Search

In five patients with idiopathic osteonecrosis (ON) of the hip, four having hypofibrinolysis mediated by high plasminogen activator inhibitor (PAI-Fx), and one with high Lp(a), our specific aim was to determine whether therapy (Rx) with the anabolic-androgenic steroid, Stanozolol (6 mg/day), would normalize PAI-Fx and Lp(a) and thus potentially ameliorate ON. Prior to Rx, none of the four patients with high PAI-Fx could normally elevate tissue plasminogen activator (tPA-Fx) after 10 min venous occlusion at 100 mm Hg. After 12-18 weeks on Rx, PAI-Fx and stimulated tPA-Fx normalized in all four patients. Prior to Rx, mean (SD) stimulated tPA-Fx was low, 0.4 +/- 0.3 IU/ml (lower limit of normal 2.28 IU/ml). On Rx, stimulated tPA-Fx normalized, rising to 2.83 +/- 1.9 IU/ml, P = .004. Prior to Rx, mean (SD) basal PAI-Fx was high, 99 +/- 68 (upper limit of normal 26.9 U/ml), and fell on Rx to 22.5 +/- 22, P = .004. In two of the five patients normalization of hypofibrinolysis or high Lp(a) was accompanied by major symptomatic improvement. Prior to Rx, and 2 years after onset of unilateral hip pain, one of the four patients with high PAI-Fx and low stimulated tPA-Fx could walk only one block painfully. After 8 weeks on Stanozolol Rx, and continuing through 54 weeks on Rx, he walked 2 miles per day without pain, despite radiographic progression of ON. In three of the four patients with high PAI and with osteonecrosis present 0.3, 2, and 6 years prior to Stanozolol Rx, there was no clinical improvement after 14-156 weeks of Rx despite normalization of stimulated tPA-Fx and PAI-Fx. The fifth patient, 1 month after onset of disabling hip pain, had normal PAI-Fx but high Lp(a) (27 mg/dl), and MRI evidence of bone marrow edema ("transient osteoporosis").(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the hypothesis that beta blocker use and hypertension are associated with high lipoprotein(a) [Lp(a)] or with reduced basal fibrinolytic activity, the authors studied relationships of hypertension and beta blockers to Lp(a), lipids, lipoproteins, apolipoproteins, and basal fibrinolytic activity in 385 patients consecutively referred for diagnosis and therapy of hyperlipidemia. A second aim was to determine possible gender differences in fibrinolytic activity among patients with hypertension. Ninety-nine patients (58 women [88% post-menopausal] and 41 men) had drug-treated hypertension. In women, hypertension was a positive, independent predictor of the major inhibitors of fibrinolysis, plasminogen activator inhibitor antigen (p = 0,017), and plasminogen activator inhibitor activity (p = 0.004). In men and women, major risk factors for atherosclerosis were significant, independent predictors of reduced basal fibrinolysis. Median Lp(a) in the 99 patients with hypertension (16 mg/dL) did not differ from Lp(a) (18 mg/dL) in normotensive patients (p > 0.1). Of the 385 patients, the 39 beta blocker users had higher plasminogen activator inhibitor activity (p = 0.01), higher triglyceride (p = 0.02) levels, and higher Quetelet Indices (p = 0.01) than non-users (n = 346). After covariance adjusting for age, Quetelet Indices, sex, and triglycerides, plasminogen activator inhibitor activity was not higher in beta blocker users than in non-users (p > 0.1). Median Lp(a) did not differ in beta blocker users (16 mg/dL) and in non-users (17 mg/dL), p greater than 0.1. Hypertensive, predominantly post-menopausal women are likely to have high plasminogen activator inhibitor activity and plasminogen activator inhibitor antigen with concurrent reduced fibrinolytic activity, as well as high fibrinogen levels. These independent coronary heart disease risk factors, along with their hypertension, may put hypertensive, post-menopausal women at increased risk for coronary heart disease.

In eight patients with Legg-Perthes disease, we assessed the etiologic roles of thrombophilia caused by protein C and protein S deficiency and hypofibrinolysis mediated by low levels of tissue plasminogen activator activity. We speculated that thrombosis or hypofibrinolysis were common causes of Legg-Perthes disease. Three of the eight patients had protein C deficiency; they came from kindreds with previously undiagnosed protein C deficiency. In one of these three kindreds there were six protein C-deficient family members (beyond the proband child), four of whom had thrombotic events as adults. One of the eight patients had protein S deficiency, as did his brother who had sustained mesenteric vein thrombosis at age 43. One of the eight patients who had normal proteins C, S, and antithrombin III had hypofibrinolysis, failing to elevate tissue plasminogen activator activity after 10 min of venous occlusion at 100 mm Hg. Plasminogen activator inhibitor, alpha 2-antiplasmin, and fibrinogen values were normal in all eight patients. Beyond their Legg-Perthes disease, none of the eight patients had evidence for venous thrombosis. Of the eight patients, four had thrombophilia and one had hypofibrinolysis, disorders that we believe contributed to thrombotic venous occlusion of the femur with subsequent venous hypertension and bone death that characterize Legg-Perthes disease.

Our specific aim was to assess within-family relationships of basal fibrinolytic activity and its determinants in hyperlipidemic probands (n = 34) with high lipoprotein (a) [Lp(a)] levels (>35 mg/dL) and their first-degree relatives (n = 74) and in hyperlipidemic probands (n = 19) with Lp(a)

In 191 newly referred hyperlipidemic patients, our specific aim was to assess relationships between levels of lipoprotein(a) [Lp(a)], lipids, apolipoproteins, regulators of basal and stimulated fibrinolytic activity, and D-dimer, a measure of in vivo fibrinolysis. Lp(a) levels correlated with none of the measures of basal fibrinolytic regulators or D-dimer. In 25 patients, levels of stimulated regulators of fibrinolytic activity and D-dimer were measured after 10-minute cuff venous occlusion. Lp(a) levels again correlated with none of the stimulated regulators of fibrinolytic activity or D-dimer. However, both basal and stimulated levels of fibrinolytic regulators and D-dimer were closely related to other major risk factors for coronary heart disease (CHD) including triglyceride, apolipoprotein (apo) A1, apo B, Quetelet index (QI), and sex. By stepwise regression in 191 patients, the following standardized partial regression coefficients were significant (P < or = .05), and model R2 and P values were as follows: basal tissue plasminogen activator (tPA) with apo B-.18, with time .17, with QI -.28, R2 = 17%, P < or = .0001; basal plasminogen activator inhibitor (PAI) with apo B..25, with time -.15, with QI .17, R2 = 14%, P < or = .0001; basal alpha 2-antiplasmin with apo A1.14, with apo B.24, with QI.17, with sex .30, R2 = 25%, P < .0001; basal plasminogen with A1.15, with apo B.21, with QI.17, with sex.17, R2 = 15%, P < or = .0001; basal fibrinogen with Lp(a).17, with QI.21, with sex.26, R2 = 14%, P < or = .0001; D-dimer with sex.15, R2 = 21%, P < or = .048. Given the absence of any relationship between Lp(a) levels and inhibition or stimulation of fibrinolysis regulators or D-dimer either in the basal or stimulated state, we postulate that Lp(a)'s major atherogenic effects are mediated by mechanisms other than reduction of fibrinolysis stimulation or in vivo fibrinolysis.

SummaryIn a 29 year old white male with osteonecrosis of both hips and a shoulder, and in his family, we measured basal and stimulated (10 min cuff venous occlusion at 100 mgHg) fibrinolytic activity to determine whether low fibrinolytic activity might be heritable and etiologically associated with osteonecrosis. The proband’s basal tPA-Fx was low, 0.08 IU/ml (normal 0.11-1.94), tPA-Ag was normal (11.6 ng/ml), plasminogen activator inhibitor activity (PAI-Fx) was very high, 119 U/ml (normal 3.5-27), as was his plasminogen activator inhibitor antigen (PAI-Ag), 202 ng/ml (normal 3.2-37.1). The proband’s basal PAI-Fx (119) and PAI-Ag (202) were respectively 6 and 13 standard deviations greater than the mean PAI-Fx (17 ± 15 U/ml) and the mean PAI-Ag (25 ± 13 ng/ml) in 172 concomitantly studied hyperlipidemic men. Alpha-2 antiplasmin, fibrinogen, plasminogen and Lp(a) were normal. Despite lowering TG to 301 mg/dl, basal tPA-Fx remained low, 0.05; PAI-Fx and PAI-Ag remained very high (109 and 191). Following venous occlusion, stimulated tPA-Fx remained very low, 0.1 (normal 2.3-11.3), but tPA-Ag rose normally to 17 (normal 8.4-31.4); stimulated PAI-Fx and PAI-Ag were very high, 134 and 223, (normal PAI-Fx 3.6-24, PAI-Ag 12-96). Stimulated D-dimer was < the 10th percentile, 0.084 μg/ml. With such high PAI-Fx available to bind tPA, occlusionstimulated tPA-Fx could not rise, and fibrinolysis could not be initiated. Neither diseases nor drugs could explain the high PAI-Fx and PAI-Ag, low tPA-Fx, or osteonecrosis. The proband’s father, mother, and sister had very high basal PAI-Ag (240, 69, 66 ng/ml), high basal PAI-Fx (24, 24, 35 U/ml), and normal basal tPA-Fx (0.6, 1.0, and 0.2 IU/ml). Basal PAI-Ag, PAI-Fx, and tPA-Fx were normal in the proband’s son (13, 12, 0.3). The proband’s very high PAI-Fx and PAI-Ag appeared to be inherited, possibly as an autosomal dominant trait, producing hypofibrinolysis. We speculate that his osteonecrosis was caused by familial hypofibrinolysis mediated by high PAI, with subsequent inability to activate fibrinolysis, resulting in inadequate lysis of venous thrombi in bone, impaired bone venous circulation, and venous hypertension of bone characteristic of osteonecrosis.

Skin necrosis associated with protein C deficiency has recently been reported to occur in hemodialysis patients. The clinical presentation and course of this syndrome appears indistinguishable from skin necrosis (purpura fulminans) seen in other settings with inherited or acquired deficiency of the naturally occurring anticoagulant proteins, protein C and S. Patients on maintenance hemodialysis may have low levels of these factors. However, patients on peritoneal dialysis have normal or elevated levels of these proteins despite documented peritoneal losses. We report two patients in whom the occurrence of protein S deficiency and subsequent skin necrosis can be related to demonstrated peritoneal dialysis-associated losses. We suggest that these losses may become critical under appropriate conditions and suggest caution in peritoneal dialysis patients requiring warfarin therapy.

The purpose of this study was to determine if factor VIII:C inhibitors completely disappear during remission and if they recur on exacerbation, are they similar to or different from the original inhibitors? To answer these questions, isofocusing, which separates proteins on the basis of their p/s, was utilized to recover inhibitors from the plasmas of six patients, five nonhemophiliacs with acquired VIII:C inhibitors and the sixth with classic hemophilia. Initially, all plasmas were studied during the presenting hemorrhagic episodes and, subsequently, following the disappearance or recurrence of the inhibitors. Following isofocusing, each fraction was tested for inhibitory activity. The method enabled us to determine that inhibitors to factor VIII:C persisted even when they could not be demonstrated by conventional methods. The inhibitory activity resulted from a composite of inhibitors, each of the group identified by its own p/. In many patients, some peaks persisted throughout the entire interval of study, whereas others disappeared and new ones appeared, suggesting that various groups of cells were capable of producing the inhibitors.

Anticardiolipin antibodies, immunoglobulin G, and M (IgG, IgM) have been associated with recurrent abortion and with maternal death. This study tested whether anticardiolipin titers would be a useful prenatal screening test to determine high-risk pregnancies. Titers were obtained at the first clinic visit in 686 patients, mean gestation, 20 weeks. The outcome variables were taken from a medical records computer data base. IgG anticardiolipin correlated inversely with birthweight (p less than 0.025), but not with gestation. IgM anticardiolipin correlated strongly with the inverse of patient age (p less than 0.0002) and with chronic hypertension (p less than 0.01), but not with preeclampsia. There was a weak correlation with the 1-minute Apgar score (p less than 0.05). Thirty-seven patients had titers of IgG or IgM greater than 3 standard deviations above the mean for nonpregnant patients. Sixteen of these patients were studied for antinuclear antibody and coagulopathy (prothrombin time, partial thromboplastin time, viper venom time) and all were normal. Six of eight patients tested had low range elevated antibody titers to double-stranded DNA. Ten placentas were examined and showed no infarctions. None of the correlations were of practical clinical utility. The biologic basis of the correlations found is of further interest. The value of anticardiolipin titers with lupus erythematosus, or with coagulopathy, was not tested.

SummaryThe plasmas of six patients with prolonged activated partial thromboplastin times were studied in detail. In five of the six, the Russell’s viper venom and prothrombin times were likewise prolonged. Five of the patients had documented systemic lupus erythematosus; one lacked the necessary criteria for this diagnosis. On quantitation, factor XI was decreased in all six; factors X and XII were diminished in five of the six. When tested for inhibitory activity, plasma from each of the patients prolonged the celite eluate inhibition test for factor XII and/or XI inhibition. In the formation of the Xa-V-phospholipid-Ca2+ complex (prothrombinase), factors X and Xa were inhibited to a greater degree than factor V or the phospholipid. Finally, each plasma was isofocused, the inhibitory fractions were identified and the clotting factor specificity of each inhibitory peak was determined.Fractions inhibitory against factors XI and XII isofocused with the IgG in each patient’s plasma. Based on the data presented from these six patients, the “lupus inhibitor” is in fact a heterogeneous collection of inhibitors directed against factors XII, XI and X rather than a homogeneous entity.

Ancrod, which produces in vivo defibrination, has been shown to improve renal function and decrease fibrin deposition and crescents in experimental glomerulonephritis. Ancrod was given for 14 days to 5 patients with glomerulonephritis, moderate to severe renal functional impairment, crescents, and/or fibrin deposition in glomeruli. 4 patients had systemic lupus erythematosus. Ancrod treatment resulted in fibrinogen levels less than 50 mg/dl without bleeding, decrease of previously elevated factor VIII and von Willebrand factor levels, and normalization of in vitro platelet hyperaggregation. Renal function improved in all 5 patients. Serial renal biopsies showed a relatively rapid decrease of glomerular thrombi and necrosis and little increase in glomerular sclerosis. Ancrod administration appears safe, and may have a role in treatment of certain types of glomerulonephritis.

• The combination of a progestogen and an estrogen (Enovid, Enovid E) has been used successfully in the management of nine patients with hereditary hemorrhagic telangiectasia (HHT) and severe epistaxis: Such therapy was instituted when epistaxis was severe and only after other therapeutic measures had failed. Seven of our patients required the 5-mg tablet (Enovid) to achieve a satisfactory clinical result; two patients received the 2.5-mg preparation (Enovid E). The eight women received cyclic therapy; the man received therapy without interruption. Because of the possibility of serious adverse effects from the drugs, it is required that each patient receive a complete medical evaluation prior to therapy and at frequent intervals while receiving therapy. Enovid therapy for HHT is not recommended for the patient with mild bleeding that can be controlled by conventional therapy. ( Arch Otolaryngol 103:148-151, 1977)

Platelet function was serially followed in a group of 13 children with SCD. Defective platelet aggregation was seen in all 4 patients studied during painful crisis and in 45 percent of patients during “asymptomatic” periods. Stypven times were shorter (perhaps reflecting increased PF-3) in the PRP of patients; however, Stypven times were slightly prolonged following freeze-thawing. Recombination experiments in 8 patients revealed no inhibition of SCD plasma on the function of platelets derived normal controls. These findings are suggestive of partial activation of platelets in SCD and may suggest a role of platelets in the genesis of the vaso-occlusive crisis common in this disorder.

An acquired bleeding diathesis was first noted in a 51-year-old patient 11 days following an exploratory laparotomy. Laboratory studies indicated the cause of bleeding to be the development of a circulating anticoagulant which inhibited factor V activity. The inhibitor, an immunoglobulin of the IgG class, was separated by use of Sephadex G-200 filtration, disc electrophoresis, and isoelectric focusing. Despite vigorous immunosuppressive, antifibrinolytic, and replacement therapy, including the use of a “prothrombin complex” and plasmaphoresis, the bleeding diathesis could not be reversed and the patient died of hemorrhage. Although inhibitors to factor V are not usually associated with major life-threatening hemorrhage, this case demonstrates that the development of such an inhibitor can be an ominous finding. The use of an aminoglycoside antibiotic in this and other patients so reported may be one of the contributing causes to the development of such an inhibitor.

Eight patients with hereditary hemorrhagic telangiectasia and severe epistaxis were treated with norethynodrel with mestranol (Enovid). Biopsy specimens of typical lesions from two patients were taken for electron microscopy before and after several months of therapy. Characteristic endothelial cell damage and necrosis were noted in the dilated venules of patients before treatment but not after. Unlined channels of blood were found in connective tissue before treatment but not after. These are thought to arise from leaks in the affected venules, and it is suggested that later endothelial ingrowth gives rise to new telangiectasias and may account for the propagation of lesions that are known to develop with age. Reduplicated basal laminae and regenerating endothelial cells were found both before and after treatment.

SummaryWe have devised an improved high pressure liquid chromatographic technique whereby serotonin, nucleosides, cyclic nucleotides, namely cAMP and cGMP, and 5’ mono-, 5’ di-, and 5’ tri-nucleotides can be analyzed. The cyclic nucleotides have been measured in pico molar quantities. All nucleotides can be quantitated in a single step separation in 75 min using a 0.0015 M phosphoric acids vs. 1 M pH 4.8 ammonium phosphate gradient. 5/10 ml of platelet-rich plasma furnishes an adequate sample for complete analysis. Nucleotide levels in platelets from 16 normal donors expressed in 1011 platelets are as follows: cAMP, 6.32 (4.15) nanomoles and AMP, 0.32(0.14); ADP, 2.48 (0.67); ATP 3.78 (0.68); GDP 0.38 (0.07) and GTP, 0.45 (0.07) micromoles. ADP and ATP values are lower than those previously published. However, the total nucleotide level approaches published values.Upon aggregation with thrombin, approximately 50% of ADP and 40 % ATP is released. Release is complete by 2 min. Thrombin is the most potent releasing agent with collagen and ADP occupying an intermediate role and epinephrine being the least effective. Upon aggregation cyclic AMP levels diminish along with other nucleotides. Patients with asthma showed depression of ADP, ATP, GDP and GTP levels.

The effects of three lasers, Argon, Nd:YAG, and Argon-pumped Dye, on three types of platelet preparations were evaluated. Either EDTA or buffered citrate served as anticoagulants. Platelets separated from plasma and suspended in buffer showed no decrease in counts following lasering, but morphologic damage was evident with transmission electron microscopy (TEM). In platelet-rich plasma, a fall in counts was noted for the Argon and the YAG (at high energy only) but was absent when the Dye laser was employed. Morphologic damage (TEM), however, was noted with all three lasers. When whole blood preparations were used, more marked changes in both RBCs and platelets were seen in samples collected in EDTA compared with citrated samples. Morphologic damage (TEM) to platelets and RBCs occurred with all three lasers. An artifactual increase in "platelet counts," the appearance of spherocytes, and an increase in plasma Hb indicated RBC injury. Both platelets and erythrocytes were sensitive to variations in power (wattage) despite constant total energy delivery.

SummaryAn abnormal fibrinogen was found in a patient associated with disabling recurrent phlebitis and pulmonary emboli, pseudotumor cerebri, gout and endometriosis. The fibrinogen is characterized by (1) abnormal side-to-side and end-to-end polymerization, (2) abnormal fibrinopeptide release, (3) a delayed γ-γ dimerization of the non cross-linked fibrin, (4) a pH optimum of 7-7.8, and (5) a deviation from normal amino acid composition with regard to lysine, aspartic acid, glutamic acid and serine. Since no defect has been found in any of her three children, and since the prothromin and partial thromboplastin times vary from time to time, it is assumed that the defect is acquired. Liver disease, usually associated with acquired abnormal fibrinogen, has been excluded as an etiological cause since liver function tests and biopsy are completely normal.

Scintillating hemianopic scotomas are usually caused either by migraine or, more rarely, vertebral-basilar insufficiency. We report two patients in whom this symptom was probably caused by platelet microthrombi or microemboli in pial vessels of the visual cortex. These patients were similar in that they had scintillating scotomas which began after the age of fifty and abnormal platelet aggregability. Since increased platelet aggregability is associated with cerebral vascular accidents and is treatable, older patients who develop teichopsias should have appropriate hematological tests.

The effects of an Argon laser on platelet aggregation were studied, since platelets may be exposed to laser energy when used intravascularly. Various preparations of platelets in platelet rich plasma (PRP) and whole blood, with or without aspirin, were tested with the aggregating agents ADP, collagen, thrombin, and epinephrine. Simultaneous release of ATP was also measured in PRP. At relatively low levels of irradiation, platelet aggregation was potentiated. Enhancement was evidenced by an increase in percent aggregation, earlier onset of the reaction, and reduction in the amount of aggregating agent required. In PRP, the mechanism of laser potentiation appeared to be the release of endogenous ATP from platelets. At relatively high levels of irradiation, platelets were destroyed and aggregation abolished. In whole blood, the mechanism was somewhat more complicated since release of ATP occurred from RBCs as well as platelets. Spontaneous aggregation following laser treatment occurred in isolated instances in PRP and in every trial in whole blood preparations. Aspirin ingestion inhibited the laser's effects in PRP but not in whole blood. These results may have important clinical implications for laser angioplasty, and the potentiated aggregation response may prove useful in laboratory studies of platelet function.

A non-hemophilic patient with an acquired inhibitor to factor VIIIC was initially diagnosed in this laboratory 20 years ago at age 63. Following its initial appearance in 1963, the inhibitor was detectable on two other occasions. We believe that this is the longest duration such an inhibitor has persisted. No sample remained from his initial admission; however, samples were available from the last 8 years of his life for retrospective study. Preparative isofocusing, affinity chromatography, and immunoglobulin subtyping were used to determine the similarities and/or differences in the inhibitor over these 8 years. The following similarities and differences were observed in both the 1975 and 1983 plasmas. Isofocusing showed that both plasmas contained peaks of inhibitory activity with pIs of 7.25, 8.26, and 8.88; the 1975 sample in addition contained two peaks with pIs of 7.77 and 9.45, whereas two other peaks with pIs of 7.64 and 7.85 were found in the 1983 sample. For the final characterization, each isofocused inhibitory peak was eluted from Protein A Sepharose and incubated with antisera to determine the immunoglobulin subtype. Each peak consisted of mixtures of IgG1 and IgG4 with both kappa and lambda light chains. It was concluded that the inhibitor was polyclonal, based on the presence of inhibitory peaks with different pIs and immunoglobulin subtypes. These findings support the conclusion that the development of and changes in the inhibitor was a dynamic process with some inhibitors (antibodies) persisting, while at the same time others with different characteristics were being formed.

Plasmas from 14 patients with factor VIII inhibitors, 10 haemophiliacs and four non-haemophiliacs, were assayed by both the agarose gel and Bethesda methods. Good correlation was observed in 34 samples from 13 patients, but there was poor correlation in three samples from a single haemophilic patient. The sensitivity of the method was increased by diluting normal platelet rich plasma (PRP) with congenital factor VIII deficient plasma. With this modification, as little as 0.4 of a Bethesda unit (Bu) could be measured accurately. The agarose method is easier to perform and requires much less technician time than the Bethesda assay (Ba). Inhibitory activity can be measured even in the presence of large amounts of transfused factor VIII or factor IX concentrates. To study the effect of factor IX concentrates on the inhibitor, the method was modified by incorporating into the gels plasmas specifically deficient in either factor VII, IX or X. Our data suggest that factor VII is probably responsible for the 'bypassing' activity of factor IX concentrates.

A patient with a factor V inhibitor resistant to all standard methods of therapy was recently reported. Because of this resistance, further investigation of the inhibitor was carried out employing the inhibitory plasma, serum, and isofocused fraction. It has subsequently been shown in vitro by use of the prothrombin time, partial thromboplastin time, and Russell's viper venom time that the activity of the inhibitor is diminished by the addition of calcium chloride or calcium gluconate to the inhibitory plasma, serum, or isofocused fraction before the addition of normal pooled plasma. This inhibitor, an IgG4 (λ) immunoglobulin appears to have a high calcium binding affinity and is markedly potentiated in acid pH. These findings suggest that there may be a role in vivo for calcium infusion as part of the clinical management of such an inhibitor and that the metabolic acidosis associated with hemorrhagic shock may potentiate this type of inhibitor.

• In an earlier report on the kidney in systemic lupus erythematosus (SLE), we described a subset of patients with circulating anticoagulants; many had glomerular and arteriolar thrombosis in the absence of necrosis and subendothelial deposits. The present study extends these observations to a larger group of patients with SLE and a circulating anticoagulant, and compares its findings with those in patients with SLE without evidence of an anticoagulant. It demonstrates (1) a higher prevalence of clinically recognizable thrombotic events in the venous and arterial circulations in patients with SLE and a detectable anticoagulant; (2) a probable shortening in life span; (3) a higher prevalence of glomerular thrombi; (4) elevated levels of factor VIII antigen and von Willebrand factor; and (5) significantly lower platelet counts and decreased in vitro platelet aggregration in response to adenosine diphosphate, epinephrine, and collagen. Since prednisone treatment often results in improvement or disappearance of a prolonged partial thromboplastin time, the test most commonly used for screening of a circulating anticoagulant, we suggest that the prevalence of this abnormality may be underestimated in patients with SLE. ( Arch Intern Med 1985;145:1389-1395)

SYSTEMIC sporotrichosis is a rare but well-recognized opportunistic fungal infection, usually occurring in patients with hematological or lymphoreticular malignant neoplasms, alcohol abuse, long-term high-dose steroid treatment, or diabetes mellitus.1-3We describe a woman who became infected with human immunodeficiency virus ([HIV], formerly denoted human T-lymphotropic virus type III/lymphadenopathy-associated virus) following transfusion therapy for an acquired factor VIII inhibitor and who developed disseminated cutaneous sporotrichosis three years later. Report of a Case A 71-year-old woman was initially seen in March 1986 with a four-month history of progressive fatigue, weight loss, fever, and multiple enlarging cutaneous ulcers. More recently she had also noted night sweats, nonproductive cough, left shoulder pain, and painless right ankle swelling. Three years before admission to the hospital, in December 1982, gross cutaneous hemorrhage developed, and she was found to have an acquired factor VIII inhibitor of high titer (25 Bethesda units) with a residual plasma factor

I was pleased to note the observations of Dr Liote and his associates regarding the association of thrombosing disorders and the presence of the lupus inhibitor in their large series of patients with systemic lupus. Worldwide, there is an increasing interest in these inhibitors, their characterization, and significance.