively). Neither plasmapheresis intensity nor freezing procedure had any influence on the levels of factors II, VII, and IX, antithrombin, or protein C. There was no evidence of substantial coagulation activation in the plasma units of either group. However, higher FVIII clotting activity/chromogenic substrate activity ratios in rapidly frozen plasmas and a significant correlation between these ratios and prothrombin fragment 1+ 2 levels suggest that rapid freezing yields both more native FVIII and greater partial activation of FVIII.Conclusion: Source plasma collected from donors undergoing intensified plasmapheresis contains markedly lower levels of IgG than plasma units produced by moderate serial plasmapheresis. The combination of intensified plasmapheresis and slower freezing of source plasma results in substantially lower levels of FV and FVIII than does moderate plasmapheresis with rapid freezing. Prospective studies should establish the optimum conditions required for the safe and economic production of source plasma for fractionation. [ABSTRACT FROM AUTHOR]

A response by H. Haubelt, C. Anders, A. Vogt, P. Hoerdt, U. T. Seyfert and P. Hellstern to a letter to the editor about their article "Variables Influencing Platelet Function Analyzer 100TM Closure Times in Healthy Individuals," in the 2005 issue is presented.

Objectives: Differences in pre-analytical and assay conditions, inappropriate reference ranges, or inflammation may have the potential to impair clinical decisions based on measurements of factor VIII (FVIII), von Willebrand factor (VWF) and fibrinogen (Fg). This study examined the impact on FVIII, VWF and Fg in plasma of freezing and thawing, different citrate anticoagulant concentrations, and inflammation, as determined by high-sensitivity C-reactive protein (hsCRP)., Materials and Methods: FVIII was determined prior to freezing and after thawing using a one-stage clotting assay (FVIII:C), an amidolytic assay (FVIII:AM) and an enzyme immunoassay (FVIII:Ag). Samples were anticoagulated with 106 or 129 mmol/L of citrate. FVIII, VWF and Fg were quantified in 300 individuals to establish reference ranges and to investigate associations with hsCRP., Results: Freezing and thawing reduced FVIII:C and FVIII:AM markedly. FVIII coagulant activities were not significantly different between samples anticoagulated with 106 or 129 mmol/L of citrate, respectively. FVIII, VWF and Fg were significantly associated with hsCRP. FVIII:C was greater than FVIII:AM and FVIII:Ag in all experiments, indicating that the presence of activated FVIII may lead to overestimation of FVIII:C., Conclusions: Standardized freezing and thawing of plasma samples appears to be indispensable if reliable FVIII results are to be obtained. Because inflammation can potentially mask deficiency states or mimic an increased risk of thrombosis, FVIII, VWF and Fg determinations should be supplemented by measurements of hsCRP., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

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.

Aspirin resistance continues to be a major challenge in patients after coronary artery bypass grafting (CABG). We investigated the impact of intravenous aspirin on platelet function in this clinical setting. Forty-two patients received 100 mg of oral aspirin once daily, beginning on day 1 after the operation. Between day 6 and 8 post operation one oral dose was replaced by an intravenous dose of 300 mg. Platelet function analyzer (PFA-100) closure times (CT), turbidimetric platelet aggregation (TPA) and impedance platelet aggregation (IPA) induced by arachidonic acid (AA), collagen and ADP were measured prior to and 1 h and 24 h after intravenous aspirin. Results obtained prior to the intravenous aspirin were compared with respective values from 120 healthy individuals. Despite the postoperative oral aspirin that was given once daily, ADP-induced TPA (ADPTPA) and IPA values induced by AA, ADP or collagen were significantly greater in patients than in controls, while PFA-100 CT were significantly shorter. Intravenous aspirin induced a significant reduction of platelet aggregability as measured by collagen/epinephrine (CEPI) CT, TPA and IPA induced by AA and collagen 1 h and 24 h after administration. Intravenous aspirin was not found to influence collagen/ADP (CADP) CT and IPA induced by ADP. Concomitantly, the number of patients with laboratory aspirin resistance as measured by CEPI-CT and TPA but not by IPA induced by AA or collagen dropped significantly. Agreement in the detection of aspirin responders and non-responders among platelet function tests was poor. Our findings indicate that the intravenous aspirin appears to be a promising approach for reducing laboratory aspirin resistance during the postoperative phase of CABG.

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.

The clinical significance of platelet function tests may be limited by the use of citrate anticoagulant. We examined the influence of BAPA, a dual inhibitor of factor Xa and thrombin, on platelet responsiveness to agonists when measured between 2 and 48 h after venipuncture. Blood samples from 24 healthy individuals were anticoagulated with citrate or BAPA. Impedance platelet aggregation (IPA) and adenosine triphosphate (ATP) release induced by ADP, collagen and thrombin-receptor activating peptide (TRAP) were determined in whole blood after a storage period between 2 and 48 h after venipuncture. Citrate resulted in significantly reduced collagen or TRAP-induced IPA and ATP release when measured 32 h and 48 h after blood collection. ADP-induced IPA and ATP release in citrated blood dropped significantly between 8 and 24 h. The length of storage of BAPA-anticoagulated blood samples over 48 h had no significant influence on platelet response to collagen and TRAP. In BAPA-anticoagulated blood, ADP-induced IPA and ATP secretion in whole blood were maintained over a storage period of 32 h. No difference in ADP-induced ATP secretion in whole blood anticoagulated with citrate and BAPA was observed, but it was largely suppressed in BAPA-anticoagulated platelet rich plasma. IPA and ATP release remain stable for at least 32 h when whole blood is anticoagulated with a dual inhibitor of factor Xa and thrombin. This would allow shipment of samples for platelet function testing on the following day. Platelet secretion studies in whole blood may include platelet activation by ADP when BAPA is used as anticoagulant.

This report describes a case where a continuous lumbar epidural anesthesia was inserted for an operation in a patient with classical hemophilia which was unknown at the time of catheter insertion. In addition to an exact description of the intervention, the anamnesis and laboratory contraindications for epidural anesthesia are discussed. Furthermore, the necessity of preoperative investigations and their value when an epidural anesthesia is planned are also discussed.

We investigated the relationship between impedance platelet aggregometry (IPA) as measured by the Multiplate system and turbidimetric platelet aggregation (TPA) induced by ADP, arachidonic acid (AA), and collagen; blood cell counts; platelet function analyzer (PFA-100) closure times (CT), and von Willebrand factor (VWF) in 120 well-characterized healthy individuals. Pre-analytical and analytical conditions were standardized comprehensively. Analytical reliability of IPA and TPA and the influence of pre-analytical variables on assay results were also examined. IPA and TPA did not change significantly between 0.5 and 5 hours after blood collection when samples were stored at room temperature. TPA and IPA showed significantly greater intra-assay imprecision than respective TPA induced by the same agonists. Intra-individual variation did not differ significantly between IPA and TPA. The lower limits of reference range (2.5th percentiles) of AAIPA, ADPIPA and collagen IPA determined AM were 37, 20 and 40 AU, respectively. ADPIPA showed significantly lower maximum aggregation values than AAIPA and collagen IPA (P < 0.0001). There were no significant differences in any parameter between males and females. No significant differences between blood group 0 and non-0 individuals were noted with respect to IPA and TPA. IPA did not change significantly during the day. In contrast, TPA measured PM was significantly lower than corresponding values determined a.m. (p < 0.0001). CEPI-CT, CADP-CT and leukocyte counts increased significantly from a.m. to p.m. (P = 0.008 and P > 0.0001, respectively). Donors had significantly greater IPA induced by any agonist than non-donors (P-values < 0.0001, 0.0001 and 0.001, respectively), whereas TPA was not significantly different between donors and non-donors. IPA did not correlate significantly with TPA nor with PFA-100 CT. ADPIPA and collagen IPA correlated significantly with platelet count. TPA was not associated with platelet count. An inverse significant correlation was observed between TPA induced by any agonist and leukocyte count, whereas leukocyte count did not influence IPA. CEPI-CT and CADP-CT correlated significantly with VWF:CBA and with each other but not with TPA. We concluded that IPA and TPA measure different aspects of platelet function. IPA results reflect interactions between platelets, red and white cells, while TPA does not. This explains discrepancies in associations of IPA and TPA with cell counts, time of day and blood donation. The clinical significance of IPA determined using the Multiplate device remains to be determined in studies on patients with platelet dysfunction and under treatment with antiplatelet agents.

We investigated the relationship between platelet function analyzer (PFA-100) closure times (CT) and bleeding time (BT), platelet aggregation (PA) induced by ADP, arachidonic acid, and collagen, blood cell counts, and von Willebrand factor (VWF) in 120 well-characterised healthy individuals. Pre-analytical and analytical conditions were standardised comprehensively. In a substantial number of cases the differences between duplicate measurements exceeded 15%. The reference range (5th and 95th percentiles) for CT with the collagen/epinephrine (CEPI) and the collagen/ADP (CADP) cartridge was 93-223 s and 64-117 s respectively. Re-examination of 11 individuals with CEPI-CT above the 95th percentile revealed considerable batch-to-batch variation of CEPI-CT. Males had significantly longer CADP than females (P = 0.002). CEPI and CADP-CT measured pm were significantly longer than corresponding values determined am (P = 0.003 and P < 0.0001 respectively). Blood group O was associated with greater CEPI and CADP-CT and lower VWF levels compared with non-O blood groups (P = 0.008, P = 0.0003 and P < 0.0001 respectively). Linear regression analysis revealed association between CEPI-CT, CADP-CT and VWF (P < 0.0001), but no relationship was found between CT and BT or between CT and PA. We conclude that VWF plasma levels modulate PFA-100 CT to a greater extent than platelet function. Establishment of reliable reference ranges and careful standardisation of pre-analytical and analytical conditions is a prerequisite for obtaining reliable PFA-100 results. Duplicate measurements are necessary.

We investigated the relationship between factor XIII, fibrinogen, blood coagulation screening tests and postoperative bleeding in 98 patients undergoing cardiopulmonary bypass (CPB) surgery. All patients received aprotinin. Blood samples were collected preoperatively (T1),after termination of CPB (T2),12 h (T3) and 24 h (T4) after surgery to determine FXIII activity, fibrinogen, platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT) and D-dimers (DD). Laboratory results were correlated with the chest tube drainage 24 h after surgery and compared between patients with 24-hour chest tube drain volumes in the lower (Group 1) with those in the upper tertile (Group 3). Median FXIII and fibrinogen levels dropped by 33.9% and 34.2%, respectively, during CPB. No association between FXIII activity and the extent of postoperative bleeding was found. However, chest tube bleeding was significantly correlated with preoperative and postoperative fibrinogen. This was confirmed by comparing Groups 1 and 3. Group 3 patients had significantly lower fibrinogen levels than Group 1 at T1 - T4, although most fibrinogen values were within or above the reference range (medians, g/l: 3.5 vs. 4.0, p = 0.043 at T1; 2.3 vs. 2.7, p = 0.015 at T2; 2.9 vs. 3.3, p = 0.008 at T3; 4.2 vs. 5.2, p = 0.002 at T4). There was also a significant relationship of platelet count, PT and APTT, as measured after CPB (T2), with postoperative chest tube drainage. In conclusion, plasma FXIII activity does not influence postoperative bleeding in patients undergoing CPB surgery. There is however an inverse association between preoperative or postoperative plasma fibrinogen levels and postoperative bleeding. These findings indicate a modulation of postoperative bleeding by fibrinogen levels.

Background: There exists a current lack of information about the composition of the different types of plasma. No direct comparisons between apheresis plasma (AP) and recovered plasma (RP) derived from in-line-filtered whole blood (WB) have been published to date., Study Design and Methods: Sixty AP units, 100 RP units from in-line-filtered WB held for 3 hours at 20 degrees C between donation and freezing, and an additional 100 RP units held for 15 hours at 20 degrees C before freezing were analyzed for coagulation factors and inhibitors, total protein, immunoglobulin G (IgG), and hemostasis and proteolysis activation markers. The influence of twice freezing and thawing on clotting factors V, VIII, and XI was also examined., Results: AP contains substantially greater activities of factor (F) V, FVIII, F IX, and FXI than RP frozen within 3 hours after WB donation. Prolonged holding of RP at 20 degrees C for more than 15 hours caused an additional reduction in FVIII, FXI, and protein S activities. Significantly greater levels of prothrombin fragments 1 and 2, platelet factor 4, and neutrophil elastase were found in RP compared with AP. IgG was lower in AP compared with RP. Twice freezing and thawing caused a marked drop in FV, FVIII, and FXI activity., Conclusion: Higher FVIII and F IX potencies in AP compared with RP can be expected to result in greater yields when used for purification of these clotting factors. AP is presumably more efficient than RP for treating coagulopathies. RP, however, may contain higher IgG levels than AP.

"Aspirin resistance" and "aspirin nonresponsiveness" are terms used both to describe both the failure of aspirin to protect subgroups of individuals from severe vascular events and to evoke an appropriate inhibition of platelet function. Several studies utilizing a broad range of platelet function tests have shown that some subgroups of individuals exhibit a reduced or completely missing antiplatelet response to aspirin. The clinical significance of aspirin nonresponsiveness for the prediction of clinical endpoints remains, however, to be determined. Thus far, only three prospective clinical trials have demonstrated a possible relationship between aspirin nonresponsiveness and subsequent vascular events. Most platelet function tests used in respective clinical studies cannot be reliably performed in clinical routine and are not interchangeable for monitoring antiplatelet treatment. 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 developed assays, including the PFA-100 system, are presently able to accomplish these objectives.

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.

Background: Previous studies in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) have restricted laboratory monitoring to the activated clotting time (ACT). It remains unknown whether the ACT-prolonging effect of abciximab is clinically equivalent to a comparable degree of anti-coagulation by heparin., Patients and Methods: 30 patients undergoing PTCA received 100 IU of heparin/kg body weight. Another 30 patients received an initial bolus of 70 IU of heparin/kg + abciximab. We determined ACT, laboratory and onsite activated partial thromboplastin time (APTT) and plasma heparin levels., Results: Despite markedly different preintervention heparin dosing, the ACTs were not significantly different between groups. After termination of PTCA, the median ACTs of both study groups were nearly equivalent (267 vs. 272 s; p = 0.79). The median ACT-prolonging effect of abciximab could be equated with 0.68 IU/ml heparin. Both APTT assays were not suitable for monitoring the anticoagulant effects during PTCA due to their high sensitivity. By contrast, the plasma heparin levels clearly reflected the different heparin doses. The weak correlation (r = 0.23) between ACTs and heparin levels in patients receiving heparin + abciximab was due to excessively prolonged ACTs in six patients (540-1,245 s). These data could be attributed to an unusually high response to abciximab. By contrast, the ACT was a reliable measure of the anticoagulant effect of heparin in patients receiving exclusively heparin., Conclusions: ACT reflects both heparin and abciximab therapy, whereas heparin levels reflect only heparin dose. The APTT assays were not suitable for monitoring the anticoagulant effects during PTCA.

Thrombophilic disorders and hypofibrinolysis were demonstrated to be risk factors in a majority of women with recurrent pregnancy loss (RPL) and infertility. We investigated the association of FV G1691A mutation, F II G20210A gene polymorphism (PM), 4G/5G PAI-1 and Alu I/D tPA PM in 32 women with infertility and 49 women with at least 2 unexplained early abortions. FV Leiden mutation was significantly more common in women with RPL (10%, p = 0.02) and infertility (19%, p = 0.0005) compared with controls (2%). PAI-1 4G PM and t-PA Alu I PM, alone or in combination, were not associated with RPL or infertility. 9/49 women with RPL showed coagulation disorders with heterozygous FV Leiden mutation (5), FXII (1), protein C (1) or protein S (2) deficiency. However, due to the small number of patients studied, no definite conclusion can be drawn., (Copyright 2003 S. Karger AG, Basel)

Background: Iron (Fe) depletion is common among regular whole-blood donors, but can be prevented through regular oral Fe supplementation. Little is known, however, about the Fe metabolism of donors undergoing intensive plasmapheresis. These donors lose considerable amounts of blood drawn for laboratory analyses and remaining in the disposable plastic sets., Study Design and Methods: Menstruating women were enrolled in a prospective placebo- controlled double-blind study. One hundred women were randomly allocated to receive either 100 mg of elemental Fe per day or placebo over 24 weeks and asked to donate plasma at 1-week intervals. Hb was determined before each plasmapheresis. Ferritin, transferrin, and Fe concentration and reticulocyte count were measured every 4 weeks., Results: Thirty donors in the placebo group and 29 receiving Fe completed the study. The total mean blood loss was 526 mL in the placebo group and 546 mL in the Fe arm (p=0.271). The number of donations with Hb values lower than 12.5 g per dL requiring prolongation of the time interval until the next plasmapheresis was significantly greater in the placebo arm. In the placebo group (n=30), ferritin levels began to decline significantly 4 weeks after entry. When the study was completed, Hb concentration and reticulocyte count also were found to be significantly lower in the placebo group than in the Fe study arm (p=0.028 and p=0.036, respectively). Hb, ferritin, and transferrin levels and reticulocyte counts did not change significantly in the Fe group during the observation period., Conclusion: Menstruating women undergoing regular plasmapheresis at short intervals are prone to develop Fe depletion. This can be prevented by regular Fe intake. Laboratory analyses in product plasma instead of serum gained from whole-blood samples could be an alternative to reduce blood loss.

The initial aim in massive transfusion (MT) is to supply crystalloids, colloids, and plasma-poor red cell concentrates (RCCs) to maintain normovolemia and oxygen supply. This frequently leads to dilution coagulopathy, which is frequently aggravated and accelerated by hypothermia, acidosis, shock-induced impairment of liver function and disseminated intravascular coagulation (DIC), and increased consumption of clotting factors and platelets at extensive wound sites. Disorders of hemostasis deteriorate the prognosis of massively transfused patients dramatically. Therefore, the second therapeutic objective is the timely administration of plasma and platelet concentrates as required to halt the microvascular bleeding (MVB) induced by impaired hemostasis. Close laboratory monitoring, to include as a minimum platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen, is essential to identify hemostatic disorders requiring therapeutic intervention. Coagulopathy promoting microvascular bleeding can be assumed when PT or APTT values exceed 1.5 times mean controls and/or when fibrinogen levels fall below 1.0 g/l. Repeated rapid infusion of 10-15 ml plasma per kg of body weight will be required to raise clotting factor levels significantly and to achieve adequate hemostasis. The turnaround time for obtaining laboratory results and for readying plasma for transfusion must be taken into particular consideration in cases of rapid blood loss.

The clinical efficacy of the therapeutic plasma used in the treatment of congenital and acquired severe coagulopathy depends on the potency of clotting factor and inhibitor activities. The composition of plasma strongly depends on the conditions under which it is produced. A low citrate anticoagulant-to-blood ratio, short intervals between donation and plasma separation and rapid freezing markedly improve the preservation of unstable coagulation factors. The influence of different leukocyte reduction filters on plasma quality still requires clarification. Recent trials on long-term storage conditions suggest that keeping plasma at -30 degrees C or colder over a period of 24-36 months prevents substantial decrease in clotting factor activities including factor VIII (FVIII). Three types of therapeutic plasma are currently available. Quarantine-stored fresh frozen plasma (FFP) contains physiological activities of therapeutically relevant plasma proteins, but carries a risk of transmitting blood-borne viruses that cannot be detected by human immunodeficiency virus (HIV) and hepatitis B and C screening. In contrast, solvent/detergent-treated plasma (SDP) and methylene blue/light-treated plasma (MBP) is virtually free of HIV and hepatitis C virus (HCV) subtypes. Virus inactivation procedures can have the consequence of reducing several clotting factors and inhibitors in SDP and MBP to varying degrees. However, pooling of plasma units before solvent/detergent (SD) treatment results in well-standardized protein levels of SDP. At least five prospective trials and four observational studies covering different clinical settings suggest that SDP and FFP do not substantially differ in their clinical efficacy or in their tolerance. By way of contrast, there is a lack of data about the clinical efficacy and tolerance of MBP compared to FFP.

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.