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Because platelets interact with fibrinolysis in a complex manner, it can be expected that with abnormal platelet numbers and quality this interference can be even more profound. The aim of this work was to study the lysis-resistance of platelet-rich clots in diseases with high platelet counts: polycythemia vera (PV), essential thrombocythemia (ET) and to make comparison with polyglobulia (PG). Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were analyzed by an in vitro clot lysis test. Plasminogen activator inhibitor-1 (PAI-1) activity was measured in plasma and in the supernatants of the washed and gel-filtered platelets after activation by thrombin. The lysis showed decreased speed of PPP-clots in PV and ET. This phenomenon was even more marked in PRP-clots from PV and ET, but further increased lysis resistance after retraction was not observed in PV and ET, most likely due to abnormal platelet functions. Our results suggest that the fibrinolytic activity is reduced in PV and ET, and may play a role both in the increased aptitude for venous thrombosis and in the arterial complications. These are partly caused by higher plasmatic PAI-1 activity as well as by more active platelet PAI-1. The PAI-1 activity was significantly higher in the supernatants of the washed and gel-filtered platelets of PV after activation by thrombin compared with controls. Other factors might have influenced the reduced fibrinolysis.

Expression of nine oncogenes was investigated in cell samples from fifteen patients with Philadelphia chromosome (Ph)-positive chronic granulocytic leukemia (CGL) both at diagnosis and at the onset of accelerated phase (AP) of the disease. The bcr-abl fusion gene, the H-ras gene and the c-myb gene were universally expressed. In comparison with the chronic phase (CP) of the disease, an increase in the levels of bcr-abl-, c-myb- and H-ras-related transcripts was found in three, two and three AP samples, respectively. Elevation of the bcr-abl-related message was associated with duplication of the Ph chromosome and amplification of the bcr-abl fusion gene in one AP sample. No CP samples were positive for c-myc or c-sis expression. On the contrary, c-myc and c-sis were expressed in three and four AP samples, respectively. The presence of c-myc-related transcript was associated with trisomy 8 with or without amplification of the c-myc oncogene in leukemia cells of two patients with CGL in AP. No changes of oncogene expression were found in four AP samples. However, we observed deletions of chromosome 13 and 17 or i(17q) in three of them, suggesting that tumor suppressor gene alterations may also be responsible for the development of AP of CGL. Our data indicate that heterogeneous alterations in oncogenes and tumor suppressor genes accompany the evolution of CGL-CP to the AP of the disease.

As published in a recent issue of Blood Coagulation and Fibrinolysis, the hybrid peptide RGDFAP, composed of RGDF (Arg-Gly-Asp-Phe) coupled to a synthetic peptide residue of the carboxy terminal part of antiplasmin (AP26) inhibited platelet activation and augmented plasmin generation and in vitro fibrin clot lysis. This peptide contains an RGD motif which provides linkage to platelet GP IIb-IIIa. The antiplasmin part of the molecule may attach free plasminogen, which in turn increases the amount of platelet surface bound plasminogen, probably yielding enhanced lytic action at the site of thrombus formation. This hypothesis was investigated and confirmed by the results of platelet-plasminogen binding assays, using FITC-labelled antiplasmin antibodies and radioligand binding analysis. Increased platelet-linked plasminogen was detected by a chromogenic method, along with the acceleration of in vitro lysis of platelet-rich clots in the presence of RGDFAP peptide.

A 24-year-old male patient was first observed with full-blown acute thrombotic thrombocytopenic purpura in 1991. Complete remission was achieved with plasma and plasmapheresis therapy, but in spite of continuous corticosteroid and aspirin administration, thrombocytopenic (megakaryocytic) relapses were observed every 26-30 days. Splenectomy and danazol failed to prevent the recurrence of the disease. Surprisingly, cyclosporin A (5 mg/kg/day) administration resulted in a complete transitional remission, but after dose reduction a less regular pattern of repeated milder recurrences was observed. Cryopreserved plasma, obtained from the patient during remission also proved to be effective in treating the last two thrombocytopenic episodes.

Forty patients with chronic granulocytic leukemia (CGL) were tested for antibodies and lymphocytes reacting with gibbon ape leukemia virus (GaLV) and baboon endogenous virus (BaEV) antigens as well as for plasma interferon levels. Antibodies reacting with envelope antigens of GaLV and BaEV were found frequently and in high titers in patients with the quiescent phase of CGL but rarely and in low titers in the accelerated and blastic phase of the disease. Results of radioimmunoprecipitation studies were in concordance with those obtained in virus neutralization experiments. Cellular and humoral cytotoxic activity of blood plasma and lymphocyte samples against autologous tumor cells showed a similar phase-specific distribution. Most of these activities could be blocked by GaLV and BaEV gp70 antigens. Elevated plasma interferon (IFN)-alpha levels were found in the quiescent and accelerated phase of CGL, whereas no significant differences could be detected between IFN levels of patients with the blastic crisis of CGL and those of the control persons. Follow up studies of four patients confirmed this stage-specific distribution of antiretroviral immune and interferon response.

Venous occlusion was used in 8 patients with liver cirrhosis and in 10 normals to investigate the pathomechanism of long-term elevation of plasma von Willebrand factor antigen (vWFAg) in liver cirrhosis. The following parameters were determined at baseline, and immediately, 60 min and 24 h after 10 min venous occlusion: vWFAg, ristocetin cofactor (RiCoF), in vitro platelet retention (Adeplat T), and tissue-type plasminogen activator (t-PA). Every baseline value in the liver cirrhosis group was significantly higher than in the controls. In both groups the 10-min values were significantly higher than their corresponding baseline results. Hence, comparing the two groups, in liver cirrhosis a significantly higher release of vWFAg and t-PA could be observed. These findings suggest on the one hand that the increased release contributes substantially to the sustained elevation of plasma vWF level in liver cirrhosis. On the other hand, the results indicate that not only the vascular surface of the diseased liver but most probably the total endothelium plays an important role in this phenomenon.

Monoclonal integration of DNA sequences related to, but not identical to HTLV-I provirus was detected in the peripheral blood lymphocytes of a Hungarian male suffering from ATL. The patient and his parents showed serological cross-reactivity with both HTLV-I and HTLV-II groupspecific antigens. Restriction enzyme analysis with EcoR1, Pstl, BamH1, HindIII and Sacl revealed structural similarity of the provirus integrated in the DNA of ATL cells to HTLV-I but not to HTLV-II. Data suggest that this provirus and HTLV-I are similar to each other along gag and pol regions, but they are different in the env region.

Platelets of anticoagulated whole blood forced at 40 mmHg through a fine filter are activated, aggregated and retained, so block the filter (platelet filter test, O'Brien JR, Salmon GP. Blood 1987; 1354-1361). Our clinical experiences with this simple and quick haemostasis test are summarized. Patients were investigated with different types of vWD (type-1 = 35, type-2A = 7, type-2B = 7, type-3 = 1), Glanzmann's thrombasthenia, congenital deficiency of cyclo-oxygenase, acquired Bernard-Soulier syndrome, FXII-, FXIII-deficiency and a control group. The cumulative drop count and the platelet retention were carefully measured during two phases of the filter test. Platelet count, bleeding time, vWF:Ag and vWF:Rcof activity were measured along with the platelet filter test. The filter was not blocked and the platelet retention was abnormally low in all patients with thrombasthenia, type-2a, type-2B, type-3 vWD. Treatment with 1-desamino-8-D-arginine-vasopressin (DDAVP) caused enhanced platelet retention in 16 patients with type-1 vWD. The test is simple, quick and cheap, has good reproducibility, and may be useful in clinical haemostasis laboratories for examination of high shear induced platelet functions.

An education program for hospital physicians and family doctors including up to date knowledge on diagnosis, prevention and treatment of venous thromboembolism has been elaborated, chiefly within the framework of hospital consensus conferences. Postgraduate consensus meetings led by representatives of specialities interested in prophylaxis of venous thrombosis have been held in 64 hospitals all over the country during the years 1996 to 2002, with a total number of more than 10,000 doctors working in hospital or general practice. In contrast to descriptive reports offered so far on drugs, the aim was a comprehensive clinical review of the problem, according to the principle of "disease management". By this way not only new diagnostic, therapeutic and prophylactic methods were presented but we managed to shape a new attitude based on new pathophysiological findings. As a result of the conferences the incidence and mortality of venous thromboembolism has decreased both on hospital and national levels. The consensus meetings acting as local interdisciplinary postgraduate forums have been supported by the Hungarian Thrombosis and Haemostasis Society and the haemostasis workshops of the country (Budapest, Debrecen, Pécs, Szombathely). Shaping the principles and methods for prophylaxis and therapy of venous thromboembolism can be regarded as a model which can subsequently be adapted to the problems of arterial thrombosis as well.

Until recently the treatment options in chronic myeloid leukaemia comprised non-curative chemotherapy (formerly busulfan and dibrommanitol, later hydroxyurea and interferon) and the potentially curative allogeneic stem cell transplantation (for the minority of patients). Increasing knowledge about the pathomechanisms of disease has led to the development of a specific and highly effective molecular therapy. This stem cell disorder, characterized by the Philadelphia chromosome is dependent on the constitutively active tyrosine kinase activity of the BCR-ABL oncoprotein. A novel promising treatment modality is the selective inhibition of the BCR-ABL tyrosine kinase, by the Signal Transduction inhibitor (STI 571) imatinib mesylate which may cause a high response rate of clinical and cytogenetic remission and raise hope for a possible cure of disease by drug therapy alone. Combination of imatinib with established or investigational antileukaemic agents may lead to an increased response rate and remission duration. Further experience will show its "final" place in the treatment algorythm of chronic myeloid leukaemia.

The frequency and mechanism of p16(INK4A) and p14(ARF) gene alterations were studied in cell samples from 30 patients with Philadelphia (Ph) chromosome-positive chronic myeloid leukaemia (CML), both at diagnosis and at the onset of the accelerated phase (AP) of the disease. No alterations in the p16(INK4A) or p14(ARF) genes were found in any of the chronic phase (CP) samples. DNA sequencing analyses detected p16(INK4A) or p14(ARF) mutations in 17 AP samples. All mutations were heterozygous without loss of the other allele. Aberrant methylation of the p16(INK4A) or p14(ARF) promoters was found in 14 of 30 AP samples. The most common situation was the simultaneous methylation of both promoters. Our data indicate that p16(INK4A) and p14(ARF) are primary targets for inactivation by promoter methylation in the acceleration of CML. Transcriptional silencing of the p16(INK4A) and p14(ARF) genes may be important in the conversion of CML from the CP to the AP.

Fludarabine is the most commonly used purine analog, its mechanism of action is complex. Fludarabine inhibits DNA synthesis, acts on non-dividing (G0 phase) cells influencing apoptosis.In our institute 47 patients were treated with fludarabine or fludarabine based combination chemotherapy. Fludarabine was given in 19 patients with chronic lymphocytic leukaemia (CLL), complete remission (CR) was achieved in one case, partial remission (PR) was obtained in 10 patients. Fludarabine was more effective in patients who received less intensive chemotherapy prior to fludarabine therapy and in those patients who had less advanced diseases. Elderly patients (over sixty years of age) also responded to fludarabine therapy. Fludarabine and cyclophosphamide combination (FCy) were used in three lymphocytic lymphoma patients, two of them obtained PR, in the third case the disease progressed. Fludarabine + mitoxantrone (Novantrone) + dexamethasone (FND) regimen was administered in nine patients who were previously heavily treated (one patient with B-CLL, one with T-CLL, one with peripheral T-cell lymphoma and six with indolent B-cell lymphoma). More patients and longer follow up is needed to determine the efficacy of FCy and FND protocol. FLAG-IDA (fludarabine, high dose Ara-C, granulocyte colony-stimulating factor, idarubicin) was applied in 16 acute leukaemia patients with poor prognosis including therapy refractory and relapsing cases. Three CR and two PR, one CR and three PR was achieved in nine patients with acute myeloid leukaemia and in seven patients with acute lymphoid leukaemia, respectively. For this reason, despite the short period of remission, this regimen can be recommended to patients who are candidate for stem cell transplantation.

Using the single-strand conformation polymorphism and heteroduplex analyses, the P53 and RB genes were analyzed in cell samples from twenty-eight patients with chronic myeloid leukemia (CML) both at diagnosis and at the onset of accelerated phase (AP) of the disease. No alterations of the P53 or RB genes were found in any of the chronic phase (CP) samples. Structural abnormalities of the P53 gene were observed in ten of twenty-eight AP samples within exons 4, 5, 7 and 9. Of the ten cases of AP disease with altered P53 genes, five patients also suffered from the deletion of the other allele. Alterations of the RB gene could be detected in six AP samples, and aberrant band patterns were found in the analysis of exons 2, 3, 4, 6, 7, 13, 14, 17, 21 and 26. Among the six AP samples with structural abnormalities of the RB gene, two showed the loss of the other allele. It is of note that alterations of both P53 and RB genes were observed in two AP samples. Our data strongly suggest that abnormalities of the P53 and RB genes and acceleration of CML are linked events in some cases of AP.

The single stranded [3H]oligonucleotide uptake by HL-60 human promyelocyte and K562 human erythroleukemia cells was stimulated 20–45-fold by DUSF (DNA uptake stimulating protein), and this effect was drastically reduced (to 1.6–13×) if the cells were induced to differentiate. The oligonucleotide uptake stimulating effect of DUSF was not altered in HL-60 and K562 cells, if the proliferation of the cells was inhibited by hydroxyurea (HU) treatment. The oligonucleotide uptake by separated granulocytes and mononuclear cells from healthy donors was not stimulated by DUSF, while the uptake of oligonucleotides by myeloid and lymphoid leukemic cells was greatly stimulated (10–15×). The uptake of oligonucleotides by differentiated mononuclear cells of healthy donors could not be stimulated by DUSF, but the oligonucleotide uptake was greatly increased (11×) by DUSF if the cells were subjected to blast transformation.

Binding studies have shown that human platelets contain binding sites for insulin with a surface density similar to that described for other cells.(1) Evidence for a reduced number and affinity of human platelet membrane insulin binding sites in non-insulin dependent diabetes mellitus (NIDDM) has been provided.(2) However, the influence of insulin and insulin receptors on platelet function has not been completely investigated and clarified. Falcon et al(3) reported phosphorylation of a subunit of the insulin receptor on platelets in response to insulin, but no alterations were detected in cAMP formation or degradation, inositol phosphate formation or phosphorylation of proteins other than the receptor itself. On the other hand Trovati et al(4) found reduced platelet aggregation responses to ADP, PAF, epinephrine, collagen and arachidonate in the presence of 40 µU/ml insulin. Their experience with an euglycemic-hyperinsulinemic clamp provided some further in vivo evidence to support the above mentioned findings. Platelet thromboxane A(2) formation was not altered in the presence of the hormone.

Chronic lymphocytic leukemia (CLL) is a heterogeneous group of diseases among the low-grade malignant lymphomas [8]. B-cell CLL (B-CLL) is the most common form of CLL in Hungary. There is still a considerable range of variability within this category itself. The course of disease is chronic and monotonous, at least morphologically, in most cases, but may be very different and varying in a minority of cases. The factors that determine the rate of advance are unknown and features associated with a poor prognosis are those reflecting advancing stage. Progress from a static phase to a more advanced and finally terminal stage may be of very different duration. While taking care of more than 200 B-CLL in- and out-patients during the last 14 years (1975–1988) in our haematologic department, several cases of different forms of advanced and terminal B-CLL were observed. It is important to distinguish two types of development of a new malignant event in B-CLL: (a) the transformation of the leukemic B-cell to a cytologically less differentiated, and clinically more agressive, cell type, representing the malignant evolution of the B-CLL clone [1–5,7,9–11,14]; and (b) the appearance of a new malignancy whose cell type is different and unrelated to that of CLL [12,13,15]. Only the first type represents a true transformation of the disease and is analogous to the well-known transformation of chronic granulocytic leukemia (CGL; the accelerated and blastic phase).

DNA sequences distantly related to the proviral DNA of HTLV-I were found in the leukemic cells of a Hungarian patient suffering from Sezary syndrome. Serum samples from the patient contained antibodies reactive with the internal core polypeptides of HTLV-1 and HTLV-I 1, but not with the env gene encoded type-specific HTLV antigens. The husband and daughter of the patient also had antibodies of the same specificity. These findings suggest the presence of a virus distantly related to HTLV-I and HTLV-II.

A severe, life-threatening bleeding episode in a 24-year-old woman suffering from type III von Willebrand's disease was treated by large doses of cryoprecipitate with unsatisfactory results. Bleeding ceased and the bleeding time normalized only after concomitant administration of platelet concentrates. In the treatment of von Willebrand's disease patients possessing platelets with absent or insufficient von Willebrand factor activity the administration of plasma concentrates together with platelets appears to be justified.

Central nervous system involvement in Hodgkin's disease is rare (Cuttner et al, 1979; Kaplan, 1980). Memory loss might occur in inflammatory and degenerative disorders of the brain, temporal lobe tumours, head injury, etc. (Walton, 1985). In most cases it is irreversible; however, occasionally a neuro-transmitter-like molecule produced by the neoplasm might be responsible for it and the syndrome can be reversible with the improvement of underlying disease

Willebrand-factor antigen level and structure analysis, ristomycin-cofactor assay, beta-thromboglobulin and thromboxane metabolite estimations were performed in 22 patients with mixed connective tissue disease to evaluate the incidence and the possible role of haemostatic alterations in the complications occurring during the course of the disease. High levels of Willebrand-factor antigen and ristomycin-cofactor activity were detected in patients with thrombocytopenia, previous thrombotic event, pulmonary vascular lesions and usually in the presence of circulating anti-endothelial antibodies. Increased platelet activation could have been found in antibody positive cases and in patients with thrombocytopenia as well. The documented alterations of endothelial and platelet functions may play important role in the vascular complications of mixed connective tissue disease.

AT III, protein C and vWF:Ag measurements are demonstrated. Values measured prior to SK administration (100%) had been compared with the mean values detected during the following 5 days (measurements were performed once each day). Changes are expressed as average values in percents. The reduction of AT III and protein C (both level and activity) reached a biologically significant degree (below 30% of absolute concentration) in two cases

The protein C activity assay of Francis and Patch (Thromb Res 1983; 32: 605-613) is based on the prolongation of the activated partial thromboplastin time in the presence of activated protein C isolated from the test samples. The assay was modified and standardized by Rapaport et al. (Am J Clin Pathol 1987; 87: 491-497), but could still only be used in patients on heparin therapy after chromatographic removal of the heparin. In this study we attempted to eliminate the heparin separation step without losing the advantages of the modified (Rapaport) method. Heparin was added to the isolated protein C to obtain a rapid and complete antithrombin effect after the thrombin activation step and polybrene was subsequently used to neutralize the excess heparin. Using this modified assay protein C activity ranged from 67 to 133% in the normal population, and from 9 to 25% in coumarin-treated patients. Precision of the modified method was acceptable in both normal and pathological PC ranges: within- and between-batch variations were 5.6 and 3.6%, and 8 and 14%, respectively. The assay correlated well (r = 0.84) with the ELISA technique in both healthy donors and non-coumarin-treated patients.

A 34-year-old woman with congenital factor XIII (FXIII) deficiency and multiple connective tissue tumours is reported. The subunit a of FXIII was totally absent in her plasma, platelets and histiocytes of breast fibroadenomas and considerably reduced in the monocytes (below 5%). The plasmatic level of subunit b was also reduced (25%). She had a bleeding tendency and habitual abortions. Fresh frozen plasma therapy permitted a successful pregnancy.

Platelet-associated IgG (PAIgG) was detected by means of anti-human IgG coated polyacrylamide beads ("Immunobeads") technique in 32 patients with chronic ITP. Both a direct test (with in vivo sensitized platelets) and an indirect test (with in vitro loaded platelets) were carried out. The percent of rosette forming beads was both in the direct test (41.2%) and in the indirect test (32.6%) significantly higher in the cases of chronic ITP patients than in the controls (2.5% and 3.2%, respectively). These results confirm the diagnostic value of this new, relatively simple and rapid method in routine clinical practice.

SummaryFour antibiotics which belong to the vancomycin group have been examined in respect of their effects on the factor VIII dependent platelet agglutination. A striking similarity between ristocetin and ristomycin was observed both in qualitative and quantitative terms, therefore ristomycin could be used to determine the so called ristocetin cofactor.Actinoidin and vancomycin inhibited platelet agglutination induced by ristocetin or ristomycin in citrate-PRP or EDTA-PRP as well as in systems containing formaldehyde- treated platelets, but did not inhibit agglutination induced by bovine factor VIII.All the four antibiotics caused plasma protein precipitation. Actinoidin was the least and vancomycin the most effective in this respect; ristocetin and ristomycin also possess this property, the effect of the latter is more considerable.Actinoidin and vancomycin did not block the immediate increase in light absorbancy in aggregometer caused by the addition of ristocetin or ristomycin to fixed platelets at concentrations which totally inhibited platelet agglutination in the presence of protein cofactor. Inhibition of this »direct effect« of ristocetin and ristomycin was observed only at higher concentrations indicating that this effect may be unrelated to the agglutination.According to our results with ristomycin derivatives the methylated carboxyl and the free phenolic hydroxyl groups may be of prime importance in the binding of ristomycin to the platelet membrane and/or to its protein cofactor. Similar data from other laboratories are confirmed and some new findings are offered.

SummaryRate nephelometry immunological antithrombin III determination was elaborated with Beckman Immunochemistry System. The measuring can be carried out within 60 sec from 20 μl plasma. The results show a close correlation with those of gained by the radial immunodiffusion method (r = 0.91) and by Coatest (Kabi-Ortho) (r = 0.77). Both laser-nephelometric and usual non-nephelometric anti-antithrombin III serum (Behring) may be applied.

Summary A 47 year old woman is reported who had life-threatening bleeding due to the spontaneous development of factor VIII:C inhibitor. Cyclosporin combined with prednisone resulted in a full recovery and complete elimination of antibody even when other therapeutic facilities failed to be effective.

Twenty-three patients in various cytological subgroups of blast phase of Ph1-positive chronic myeloid leukaemia were investigated cytogenetically The correlation between prognosis and the cytological and cytogenetic features of blast cells was studied. The best prognosis was found in the myeloid group, followed by the lymphoid, myelomonocytic, megakaryoblastic and finally the promyelocytic groups, in this order. As regards the prognostic significance of the cytogenetic finding, the survival seemed to be the longest among patients with mosaic karyotypes i.e. when further aberrations occurred in some Ph1-positive cells. The course of the disease was the most favourable in the presence of i(17q), especially in patients whose cells had i(17q) as the only aberration. The most severe course of the disease could be found in patients with +8 and/or two Ph1. The results demonstrate the usefulness of chromosome investigations in distinguishing the different cytogenetic subgroups in terminal stages of CML, which also differ prognostically from each other.

The appearance of dual-marked (D) lymphocytes, i.e. lymphocytes having both T and B markers, was investigated in patients with acute (ALL) and chronic lymphocytic leukaemia (CLL) as well as with non-Hodgkin's lymphoma (NHL). E-rosette and immunobead-rosette techniques were combined and simultaneously administered, and the combination was found to be simple, fast and reproducible. D cells could be detected also in normal peripheral blood, however, only in a low percentage. In the blood of 4 patients suffering from ALL, in 2 with CLL and in 1 with NHL the number of D cells were increased significantly. In ALL the relative number of these cells decreased during remission and increased in relapses; thus the determination of the relative frequency of D cells might have prognostic value and could be useful in the choice of an optimal therapeutic protocol.

The case of a 52-year-old woman with congenital cyclo-oxygenase deficiency, signs of generalized atherosclerosis and a moderate bleeding tendency is reported. Secondary platelet aggregation was absent. Platelet aggregation induced by arachidonic acid failed totally while that induced by calcium ionophore was normal. No malondialdehyde formation could be detected in her platelet-rich-plasma. The life-long deficiency of cyclo-oxygenase had not protected her from progressive vascular disease. This case suggests that the chronic intake of large doses of aspirin cannot prevent arterial disorders.

Differential diagnostic importance of acid phosphatase and beta-glucuronidase reactions was studied in bone marrow smears of 52 patients with acute leukaemias. Both reactions showed either diffuse or simultaneously diffuse and granular positivity in the medullary blast cells of 34 patients suffering from ANLL. A strong diffuse positivity of acid phosphatase suggested the possibility of AMOL. Beta-glucuronidase and acid phosphatase reactions were exclusively granular in every positive case of ALL. Increased acid phosphatase activity was found in T-ALL while beta-glucuronidase showed increased activity also in (non-T, non-B)-ALL on several occasions.

Thromboembolism in patients with prosthetic heart valves remains a major time-related problem (Sullivan 1971, Dale 1976, Chesebro 1983). Patients receiving anticoagulant plus antiplatelet agent have the lowest incidence of thromboembolism but the risk of bleeding is not negligible. The laboratory control of combined therapy is unsolved.This study considers the thromboembolic prophylaxis of 38 patients with prosthetic heart valve. Cou-marol treatment was combined with ASA (1 000 mg/week, 36 months follow up).Prothrombin ratio was used in control of the oral anticoagulant therapy. Malondialdehyde production was measured parallel with the so-called malondialdehyde-ratio (MDA-ratio = malondialdehyde level of patient/ control plasma). MDA-ratio, platelet aggregation, thromboxane and prostacycline metabolites were studied 48 hours after 500 mg ASA intake. The average of MDA-ratio was 0.42 ± 0.23 (from 137 measurements). The therapeutic range of MDA-ratio is 0.7 - 0.2. Value below 0.2 means overdosed, over 0.7 means an ineffective ASA therapy. Normal first and second phase platelet aggregation was observed in 23 % of cases when MDA-ratio was below 0.5. Only in 4 % of patients with MDA-ratio over 0.7 was found an abnormal platelet aggregation. The mean prothrombin ratio was 1.59 ± 0.22.No gastrointestinal bleeding or thromboembolism was observed during the 36 months follow up. Contrary to the literary data (Chesebro 1983) coumarol plus small dose ASA did not result excessive bleeding and can be suggested for patients with prosthetic heart valve. Examination of both the prothrombin and the malondialdehyde ratio with study of platelet aggregation is recommended as laboratory control.

The platelet membrane insulin receptors of healthy and non-insulin dependent (type 2) diabetic patients were studied. Receptor number and affinity proved to be decreased in type 2 diabetes mellitus. The changes in platelet insulin receptor characteristics are in good correlation with the alterations reported in other tissues or cells. The possible role of these phenomena in the pathogenesis of disturbed platelet function in diabetics needs further investigation.

In order to investigate the relationship between the in vivo platelet activation in diabetes mellitus and the endothelial damage connected with the diabetic micro- and/or macroangiopathy, plasma levels of beta-thromboglobulin (B-TG) and of factor VIII-related antigen (VIII R:Ag) were studied (1) in juvenile-onset (Type I) diabetics without clinical signs of angiopathy (age under 12 years) and (2) in mostly maturity-onset (Type II) diabetics with and without overt angiopathy (age between 14 and 60 years). Normal controls and nondiabetics with atherosclerosis were also studied. Plasma levels of both proteins were found to be elevated in all the groups of diabetic and atherosclerotic patients in comparison with the controls. Highest levels were found in adult diabetics with angiopathy and in atherosclerotics even without diabetes, but values of the diabetic children were also elevated. The data suggest a causal relationship between the vascular damage and the enhanced platelet reactivity in which the former may play the primary role.