Transfusion-associated Chagas' disease in Texas: report of a case.

A 59-year-old woman with metastatic colon cancer, immunosuppressed secondary to chemotherapy and prolonged granulocytopenia, developed acute Chagas' disease that was fatal. During her illness, she received transfusions with large numbers of blood components. Although we were unable to identify an infected donor, we believe her infection was acquired from transfusion of a contaminated blood component. Recently, three similar cases were reported in North America. An influx of immigrants from areas in which Chagas' disease is endemic may account for the increased number of cases of transfusion-associated Chagas' disease in this country.

Use of cardiopulmonary bypass for thrombectomy in acute superior vena cava syndrome.

An increasing incidence of nonmalignant, indwelling catheter cases has been reported in relation to superior vena cava syndrome. Such cases may be life-threatening, with rapid development of facial and neck edema and the production of respiratory distress. This is the first reported case of atrial and superior vena caval thrombectomy requiring cardiopulmonary bypass; it is only the second case reported in which operative thrombectomy has been used. Because of the problems associated with an increase in the use of indwelling venous catheters and the satisfactory results we obtained in this case, such an aggressive form of treatment for acute, benign superior vena cava syndrome may be used more frequently in the future.

Effects of colchicine and vinblastine on platelet contractility and release.

Pre-incubation of normal platelet-rich plasma for 30 minutes at 37 degrees C with concentrations of colchicine (2.5 x 10(-4)M) or vinblastine (1.1 x 10(-4)M) which disrupt platelet microtubles did not inhibit aggregation induced by ADP or collagen. Even following pre-incubation of platelets with a 10-fold higher concentration of colchicine (2.5 x 10(-3)M), platelets released 14C-serotonin and aggregated in response to collagen. In the presence of a 10-fold higher vinblastine concentration (1.1 x 10(-3)M), platelets lysed and released 51Cr. Dynamic viscoelastic measurements on recalcified platelet-rich plasma in a Weissenberg rheogoniometer demonstrated that neither colchicine (2.5 x 10(-4)M to 5 x 10(-3)M) nor vinblastine (1.1 x 10(-4)M) interferes with the initiation, rate of generation, or extent of contractile force produced in platelet-fibrin clots. These results indicate that polymerized tubulin is not essential for collagen-induced release of platelet dense granule contents. In addition, intact tubulin polymers are not required to support the platelet surface configuration necessary for platelet-fibrin adherence and the platelet contractile events which result in platelet-fibrin clot retraction.

Morphine-induced immune thrombocytopenia.

Sudden thrombocytopenia that was temporally related to the administration of morphine sulfate developed in a 23-year-old woman. A morphine-dependent platelet antibody was found in her serum by chromic chloride Cr 51 platelet lysis. The antibody was complement dependent, present in the IgG immunoglobulin fraction, and its drug-dependent platelet lytic activity was demonstrable with several narcotic analgesics in addition to morphine. The antibody activity declined over an eight-month period following recovery from thrombocytopenia. To our knowledge, morphine-induced immune thrombocytopenia has not previously been described.

Bernard-Soulier disease: a study of four patients and their parents.

Two families with Bernard-Soulier disease, including four patients and three of their parents, were studied and detailed clinical summaries are presented. One patient in each family has suffered severe bleeding problems while the other affected sibling is less severely affected. There has been no excessive bleeding in any of the parents or other family members. The patients demonstrated the abnormalities characteristic for Bernard-Soulier disease: thrombocytopenia, giant platelets, prolonged bleeding time, abnormal platelet aggregation to human FVIIIvWF and ristocetin or bovine FVIIIvWF alone, defective ristocetin-induced binding of human 125I-FVIIIvWF multimers, decreased platelet lysis by a drug-dependent antibody and complement, and a decreased concentration of membrane glycoprotein I. The parents had normal platelet counts, bleeding times, and FVIII-mediated aggregation. However, the parents had abnormally large platelets decreased sensitivity to lysis by a drug-dependent antibody and complement, and a decreased concentration of membrane glycoprotein I. Therefore the heterozygous state for Bernard-Soulier disease is recognizable by platelet membrane abnormalities although there is no defect of platelet function and no excessive bleeding. Red cell membrane proteins of one patient were normal, suggesting that phenotypic expression of the Bernard-Soulier disease defect is restricted to platelets.

Platelets, von Willebrand factor, and prostaglandin I2.

Depending on the time of addition, prostaglandin I2 (PGI2; greater than or equal to 10(-9) M) either inhibits or reverses platelet agglutination mediated by human factor VIII-related von Willebrand factor activity (FVIIIvWF) and ristocetin, or bovine FVIIIvWF alone. 6-Keto-PGF1 alpha, the inactive metabolite of PGI2, is without effect, PGI2 inhibition is potentiated by the phosphodiesterase inhibitor, theophylline, and is not the result of PGI2 suppression of ADP release. PGI2 (+/- theophylline) does not inhibit ristocetin-induced binding of purified human 125I-FVIIIvWF multimers to washed platelets or to platelets treated with PGI2 and then formalin fixed (although subsequent agglutination of these platelets is impaired). Washed platelets treated previously with 2-aminoethylisothiouronium bromide (AET), an agent that reduces disulfide bonds and alters platelet membranes, also bind human 125I-FVIIIvWF multimers without agglutinating. We conclude that FVIIIvWF-mediated agglutination requires both functional platelet FVIIIvWF binding sites and platelet-platelet cohesion sites, and that platelet surface cohesion sites are altered by AET and PGI2. PGI2 from adjacent intact endothelial cells may prevent excessive platelet accumulation on exposed subendothelium without suppressing an essential hemostatic process--the binding of platelets to subendothelial FVIIIvWF.

Type IIB von Willebrand's disease: unusual response to cryoprecipitate infusion.

A 16-year-old boy had IIB von Willebrand's disease. The disorder is characterized by prolonged bleeding times; normal plasma levels of factor VIII-coagulant activity, factor VIII-ristocetin cofactor activity, and factor VIII-related antigen; abnormal (anodal) mobility of plasma factor VIII-related antigen on two-dimensional crossed immunoelectrophoresis; and enhanced binding of plasma factor VIII-related antigen to normal platelets in the presence of ristocetin. These variables were measured at time periods after an infusion of normal cryoprecipitate into the patient. The electrophoretic mobility of his plasma factor VIII-related antigen was normal 15 minutes after the infusion but became abnormal (anodal) by 4 hours. His bleeding times were normal after 24 hours and did not correlate with plasma levels of factor VIII-coagulation activity, factor VIII-ristocetin cofactor, factor VIII-related antigen, or the electrophoretic mobility of his plasma factor VIII-related antigen. These results imply that the abnormal factor VIII/von Willebrand factor multimers in the plasma of these patients can associate with normal factor VIII/von Willebrand factor multimers and delay the deposition of the normal multimers into subendothelial surfaces. This may require cryoprecipitate infusions 24 hours before elective surgical procedures.

Interaction of platelets, von Willebrand factor, and ristocetin during platelet agglutination.

Ristocetin induces platelet agglutination in the presence of human factor VIII-associated ristocetin cofactor (vWF). The specificity, extent, and tenacity of binding among these reactants during agglutination and deagglutination were examined. Purified human vWF polymers were radioiodinated and reisolated. Radioiodinated vWF, a disulfide-linked polymer of 230,000 dalton subunits, attached to formalinized human platelets only in the presence of ristocetin. This binding reached equilibrium within 30 sec, and as ristocetin concentrations were raised from 0.2 mg/ml, the extent of attachment increased progressively to reach maximum at 0.5 to 0.6 mg/ml ristocetin. Ristocetin-induced binding was inhibited by vancomycin, unlabeled-purified vWF polymers, normal and hemophilia A plasma, and rabbit anti-human vWF. Binding was not impaired by plasma without detectable vWF or by naturally occurring human IgG antibodies to factor VIII coagulant activity. When formalinized platelets were pelleted from suspensions containing 125I-ristocetin, small quantities of radiolabeled ristocetin associated with platelets both in the presence or absence of vWF. About 95% of the attached 125I-ristocetin was removed by subsequent washes in buffered saline. The attachment of unmodified ristocetin or 125I-ristocetin to platelets, or the formation of complexes with vWF, could not be detected by agarose column chromatography, sucrose cushion ultracentrifugation, or equilibrium dialysis. These results indicate that (1) the initial binding of human vWF polymers to platelets is a specific interaction which requires the presence of ristocetin; (2) ristocetin and human vWF do not form persistent complexes in solution; and (3) the association of ristocetin and platelets is of low affinity.

Prothrombin Houston: a dysprothrombin identifiable by crossed immunoelectrofocusing and abnormal Echis carinatus venom activation.

A 72-yr-old male with a lifelong history of easy bruisability and posttraumatic bleeding had a prolonged prothrombin time and activated partial thromboplastin time. His plasma Stypven, Taipan, and Echis carinatus venom clotting times were prolonged. The presence of a dysprothrombin was confirmed by the discrepancy between plasma prothrombin coagulant activity and prothrombin antigen levels. His plasma prothrombin was capable of being completely absorbed onto and then eluted from barium sulfate. Crossed immunoelectrophoresis of his plasma prothrombin, and normal plasma prothrombin, into agarose containing rabbit anti-human factor II antibody were similar. Crossed immunoelectrofocusing, a procedure combining isoelectric focusing in disc gels with electroimmunoassay in the second dimension, demonstrated that the patient's prothrombin antigen was more basic than normal. The eluate from barium sulfate absorbtion of patient plasma, when reacted with Echis carinatus venom (which directly cleaves prothrombin to thrombin) clotted purified fibrinogen at a rate slower than normal plasma eluate. SDS-slab gel electrophoresis revealed that the prothrombin present in the patient's eluate was cleaved by Echis carinatus venom. These studies suggest that the coagulopathy of prothrombin Houston results from the generation of a dysfunctional thrombin.

Differential effects of cytochalasin B on platelet release, aggregation and contractility: evidence against a contractile mechanism for the release of platelet granular contents.

Cytochalasin B alters the structure and functional properties of filamentous actin. Platelet-mediated clot retraction in dilute platelet-rich plasma (PRP) is inhibited progressively at cytochalasin B concentrations of 0.01 mg/ml, 0.05 mg/ml and 0.1 mg/ml. Dynamic rheological measurements of recalcified PRP in a Weissenberg Rheogoniometer indicate that platelet contractility (as reflected in measurements of elastic moduli) is reduced by 33%, 57% and 63% at cytochalasin B concentrations of 0.01, 0.05 and 0.1 mg/ml, respectively. In contrast, pre-incubation of human platelet-rich plasma (PRP) with 0.01 mg/ml or 0.05 mg/ml cytochalasin B does not inhibit collagen-induced [14C]serotonin release on collagen-induced-platelet aggregation, which is dependent on the release of ADP from platelet dense granules. Even at a cytochalasin B concentration of 0.1 mg/ml, collagen-induced [14C-]serotonin release and aggregation are impaired only moderately. Cytochalasin B does not interfere with the uptake by platelets of [14C-]-serotonin, or with the kinetics and extent of clot formation in platelet-free plasma. Thus, concentrations of cytochalasin B which impair platelet contractility do not inhibit the release of platelet dense granule contents. It is concluded that neither the platelet release reaction nor platelet aggregation is dependent on platelet contractile mechanisms.

Quinidine-induced thrombocytopenia with pulmonary hemorrhage.

Examination of an elderly man with quinidine sulfate-induced thrombocytopenia complicated by pulmonary hemorrhage failed to identify any underlying pulmonary disease contributing to the bleeding All bleeding ceased, and pulmonary infiltrates disappeared after the platelet count returned to normal. Special studies indicated a high titer quinidine-dependent IgG antibody level in the patient's serum and a strongly positive quinidine patch test result on his forearm. The pathogenesis of pulmonary hemorrhage is considered in view of these studies.

Fibrinogen Houston: a dysfibrinogen exhibiting defective fibrin monomer aggregation and alpha-chain cross-linkages.

A 38-year-old male patient with a life-long history of easy bruising and mild bleeding had a prolonged activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). Reptilase (Bathrops atrox) clotting time was normal. His undiluted and diluted plasma prolonged the APTT, PT, and TT of normal plasma. Fibrin produced from patient plasma was insoluble in 5 M urea. Plasma fibrinogen level was increased when measured as clottable protein and by Laurell electroimmunoassay. Specific assays of plasma factors II, V, VII, X, VIII, IX, XI, and XII were normal. A circulating antithrombin in patient plasma was excluded by demonstrating normal thrombin-induced platelet aggregation of gel-separated platelets in the presence of patient plasma. Purified patient fibrinogen reproduced the anticoagulant effect of patient plasma. Patient fibrinogen antigen was similar to normal fibrinogen antigen by immunodiffusion, immunoelectrophoresis (pH 5.2 and 8.6), and crossed immunoelectrophoresis. His unreduced purified fibrinogen had normal migration on polyacrylamide slab gels. Also, the migration in gel slabs of A alpha, B beta and gamma-polypeptide chains, produced by mercaptoethanol reduction of purified patient fibrinogen, was similar to reduced normal fibrinogen. Thrombin-induced total fibrinopeptide release was normal. However, fibrin monomers produced from patient fibrinogen by thrombin (devoid of fibrinopeptides A and B) reaggregated abnormally; fibrin monomers produced by reptilase (devoid of only fibrinopeptides A) reaggregated normally. Fibrin generated from patient plasma in the presence of factor XIII and calcium, was defective in the formation of covalently bonded alpha-alpha polymers and demonstrated an increased susceptibility to the lytic effects of plasmin (generated in vitro by the addition of streptokinase).

AET-treated platelets: their usefulness for platelet antibody detection and an examination of their altered sensitivity to immune lysis.

2-Aminoethylisothiouronium bromide (AET) increases the sensitivity of blood cells to complement-mediated immune lysis. We compared the sensitivities of untreated or AET-treated platelets to immune lysis induced by different types of platelet antibody in the 51Cr platelet lysis test. AET platelets were 8-16 times more sensitive to autoantibody and alloantibody, but 8-16 times less sensitive to drug-dependent antibody. AET-platelets bound similar amounts of alloantibody but less drug-dependent antibody, and they lysed at higher complement dilutions than did untreated platelets. AET-platelets detected 10 of 25 autoantibodies, 9 of 9 alloantibodies, and 5 of 8 drug-dependent antibodies. Untreated platelets detected 1 of 25, 6 of 9, and 7 of 8 of these respective platelet antibodies. The use of AET-platelets in the 51Cr platelet lysis test increases its sensitivity for detecting non-drug-dependent platelet antibodies. AET-platelets resemble paroxysmal nocturnal hemoglobinuria (PNH) platelets in their enhanced sensitivity to complement-mediated lysis. They differ from PNH platelets in their insensitivity to immune lysis induced by drug-dependent antibodies and, in this respect, are similar to Bernard-Soulier syndrome platelets.

Posttransfusion purpura: therapeutic failure of PlAl-negative platelet transfusion.

The effect of platelet type-specific transfusion in posttranfusion purpura is reported. Seven days after receiving 4 units of whole blood during total hip replacement a 69-year-old woman developed fulminant thrombocytopenic purpura. Her undiluted serum inhibited the clot retraction of PlAl-positive but not PlAl-negative blood. Anti-PlAl titer of her serum, determined by 51Cr platelet lysis technique, was 1:64. The serum had no lytic activity against platelet-rich plasma from two PlAl-negative donors. No anti-HLA antibody was detectable in the serum by lymphocytotoxicity technique, and serum obtained prior to transfusions had no platelet lytic activity. Four units of PlAl-negative platelet concentrate were administered, the first instance in which this treatment has been used. No rise in platelet count ensued, and the patient succumbed to purpura. Exchange transfusion or plasmapheresis remain the treatments of choice.

Heparin-induced thrombocytopenia: association with a platelet aggregating factor and arterial thromboses.

Eleven patients with heparin-induced thrombocytopenia were studied. Thrombocytopenia appeared 3-16 days following the initiation of prophylactic or therapeutic doses of heparin. The mean lowest platelet count recorded was 48,000/mm3. When heparin was stopped, recovery from thrombocytopenia began within 24 hours and was complete by ten days. Two patients developed fatal thromboses, and two others had myocardial infarctions while thrombo-cytopenic. In the serum of seven patients, including three of the four with arterial thrombosis, a heparin-dependent platelet aggregating factor was present. The factor caused release of platelet 14C serotonin but did not lyse platelets. It was present in the globulin fraction of all positive sera, and in one serum studied it was isolated in the IgG/IgA immunoglobulin fraction. The factor was not present in 16 normal sera or in the sera of 15 nonthrombocytopenic patients receiving heparin. Our observations suggest that heparin-induced thrombocytopenia is common and that, in some patients it may be accompanied by severe arterial thrombosis. In vivo platelet aggregation is a possible explanation for the thrombocytopenia and the thrombosis in this disorder.

Idiopathic thrombocytopenic purpura occurring in Hodgkin disease after splenectomy: report of two cases and review of the literature.

The occurrence of idiopathic thrombocytopenic purpura (ITP) in Hodgkin disease is uncommon. Even more unusual is the development of ITP in Hodgkin disease following splenectomy. This report describes two patients with Hodgkin disease who developed severe ITP with negative platelet antibody studies very soon after splenectomy (20 days in one and three months in the other). A review of the literature of 21 other patients with well-documented ITP and Hodgkin disease indicated that ITP occurring in Hodgkin disease may be more severe and refractory to therapy than ITP unassociated with Hodgkin. Nodular sclerosis or mixed cellularity histologic types of Hodgkin disease were present in all but one of the patients with ITP and Hodgkin disease, and males constituted 65% of cases. There appeared to be no correlation between the onset of ITP and activity of Hodgkin disease. Of five splenectomized patients with Hodgkin disease who developed ITP and were treated with immunosuppressive drugs for thrombocytopenia, three had an excellent response and two had a good response, suggesting that the combination of corticosteroids and immunosuppressive drugs may be indicated at the outset in patients with Hodgkin disease who develop ITP following splenectomy.

Telangiectasia and von Willebrand's disease in two families.

Two families are described with members who have both von Willebrand's disease and telangiectasias. Family A has four members in three consecutive generations that have both von Willebrand's disease and telangiectasias. von Willebrand's disease in this family is characterized by decreased ristocetin cofactor (FVIII-vWF), variably depressed factor VIII coagulant (FVIII-AHG), and factor VIII-related antigen (FVIII-AGN) levels. FVIII-AGN mobility on two-dimensional crossed immunoelectrophoresis was found to be normal. Four generations in Family B have von Willebrand's disease characterized by decreased FVIIII-AHG, FVIII-vWF, FVIII-AGN, and prolonged template bleeding times. Two members of this family also have telangiectasias and recurrent gastrointestinal bleeding. Results in these two families suggest an association between von Willebrand's disease and telangiectasia--perhaps a defect in vascular endothelial cell function.