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Biomedical subjects

M Böck

Publications and source records attributed to M Böck.

At least 19 recordsLinked to original sources

Platelet concentrates derived from buffy coat and apheresis: biochemical and functional differences.

Today, platelet concentrates are generally produced from whole blood by differential centrifugation (buffy coat-derived platelet concentrates--PCs) or by plateletpheresis (apheresis-derived platelet concentrates--APCs). As PCs are characterized by a lower number of platelets than APCs, four to six PCs are customarily combined in order to obtain an equivalent dose. In the 1970s and 1980s, the use of PCs exceeded that of APCs by far; in contrast, since the beginning of the 1990s, APCs comprise more than half of all transfused platelets. However, the selection of PCs or APCs for transfusion to thrombocytopenic patients is still a matter of debate. The present paper compares biochemical and functional properties of both platelet preparations in vitro. Besides plasma parameters (e.g. platelet factor 4 (PF4), P-selectin, C3a-desarginin, plasma coagulation factors), platelet function was analysed by aggregometry and the PFA 100 system. APCs are characterized by a better preservation of ADP and collagen-induced platelet aggregation, and shorter closure times of the PFA 100 test system during storage. The improved primary in vitro haemostatic capacity of APCs is presumed to be owing to a lower cellular activation rate in these preparations. This hypothesis is supported by the higher plasma concentrations of PF4, beta-thromboglobulin and P-selectin found in PCs compared with APCs. The concentrations of C3a-desarginin in PCs exceed those in APCs by far. Additionally, thrombin generation is higher in PCs than in APCs. These data suggest that APCs are characterized by a superior haemostatic capacity over PCs in vitro. However, in vivo studies should be performed to confirm these findings in the patients' circulation also.

Biomarkers↗

Can a coated Dacron vascular graft maintain a heparin-induced thrombocytopenia type II?

In the course of reconstruction of peripheral arterial occlusion processes, two gelatin-coated Dacron grafts and one collagen-coated Dacron patch were implanted in a 52-year-old male patient. Eight days following low-dose heparinization (5 days prior to surgery, 3 days postoperatively) with unfractionated heparin, with no clinical symptoms present, a dramatic isolated thrombocyte depression occurred, from 212 Gpt/l prior to surgery to 14 Gpt/l on postoperative day 3. Laboratory tests verified an HIT type II [heparin-induced platelet aggregation assay (HIPAA) and ELISA]. Despite immediate discontinuation of heparin and commencement of an anticoagulant therapy with Revasc and Refludan, an 8-week thrombocyte depression occurred which was eliminated only temporarily by administration of gammaglobulin. The specific antibody tests turned out positive for more than 5 months. Having ruled out other causes of thrombocytopenia, we assume that the case presented was either due to an interaction not elucidated to date or triggered by the grafts (gelatin/collagen/Dacron). The manufacturers of the grafts have disputed a heparinoid action.

Arterial Occlusive Diseases↗

[Significance and incidence of type II heparin-induced thrombocytopenia. A prospective study].

AIM: The incidence of heparin-induced thrombocytopenia (HIT type II) as a consequence of postoperative thrombosis prophylaxis after hip or knee prosthesis was investigated in this study. Furthermore the platelets count was postoperatively analysed in patients without HIT II. PATIENTS AND METHODS: Patients with knee and hip prosthesis were included in a prospective study during an 8 months period. All patients received 3 x 5,000 Liquemin (Hoffmann-LaRoche) from the day of the operation until discharge. In cases with a platelet count drop of more than 40% and in patients with clinically manifest thrombosis or embolism a HIT type II test was initiated. RESULTS: 5 of 252 patients included in this study developed a HIT type II. The platelet count drop was on average 65.7% (40.9-81.6). One patient died of a lung embolism (lethality 20%). Four patients were treated with Hirudin and 1 patient with Danaproid-Natrium. There was no drop of the platelet count between the 5th and 7th postoperative day of more than 15% in the other patients without HIT type II. CONCLUSION: In operative departments not enough attention is paid to HIT type II. Knowing the risks with an appropriate monitoring HIT type II can be early detected. Under these conditions the advantages of a heparin prophylaxis outweigh the risk of developing a HIT type II with it's life threatening sequelae.

Aged↗

[Heparin-induced thrombocytopenia type II: reexposure to heparin].

HISTORY AND ADMISSION FINDINGS: At the age of 55 years a now 70-year-old man had his aortic valve replaced by a prosthetic (Björk-Shiley) valve, and 11 years later a VDD pacemaker had been implanted. 18 months before the latest admission he had been hospitalized for treatment of staphylococcal endocarditis involving the aortic prothesis. At that time thrombocytopenia developed during heparin administration, diagnosed clinically and with the heparin-induced platelet activity (HIPA) test as type II heparin induced thrombocytopenia. His latest admission was for the diagnosis and treatment of peripheral arterial disease of the right leg (Fontaine stage IIb). INVESTIGATIONS: Right popliteal and pedal pulses were not palpable. He was able to walk pain-free for only 70 m. Doppler sonography demonstrated an arm-leg index on the right of 0.7. Angiography revealed marked stenosis in the right superficial femoral artery and a filiform stenosis in the right popliteal artery. TREATMENT AND COURSE: Both stenoses were relieved by percutaneous transluminal balloon angioplasty, in the course of which 5000 IU heparin were administered as a bolus intraarterially. Postoperative anticoagulation was maintained for 2 days with recombinant hirudin. There was no evidence of platelet reduction or heparin-induced antibodies despite the renewed infusion of heparin. CONCLUSION: Single re-administration of heparin in a patient who had developed a type II heparin-induced thrombocytopenia several years before does not necessarily lead to a booster of antibodies and thus to a reduction of platelets in the peripheral blood. It is a moot point whether the course in this case was an exception or the rule.

Aged↗

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

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

Aged↗

Standardization of the PFA-100(R) platelet function test in 105 mmol/l buffered citrate: effect of gender, smoking, and oral contraceptives.

The PFA-100(R) (PFA) diagnostic system for the detection of platelet dysfunction was evaluated to determine reference ranges in a normal population. The PFA determines the primary haemostasis capacity (PHC) of anticoagulated whole blood, expressed by the system's closure time (CT). In this study the CT reference ranges were determined for blood samples collected in 105 mmol/l (3.2%) buffered citrate and the effect of gender, smoking, and use of oral contraceptives on reference ranges was assessed. Each of the 309 healthy blood donors from five blood centres was confirmed to have normal platelet function before inclusion in the study. Blood samples were tested in duplicate with both the collagen/epinephrine (Col/Epi) and collagen/ADP (Col/ADP) test cartridges. PFA reference ranges (90% central intervals of measured closure times) for both cartridge types were similar for all groups. Subgroup analysis showed that neither gender nor oral contraceptive usage had any effect on PHC. The 95% cut-off value for the Col/Epi CT was slightly higher for smokers than for non-smokers, an effect more pronounced in female than in male donors. However, the small difference did not justify establishment of specific reference ranges for smokers. Data from all included subjects were pooled to calculate the CT reference ranges for blood samples collected in 105 mmol/l buffered citrate (Col/Epi 82-150 s; Col/ADP 62-100 s). Normal levels of fibrinogen, as well as normal platelet counts and normal haematocrit levels, appeared not to influence the PHC. Because slight but significant differences of the reference ranges were observed between some of the participating sites, in-house confirmation of these reference range guidelines is recommended.

Adolescent↗

Transforming growth factor beta is increased in plasma of patients with hematologic malignancies after transfusion of platelet concentrates.

BACKGROUND: Transforming growth factor beta 1 (TGF-beta 1) acts as a potent inhibitor of bone marrow proliferation. High concentrations were found in human platelets, which release this cytokine during storage. STUDY DESIGN AND METHODS: TGF-beta 1 levels during a storage period of 5 days were compared in the plasma of platelet concentrates prepared by apheresis or by the buffy coat method. In addition, TGF-beta 1 plasma levels were monitored in patients with hematologic malignancies before and after transfusion. RESULTS: TGF-beta 1 levels in the supernatant of platelet concentrates were found to be 55 times higher than those in the plasma of healthy volunteer donors. During storage, an additional increase was observed. Accordingly, the transfusion of platelet concentrates resulted in a significant increase of plasma TGF-beta 1 levels in patients with hematologic malignancies (before transfusion: 2.2 +/- 0.5 ng/mL; after transfusion: 2.9 +/- 0.6 ng/mL), and these higher levels persisted for at least 4 hours. CONCLUSION: Because TGF-beta 1 reduces the clonogenic capacity of hematopoetic progenitor cells, a myelosuppressive effect of platelet transfusions is suggested.

Adult↗

[Morphologic and functional changes in thrombocytes after deep freezing with DMSO].

BACKGROUND: During the past decade much work has been carried out towards establishing the optimum method for cryopreservation of platelets. Among the various cryoprotectants dimethyl sulfoxide (DMSO) has been shown to be the most effective. This report describes ultrastructural and functional changes of platelets during the deep-freezing process with DMSO. MATERIALS AND METHODS: Single-donor platelet concentrates were cryopreserved in liquid nitrogen by use of DMSO. Before, during and after the freezing process samples were taken for analysis of ultrastructure and platelet function. RESULTS: While after isolation and addition of DMSO a normal ultrastructure of platelets could be observed, clear signs of beginning cell necrosis were detected after thawing and resuspension in autologous plasma. Fibrinogen-binding capacity and platelet aggregation were significantly diminished. CONCLUSIONS: Although cryopreserved platelets are characterized by hemostatic effects in vivo, it seems conceivable that these effects could be improved by further development of platelet-freezing techniques.

Blood Platelets↗

[Cryopreservation of erythrocytes: detailed quality control].

It has been well established that cryopreservation of red cells with glycerol is a suitable method for long-time storage. Therefore, many data for quality control have been published. Most measurements, however, are restricted to the final product. Less information is available about the particular steps of cryopreservation. The present paper describes in detail the results of quality control measurements during the procedure. Although the final product meets the demand of the WHO for cryopreserved red cells, it could be demonstrated that erythrocytes are remarkably damaged by the deep-freezing process. Further experiments seem to be necessary in order to improve the details of the deep-freezing procedure.

Blood Preservation↗

[Leukocyte depletion of blood products. Indications and technical implementation].

Leukocytes contaminating donated blood are considered to be responsible for many of the side effects associated with blood transfusions. These include HLA sensitization and its sequelae, as also graft versus host reaction, transmission of CMV. The present article summarizes the indications for leukocyte depletion and its technical execution.

Blood Component Transfusion↗

Quality control of platelet concentrates by the Thrombostat 4000.

Quality control of platelet concentrates (PC) is an important prerequisite for good transfusion praxis. However, direct measurement of platelet function is complex, since available methods (e.g. aggregometry, serotonin release) are time consuming and require special equipment. Therefore a test system is needed, which is easy to handle, fast, and achieves reliable results. The present paper compares the results of conventional platelet function tests with those of a modified in-vitro bleeding test (IVBT) (Thrombostat 4000) in liquid-stored and cryopreserved PCs. A high correlation between aggregometry, serotonin release, GMP 140 expression upon stimulation, and IVBT was demonstrated. Therefore IVBT seems to be a good alternative to the conventional platelet function tests for quality control of PCs. In addition, a good correlation between the results of IVBT of patients' blood after PC transfusion and IVBT of patients blood before transfusion supplemented with platelets of the respective PC could be found. Therefore IVBT seems to be able to predict PC transfusion success. However, since these data were obtained in a small sample undergoing bone marrow transplantation, further studies are needed to verify this hypothesis.

Bleeding Time↗

[Post-transfusion rise in thrombocytes: observations in a hematologic-oncologic patient sample].

OBJECTIVE: Aim of the present analysis was the evaluation of clinical conditions and product-specific parameters influencing posttransfusion platelet increment. DESIGN: 400 single-donor platelet transfusions were analyzed for patient- and concentrate-specific factors influencing posttransfusion platelet increment. Statistical analysis was performed by the General Mixed Model Analysis of Variance. SETTING: Department of hematology and oncology at a university hospital. PATIENTS: 46 patients (24 male, 22 female; age 17-80 years). INTERVENTIONS: Single-donor platelet transfusions. RESULTS: As demonstrated earlier, splenomegaly, body temperature, and bone marrow transplantation could be proven as factors reducing posttransfusion platelet increment. In addition, hepatomegaly and application of antibiotics had negative effects on platelet increment. Among the product-specific parameters leukocyte contamination and pretransfusion storage time reduced transfusion success significantly. CONCLUSIONS: Clinical factors influencing posttransfusion platelet increment can hardly be controlled. In contrast, concentrate-specific parameters can be influenced by preparation technique and storage procedure. Therefore, high value should be set on low leukocyte contamination and short pretransfusion storage time of platelet concentrates.

Adolescent↗

Complement activation during storage of single-donor platelet concentrates.

Single-donor platelets are stored up to 5 days prior to transfusion. Since contact of plasma to plastic surfaces may lead to complement activation, we investigated whether there is any increase in the complement factors C3a, C4a and C5a in routinely stored single-donor platelet concentrates. C3a levels increased about 40-fold during a 7-day storage. C4a levels also increased with storage time but to a lesser extent. By contrast, C5a levels remained stable throughout this period. ADP- and collagen-induced aggregation was impaired after storage of platelets, indicating severe functional injury. In platelet-poor plasma stored under identical conditions a comparable increase in C3a and C4a concentrations was observed. The loss of platelet function during storage might at least in part be due to the excessive anaphylatoxin concentrations observed.

Blood Donors↗

[Quality control of stored platelet concentrates by means of flow cytometry].

Storage of single-donor platelets is currently limited to 5 days. During this period, however, numerous morphologic and biochemical changes have been observed. The present study describes increased binding of anti-GMP 140 to stored single-donor platelet concentrates; this reveals a progressive activation process. In contrast, when stored platelets are stimulated with ADP, GMP 140, expression is reduced indicating a diminished release reaction. Additionally, the GP IIb/IIIa receptor complex and its fibrinogen-induced binding site (LIBS1) are reduced by storage time, demonstrating a diminished fibrinogen binding. Further experiments have to clarify whether these changes observed in vitro translate into a reduced hemostatic capacity after transfusion in vivo.

Blood Donors↗

[Post-transfusional platelet increment: effect of clinical factors].

The results of platelet transfusions depend upon a variety of different conditions; besides alloimmunization, a lot of clinical factors are responsible for transfusion success. The present paper tries to work out clinical findings, which are related to successful or unsuccessful platelet transfusions. The following criteria could be identified to influence posttransfusion platelet increment: hepatomegaly, splenomegaly, diagnosis, antibiotics, number and time of previous platelet transfusions. AB0 compatibility, pretransfusion storage time and leucocyte contamination. Therefore, in platelet transfusion therapy a high value should be set on AB0 compatibility, brief storage time and low leucocyte contamination, since these parameters--in contrast to the other influencing factors--can easily be controlled.

Adolescent↗