Triton X contaminating platelet lysate critically affects the measurement of von Willebrand factor ristocetin cofactor activity.
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Antigens↗
Biomedical subjects
G Castaman
Publications and source records attributed to G Castaman.
Clinical significance of fibrinopeptide A in acute lymphocytic and non-lymphocytic leukaemia.
Fibrinopeptide A (FPA) was systematically investigated in 74 patients with acute leukaemia at different stages of the disease (50 with non-lymphocytic leukaemia, ANLL; 24 with lymphocytic leukaemia, ALL). At diagnosis, 75% of the cases had high FPA levels (86% in ANLL and 54% in ALL) with significantly higher levels in ANLL than in ALL (13.4 vs 4.4 ng/ml; p less than 0.001). Patients with DIC (20 cases in ANLL and 1 case in ALL) had significantly higher levels (p less than 0.001). FPA levels were neither correlated with fibrinogen or FDP levels nor with blast cell count. During chemotherapy, median FPA did not show significant changes whereas, at the end of therapy, a return toward normality was generally observed both in ALL and ANLL apart from the group of patients with acute promyelocytic leukaemia. Among the 24 patients who entered post-remission follow-up (13 ANLL and 11 ALL), 10 cases out of the 11 relapsing (6/6 with ANLL and 4/5 with ALL) had increased FPA 1 to 2 months before the ascertainment of the relapse. However, 16% and 9% of the samples obtained on different occasions, respectively from ANLL and ALL cases in maintained first remission, showed FPA above the normal limit. This study demonstrates that subclinical activation of blood coagulation, as indicated by high FPA level, is common both in lymphocytic and non-lymphocytic leukemia and suggests that this phenomenon is related to disease activity.
Adolescent↗
Clinical effectiveness of desmopressin in a case of acquired von Willebrand's syndrome associated with benign monoclonal gammopathy.
A case of acquired von Willebrand's syndrome (avWs) secondary to benign monoclonal gammopathy, is described, in which desmopressin (DDAVP) has proven effective repeatedly in preventing bleeding after tooth extraction. The laboratory pattern was similar to that of congenital type IA von Willebrand's disease. After DDAVP, prolonged bleeding time and factor VIII/von Willebrand factor activities were normalized. The disappearance rate of the elicited activities was similar to that observed in patients with congenital disease. This report adds to the scarce data concerning the haemostatic effectiveness of DDAVP in avWs and suggests that this agent might also be used in controlling or preventing bleeding in patients with the acquired disease, selected on the basis of their biological responsiveness to a test-infusion.
Deamino Arginine Vasopressin↗
von Willebrand factor abnormalities in two patients with uraemia.
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Adult↗
Erythema multiforme after intravenous immunoglobulin.
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Erythema Multiforme↗
Hyper-responsiveness to DDAVP for patients with type I von Willebrand's disease and normal intra-platelet von Willebrand factor.
Desmopressin (DDAVP) has gained wide acceptance as the drug of first choice in the treatment or prevention of haemorrhages in the majority of patients with von Willebrand's disease (vWd). However, data concerning the clinical effectiveness of DDAVP refer generally to mild vWd, with factor VIII and vW factor levels usually above 20% of normal. In 14 patients with type I vWd characterized by very low plasma levels of factor VIII coagulant activity (VIII:C) and vWf, measured as ristocetin cofactor activity (lower than 20% and 3% of normal respectively), but with a normal intraplatelet content of vWf, a test infusion of DDAVP (0.4 microgram/kg) elicited a very marked increase of VIII:C and vWf and normalized the bleeding time. All these patients subsequently underwent tooth extraction after DDAVP infusion. The incidence of bleeding was remarkably low, with only two minor late bleeding episodes easily stopped by repeating DDAVP infusion. Compared to the cases of type I vWd with unknown intraplatelet vWf content reported in the literature, this subgroup of patients had a more marked, albeit short-lived, increment of VIII:C and vWf.
Adolescent↗
von Willebrand disease "Vicenza" with larger-than-normal (supranormal) von Willebrand factor multimers.
When normal volunteers or patients with type I von Willebrand disease (VWD) are given desmopressin (DDAVP), a set of larger-than-normal (supranormal) von Willebrand factor (VWF) multimers, similar to those present in VWF-containing cells such as platelets megakaryocytes and endothelial cells, appear transiently in postinfusion plasma. In two kindreds with mild lifelong bleeding symptoms transmitted as an autosomal dominant trait, all ten symptomatic members (but none of the five asymptomatic members) had a supranormal multimeric structure for plasma VWF, apparently identical to that seen for postdesmopressin normal plasma. Plasma factor VIII coagulant activity (VIII:C), VWF antigen (VWF:Ag), ristocetin-induced platelet agglutination, and ristocetin cofactor (RiCof) activity were low. Platelet VWF:Ag and RiCof levels (tested for three patients only) were normal. Bleeding times were normal or slightly prolonged. The patients' platelet multimeric structure was the same as that for normal platelets. After desmopressin infusion the plasma VWF multimeric structure remained supranormal as for preinfusion plasma, with VIII:C VWF:Ag and RiCof increasing markedly over baseline values and disappearing at a normal rate. Examination of the VWF subunit composition from three of these patients indicated that proteolytic processing of their VWF did not differ from normal. This study describes the first variant of VWD with a supranormal multimeric structure.
Blood Platelets↗
Calibration of lyophilized standards for ristocetin cofactor activity of von Willebrand Factor (vWF) requires vWF-deficient plasma as diluent for dose-response curves.
Calibration of local standards for ristocetin cofactor activity of von Willebrand's factor (vWF:Rcof) against reference preparations is required to achieve a better standardization of this measurement. We have observed that in calibration assays (multiple line parallel bioassay) for vWF:Rcof, measured aggregometrically, the type of diluent used to obtain the dose-response curves exerted a critical influence on the final potency estimation when a fresh-frozen plasma against a lyophilized standard or two lyophilized preparations were to be compared. This pattern was observed with various commercial standards and also with the First International Reference Preparation for Factor VIII-Related Activities in Plasma. The choice of diluent was not relevant if two fresh-frozen plasma preparations were to be calibrated. Systematic experiments using as diluents Tris-saline, Tris-buffered-albumin solution or vWF-deficient plasma (vW-plasma) showed that the ratio lyophilized/fresh-frozen preparations was invariably lower with albumin solution than with vW-plasma. Tris-saline partially corrected this discrepancy, but yielded less precise estimates. Preliminary results with cryosupernatant-plasma seems to indicate that this material is a valid substitute for vW-plasma, but confirmatory experiments are required. For the moment, plasma obtained from patients with severe type III vW-disease should be considered the "ideal" diluent for calibration assays involving lyophilized preparations.
Freeze Drying↗
Recurrent life-threatening epistaxis in a child with Bernard-Soulier syndrome controlled by bilateral ligation of external carotids and ethmoidal arteries.
Bilateral ligation of external carotids and ethmoidal arteries proved successful in controlling severe recurring epistaxis in a 13-year-old patient with Bernard-Soulier syndrome. In this child, epistaxis was the major bleeding symptom. Despite massive substitutive therapy, the patient suffered several life-threatening episodes of hypovolaemic shock. Although epistaxis is not reported as a cause of death in patients with haemostasis defect, our case might suggest that in selected cases with inherited platelet defect and intractable epistaxis so severe as to make normal or near-normal life impossible, surgical treatment could be considered.
Adolescent↗
Epidemiological investigation of the prevalence of von Willebrand's disease.
To evaluate the prevalence of von Willebrand's disease (vWd) we carried out an epidemiological investigation among school children of the Veneto region in northern Italy. A total of 1,218 of 1,281 possible children participated in the study. They were 11 to 14 years of age, and all attended secondary schools in two distinct small areas, 70 km apart, between which there is no social contact. A blood sample was taken from each subject for determination of the blood group and von Willebrand factor (vWf) level (measured as ristocetin cofactor and expressed in IU/dL after calibration of the internal pool against an international standard), and the parents were given a questionnaire concerning hemorrhagic symptoms in the members of the family in the last three generations. Separate normal ranges were calculated for blood group O and non-O subjects (1,166 children and 289 adults) with a nonparametric method because the distribution curves of the reference values did not fit the gaussian distribution. Diagnoses of vWd were considered only for children who had low vWf levels and were members of a family with a convincing bleeding history (case of "probable vWd"). A final diagnosis was assigned if, in addition to these criteria, at least one other family member on the side with hemorrhagic history had a low vWf level. Of the 1,218 children examined, ten were classified as having vWd (0.82%). Taking into account the 90% confidence interval for the lower limit of the normal range, this figure could range from 7 (0.57%) to 14 (1.15%). All these subjects were mildly to moderately affected and presented features of heterozygous classic vWd (type I). Affected subjects were distributed evenly in the two areas examined. Our results suggest that the prevalence of vWd might be much higher than previously reported and that a different screening approach might be of use for patients with mild bleeding diathesis.
Adolescent↗
A contribution to the pathology of acquired plasma factor XIII deficiency.
The biologic activity of Factor XIII was measured in four groups of patients: 20 with liver cirrhosis, ten with acute DIC, 30 with acute leukemia with DIC, and 20 with acute leukemia without DIC. In all groups, the plasma Factor XIII transamidating activity was reduced, but this deficiency was more evident in patients with DIC alone or with leukemia and DIC. The immunologic determination of the a and b subunits of Factor XIII was also performed. Both subunits were below the normal range in the groups of patients studied, except for subunit b, which was normal in patients with leukemia without coagulopathy. Acute DIC patients showed an equally reduced level of both subunits, whereas in patients with leukemia, even in the presence of a complicating coagulopathy, a lesser decrease of subunit b than subunit a was found. Both subunits were equally reduced in patients with cirrhosis, suggesting an impaired synthesis of these proteins. In conclusion, our findings do not support the use of Factor XIII subunit measurements in distinguishing between thrombin- or protease-mediated consumption coagulopathy, and they seem to suggest that the deficiency pattern of the subunits is not accounted for by a simple pathogenetic mechanism.
Acute Disease↗
Erythrocyte fragmentation in disseminated intravascular coagulation (DIC) in acute leukaemia.
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Acute Disease↗
The von Willebrand factor.
Von Willebrand factor (vWf) is a multimeric and multivalent adhesive protein which is essential for platelet adhesion to subendothelium and for stabilization of factor VIII procoagulant activity in circulation. The quantitative measurement of vWf involves essentially two different approaches. The first is based on the interaction between vWf and Gp Ib of the platelet membrane in presence of ristocetin (ristocetin cofactor activity, RiCof) and depends not only on the amount of the factor but also on its ability to bring about this interaction, large multimers being more active. The second approach involves the immunological quantitation of vWf (vWf:Ag) by its interaction with specific polyclonal or monoclonal antibodies as measured by several methods, i.e., electroimmunoassay, immunoradiometric assay and immunoenzymatic assay. Although in the majority of type II von Willebrand disease (vWd) with dysfunctional vWf there is a discrepancy between RiCof and vWf:Ag, it should be emphasized that RiCof activity does not entirely reflect the 'true' activity of vWf since it does not explore all the functions of this factor; furthermore, the relationship between degree of multimerization and RiCof level is not always tenable, as for example in vWd 'Vicenza'. For the diagnosis of congenital and acquired vWd RiCof assay together with family investigation is the eligible test, with an estimated ability to detect at least 50% of the carriers of the abnormal gene, including mildly affected patients; vWf:Ag appears less sensitive and, on the basis of studies carried out in our laboratory, a relative sensitivity of 64% is proposed. Both assays require the definition of separate normal ranges for children and adults and for 0 and non-0 blood group subjects; a nonparametric approach in a large sample of normal subjects is advisable. With RiCof assay performed by an aggregometric method using formalin-fixed platelets an interassay variability of 6% and 8.5% respectively for high- and low-control plasma was found in our laboratory. With vWf:Ag assayed by an ELISA method a variability of 7% for low- and 6% for high-control plasma was found. Thus, both methods appear sufficiently precise for clinical use. The use of an internal pool calibrated against an international standard allows to perform comparable interlaboratory measurements. To further improve standardization of these assays, collaborative studies seem urgently required.
Adult↗
A new Italian family with severe prekallikrein deficiency. Desmopressin-induced fibrinolysis and coagulation changes in homozygous and heterozygous members.
In this paper we report the case of a new Italian family with severe cross-reacting material prekallikrein deficiency (CRM-). The proposita is a 22-year-old woman referred for evaluating an extremely prolonged activated partial thromboplastin time (APTT) detected during a routine screening. No clearcut bleeding history was reported. Prekallikrein antigen and activity were not measurable. The other contact-phase factors were within the normal range. Using an electromechanical coagulometer, six different commercial reagents yielded a markedly prolonged APTT (ratio greater than 2). By prolonging the incubation time up to 10 min, APTT was normalized only with reagents employing ellagic acid as activator. On the contrary, APTT remained markedly prolonged using particulate activators (i.e. micronized silica and celite). No differences were observed using either rabbit or bovine brain cephalin. APTT was also performed on a laser automated ACL instrument; in this case reagents using ellagic acid yielded only moderately prolonged APTT values (ratio 1.3 vs 1.4). The intrinsic fibrinolytic activity, as assessed by blood activator inventory test, was found to be moderately reduced (about 50% of normal) in the proposita, whereas normal values were measured in the heterozygous relatives. After infusion of 0.3 micrograms/kg 1-desamino-8-D-arginine vasopressin (DDAVP), kallikrein levels did not change in the proposita and her heterozygous relatives. A normal release of tissue-plasminogen activator, as assessed by fibrin-plate assay, was observed in all family members including the proposita.
Adult↗
A follow-up study of 49 adult patients with idiopathic thrombocytopenic purpura treated with high-dose immunoglobulins and anti-D immunoglobulins.
BACKGROUND: We analyze here short- and long-term results in 49 patients with idiopathic thrombocytopenic purpura (ITP), consecutively treated with high-dose (h.d.) immunoglobulins (Ig) or anti-D Ig. The major aims of this study were to assess the prognostic power of some patient characteristics and to verify the possibility that repeated courses of treatment can induce a stable remission. Moreover, the relative efficacy and safety of these two treatments were compared. PATIENTS AND METHODS: Group A included 28 patients with chronic ITP and 17 with ITP of recent onset who were receiving h.d. Ig; Group B included 5 patients with ITP of recent onset and 7 with chronic ITP treated with anti-D Ig. Eight cases, receiving both treatment, were included in both groups. Response to treatment was defined as any increase in platelet count above 30 x 10(9)/l, when the platelet count was less than 10 x 10(9)/l, or any doubling of the basal platelet count otherwise. Remission was defined as any platelet count higher than 100 x 10(9)/l lasting for 3 months or longer without therapy. RESULTS AND CONCLUSIONS: Cumulative response and remission rate was not statistically different in the two groups. Multivariate logistic regression analysis showed no influence of sex, previous therapy or duration of disease. Patients older than 60 years were definitely less responsive to h.d. Ig (58% vs 92%, p = 0.03). In Group A, two patients obtained remission after the first course of h.d. Ig. No additional remissions were obtained by repeated courses of h.d. Ig, apart from a single case of ITP of recent onset.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
An unusually prolonged case of heparin-induced thrombocytopenia and disseminated intravascular coagulation.
An unusually prolonged case of heparin-induced severe thrombocytopenia and decompensated disseminated intravascular coagulation (DIC) is described. The patient, treated with heparin at a dosage of 25,000 units/day for 3 days and 12,500 units/day for an additional 4 days because of a clinically suspected deep venous thrombosis, developed (4 days after the discontinuation of heparin) a clinical and laboratory picture of severe DIC, manifested by subcutaneous hematomas and ecchymoses. Platelet count was 24 x 10(9)/l, fibrinogen level 89 mg/dl and fibrin-degradation products between 3,200 to 6,400 ng/ml. A thorough laboratory and instrumental evaluation failed to demonstrate any underlying disorder. No heparin-dependent aggregating factor was detected in the serum of the patient. The patient recovered spontaneously. Whereas fibrinogen and fibrin-degradation products reverted to normality within four weeks, platelet count normalization was delayed until the sixth week after heparin discontinuation.
Aged↗
Fulminant sepsis in adults splenectomized for idiopathic thrombocytopenic purpura.
BACKGROUND AND METHODS: Splenectomy is still a mainstay in the treatment of idiopathic thrombocytopenic purpura (ITP). Although the risk of fulminant sepsis after splenectomy in children and in adults has been known for a long time, the true prevalence of fulminant sepsis in adults splenectomized for ITP has still not been well established, despite many anecdotal reports. In this paper we have tried to estimate this risk by reviewing the available literature and by analyzing a large cohort of adults splenectomized for ITP at our Institute since 1970. RESULTS: Two cases of fulminant sepsis (a 21-year-old man and a 24-year-old woman) were traced in a group of 133 splenectomized adults, with a crude incidence of 1.5% or, equivalently, of 0.17 cases per 100 patient-years. No case of sepsis occurred in a control group of 323 non splenectomized ITP adults. This estimation seems sufficiently precise for the large population analyzed and the duration and completeness of follow-up (1,126 patient-years, mean 101 months, 2 patients lost from follow-up), and it is in agreement with the estimations yielded by a literature review (1.8%). CONCLUSIONS: The risk of fulminant sepsis seems to be a real hazard in adults splenectomized for ITP, and a conservative approach in recommending splenectomy seems advisable. Antipneumococcal vaccination should also be recommended.
Adolescent↗
Long-lasting remission after high-dose intravenous immunoglobulins in a case of relapsing thrombotic thrombocytopenic purpura.
Long-lasting remission after high-dose intravenous immunoglobulins in a case of relapsing thrombotic thrombocytopenic purpura (TTP) is reported. The patient had two early relapses after intensive plasma-exchange therapy. Serum platelet aggregating factor was absent. High-dose intravenous immunoglobulins (i.v. Ig) (0.4 g/Kg/day for 5 days) were infused. Platelet count promptly rose and 7 days after the completion of immunoglobulins complete response was obtained. The patient is still in complete remission, without further Ig infusion, 19 months later. This case adds to the anecdotal reports on the effectiveness of Ig, even when not associated with other treatments, in TTP. High-dose i.v. Ig could be successfully used in relapsing or unresponsive patients with TTP.
Blood Coagulation Factors↗