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Biomedical subjects

G Castaman

Publications and source records attributed to G Castaman.

142 records · Page 8Linked to original sources
PubMedDate not supplied

Fibrinolytic studies in 13 unrelated families with factor XII deficiency.

BACKGROUND AND METHODS: We report the results of extensive "in vitro" fibrinolytic studies in 18 homozygous and 14 obligatory heterozygous subjects belonging to 13 unrelated families with factor XII deficiency. All homozygotes had unmeasurable factor XII activity (XII:C) and antigen (XII:Ag). None had bleeding symptoms, whereas a myocardial infarction occurred in one of them at age 51. In heterozygotes XII:C and XII:Ag were 55.9 +/- 14.1% and 52.1 +/- 16.4% (corresponding figures in 40 normals 100.6 +/- 18.3% and 101.5 +/- 29.7%). Total intrinsic fibrinolytic activity was assayed on fibrin plates in the dextran sulfate euglobulin fraction of plasma from resting subjects, to which flufenamate was added to inhibit blood plasminogen activator inhibitors. RESULTS: Fibrinolytic activity was reduced in all homozygotes (40 +/- 12 BAU/ml) in comparison to heterozygotes (103 +/- 12 BAU/ml) and normals (98 +/- 20 BAU/ml). The addition of purified activated beta-XII led to a complete restoration of fibrinolysis in homozygotes. The addition of anti-urokinase antibodies completely suppressed the reduced intrinsic fibrinolytic activity in homozygotes (4 +/- 7 BAU/ml), whereas a reduction to about 50% was evident in heterozygotes and normals. CONCLUSIONS: Our data confirm that reduced "in vitro" intrinsic fibrinolytic activity is a common finding in homozygous factor XII deficiency and that two independent mechanisms, one factor XII-dependent and urokinase-independent and the other factor XII-independent and urokinase-dependent, are responsible for the generation of intrinsic fibrinolysis in human plasma.

Adolescent↗
PubMedDate not supplied

Thrombotic complications during L-asparaginase treatment for acute lymphocytic leukemia.

We report 2 new cases of thrombosis occurring in a cohort of 21 consecutive patients with acute lymphocytic leukemia treated with L-asparaginase (L-ase), 6,000 U/die s.c. or i.m. days 15-21 from start of chemotherapy, according to the GIMEMA LAL 0288 protocol. The first patient died of massive diffuse thromboembolism (thrombosis of sagittal sinus and of suprahepatic veins and pulmonary arteries; multiple hepatic and splenic infarctions) associated with markedly reduced levels of protein C, antithrombin III and plasminogen. In the second patient, portal vein thrombosis developed soon after the completion of L-ase. Antithrombin III was reduced, whereas protein C level was normal. Therapy with fresh frozen plasma and subcutaneous calcium heparin (12,500 U twice daily) proved successful, and 8 days later abdominal echotomography revealed the complete disappearance of the thrombus. The incidence of thrombosis is similar to that previously found in a cohort of consecutive patients treated at our Department with a different schedule and dosage of L-ase administration, and similar to that reported in previous series.

Adolescent↗
PubMedDate not supplied

[Therapy with high-dose intravenous gamma globulin in the newborn infant with thrombocytopenia from passive immunization].

High doses of gammaglobulin intravenously have been found useful in controlling thrombocytopenia of a neonate born to a mother who developed acute idiopathic thrombocytopenic purpura during pregnancy. Administration of 0.4 gm/kg/day of intact gammaglobulin intravenously for five days was followed by dramatic rise of platelet count without any side-effect. After 1 month the platelet count was still normal. Passively-acquired immune thrombocytopenia of the newborn consequently is another indication for intravenous gammaglobulin therapy.

Humans↗
PubMedDate not supplied

Polycythemia vera and essential thrombocythemia in young patients.

BACKGROUND AND METHODS: Polycythemia vera (PV) and essential thrombocythemia (ET) in young patients are rarely reported. Their natural histories seem to differ from those of older patients and the best treatment is still uncertain. In this follow-up study we have evaluated a cohort of 64 consecutive patients younger than 40 to determine the incidence of thrombohemorrhagic events and the long-term outcome. RESULTS: Twenty-eight patients (20 M; 8 F) had PV, and 36 ET (21 F, 15 M). Mean follow-up was 8.2 years (range 4 months-16.7 years) in PV and 6.5 years (range 5 months-15 years) in ET. Thrombohemorrhagic symptoms were present at diagnosis in 10/28 patients (35%) with PV and in 12/36 patients (33%) with ET; during follow-up in 15/28 PV patients (53%) and in 13/36 ET patients (36%). Thrombotic events were the most frequent symptoms, both at diagnosis (52% in PV, 65% in ET) and during follow-up (43% in PV, 52% in ET). A total of 19/28 PV patients (67%) and 17/36 ET patients (47%) had thrombotic complications. Hemorrhagic complications at diagnosis were 4% and during follow-up 13% in PV, and 15% and 13% in ET. A total of 5/28 (18%) PV and 6/36 (17%) ET patients had hemorrhagic events. No laboratory parameter, including platelet count, was predictive of these events. Five PV patients had major thrombotic complications (18%). Four PV patients died (14%), 2 because of ANLL (7%), 2 because of thrombotic events (7%). Four ET patients experienced major complications, in three cases thrombotic (8.3%), in one hemorrhagic. No leukemic transformation occurred in ET and no ET patient died. CONCLUSIONS: In our experience, severe thrombohemorrhagic complications are present in young patients with PV and ET, which excludes young age as a favorable prognostic factor. Treatment also seems advisable for young patients and myelosuppressive treatment might be required. Prospective studies are urgently needed to assess the best treatment for this particular subset of patients.

Actuarial Analysis↗
PubMedDate not supplied

Is ticlopidine a safe alternative to aspirin for management of myeloproliferative disorders?

BACKGROUND: Bleeding and thrombosis are frequent complications in patients with chronic myeloproliferative disorders (cMPD). Antiplatelet therapy is extensively used by many physicians for primary prophylaxis of thrombotic events, even though there have been no prospective trials that demonstrate clinical benefit. The use of aspirin has been associated with a heavy incidence of serious hemorrhages, particularly of gastrointestinal origin. This evidence is mainly based on data from patients treated with dosages far higher than those presently recommended. Moreover, patients with bleeding symptoms or prolonged bleeding time (BT) had not usually been excluded from treatment. METHODS: In this study 58 patients with cMPD and thrombocytosis were treated with aspirin (325-500 mg/day, 31 patients) or with ticlopidine (500 mg/day 27 patients). Only patients with negative bleeding histories and normal BT were considered. Ticlopidine, a drug not extensively investigated in cMPD, was reserved only for patients with histories of gastritis, gastric discomfort, peptic ulcer and/or intolerance to aspirin. All other patients were given aspirin combined with antacids in a buffered preparation. RESULTS AND CONCLUSIONS: Average follow-up was 2 years. Aspirin was associated with a high incidence of gastrointestinal hemorrhages (5/31). Ticlopidine was tolerated better and no bleeding complications were recorded. Both drugs were similarly effective in relieving erythromelalgia and painful paresthesia in almost all cases with these symptoms within 24-48 hours.

Adult↗
PubMedDate not supplied

Treatment of idiopathic thrombocytopenic purpura (ITP) in patients with refractoriness to or with contraindication for corticosteroids and/or splenectomy with immunosuppressive therapy and danazol.

BACKGROUND: The best treatment for patients with idiopathic thrombocytopenic purpura (ITP) who are refractory to or have contraindications for splenectomy and corticosteroid remains uncertain. We report here our experience with vinca alkaloids (VA), azathioprine (Azp) and danazol in 33 such patients (6 M/27 F), median age 66 (23-83). PATIENTS: Group A (n = 19), Group B (n = 11), Group C (n = 17) patients were treated with VA, Azp and danazol. Fourteen patients were given more than one immunosuppressor agent. Sixteen patients were given 2 mg/week bolus infusions of vincristine (Vcr), while weekly slow infusions of vinblastine (Vnb, 0.1 mg/kg), for 2-4 weeks, were administered to the remaining 3 cases of Group A. Azp was administered at a daily dose of 150 mg for a median duration of 6 months. Danazol was administered at a median daily dose of 400 mg (400-800 mg), for a median length of 5 months. Response was defined as any increase of platelet count to higher than 30 x 10(9)/l, when platelet count was < 20 x 10(9)/l or any doubling of the basal platelet count otherwise. Remission, any increase of platelet count to higher than 100 x 10(9)/l lasting for 3 months or longer without therapy. RESULTS AND CONCLUSIONS: In Group A, there was a response rate of 63%, with 2 remissions (10%). All responses were observed after the first infusion. Two additional patients, who responded transitorily to VA, went into spontaneous remission 19 and 51 months after the last infusion of VA. In Group B, the response rate was 45%, with 1 remission (9%). The response was never observed before one month. One additional patient went into spontaneous remission 60 months after stopping Azp. In Group C, the response rate was 56% with 2 remissions (12%); 2 patients relapsed while on therapy, 4 continue to require therapy and 1 died from a stroke while on therapy. Four patients in Group A and two in Group B discontinued the therapy because of severe side effects. Danazol was generally well tolerated but for one patient was interrupted after only 5 days because of severe dyspepsia. In conclusion, the clinical usefulness of VA and Azp is very limited and burdened by severe side-effects. Danazol seems to be safer but no more effective and its long-term toxicity is not known. There were two hemorrhagic deaths in this series of patients.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Adult patients with the nephrotic syndrome: really at high risk for deep venous thromboembolism? Report of a series and review of the literature.

BACKGROUND: The reported incidence of thromboembolic episodes in people with nephrotic syndrome (NS) ranges from 6% to 44% and it has been ascribed to the presence of a hypercoagulable state, as suggested by abnormalities of several hemostatic parameters in these patients. However, the results of the studies are often contradictory and fragmented and are rarely based on prospective studies. To assess the incidence of venous thrombosis and the pattern of abnormalities of the hemostatic parameters in NS, we planned a prospective study of a group of patients with NS. PATIENTS AND METHODS: Thirty-six consecutive patients with NS were enrolled during a 9-month period. Every 4-6 months, clinical history was collected and physical examination was carried out. Blood samples for laboratory investigation were taken at entry into the study and 24 months later. A critical review of the literature was also carried out (Medline database and Current Contents). RESULTS: During the follow-up (mean 45.2 months), no thrombotic symptoms were recorded, PTT, PT, TT and mean AT-III levels were within the normal range, whereas fibrinogen, plasminogen, protein C and S, heparin cofactor II levels were significantly higher than normal both at entry into the study and 24 months later. No patient was positive for antiphospholipid antibodies. Slightly decreased levels of AT-III and heparin cofactor II were found in only two cases. CONCLUSIONS: Our study confirms neither the high incidence of thrombotic complications in NS nor the presence of abnormalities of hemostatic parameters commonly associated with venous thromboembolism.

Adolescent↗
PubMedDate not supplied

Acquired plasma factor XIII deficiencies.

Coagulation factor XIII (FXIII) is of paramount importance in the process of fibrin stabilization, which is the final step of the coagulation cascade. The clinical significance of defective fibrin stabilization is highlighted by the severe hemorrhagic manifestations of congenital FXIII deficiency. In this paper we review the pathophysiology, clinical presentation and therapy of acquired plasma FXIII deficiencies, caused by specific inhibitors or associated with other clinical conditions. For acquired severe FXIII deficiency caused by factor-specific inhibitors, the need for prompt diagnosis and treatment is emphasized by the high hemorrhagic risk and mortality. For moderate reduction of FXIII secondary to other conditions, we discuss the relative importance of FXIII reduction in the development of clinical symptoms and the role of substitution treatment.

Acute Disease↗
PubMedDate not supplied

Fibrinogen survival and fibrinopeptide A in acute leukemia.

BACKGROUND. Hypofibrinogenemia and increased fibrin(ogen) degradation products in acute leukemia have been attributed to intravascular thrombin generation triggered by leukemic cells. However, the strict relationship between fibrinogen catabolism and turnover of fibrinopeptide A (FPA), which is a sensitive and specific marker of thrombin activity, has not been evaluated in acute leukemia (AL) with or without disseminated intravascular coagulation (DIC) to see whether mechanisms other than thrombin activity could be responsible for fibrinogen consumption. We report here the 125I-fibrinogen kinetics and FPA measurements in 19 patients with AL, 6 of them with DIC. METHODS AND RESULTS. Radiolabelled fibrinogen kinetics were studied in all the patients concomitantly with the start of chemotherapy. Fibrinopeptide A was measured by a radioimmunoassay at time of diagnosis and during chemotherapy. The kinetics of disappearance of radiolabelled fibrinogen where biphasic, with a rapid phase in the first 1-3 days of chemotherapy and a subsequent slow phase associated with the reduction or disappearance of blast cells. Patients with DIC had a significantly shorter half-life and turnover than patients without DIC. The latter group had significant shortening of these parameters in comparison to normal subjects. The thrombin-dependent catabolic rate of fibrinogen, calculated from the mean level of FPA during the first phase of disappearance curve and by assuming 2 moles of FPA generated per mole of fibrinogen, was similar in patients without DIC and in normal subjects, whereas patients with DIC had a significantly higher catabolic rate, even though the increase was not sufficient to account for all the turnover of fibrinogen. No relationship was observed between fibrinogen turnover and FPA turnover.

Acute Disease↗
PubMedDate not supplied

Erwinia- and E. coli-derived L-asparaginase have similar effects on hemostasis. Pilot study in 10 patients with acute lymphoblastic leukemia.

BACKGROUND: L-asparaginase (L-ase) affects the synthesis of several hemostatic factors, including the naturally occurring clotting inhibitors antithrombin III, protein C and S, and thromboembolic events are a well-recognized complication of the hypercoagulable state resulting from this treatment. Recently, in addition to the widely used E. Coli-derived L-ase, a new L-ase derived from Erwinia Carotovora has been introduced into clinical studies. This formulation seems to have lesser side-effects, but data on its effects on the hemostatic system are very limited. We report here the hemostatic changes observed in 10 adult patients with acute lymphoblastic leukemia (ALL) treated with Erwinia- or with E. Coli-derived L-ase. METHODS AND RESULTS: The decreases (percentages of basal level) of antithrombin III, protein C and plasminogen (functional assays) were similar in both groups of patients (about 50% of the basal value 6 or 8 days after starting L-ase) and so were the number of instances in which the level of these proteins fell below 70% of normal. On the contrary, the fibrinogen level (PT-derived method) was less severely decreased by Erwinia L-ase (34% of basal value for E. Coli L-ase versus 58% for Erwinia L-ase; P = 0.048) and there were more instances in which the fibrinogen level was less than 100 mg/dL than with E. Coli L-ase (40% versus 16%; P = 0.051). Thrombin-AT-III complexes (ELISA) showed similar pattern during both treatments. Two patients treated with Erwinia L-ase had moderate hyperglycemia, requiring insulin treatment but not L-ase discontinuation. No allergic reaction or pancreatitis was observed. A patient in the Erwinia L-ase-treated group developed deep venous thrombosis on day 7 after the start of L-ase and was treated with subcutaneous heparin (12,500 U x 2/day), with prompt improvement. CONCLUSION: This study shows that the two L-ase formulations have similar effects on hemostasis. Patients treated with Erwinia L-ase may develop thrombotic symptoms, as already reported for E. Coli-L-ase.

Adolescent↗
PubMedDate not supplied

Fulminant sepsis in adults splenectomized for Hodgkin's disease.

BACKGROUND AND METHODS: Laparotomy with splenectomy still remains important for staging Hodgkin's disease (HD). The risk of fulminant sepsis (FS) after splenectomy is well known, but the incidence of FS in splenectomized HD adult patients has not been accurately assessed. In this study we have tried to assess this risk and its duration and to evaluate the role of HD "per se" in causing FS. RESULTS: Six cases of FS were traced in a group of 226 splenectomized adults, with a crude incidence of 2.65%. Age at the time of the event ranged from 23 to 41 years and time after splenectomy from 46 to 98 months. Four patients were disease-free when sepsis occurred. In 4 cases the causative agent was isolated (3 Streptococcus Pneumoniae, 1 Streptococcus alpha Haemolyticus). The mortality rate was 66%, while net probability of death (life table) at 10 years was 2.6%. M/F rate was 0/6 (P = 0.01). The incidence of FS was 0.33 cases per 100 patient-years (I.C. 95% = 0.12-0.72). There seems to be no relationship to histological type, clinical stage or age at splenectomy. No case of sepsis occurred in a control group of 281 non-splenectomized HD adults (P = < 0.01), despite the more advanced disease present in these cases on the average. CONCLUSIONS: The frequency of FS, the causative agents, the mortality rate, the duration of risk are similar to those previously reported. Prompt treatment of any febrile disease in HD splenectomized patients and a policy of antipneumococcal (and possibly of anti-meningococcal) vaccination seem advisable.

Adolescent↗
PubMedDate not supplied

Acute renal failure after high-dose intravenous immune globulin in a patient with idiopathic thrombocytopenic purpura.

High-dose intravenous immunoglobulin (IVIG) is considered a safe and efficacious treatment for patients with a variety of hematological and non hematological diseases, including patients with idiopathic thrombocytopenic purpura (ITP) not responsive or with contraindications to corticosteroids and/or splenectomy. Side-effects are usually minor, but severe reactions have been rarely reported. We describe the case of a patient with ITP, without pre-existing renal disease, who developed a severe transitory acute renal failure following administration of IVIG, promptly reversed after hemodialysis.

Acute Kidney Injury↗
PubMedDate not supplied

Gestational thrombocytopenia: a prospective study.

Gestational thrombocytopenia (GT) is commonly observed in pregnancies with otherwise limited obstetric and hematologic complications. However, few data are available on the natural history of the disease, and on the recurrence of thrombocytopenia in subsequent pregnancies. From June 1987 to December 1993, 37 consecutive patients with GT were enrolled in a prospective study, with a total of 41 pregnancies observed. Vaginal delivery was carried out in 33/41 (80%); two patients were transfused fused with packed red cells for obstetric hemorrhage (post-partum uterine atony). Neonatal bleeding did not occur. In all newborns platelet count was performed within 24 hours after delivery: 2 newborns had mild (80 and 75 x 10(9)/L) and 1 severe thrombocytopenia (12 x 10(9)/L) at birth; all of them recovered to a normal platelet count within 10 days without treatment. Twenty-eight out of 3% patients were followed for 12 months after delivery; in 23 a normalization of platelet count occurred within 1-5 months from delivery; in 5 mild thrombocytopenia (100-120 x 10(9)/L) persisted during follow-up. Four patients had a second pregnancy and recurrence of thrombocytopenia was observed in all of them. GT is rarely associated with bleeding episodes during pregnancy and partum, and recovers spontaneously within few months after delivery but thrombocytopenia can recur in subsequent pregnancies. Severe thrombocytopenia is not observed in newborns so that a conservative management is warranted.

Adult↗
PubMedDate not supplied

Pilot study on the safety and efficacy of desmopressin for the treatment or prevention of bleeding in patients with hematologic malignancies.

BACKGROUND AND OBJECTIVES: Desmopressin is the treatment of choice for patients with von Willebrand's disease and mild hemophilia A. This compound is also useful in other congenital and acquired disorders of hemostasis, reducing the need for blood derivatives with the inherent risks of infections and alloimmunization. The following article presents a pilot study on the safety and efficacy of desmopressin for the treatment or prevention of bleeding in 15 patients with thrombocytopenia associated with hematologic malignancies. METHODS: Cases were consecutively recruited from February to June 1995. Fifteen patients were treated with desmopressin for prevention or treatment of bleeding. Desmopressin was diluted in 100 mL of isotonic saline and infused for 30 minutes. Bleeding time (BT) was carried out using the Simplate II device, making two standardized incisions on the forearm: the mean between the two incisions was recorded. RESULTS: Significant reduction of BT was observed in three out of four patients with myelodysplastic syndrome who were successfully treated for active bleeding or dental extraction. In the remaining patients, the effect of desmopressin on BT was not tested. Nevertheless, in all of them bleeding mainly due to epistaxis or persistent gum oozing was stopped by a single infusion of desmopressin. In three patients, desmopressin infusion had been successfully administered on a different occasion. No side effects were observed. INTERPRETATION AND CONCLUSIONS: Desmopressin could be a safe and immediately effective option for the treatment or prevention of bleeding in selected patients with hematologic malignancies.

Adult↗