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Biomedical subjects

H J Weiss

Publications and source records attributed to H J Weiss.

At least 109 records · Page 6Linked to original sources
PubMed1978

Effect of shear rate on platelet interaction with subendothelium in citrated and native blood. I. Shear rate--dependent decrease of adhesion in von Willebrand's disease and the Bernard-Soulier syndrome.

Previous studies have demonstrated impaired adhesion of platelets to the subendothelium in von Willebrand's disease. These studies were performed by circulating (in a closed system) citrated whole blood through a chamber containing everted segments of rabbit aorta from which the endothelium had been removed by balloon catheter. The average wall shear rate was 800 sec-1, and the perfusion time was 10 min. In the present study we measured the interaction of platelets with subendothelium in native (nonanticoagulated) blood, using a recently described technique in which the vessel segments are perfused with directly sampled venous blood. The system was open; that is, the blood was not recirculated. We used blood flow rates of 20, 40, and 50 ml/min, which correspond to calculated shear rates of 1300, 2600, and 3300 sec-1 and perfusion times of 3, 2, and 2 min, respectively. For comparison, parallel studies at 1300 sec-1 were also obtained with citrated blood. In normal subjects, at a shear rate of 1300 sec-1, platelet adhesion was less in native blood than in citrated blood, but thrombus formation was greater. Platelet adhesion in five patients with von Willebrand's disease was decreased in both citrated and native blood. The magnitude of the adhesion defect was strongly dependent on the shear rate. Thus, in citrated blood studied at a shear rate of 1300 sec-1, adhesion was 75% less than in normal subjects, whereas in previous studies at 800 sec-1 the reduction in adhesion was 29%. In native blood, adhesion in von Willebrand's disease was normal at a shear rate of 1300 sec-1, whereas 53% and 77% reductions in adhesion were obtained at shear rates of 2600 and 3300 sec-1, respectively. The latter shear rates studied, adhesion of platelets in native blood was also decreased in the Bernard-Soulier syndrome but was normal in hemophilia and afibrinogenemia. Our findings with native blood provide further evidence that impaired adhesion of platelets to the vessel wall accounts for the hemostatic defect in von Willebrand's disease. In addition, this adhesion defect is shear rate-dependent.

Adolescent↗
PubMed1978

Phylogenetic studies with pemphigus and pemphigoid antibodies.

Indirect immunofluorescence (IF) studies were performed on skin from a variety of vertebrate specimens and IgG fractions from pemphigoid and pemphigus sera. Pemphigoid antigen was present in fish, amphibian, reptilian, avian and mammalian skin, whereas pemphigus antigen was observed in avian and mammalian skin only.

Animals↗
PubMed1977

Platelet interaction with collagen fibrils in flowing blood. II. Impaired adhesion-aggregation in bleeding disorders. A comparison with subendothelium.

Anticoagulated whole blood from patients and control subjects was circulated through an annular perfusion chamber in which the fibrillar collagen of alpha chymotrypsin-digested subendothelium and intact subendothelium were exposed. The blood flow conditions corresponded to those in arteries (830 sec-1 wall shear rate). Platelet surface interaction was measured morphometrically. Decreased adhesion to fibrillar collagen associated with normal spreading and normal adhesion-induced formation of platelet thrombi was found with blood of patients with von Willebrand's disease and the Bernard Soulier Syndrome, indicating a defect in the initial attachment reaction of platelets with collagen. Platelets of patients with thrombasthenia did normally adhere to the collagen fibrils and also lost their subcellular organelles during this reaction, but they totally failed to adhere to each other. In storage pool disease platelet thrombus formation was consistently inhibited whereas adhesion and spreading was inhibited in some patients and normal in others. In contrast adhesion was always normal after ingestion of aspirin which consistently caused a marked inhibition of platelet thrombi. These findings correspond -- in essence -- to those previously described on intact subendothelium. However, the observed defects are more pronounced on the fibrillar collagen than on intact subendothelium.

Animals↗
PubMed1977

Stabilization of factor VIII in plasma by the von Willebrand factor. Studies on posttransfusion and dissociated factor VIII and in patients with von Willebrand's disease.

In normal plasma, the ratio of the procoagulant activity of factor VIII (VIII(AHF)) to that of the von Willebrand factor activity (ristocetin cofactor, VIII(VWF)) or factor VIII antigen (VIII(AGN)) is approximately 1, but ratios > 1 (e.g., VIII(AHF) > VIII(VWF) or VIII(AGN)) may be observed in some patients with von Willebrand's disease and in the "late" posttransfusion plasmas of patients with this disorder. The lability of VIII(AHF) was studied by incubating plasma, diluted 1:10 in imidazole buffer pH 7.1, for 6 h at 37 degrees C. With normal plasmas, 77+/-12% (SD) of the original VIII(AHF) activity remained after incubation. VIII(AHF) was labile (e.g., 35-55% residual activity) in the "late" posttransfusion plasmas (VIII(AHF) >> VIII(VWF)) of a patient with von Willebrand's disease, but not in the "early" posttransfusion plasmas (VIII(AHF) approximately VIII(VWF)). VIII(AHF) was also labile in the (base-line) plasmas of three patients with von Willebrand's disease in whom the ratios of VIII(AHF) to VIII(VWF) were 4.4 to 8.1, but not in the plasmas of four other patients in whom the ratio was approximately 1. The electrophoretic mobility of factor VIII antigen was increased in two of the three patients with labile VIII(AHF). In both of these patients, and in the late posttransfusion plasmas, labile VIII(AHF) activity could be stabilized by the addition of purified von Willebrand factor (lacking VIII(AHF) activity) or by hemophilic plasma, but not by plasmas of patients with severe von Willebrand's disease. Thus, VIII(VWF) may serve to stabilize VIII(AHF) and this might explain the posttransfusion findings in von Willebrand's disease.

Blood Coagulation Factors↗
PubMed1976

Prostaglandin E2 potentiation of platelet aggregation induced by LASS endoperoxide: absent in storage pool disease, normal after aspirin ingestion.

Patients with storage pool disease and normal subjects who ingest aspirin show diminished collagen-induced platelet aggregation and an absent second wave of aggregation with ADP or adrenaline. These 'second-phase' aggregation responses are thought to be mediated by cyclic endoperoxide ('labile aggregation stimulating substance', LASS) that is derived from arachidonic acid and is the precursor of prostaglandin E2 (PGE2) and PGE2alpha. Furthermore, although PGE2 does not directly aggregate platelets, it markedly potentiates LASS-induced aggregation. The platelets of six patients with storage pool disease were capable of converting arachidonic acid to LASS, but the potentiation of LASS-induced aggregation by PGE2 was markedly diminished. In contrast, PGE2-potentiation of LASS aggregation was not reduced after aspirin ingestion. The effects of aspirin can be attributed entirely to its ability to block the enzymatic conversion of arachidonic acid to LASS and PGE2. These findings explain why a mutual correction of the aggregation defects is often seen when aspirin-treated platelets are mixed with storage pool-deficient platelets. This is because 'aspirin platelets' aggregate to the mixture of LASS and PGE2 produced by the storage pool-deficient platelets, which are themselves unresponsive. The findings in storage pool disease support previous conclusions that prostaglandin sensitization of platelets to the pro-aggregatory effects of LASS is an important factor in irreversible aggregation, and could be clinically important.

Adenosine Diphosphate↗
PubMed1976

Concentration-dependent dissociation of factor VIII in 1 M NaCl.

Plasma, cryoprecipitate, Hemofil, and human factor VIII concentrate were dissolved in 1.0 M NaCl and chromatographed on Bio-Gel A-5m. With high concentrations of factor VIII the activity eluted as a symmetrical peak in the void volume; with a low factor VIII concentration the procoagulant activity was retarded. Dilution curves were performed for several human factor VIII concentrates. When the concentration of factor VIII was decreased, elution patterns showed a gradual transition from a peak in the void volume to a peak with a Ve/Vo of 1.7. Cryoprecipitate exhibited a similar behavior in 1.0 M NaCl, but the percent dissociation was greater than expected at high concentrations of factor VIII. When gel filtration was performed with 0.25 M CaCl2, significant dissociation occurred at all concentrations of factor VIII tested. The behavior of factor VIII in 1.0 M NaCl closely fit a theoretically derived curve for the dissociation of a protein from its binder. We conclude that the dissociation of factor VIII in 1 M NaCl is dependent on the concentration and purification of the procoagulant protein.

Animals↗
PubMed1975

[Adhesion and aggregation in the subendothelium: hereditary platelet function disorder].

Platelet adhesion to a thrombogenic surface and adhesion-induced aggregation were investigated using a perfusion system at a blood flow rate similar to that observed in arteries. Morphometric measurements revealed diminished adhesion of platelets but normal surface-induced aggregation with blood of patients with von Willebrand's disease and with Bernard-Soulier syndrome. In contrast, surface-induced aggregation was defective with blood of patients with storage pool disease, thrombasthenia and with blood of healthy volunteers after Aspirin ingestion. These findings may explain the defective hemostasis in these patients. They suggest that platelet adhesion and aggregation are governed by different mechanisms.

Aorta↗
PubMed1975

Impaired interaction (adhesion-aggregation) of platelets with the subendothelium in storage-pool disease and after aspirin ingestion. A comparison with von Willebrand's disease.

Possible defects in the interaction of platelets with the subendothelial surface were evaluated in six patients with storeage-pool disease, nine patients with von Willebrand's disease and seven normal subjects who ingested aspirin. Citrated blood was perfused through a chamber containing everted segments of rabbit aorta previously denuded of endothelium by means of a ballon catheter. With normal blood, 83.3 +/- 1.9 per cent (S.E.M.) of the surface was covered by adherent platelets. Platelet adhesion was normal after aspirin ingestion (89.7 +/- 4.6 per cent) and decreased in some patients with storage-pool disease. The most striking defect in both circumstances was the virtual absence of platelet thrombi. In contrast, decreased adhesion (57.3 +/- 3.4 per cent), but normal thrombus formation, was characteristic of von Willebrand's disease. These types of defects in platelet adhesion and aggregation may account for the hemostatic defects in a variety of bleeding disorders. The findings further suggest the possible usefulness of aspirin as an antithrombotic agent.

Adenosine Diphosphate↗
PubMed1975

Abnormalities of factor VIII and platelet aggregation--use of ristocetin in diagnosing the von Willebrand syndrome.

Ristocetin was used to study platelet aggregation in platelet-rich plasma and to assay the von Willebrand factor activity of factor VIII (VIII-VWF). Ristocetin-induced platelet aggregation (RIPA) was decreased in 13 of 18 patients with von Willebrand's disease (VWD) who had decreased plasma levels of VIII-VWF. The five patients with normal RIPA appeared to have mild VWD but did not constitute a separate subclass. RIPA was also abnormal in some patients with intrinsic platelet defects, but in no case was the defect corrected by normal plasma. The latter type of correction appears to be specific for VWD. Aspirin ingestion inhibited the second phase of RIPA (at low concentrations of ristocetin only) but did not affect the initial phase of aggregation or the level of VIII-VWF. We also studied a group of patients who had both abnormalities of the factor VIII complex and intrinsic platelet defects, such as impaired collagen-induced aggregation, as well. The findings in these patients and in those with typical von Willebrand's disease appear to comprise a spectrum of disorders (the von Willebrand syndrome) in which some abnormality of the factor VIII complex is associated with impaired platelet function. At present, ristocetin would appear to be a useful reagent for evaluating patients with bleeding disorders and for studying patients with the von Willebrand syndrome.

Adenosine Diphosphate↗
PubMed1975

Metal ion contents of gel-filtered platelets from patients with storage pool disease.

Platelets from nine patients with storage pool disease (SPD) and from ten control subjects were isolated by gel filtration into a suspension medium permitting the direct determination of platelet Mg-2+, Ca-2+, and K+ levels. The total intracellular levels of ATP and ADP, as well as the incorporation patterns of 14-C-adenine into the metabolic nucleotide pool, were also determined in these platelet suspensions. The gel-filtered platelets (GFP) from SPD patients exhibited slightly lowered levels of ATP and substantially reduced amounts of ADP, in agreement with previous studies using PRP suspensions. Diminished aggregation responses to ADP, epinephrine, and to collagen in particular, similar to those observed previously in PRP, were obtained in GFP from SPD patients. However, GFP from the patients exhibited more variable aggregation responses to addition of ADP and epinephrine than did GFP from the control subjects. Increases in the extent of radioactive hypoxanthine formation, observed previously in normal platelets as a result of isolation into the suspension medium used in these studies, were significantly reduced in the GFP from SPD patients. The levels of platelet Mg-2+ and K+ determined in GFP from the patients were not significantly different from the levels of these ions in GFP from control subjects. However, substantial reductions in platelet Ca-2+ were found in the SPD platelets. A strong correlation was obtained between this reduction in platelet Ca-2+ and the reduction in ADP in these platelets. No such correlation was apparent between the ATP and Ca-2+ deficiencies. These results suggest that a major portion of platelet Ca-2+ may be located in the dense granules and support previous hypotheses that granular ADP and/or Ca-2+ may play a role in the release reaction. The finding of normal levels of platelet Mg-2+ and K+ in SPD platelets, however, suggests that these latter ions are not located in the dense granules.

Adenine↗