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Biomedical subjects

E C Lian

Publications and source records attributed to E C Lian.

At least 37 records · Page 2Linked to original sources
PubMed1989

Combination immunosuppressive therapy after factor VIII infusion for acquired factor VIII inhibitor.

STUDY OBJECTIVE: To evaluate the effectiveness of combined cyclophosphamide, vincristine, and prednisone (CVP) therapy after antigenic stimulation with factor VIII in the eradication of factor VIII inhibitor. DESIGN: Factor VIII activity and inhibitor titer were measured before and after FVIII-CVP therapy and patients with factor VIII inhibitor were followed for at least 2 years. SETTING: The first course of therapy was carried out in the hospital when nonhemophiliac patients were admitted for bleeding. Otherwise, treatment was administered at the outpatient clinic. PATIENTS: From 1975 to 1986 we studied 12 nonhemophiliac and 5 hemophiliac patients with factor VIII inhibitor treated with FVIII-CVP and followed at our clinic. INTERVENTION: Patients were infused with one dose of factor VIII concentrate, 50 to 100 U/kg body weight, followed by cyclophosphamide, 500 mg on day 1 and 200 mg/d on days 2 to 5; vincristine, 2 mg on day 1; and prednisone, 100 mg/d on days 1 to 5. This regimen was repeated every 3 to 4 weeks. RESULTS: Of 12 nonhemophiliac patients, 11 responded after 1 to 3 courses of FVIII-CVP with complete disappearance of the inhibitor without recurrence. Among 5 patients with hemophilia who were given 3 to 8 courses, only 1 patient responded with a transient disappearance of inhibitor. Mild neutropenia and infection occurred in 3 patients and required antibiotic treatment. CONCLUSION: Factor VIII-CVP therapy is highly effective in the eradication of factor VIII inhibitor in nonhemophiliac patients but not in patients with hemophilia.

Adult↗
PubMed1988

Mechanism of rabbit platelet agglutination induced by acidic mucopolysaccharide extracted from Stichopus japonicus Selenka.

The effects of acidic mucopolysaccharide extracted from sea cucumber (Stichopus japonicus Selenka) (SJAMP) on rabbit platelets were studied. Using citrated platelet-rich plasma (PRP), washed platelets, and formaldehyde fixed platelets from 10 New Zealand white rabbits, we investigated the effects of platelet inhibitors and various plasma and its fractions on SJAMP-induced agglutination. It was found that the tracing of platelet agglutination induced by SJAMP showed a single phase without a lag period. The lowest concentration of SJAMP required for the agglutination of rabbit platelets was approximately 2 micrograms/ml, and the magnitude of agglutination induced by SJAMP was concentration dependent. In 8 out of 10 rabbits, the platelets in PRP were agglutinated by 10 micrograms/ml of SJAMP. Platelet inhibitors, such as aspirin, indomethacin, apyrase, antimycin, 2-deoxy-D-glucose and EDTA did not inhibit the agglutination induced by SJAMP. Washed rabbit platelets were not agglutinated by SJAMP even though the concentration of SJAMP was raised up to 50 micrograms/ml. When rabbit plasma, serum, or 50-60% ammonium sulfate saturated plasma fraction was added to the reaction mixture, agglutination of washed platelets by SJAMP was recovered completely. But human plasma or fibrinogen did not have any effect on the reactivity of washed rabbit platelets to SJAMP. From these data we conclude that the SJAMP-induced rabbit platelet agglutination is independent of energy metabolism but requires plasma cofactor(s) other than fibrinogen. The plasma cofactor is present in 50-60% ammonium sulfate saturated plasma fraction.

Animals↗
PubMed1988

Aggregation of human platelets by acidic mucopolysaccharide extracted from Stichopus japonicus Selenka.

The acidic mucopolysaccharide extracted from sea cucumber (Stichopus japonicus Selenka) (SJAMP) has been shown to cause platelets to aggregate. Using citrated platelet-rich plasma (PRP), washed platelets and formaldehyde-fixed platelets from humans, we investigated the effects of platelet inhibitors and various plasmas and their fractions on SJAMP-induced platelet aggregation. It was found that the lowest concentration of SJAMP required for the aggregation of human platelets was about 0.4 micrograms/ml and the magnitude of aggregation induced by SJAMP was concentration dependent. The platelets were aggregated by SJAMP at 10 micrograms/ml in 25 out of 28 (89%) normal subjects tested. Platelet inhibitors such as PGE1, aspirin, indomethacin, apyrase, antimycin, 2-deoxy-D-glucose and EDTA inhibited by 70 to 100% the aggregation induced by SJAMP. Washed platelets alone were not aggregated by SJAMP. In the presence of fibrinogen, washed platelets were aggregated by SJAMP but formaldehyde-fixed platelets were not. These data indicate that the SJAMP-induced human platelet aggregation requires extracellular calcium, fibrinogen, and energy metabolism. The second phase of aggregation is dependent upon the release of ADP, and cyclooxygenase pathway.

Animals↗
PubMed1988

Thrombotic thrombocytopenic purpura.

Platelet thrombus formation in small vessels is triggered by certain stimuli, including vascular injury, primary platelet agglutination, or both. The formation and dissolution of platelet thrombi is modulated by proteolysis, plasma factors, PGI2 synthesis and stability, and immune mechanisms. Some recent evidence now suggests that there is a subset of thrombotic thrombocytopenic purpura (TTP) patients possessing a specific platelet agglutinating factor that triggers the intravascular platelet agglutination. Identification and classification of TTP patients into subgroups with common triggering agents, and further clarification of the role of modifying factors will enable us to understand the disease better and to improve therapy.

Humans↗
PubMed1988

Platelet-agglutinating protein P37 from a thrombotic thrombocytopenic purpura plasma forms a complex with human immunoglobulin G.

We have previously reported the purification of a 37-kd platelet-agglutinating protein (PAP p37) from the plasma of a patient with thrombotic thrombocytopenic purpura (TTP) that was shown to be present in a subset of TTP patients. The platelet agglutination induced by PAP p37 has been shown to be inhibited by IgG from normal human adults and the same TTP patient after recovery. To elucidate the mechanism of inhibition of IgG, the interaction between PAP p37 and IgG was studied. The complex formation was demonstrated by the binding of fluid-phase IgG from normal adults and the same TTP patient after recovery to adsorbed PAP by using an enzyme-linked immunosorbent assay. The binding was specific, concentration dependent, and saturable. IgG purified from a 5-month-old baby and the same TTP patient during active disease did not form complex with PAP p37. The IgG covalently cross-linked to Sepharose 4B bound 125I-PAP p37 but not 125I-fibrinogen. Sucrose density gradient ultracentrifugation of a mixture of 125I-PAP p37 and IgG also revealed the fluid-phase complex formation with a sedimentation value of 19S. Complexes of molecular weight ranging from 180,000 to over 350,000 daltons were also detected by molecular sieve chromatography. The IgG that was bound to PAP p37 conjugated to Sepharose 4B inhibited the agglutination of washed platelets induced by TTP plasma containing PAP p37, whereas the IgG that was not bound to PAP p37 did not have a significant inhibitory effect. The complex formation between PAP p37 and specific IgG is likely to account for the in vitro inhibition of TTP plasma-induced agglutination and, at least partly, the in vivo successful treatment with specific IgG-containing normal plasma.

Blood Proteins↗
PubMed1986

Synovectomy of the knee for hemophilic arthropathy.

Synovectomy of the knee for the control of recurrent hemarthrosis was performed in thirteen patients with hemophilic arthropathy. Preoperatively, all patients had experienced an average of three bleeding episodes into the affected joint per month, and had been unresponsive to at least six months of medical management. Radiographically, all knees had either Stage-II or Stage-III hemophilic arthropathy. The average age of the patients at the time of synovectomy was sixteen years and the average length of follow-up was 7.3 years (range, two to eleven years and seven months). Although the motion of the knee remained unchanged postoperatively in two patients, ten patients had an average loss of 41 degrees. One patient eventually required an arthrodesis. Radiographically, there was slight further joint deterioration after synovectomy, and no knee progressed beyond Stage-III hemophilic arthropathy. Only one patient in our series had a recurrent spontaneous hemarthrosis of the synovectomized knee, although two others had traumatic bleeding episodes. The complications included three immediate postoperative hemarthrosis requiring surgical evacuation, isoimmune hemolytic anemia in one patient, patellofemoral adhesions in two knees, and a total fibrous ankylosis that required a knee arthrodesis in one patient. It was concluded from our study that chronic recurrent hemarthrosis and the pain associated with persistent synovitis in the hemophilic knee can be effectively eliminated for as many as twelve years after open synovectomy, although usually with significant loss of motion of the knee. This procedure also appeared to slow the progression of arthropathy, and no patient had been considered for a total knee replacement at the time of writing.

Adolescent↗
PubMed1985

Novel platelet-agglutinating protein from a thrombotic thrombocytopenic purpura plasma.

A novel platelet-agglutinating protein (PAP) was purified approximately 2,000-fold from the plasma of a patient with thrombotic thrombocytopenic purpura (TTP) by ammonium sulfate fractionation, DEAE-Sephacel and concanavalin A-Sepharose chromatographies. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with and without reduction, this preparation revealed a major protein band with a molecular weight of 37,000, and a minor band with a molecular weight of 32,000-34,000. After elution from the gel, only the 37,000-mol wt protein corresponding to the major band induced the platelet agglutination. When four normal plasmas and the recovery plasma from the same TTP patient were subjected to the similar purification steps, the 37,000-mol wt major band was absent. The 125I-PAP bound to the platelets in a concentration-dependent manner. The platelet agglutination induced by PAP was not inhibited by hirudin, heparin in the presence of antithrombin III, phenylmethylsulfonyl fluoride, apyrase, aspirin, or prostaglandin I2. However, it was inhibited by IgG from normal adults and from the same TTP patient after recovery. The anti-37,000-mol wt PAP antiserum prepared in the rabbit formed a single precipitin line against the highly purified PAP. Using this antiserum in the Western immunoblotting, the 37,000-mol wt protein band was found in the three TTP plasmas, of which the platelet-agglutinating activity was inhibited by the anti-37,000-mol wt PAP IgG. The 37,000-mol wt immunoprecipitin band was absent in the plasmas obtained from another two TTP patients, two normal subjects, two patients with idiopathic thrombocytopenic purpura, and two patients with disseminated intravascular coagulation. These results suggest that the 37,000-mol wt PAP is present only in certain cases of TTP, and is likely to be responsible for the formation of platelet thrombi in the microcirculation.

Adult↗
PubMed1985

Investigation of the role of von Willebrand factor in thrombotic thrombocytopenic purpura.

Von Willebrand factor (vWF) has been implicated to function as a cofactor in platelet aggregation induced by thrombotic thrombocytopenic purpura (TTP) plasma. To investigate further this role of vWF, we have used rabbit monospecific anti-FVIII/vWF antibodies and a monoclonal antibody to platelet glycoprotein Ib (GP Ib) that blocks the ristocetin-induced platelet aggregation. The monoclonal anti-platelet GP Ib antibody inhibited the platelet aggregation induced by ristocetin in the presence of normal plasma, but not that by any of the five TTP plasma samples. The TTP plasma samples from five patients were incubated with the monospecific antibodies to FVIII/vWF. In all of the samples, the FVIII/vWF:Ag was drastically reduced; however, there was almost no effect on the platelet-aggregating activity. Therefore, it is concluded that vWF is unlikely to play a major role in platelet aggregation induced by majority of TTP plasmas and that the site of platelet GP Ib, to which vWF binds in the presence of ristocetin, is not involved in TTP plasma-induced aggregation.

Antibodies, Monoclonal↗
PubMed1984

Purification and some properties of a protein obtained from normal human plasma which inhibits the platelet aggregation induced by thrombotic thrombocytopenic purpura plasma.

Plasma from patients with thrombotic thrombocytopenic purpura (TTP) caused the aggregation of washed human platelets, which was inhibited by preincubation with normal plasma. Using salt fractionation, ion exchange chromatography, and preparative agarose gel electrophoresis, we purified a protein from normal plasma which inhibited the platelet aggregation caused by TTP plasma. On SDS polyacrylamide gel, the purified inhibitor gave a single band with a M.W. of 150,000. The antiserum against the purified protein neutralized the activity of the inhibitor and formed an identical precipitin line against normal and TTP plasma.

Blood Coagulation Factors↗
PubMed1984

Two successful pregnancies in a woman with chronic thrombotic thrombocytopenic purpura treated by plasma infusion.

A 21-year-old primigravida in her 20th week of pregnancy developed TTP. She was managed with weekly or semiweekly plasma infusions and delivered a healthy 1.6 kg baby 2 weeks prior to the expected date of delivery. After delivery she continued to have active TTP with thrombocytopenia which responded repeatedly to plasma infusion though their frequency gradually decreased to about one unit every 3-4 weeks. Three years after the birth of the first child she conceived again and was easily managed with repeated plasma infusions although the frequency and amount of plasma required to prevent thrombocytopenia were increased. She delivered a normal 3.4 kg term baby after which she again had a decreased plasma requirement. This is the first report of a woman with 5 years of active TTP managed with plasma alone. She experienced two pregnancies in which both mother and infant survived. We believe that the use of plasma in the management of TTP during pregnancy will improve the survival rate of both mother and infant. At the time of second birth, the platelet count was low in the mother but normal in the baby. This suggests that the platelet depressing factor of this patient does not cross the placental barrier.

Adult↗
PubMed1984

Inhibition of platelet-aggregating activity in thrombotic thrombocytopenic purpura plasma by normal adult immunoglobulin G.

Plasma from patients with thrombotic thrombocytopenic purpura (TTP) caused the aggregation of autologous and homologous platelets, and effect which was inhibited by normal plasma. IgG purified from seven normal adults at a concentration of 0.7 mg/ml completely inhibited the platelet aggregation induced by plasma obtained from two TTP patients with active disease. The inhibition of platelet aggregation by human adult IgG was concentration dependent, and the inhibitory activity of human IgG was neutralized by rabbit antihuman IgG. Fab fragments inhibited the TTP plasma-induced platelet aggregation as well as intact IgG, whereas Fc fragments had no effect. Platelet aggregation caused by ADP, collagen, epinephrine, or thrombin was not affected by purified human IgG. The prior incubation of IgG with TTP plasma caused a significantly greater reduction of platelet aggregation by TTP plasma than that of IgG and platelet suspension, suggesting that the IgG inhibits TTP plasma-induced platelet aggregation through direct interaction with platelet aggregating factor in TTP plasma. IgG obtained initially from five infants and young children under the age of 4 yr did not possess any inhibitory activity. When one of the children reached 3 yr of age, his IgG inhibited the aggregation induced by one TTP plasma, but not that caused by another plasma. The IgG procured from the same boy at 4 yr of age inhibited the aggregation induced by both TTP plasmas. The IgG purified from the TTP plasma during active disease failed to inhibit the aggregation caused by the same plasma. After recovery, however, the IgG effectively inhibited aggregation. These observations suggest that platelet-aggregating factors present in the TTP plasma are heterogeneous in nature and that the IgG present in the normal adult plasma, which inhibits the TTP plasma-induced platelet aggregation, may be partially responsible for the success of plasma infusion therapy in TTP.

Adult↗
PubMed1983

Chronic inflammatory polyradiculoneuropathy complicated by factor VIII antibody.

A 66-year-old man with a 45-month course of chronic inflammatory polyradiculoneuropathy developed a coagulopathy due to an antibody to factor VIII. Despite clinical improvement in the neurologic disease at the onset of the coagulation disorder, antibody to peripheral nerve myelin was demonstrated in high titer. Antibodies to factor VIII and peripheral nerve myelin were both of the IgG class, but were immunologically distinct. This previously unreported association lends further credence to a disturbance in immunoregulation in chronic inflammatory polyradiculoneuropathy.

Aged↗
PubMed1981

Effects of platelet inhibitors on the platelet aggregation induced by plasma from patients with thrombotic thrombocytopenic purpura.

Antiplatelet drugs have been used in the treatment of thrombotic thrombocytopenic purpura (TTP) but there in vivo efficacy remains controversial. It has been shown that, in vitro, the plasmas obtained from patients with TTP induced the aggregation of washed platelets from normal donors as well as patients in remission. The effects of platelet inhibitors on the TTP plasma-induced platelet aggregation were examined. It was found that aspirin, indomethacin, ibuprofen, sulfinpyrazone, 5, 8, 11, 14-eisacotetraynoic acid, prostaglandin E1, prostaglandin I2, dBcAMP, apyrase, creatine phosphate/creatine phosphokinase, antimycin, 2-deoxy-D-glucose, dipyridamole, clofibrate, dextran 40, dextran 70, dibucaine, xylocaine, methylmaleimide, and ethylenediamine tetraacetic acid had little or no effect at all. These data lead us to conclude that at least in certain cases, antiplatelet drugs probably play a limited role in the treatment of patients with TTP.

Adenosine Diphosphate↗
PubMed1980

'Storage pool disease' of platelets. Association with multiple congenital cavernous hemangiomas.

A women with congenital cavernous hemangiomas and a bleeding diathesis since childhood was found to have a qualitative platelet defect characterized by the absence of a second-phase aggregation induced by epinephrine, adenosine diphosphate (ADP), and collagen, accompanied by decreased levels of adenosine triphosphate (ATP) and ADP, with a high ATP-ADP ratio consistent with the diagnosis of "storage pool disease" of the platelets. There was no evidence of disseminated intravascular coagulation or circulating antiplatelet antibodies. The bleeding tendency responded to platelet transfusion.

Adenosine Diphosphate↗
PubMed1979

Recent therapeutic advances in thrombotic thrombocytopenic purpura.

Whole plasma infusion, in our experience, has been highly effective in the management of patients with thrombotic thrombocytopenic purpura. The effectiveness of plasma infusion in the treatment of this severe disorder implies the deficiency of a factor in the patient's plasma. Furthermore, we have observed that when platelets are suspended in plasma obtained during active, untreated thrombotic purpura, aggregation occurs. This effect is neutralized by preincubation of the thrombotic thrombocytopenic purpura plasma with normal plasma. Thus, there is both a correlation with the clinical pathogenic mechanism, disseminated platelet aggregation, and with the therapeutic response to plasma infusion. Based upon our experience and the concept that thrombotic thrombocytopenic purpura is a plasma factor deficiency state, we recommend initial infusion of a full plasma volume equivalent over the first 24 hours. This should be done under an intensive care setting. After this initial plasma infusion, we advise the infusion of 3 units of plasma daily until a full remission is obtained. When the clinical situation has stabilized, we stop the daily plasma infusions and cautiously observe for recurrence of the manifestations of thrombotic thrombocytopenic purpura. If there is a recurrence, plasma is again infused in substantial quantity during the first 24 hours and then 3 units daily until a full remission is again evident. Whether the plasma requirement might be attenuated or the course of the disease shortened by the concomitant use of antiplatelet agents, corticosteroids or other means remains to be determined.

Adolescent↗
PubMed1979

Presence of a platelet aggregating factor in the plasma of patients with thrombotic thrombocytopenic purpura (TTP) and its inhibition by normal plasma.

Three patients with thrombotic thrombocytopenic purpura (TTP) were treated by infusion of normal plasma with dramatic responses. The plasmas collected from these patients during relapse induced in vitro aggregation of washed platelets from both normal donors and the patients during remission. The platelet aggregating factor was not dialyzable or adsorbable by Al(OH)3 and was not inactivated by diisopropylfluorophosphate, hirudin, or heparin in the presence of normal amounts of antithrombin. In contrast to the platelet aggregation induced by platelet isoantibody, the platelet aggregating activity of TTP plasma diminished as a function of time when it was incubated with normal plasma at 37 degrees C. These observations suggest that at least some instances of TTP appear to be due to deficiency of a plasma inhibitor to counteract a platelet aggregating factor demonstrated to be present in the plasma of these patients.

Adolescent↗