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Biomedical subjects

G Myllylä

Publications and source records attributed to G Myllylä.

At least 37 records · Page 2Linked to original sources
PubMed1992

Antiphospholipid antibodies and thrombosis in systemic lupus erythematosus: comparison of three lupus anticoagulant assays and anticardiolipin ELISA in 188 patients.

The presence of antiphospholipid antibodies (aPL) in 188 unselected patients with systemic lupus erythematosus was studied using the recalcification time, kaolin clotting time (KCT), dilute Russell's viper venom time (dRVVT) and anticardiolipin ELISA (aCL) to identify patients with a high or low risk of thrombosis among patients with aPL. aPL were detected by at least one method in 104 (55%) of the patients. Despite heterogeneity, lupus anticoagulant (LA) methods correlated reasonably well with each other (r = 0.736-0.968), but poorly with aCL (r = 0.241-0.549). Positivity in LA assays and immunoglobulin G (IgG)-aCL were associated with patients who experienced thrombosis (P less than 0.001 for all assays). Patients with both LA and aCL had experienced thrombosis more often than those having only one (odds = 6.3, P less than 0.001). When patients with aPL were ranked by relative strength of the finding and divided into tertiles, a history of thrombosis was associated with membership in the strongest tertile of at least one assay (odds = 4.2, P = 0.002). LA and aCL had similar sensitivities for thrombosis (61% and 63%, respectively), but LA was more specific than aCL (79% vs 53%). The best combination of two assays was KCT with dRVVT (61% sensitivity, 87% specificity). Maximal sensitivity (71%) for thrombosis could be achieved by adding IgG-aCL to these two assays, but specificity was lower (73%). In conclusion, a high thrombotic risk among patients with aPL was indicated by the simultaneous presence of both LA and aCL, strongly positive aPL, and, among aCL, IgG-class antibodies.

Adolescent↗
PubMed1992

Platelet activation during acute phase after multiple trauma.

The acute phase after multiple trauma is associated with both thrombotic phenomena and a bleeding diathesis. To evaluate the activation of platelets, beta-thromboglobulin (BTG) in plasma and serum and thromboxane B2 (TxB2) in serum were measured in 14 patients with multiple trauma. BTG in plasma was significantly increased on days 1, 2 and 10 to 14 after the trauma. The highest median value 90 micrograms/l was measured on day 1. BTG in serum was significantly reduced 1 to 7 days after the trauma (median levels 4450-9100 micrograms/l). TxB2 was significantly reduced (median levels 18-97 ng/l) on days 1 to 14. The increased plasma levels of BTG is due to the posttraumatic activation of platelets in vivo. The reduced levels of serum BTG and TxB2 reflect the deficient functional capacity of circulating platelets to respond to extreme stress. Therefore, platelet count alone may correlate poorly with the haemostatic potential and may underestimate the need of platelet transfusions.

Acute-Phase Reaction↗
PubMed1991

Cytoskeleton-dependent release of human platelet epidermal growth factor.

To study the source of immunoreactive epidermal growth factor (ir-EGF) released by thrombin formation we removed 99.9% of the leukocytes normally present in platelet-rich plasma and induced coagulation with 30 mM of Ca2+. The absence of leukocytes did not reduce the amount of ir-EGF released; thus platelets are most likely the only source of the ir-EGF released during aggregation. To identify the site of ir-EGF in platelets we exposed washed platelets to collagen or thrombin and compared the kinetics of releases of ir-EGF, beta-thromboglobulin (bTG, an alfa-granule marker), ATP (dense granule marker), N-acetyl-beta-D-glucosaminidase (NAGA, a lysosome marker) and lactate dehydrogenase (LDH, a cytoplasmic marker). Release of ir-EGF started immediately and continued linearly. The process differed clearly from the releases of the granule markers, which occurred readily, and were completed in a few minutes. The release of ir-EGF also differed from the leakage of LDH, the start of which was delayed greater than 5 min, but then proceeded linearly. Cytochalasin B inhibited the release of hEGF, but demecolcine had no effect. We conclude that the ir-EGF released from platelets during aggregation derives neither from the granules nor the cytoplasma. The assembly of cytoskeleton is needed for its release.

Blood Platelets↗
PubMed1991

Heparin rebound: a comparative study of protamine chloride and protamine sulfate in patients undergoing coronary artery bypass surgery.

Heparin rebound has been suggested to occur when protamine sulfate, but not protamine chloride, is used to neutralize heparin. This study was undertaken to compare these two protamine salts in 32 patients undergoing coronary artery bypass surgery. Initial heparin and subsequent protamine doses were determined by constructing a heparin-activated coagulation time response curve. Heparin was neutralized either with protamine sulfate or protamine chloride. The total protamine/heparin dose ratio was 0.71 +/- 0.05 for protamine sulfate and 0.77 +/- 0.07 (mg/100 U) for protamine chloride. The initial neutralization effect, the subsequent behavior of the plasma heparin level, and the various coagulation parameters did not differ significantly between the groups. Two hours after neutralization, a small and temporary increase of plasma heparin level was observed in both groups. The postoperative blood losses were comparable in both groups. Thus, protamine chloride was not a clinically superior antidote to heparin than protamine sulfate. The observed heparin rebound levels were low and clinically insignificant in terms of blood loss, but they were associated with slight changes in coagulation monitoring.

Blood Coagulation↗
PubMed1991

Prevention of alloimmunization in patients with acute leukemia by use of white cell-reduced blood components--a randomized trial.

Platelet refractoriness arising from HLA alloimmunization is a serious complication of transfusion therapy. In a prospective randomized trial, white cell (WBC)-reduced blood components were compared to standard platelet and red cell concentrates with respect to alloimmunization, refractoriness, and platelet increments after transfusion. Sixteen of 31 adult acute leukemia patients received only WBC-reduced platelet concentrates (PCs) and red cells (RBCs), with fewer than 10(6) WBCs per unit. Fifteen control patients received standard blood components with a mean of 0.1 x 10(9) (PCs) and 1 x 10(9) (RBCs) WBCs per unit. Platelet loss during cotton-wool filtration averaged 14 percent (range, 3-32%) from fresh PCs and 24 percent (range, 9-62%) from stored PCs. Filtration did not change corrected increments (CI) measured after transfusion of fresh PCs. The Cl 1 hour after filtration of stored PCs diminished by 27 percent, but the difference was smaller after 18 hours, which suggests better survival of WBC-reduced platelets. The number of platelet units transfused did not differ in the two groups. No patient in the WBC-reduced group developed permanent platelet refractoriness; transient HLA antibodies of low titer developed in two patients. In the control group, one patient became refractory because of immunization and two developed transient HLA antibodies. It can be concluded that the reduction of WBCs in blood components can effectively prevent alloimmunization.

Adolescent↗
PubMed1991

Familial clustering of defective release of t-PA.

91 unrelated patients with idiopathic or familial deep vein thrombosis (DVT) and 72 (34 with DVT) relatives from 26 families were screened for hypofibrinolysis by measuring tissue plasminogen activator antigen (t-PA:Ag) after venous occlusion (VO) for 10 and 20 min and by measuring t-PA inhibitor activity (PAI) at rest. 21 healthy subjects served as controls. Defective release of t-PA:Ag was found in eight out of the 91 patients (9%). A partial family study of six of these eight patients was performed. This study included 10 family members with and 21 without DVT. A defective release of t-PA:Ag was found in 50% (5/10) of the family members with DVT, which is significantly more frequent than the 9% (8/91) prevalence in the unrelated patients (P less than 0.001). Furthermore, 24% (5/21) of asymptomatic members of these families also had defective release of t-PA:Ag. In the 18 families where the propositus had a normal level of t-PA:Ag, none of the 24 studied family members with DVT had defective release of t-PA:Ag. In contrast to the defective release of t-PA:Ag, increased basal level of PAI did not show familial clustering. In conclusion, low release of t-PA during VO shows familial clustering in a proportion of the cases.

Adult↗
PubMed1991

Albumin, HES 120 and dextran 70 as adjuvants to red blood cell concentrates: a study on colloid osmotic pressure changes in vitro.

An in vitro model of surgical bleeding was developed to simulate continuous blood loss and replacement therapy with plasma substitutes and red cell concentrates. The model was used to determine the lowest colloid concentration in vitro for each of the plasma substitutes that sustains colloid osmotic pressure above 2.4 kPa (or 18 mmHg) when used up to the recommended maximal total dose. Plasma, supernatant separated from red cell concentrates and dextran 70, hydroxyethyl starch 120 or albumin were mixed to create dilutions imitating plasma composition in the course of clinical blood loss and replacement therapy. The relative volume of each component was calculated according to the model when the bleeding was equal to multiples of 10% of blood volume up to a blood loss of 120%. Our measurements indicate that the colloid concentrations of 5.0% for albumin, 4.0% for hydroxyethyl starch 120 and 3.5% for dextran 70 preserve colloid osmotic pressure above 2.4 kPa.

Albumins↗
PubMed1991

Low prevalence of antibodies against human immunodeficiency virus in Finnish haemophiliacs.

National yearly surveys were carried out between 1985 and 1989 to determine the prevalence of antibodies for human immunodeficiency virus (HIV) in Finnish patients with bleeding disorders. From 192 out of the 214 haemophiliacs (90%) tested, 2 patients were positive for anti-HIV. No seropositivities were found after 1985. Fourteen out of 21 patients (67%) with type III von Willebrand's disease, and 7 out of 8 patients (88%) with factor XIII deficiency were tested with negative results. The low prevalence of anti-HIV (0.94%; 2/213 tested), is mainly due to the self-sufficiency for clotting factors, the low prevalence of HIV in the population, and the use of cryoprecipitate during the critical period.

Adolescent↗
PubMed1990

Effective prophylaxis against platelet refractoriness in multitransfused patients by use of leukocyte-free blood components.

Development of permanent platelet refractoriness is a major problem in multitransfused patients with diseases such as leukemia, aplastic anemia, or pediatric solid tumors. We tried to prevent alloimmunization in these patients by systematic use of leukocyte-free blood components with less than one million of contaminating leukocytes per unit of platelets or red cells. Our study group comprised 26 patients with a minimum of 10 platelet transfusions per patient. These patients were compared with a historical reference group of 21 patients who had received standard blood products. In the leukocyte-free group none developed platelet refractoriness, in contrast to the reference group where 11 of the 21 patients became refractory to random platelets. The median corrected platelet increment for random pooled platelets was significantly higher in the leukocyte-free group compared with the reference group. The increasing number of transfusions did not correlate with the development of platelet refractoriness; instead we propose that the lower limit of antigenic exposure is important. We conclude that systematic use of leukocyte-free blood components effectively prevents development of platelet refractoriness and contributes to optimal supportive care of children with cancer.

Blood Platelets↗
PubMed1990

Platelet autoantibodies detected by immunoblotting in systemic lupus erythematosus: association with the lupus anticoagulant, and with history of thrombosis and thrombocytopenia.

71 patients with systemic lupus erythematosus (SLE) were studied for the occurrence of platelet antibodies by immunoblotting. Binding of IgG antibodies to platelet protein antigens was observed in 39 of the 71 patients. The most frequently detected and exceptionally strongly reacting antibodies were directed against platelet protein antigens with an approximate molecular weight of 65 kDa under nonreducing conditions. These antibodies were autoreactive and, when followed, they usually persisted. Interestingly, in this group of well-defined SLE patients, platelet antibodies against the most common targets (65 kDa) were significantly associated with the lupus anticoagulant, a history of thrombocytopenia and thrombosis, particularly with arterial occlusions. The lupus anticoagulant, on the other hand, correlated significantly only with venous thrombosis. In addition to the lupus anticoagulant, platelet antibodies against this unknown platelet protein may thus be a marker of a higher risk of thrombosis in SLE patients.

Adolescent↗
PubMed1989

Familial hypofibrinolysis and venous thrombosis.

Nine patients with, and 11 without, venous thromboses (DVT) from two families were studied. In family 1, four members with, and one without, DVT had t-PA activity below the lower limit of the controls (21.3 IU/ml, n = 19) after 20 min venous occlusion (VO). After VO t-PA antigen (t-PA:Ag) was below the lowest value of the controls (22.8 ng/ml) in all five cases with low t-PA activity. All the family members, both with and without thrombosis, had normal t-PA inhibitor activities (PAI). In family 2 t-PA activity after VO was low in three symptomatic and four asymptomatic family members. t-PA:Ag was also low in four of these. PAI level was normal in all but one family member. Mild type I von Willebrand's disease was discovered in four members of family 2. Deficient t-PA:Ag response was found in two of these. Antithrombin III, protein C and protein S were normal in both families. It is concluded that low fibrinolytic capacity, independent of PAI, is associated with familial DVT. Our data suggests autosomal dominant inheritance.

Adult↗
PubMed1989

Characterization of material with epidermal growth factor immunoreactivity in human serum and platelets.

We investigated the molecular nature of the epidermal growth factor immunoreactivity (ir-EGF) in serum and platelets of normal subjects. In serum, ir-EGF appeared and increased during spontaneous blood coagulation, reaching a plateau in 2 h. The mean plateau measured by time-resolved immunofluorometric assay was 778 pg/mL [130 pmol/L; range, 465-1352 pg/mL (78-225 pmol/L)] for men (n = 66), and 774 pg/mL (129 pmoL/L; range, 521-1114 pg/mL (87-186 pmol/L)] for women (n = 33). Serum samples (n = 9), when examined under nonreducing conditions by high performance liquid chromatography, contained three mol wt components. Their approximate proportions averaged 56 +/- 6% (+/- SD) for a 140K component, 22 +/- 9% for a 67K component, and 22 +/- 6% for a component coeluting with the 6K EGF standard. The molecular size distribution of ir-EGF released from isolated platelets varied with the treatment of the platelets. After stimulation with a Ca2+ ionophore, the proportions of the 140K, 67K, and 6K components were 61 +/- 11%, 20 +/- 8%, and 17 +/- 4% (n = 5), respectively, as in serum. In addition, we found a small amount, (approximately 1%) of a 17K component. When platelets (n = 6) were ruptured by sonication and repeated freeze-thawing, the 67K component formed 53 +/- 7% of the total; the proportions of the 140K, 17K, and 6K components were 14 +/- 7%, 2.1 +/- 0.7%, and 31 +/- 4%, respectively. Under reducing conditions the 17K and 6K components remained intact, but part of the 140K component and all of the 67K component were cleaved to a 35-37K form. After protease digestion of the higher mol wt components, the ir-EGF was exclusively of the 6K form. The 67K and 6K components bound to the EGF receptor, whereas the 140K component bound inconsistently. We conclude that treatment of platelets with Ca2+ ionophore produces ir-EGF components similar to those found in incubated serum but different from those obtained by freeze-thawing. The 67K mol wt component appears to be the main storage form of EGF in platelets; at least two independent mechanisms appear to exist for EGF release.

Blood Coagulation↗
PubMed1989

Age-dependent increase of Campylobacter pylori antibodies in blood donors.

Antibodies against Campylobacter pylori were determined in 500 blood donors aged 18 to 65 years. Acid extract from a C. pylori strain was used as antigen in enzyme immunoassay. The proportion of donors with high antibody titers increased with age. For IgG antibodies it was 10% in the age group from 18 to 25 years but 60% in the group from 56 to 65 years; the increase for IgA and IgM antibodies was from 5 to 42% and from 7 to 21%, respectively. The geometric mean titers of those with high values showed no clear changes with age, which would imply chronic antigenic stimulus.

Adolescent↗
PubMed1988

Platelet associated IgG, platelet mean life span and treatment with intravenous immunoglobulin in idiopathic thrombocytopenic purpura.

The clinical significance of platelet associated IgG in ITP detected by direct platelet suspension immunofluorescence test (PSIFT) was studied. The platelet mean life span (MLS) was measured with 111In-labelled platelets in 17 adult patients. All the patients had shortened platelet MLS. The direct PSIFT was positive in 14 patients. Patients were initially treated with prednisone; 12 patients with poor response to the drug were splenectomised. 8 of these 12 patients were treated with intravenous immunoglobulin (IvIg) before splenectomy. The response to IvIg was as good or better in the 3 patients with negative PSIFT, than in the 5 patients with positive PSIFT.

Adolescent↗
PubMed1988

New transfusion practice and haemostasis.

Haemostatic deficiency following blood transfusion and surgery is caused by multifactorial mechanisms. Various protocols of component therapy have been used to prevent the haemostatic abnormalities and bleeding tendency. In planning the protocols, the defect is considered to be mainly due to dilution. Prophylactic use of fresh frozen plasma and/or platelet concentrates have not proved to be very effective. Treatment of the bleeding tendency should therefore be based on specific diagnosis of the haemostatic defect.

Blood Coagulation Disorders↗
PubMed1987

A study of haemostasis following the use of high doses of hydroxyethyl starch 120 and dextran in major laparotomies.

The safety of plasma expanders, hydroxyethyl starch 120 and dextran 70, administered in the highest recommended doses (20 ml/kg) as adjuncts of component therapy of surgical blood loss was studied in patients undergoing major abdominal surgery and compared with a group receiving 4% albumin solution for initial haemodilution and whole blood for further blood loss replacement. Each group consisted of five patients in a relatively severe surgical, but good general condition including a normal haemostatic function and serum albumin level. The dilutional effect of the expanders on serum albumin and prothrombin-proconvertin level was observed during the day of operation. On the first postoperative day these values were equally low in all groups. Platelet count and bleeding time remained on a safe level throughout the study in all groups. Partial thromboplastic time values were unchanged. The factor VIII procoagulant (C), related antigen (R:Ag, vWF:Ag) and ristocetin cofactor levels, which were high preoperatively due to the underlying disease, remained at a safe level throughout the study. The increase in factor VIII related antigen associated with the hypercoagulable state induced by the surgical trauma was prevented by the plasma expanders. We conclude that dextran and hydroxyethyl starch can be used safely in a dose of 20 ml/kg in component therapy of surgical blood loss, provided that haematocrit is kept at an acceptable level, attention is paid to the postoperative hypoproteinaemia, and the patient has a normal haemostatic function preoperatively.

Adult↗