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[Thrombagglutination test (TAT) in hyper- and hypocoagulation].

Breddin thrombagglutination test is followed up in patients with hypercoagulation states--atherosclerosis, atherosclerotic myocardiodysthrophia, angina pectoris gravis and acute myocardial infarction and hypocoagulation states--esential and symptomatic thrombopenia. TAT is positive in 88% of the patients with atherosclerosis and in patients with angina pectoris gravis and myocardial infarction TAT is Vth stage in 100%. TAT is zero stage in 91% in patients with thrombopenia and only in 9%-I stage. The term "zero stage" is introduced.

Agglutination Tests↗

[Epidemiologic, clinical and therapeutic aspects of chronic lymphoid leukemia: apropos of 120 cases].

We retrospectively studied 120 cases of chronic lymphocytic leukemia diagnosed between January 1988 and December 1998. The median age of our patients was of 66 years, 75% among them were male. The discovery of the illness was fortuitous in 20% of the cases, the peripheral adenopathy and the splenomegaly were noted respectively in 72 and 48% of the cases. The blood lymphocytosis was on average 51.109/1 with extremes of 5 and 818.109/1. Anemia was noted in 71% of the cases and a thrombopenia in 42%. Fifty patients were classified C stage of BINET and sixty elevated risk according to RAI. The therapeutic attitude was according to patient's age and the CLL stage. Thus, 94 patients received a chemotherapy and a complete or partial response was observed in 58 of the cases. The overall survival at 5 years were 47%. The retained prognostic factors were the stage according to the classifications of BINET and RAI, the thrombopenia and the lymphocytosis blood overhead 100.109/1.

Adult↗

[pp65 antigenemia in evaluation of cytomegalovirus infection after kidney transplantation].

INTRODUCTION: Cytomegalovirus (CMV) infection is the most common infectious complication after organ transplantation. Serology is useful only for detecting previous CMV infection. Dissatisfied with serologic follow-up after kidney transplantation, three years ago we introduced detection of CMV antigenemia by an immunocytochemical method using a monoclonal antibody specific for the pp65 CMV matrix protein. This test allows for quantification of positive leukocytes. The purpose of this paper is to present our three-year experience. PATIENTS AND METHODS: From May 1999 till May 2002 CMV antigenemia was examined in 76 patients: 55 patients submitted to kidney transplantation during the study period, and 21 patients previously. Antigenemia became positive at 25.68 +/- 15.51 days after transplantation. These 76 patients were divided into three groups according to the number of positive cells per 200,000 leukocytes: < 5 (group I), 6-20 (group II) and > 20 (group III). The groups consisted of 23, 20 and 11 patients, respectively. The percentage of patients treated by ganciclovir was 4.34%, 15% and 100%, respectively. In group I only one patient received ganciclovir because of geographic indication, in group II three patients because of septicemia, thrombopenia and leukopenia and previous miliary tuberculosis. RESULTS: One patient from group III with steroid diabetes died from pneumonia with abscess formation three days from admission. In another two patients, interstitial pneumonia and abscess of the arm developed. Five patients had an acute rejection episode each and were treated by high doses of methylprednisolone. Five patients had elevated temperature, transaminases were elevated in five patients, and neutropenia with or without thrombopenia was found in six patients. One patient had recurrent CMV disease and lymphocele. Two patients had preemptive treatment by ganciclovir based on positive CMV antigenemia. DISCUSSION: Various centers differ according to the approach to treatment of CMV infection, ranging from prophylaxis to deferred treatment for CMV disease. Determination of pp65 CMV antigenemia allowed us a safe follow-up of patients after kidney transplantation. Compared with previous serologic follow-up antigenemia is a considerable progress. We did not use CMV prophylaxis because it is more expensive and can cause resistance to ganciclovir. A promising novel drug valganciclovir will allow for good prophylaxis owing to its better absorption from the gut. Based on our three-year experience, optimal cut-off for antigenemia has been set at 20 positive cells per 200,000 leukocytes. The existence of symptoms or changes in the level of leukocytes, platelets or transaminases goes in favor of treatment decision. CONCLUSION: Cytomegalovirus pp65 antigenemia is a reliable tool in the follow-up of patients after kidney transplantation. Patients with primary CMV infection, those with rejection episode and threshold of 20 positive cells require preemptive treatment with ganciclovir. The measurement of pp65 CMV antigenemia has clinical, analytical and cost-effective advantages. Intensive monitoring for CMV infection allows for quick and specific detection of active CMV infection. This approach avoids resistance to ganciclovir. The method is simple and specific without expensive equipment. Avoidance of unnecessary prophylaxis adds to its cost-effectiveness.

Antigens, Viral↗

[Thrombosis, immunology and drugs].

Diagnosis of thrombopenia due to heparin in sometimes false. We present a case with venous thrombosis in whom the suspicion of thrombopenia induced by heparin finally proved to be a quinidine induced lupus. Related to this observation we emphasise the importance of immunological investigation in patient with venous thrombosis.

Diagnosis, Differential↗

[Repeated abortions, sterility and systemic dysimmunopathy (author's transl)].

A patient with lupus disease had a previous medical history of five recurrent temporary bouts of thrombopenia which were followed by spontaneous abortions. This raises the two-fold problem of the relationship between circulating immune complexes disease and thrombopenia, and dysimmunopathy and pregnancy disorders. The hypothesis is raised of a trophoblastic necrotizing angeitis due to abnormal immunity processes involved in some cases of sterility, spontaneous abortions, and even nephropathies during pregnancy.

Abortion, Habitual↗

Acute renal failure associated with an accidental overdose of colchicine.

CASE SUMMARY: A 47-year-old man with a history of polyarticular gout was admitted to the nephrology service because of severe renal insufficiency (creatinine 6.25 mg/dl). Three days before admission he had a pain crisis in his knees and ankles and self-administered 20 x 1 mg granules of colchicine p.o. over a period of 4 - 5 hours together with six suppositories each containing 100 mg of indomethacin. The patient began vomiting within 24 hours, experienced diarrhea which persisted for three days and then came to the hospital. The patient reported oliguria during the preceding 24 hours. In hospital, attempts to correct water and electrolyte balance were initiated. The patient became stabilized hemo-dynamically, the diarrhea disappeared within 24 hours, diuresis resumed and the renal function progressively improved. Leukopenia and thrombopenia were diagnosed, the transaminases increased: AST = 79 U/l, ALT = 132 U/l on the eighth day after taking the colchicine. The serology for hepatitis A, B, C and HIV viruses was negative; the serology for CMV and VEB revealed a previous infection. After being discharged from hospital 11 days after admission, the patient presented with the following parameters: hematocrit 39%, leukocytes 5,920/microl (3 470 neutrophils), prothrombin time 13 seconds, urea 44 mg/dl, creatinine 1.29 mg/dl, AST 16 U/l and ALT 35 U/l. DISCUSSION: The patient mistakenly ingested 20 mg ofcolchicine p.o. (0.22 mg/kg). The intoxication was associated with gastroenterocolitis, dehydration and renal failure during the first three days after ingestion. The patient also developed leukopenia, thrombopenia and mild hepatocellular injury. Renal failure due to colchicine intoxication is due to various factors such as depletion of volume/hypotension, rhabdomyolysis and multiorgan failure. In this case, the hypovolemia was probably the fundamental cause of the acute renal insufficiency as demonstrated by the quick recovery after administering fluids. It is possible that indomethacin may have enhanced the toxic effect of colchicine on the kidneys and bone marrow. Some colchicine intoxications, as in this case, are caused by an error in interpreting the dose for treating an acute attack of gout. A way to prevent these errors would be to use a low-dose treatment protocol.

Acute Kidney Injury↗

[The practice guideline 'Blood transfusion' (third integral revision)].

The revised and expanded practice guideline 'Blood transfusion' describes the whole transfusion chain within the hospital for the first time. Despite compatibility tests before transfusion (determination of the ABO and Rhesus blood groups and detection of clinically relevant antibodies (C, c, D, E, e, Fy(a), Fy(b), Jk(a), Jk(b), M, S and s)), transfusion reactions can occur. So that a transfusion reaction can be recognised in time, the patient must be observed intensively for the first 5-10 minutes after the start of any new transfusion and the vital functions must be recorded. In patients with a Hb level of 4-6 mmol/l, the decision whether or not to transfuse should be made dependent on the patient's other characteristics. Thrombocyte transfusion is not indicated in case of thrombopenia due to increased breakdown or pooling. If leukaemia, tumour infiltration or drug toxicity is the underlying cause of thrombopenia, then a platelet count of 10 x 10(9)/l or 20 x 10(9)/l should be the transfusion trigger. Reduction of the number of blood transfusions can be achieved by the administration of epoetin in case of renal insufficiency: transfusion can thus be avoided in more than 70% of the patients concerned. Autotransfusion during surgery with severe blood loss also results in a reduction of the number of allogenic blood transfusions.

ABO Blood-Group System↗

Targeting, toxicity, and efficacy of 2-step, pretargeted radioimmunotherapy using a chimeric bispecific antibody and 131I-labeled bivalent hapten in a phase I optimization clinical trial.

UNLABELLED: Safety, targeting, and antitumor efficacy of pretargeted radioimmunotherapy using anti-carcinoembryonic antigen (CEA) hMN-14 x m734 bispecific antibody (BsmAb) and 131I-di-diethylenetriamine pentaacetic acid (DTPA)-indium hapten were evaluated in a phase I study performed on patients with CEA-expressing tumors. METHODS: Twenty-two patients with nonmedullary thyroid carcinoma (non-MTC) (group I, 13 patients) or medullary thyroid carcinoma (MTC) (group II, 9 patients) were enrolled. These patients received a 75 mg/m2 (11 patients) or 40 mg/m2 (11 patients) dose of BsmAb and escalating activities of (131)I-di-DTPA-indium 5 d later. Toxicity and tumor response were assessed in 20 patients who received a therapeutic (>2.2 GBq) hapten dose of radioactivity. RESULTS: The percentage of lesions detected by immunoscintigraphy after injection of the therapeutic dose of hapten was 70% on an anatomic-site basis. High bone uptake was relatively frequent. A transient grade I or II hepatic toxicity was observed in 5 patients (45%) injected with 75 mg/m2 of BsmAb and in 1 patient (11%) injected with 40 mg/m2. No other nonhematologic toxicity was observed. With 75 mg/m2 of BsmAb, hematologic toxicity was high: 5 cases of grade III or IV leukopenia (45%) and 5 cases of grade III or IV thrombopenia (45%). With a 40 mg/m2 dose of BsmAb, hematologic toxicity was reduced significantly: 3 cases of grade III or IV leukopenia (33%) and 1 case of grade III or IV thrombopenia (11%) (P = 0.02). Toxicity was significantly higher in MTC patients than in non-MTC patients (P = 0.019). Nine cases of tumor stabilization of 3 mo to more than 12 mo were observed (45%), 6 in the MTC group and 3 in the non-MTC group. The rate of disease stabilization was significantly higher with 75 mg/m2 of BsmAb (64%) than with 40 mg/m2 (22%) (P = 0.04). Human antimouse antibody elevation was observed in 1 patient (8%) and human antihuman antibody in 4 (33%). CONCLUSION: A BsmAb dose of 40 mg/m2 and a 5-d interval appeared to be a better dose/schedule regimen, with acceptable toxicity. Under these conditions, the maximal tolerated activity was 3 GBq of 131I-di-DTPA-indium in MTC patients. In non-MTC patients, dose escalation should continue.

Adult↗

[Intravascular coagulation in acute promyelocytic leukemia: analysis of coagulation and fibrinolysis parameters].

Eight pts with acute myeloid leukemia were studied to assess coagulation and fibrinolysis disturbances as a cause of hemorrhages associated to thrombopenia. Fibrinogen, products of fibrinogen to fibrin degradation, D-dimer, antithrombin III, protein C, plasminogen and alpha-2 antiplasmin determinations were performed at admission, during and after chemotherapy. All pts were on heparin during induction chemotherapy. Coagulation activation, which increased with the onset of chemotherapy (increases in D-dimer) and a decreasing trend at the end of the antileukemic therapy (normalization of fibrinogen levels) was observed. During the whole observation period alpha-2 antiplasmin levels remained very low. No significant changes were observed in antithrombin III or protein C levels. In conclusion, disseminated intravascular coagulation with associated thrombopenia is an important event in acute leukemia and an increased fibrinolytic activity due to low alpha-2 antiplasmin levels may take part in the genesis of hemorrhage. These data suggest that both heparin administration and the use of antifibrinolytic drugs may have a therapeutic effect.

Adolescent↗

[Rhabdomyolysis caused by severe sepsis: discussion on its role in the development of acute renal failure].

Rhabdomyolysis was evaluated by measurement of total creatine kinase (CK) and lactic dehydrogenase (LDH) in 19 patients with severe sepsis; 12 developed acute renal failure (Group B) and 7 did not (Group A). Results were compared to 7 patients with trauma (Group C) and 6 patients with chronic renal failure and minor infections (Group D). CK was higher (p less than 0.005) in Group B than in A. Results in Group C were similar to those in A. Elevation of CK correlated to increases in creatinine (r = 0.655, p less than 0.005). CK levels of Group D patients were lower than those of Group B. Blood pressure, lactate and pO2 were similar in both groups but thrombopenia was noted in Group B patients. Our results suggest that rhabdomyolysis and thrombopenia play a role in the development of renal failure in patients with severe sepsis.

Acute Kidney Injury↗

[Heparin-induced skin necrosis, thrombocytopenia and pulmonary thromboembolism. Presentation of 2 cases].

Two patients with skin necrosis in the injection points after subcutaneous prophylactic porcine calcium heparin administration are reported. In addition, both patients had thrombopenia, deep venous thrombosis and pulmonary thromboembolism. The review of similar cases suggests that skin necrosis is another feature of the thrombopenia and multiple vascular thrombosis syndrome associated with heparin administration. Data from the literature suggest that there is a common immunologically-mediated pathogenetic mechanism responsible for these phenomena through the production of platelet aggregates and immune reaction in endothelial cells. Paradoxically, the continuation of therapy with intravenous sodium heparin was not followed in our patients by new complications despite the theoretical risk.

Adult↗

[Thrombopenic purpura associated with human immunodeficiency virus infection. Analysis of 24 cases].

In 24 cases of thrombopenic purpura associated with human immunodeficiency virus infection the clinical, immunological and therapeutic features were evaluated. Thrombopenia resulted in clinical manifestations in 20 patients. Splenomegaly was found in only one fourth of patients. Antiplatelet antibodies were found in 9 patients, and thrombopenia was associated with anemia in 37% of cases and with leukopenia in 21%. Bone marrow examination showed megakaryocyte hyperplasia in two thirds of the patients. The major immunological abnormalities were an inverted helper/suppressor T lymphocytes ratio, a reduction in the number of helper T lymphocytes, polyclonal hypergammaglobulinemia, and increased serum concentrations of circulating immunocomplexes. The different therapeutic modalities, steroids, vincristine, danatrol and plasma exchange, resulted in short responses; only two patients had normal platelet counts. The median follow-up was 14 months; during this time three patients fulfilled the criteria of acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Relationship between myelosuppression and chemotherapeutic response in small cell bronchogenic carcinoma.

Most cancerocidal agents have myelosuppression as their major toxicity. In some clinical studies it has been possible to show a relationship between the amount of administered drug and the therapeutic efficacy. Within any defined protocol, however, there may be much variability in the severity of myelosuppression. We attempted to determine whether the tumor response might be related to this toxicity. We evaluated a total of 177 patients with small cell bronchogenic carcinoma, treated by five successive regimens of combination chemotherapy, consisting of either cyclophosphamide and vincristine alone or with doxorubicin or doxorubicin plus bacillus Calmette-Guerin (BCG) or doxorubicin plus methotrexate, for a number of prognostic factors (age, sex, extent of disease, performance status, sites and number of metastases, serum LDH and alkaline phosphatase, weight loss, leukopenia, and thrombopenia). Leukopenia (mean 415 +/- 478/mm3, range 0-2000/mm3) had a weak influence on the incidence of complete remission, which was highest with the least severe nadir (P = 0.027). Thrombopenia was a nonsignificant factor (P = 0.738). Both leukopenia and thrombocytopenia had no influence on the overall survival. Because these drug combinations were based on cyclophosphamide, which requires metabolic activation, we evaluated the relationship of myelosuppression and the incidence of response in a second group of patients with small cell bronchogenic carcinoma treated with a VP16, cyclophosphamide, doxorubicin, vincristine sulfate protocol. In this analysis, no relationship could be detected between remission and myelosuppression. Granulocytopenia or thrombocytopenia also-showed no significant influence on the achievement of long-term survival beyond 36 months.

Antineoplastic Combined Chemotherapy Protocols↗

[Platelet function in systemic lupus erythematosus (author's transl)].

The platelet function was studied in 23 patients with systemic lupus erythematosus, all of whom met the diagnostic creteria established by the American Rheumatism Association. They were not under any treatment, especially with any drug that might interfere with platelet function. The same study was performed on a control group composed of volunteers donors at a blood bank. The platelet count was definitely lower in the patients with lupus than in the control subjects (p less than 0.0005), although a clear thrombopenia was observed in only two indivduals (8.7 percent). Anti-platelet antibodies were found in only six cases (26 percent). There was a linear correlation between thrombopenia and the presence of hemorrhagic diathesis and low levels of C4 and CH50 components. Plateler adhesiveness was clearly lower in the lupus group than in the control group (p less than 0.0005). The presence of kidney disease determined a greater impairment of the platelet adhesiveness (p less than 0.0025). A notable defect on platelet aggregation was induced by ADP, adrenaline and collagen. This was more apparent in the group of patients exhibiting a higher degree of clinical activity and in those who showed a serum complement decrease. The mechanism responsible for this thrombopathy appears to be an interference in the platelet function due to the presence of circulating immunocomplexes. They adhere to the platelet membrane blocking its function and inhibiting the release of the necessary thrombocytic components for the second phase of the aggregation. This platelet alteration is not usually manifested clinically; for this reason no relationship was found between this platelet defect and the presence of hemorrhagic symptoms in our patients. The condition is reversible and may disappear after therapy with steroids and/or immunosuppresive agents.

Adolescent↗

[Diagnosis and therapy of idiopathic thrombocytopenic purpura].

To the diagnostics of the idiopathic thrombopenia caused by autoantibodies belong: 1. the clinical findings such as type of haemorrhage and the controls of the capillary function. 2. the proof of antibodies, in which case positive findings are proving, but negative ones do not exclude the immune thrombopenia, 3. smear of the sternal marrow with judgment of the megakaryocytes and formation of thrombocytes, 4. isotopic control of the survival time of the thrombocytes, which is reserved to special insitutions. As therapy essentially three forms have developed: 1. Therapy with glucocorticoids, 2. Immunosuppressive drugs, 3. Splenectomy. In own observations of 48 patients the glucocorticoids bring an actual improvement only for 7 patients, the others fail in therapy or show only a partial remission. The least prospects are in the immunosuppressive drugs, being equal whether preceding or accompanying a glucocorticoid therapy was performed. Most successes (11 out of 16 patients) are to be stated in splenectomy. Following an after-control of all therapeutic methods together a successful therapy results only in one third, in the next two thirds the therapy either fails or at most evokes a partial remission.

Coombs Test↗

[Acute positive Tdt leukemia with megakaryoblastic involvement. Apropos of an observation of an infant].

After observation of a 10 month-old infant hospitalised for acute thrombopenia associated with signs of marked radiological hyperostosis, the initial medullograms showed a rich bone marrow free of blast cells. Subsequent complications of the thrombopenia were anemia, neutropenia and circulating blastosis. Marrow aspirations at various sites were unsuccessful. X-rays showed a worsening of the conditions and the child suffers attacks of intense pain. Ultrastructural cytochemistry and Tdt disclosed by immunofluorescence showed that the majority of blasts possessed Tdt and 2-3% were PPO positive. The presence of these 2 markers may correspond either to the presence of a promegakaryoblastic leukemia with aberrant Tdt, or to the coexistence of 2 types of blasts cells.

Acute Disease↗

[Snake bites and coagulation disorders].

Within a period of 6 years 8 patients with 12 bites by potentially hemotoxic snakes (crotalids, viperids) were hospitalised in various clinics of the Basle area. All the patients were snake owners. One patient was hospitalized 3 times, 2 patients twice and the others once. In two cases no signs of envenomation were noted after an observation period of 12 hours. Ten bites were followed by local cytotoxic symptoms e.g. oedema and suffusions. Among this group only 6 cases had further signs of systemic, hemotoxic envenomation with decrease of the activity of various coagulation factors. Complete defibrination was seen in 4 patients, but only in 2 cases with additional thrombopenia did overt clinical symptoms of bleeding complications (urological bleeding) occur. Bleeding complications of the central nervous system or of the gastrointestinal tract were not seen. Antivenin was used in three patients and coagulation mechanisms recovered within 24 hours. One patient with complete defibrination, thrombopenia and overt bleeding (macrohematuria) refused antivenin. His coagulation parameters started to improve after 7 days and became normal on day 11.

Adult↗

[Circulating anticoagulants with antiprothrombinase activity in systemic lupus erythematosus (author's transl)].

Circulating anticoagulants with antiprothrombinase activity were detected in 14 out of 49 patients (i.e. 29%) presenting with severe forms of systemic lupus erythematosus (SLE) predominantly renal (29) or extrarenal (20). Nine of these 14 patients had thrombopenia and 8 had a falsely positive Wassermann test. The anticoagulants were more frequently encountered in patients with severe extrarenal manifestations (9/20 cases) than in patients with severe proliferative renal lesions (5/29 cases). They were found in 5 out of 10 patients with arterial and/or venous thrombosis. Anticoagulant levels paralleled the course of the disease during treatment. No haemorrhage was observed in 14 percutaneous renal biopsies performed on 11 patients free from outer coagulopathies. This suggests that the presence of antiprothrombinase anticoagulants in the blood of patients without thrombopenia or other coagulation disorders is compatible with surgery or biopsy of the kidney.

Blood Coagulation↗