Disseminated varicella-zoster virus infection with the syndrome of inappropriate antidiuretic hormone.

A patient with non-Hodgkin's lymphoma who was previously treated with chemotherapy and radiotherapy was seen with intestinal pseudoobstruction due to paralytic ileus associated with herpes zoster (varicella zoster) infection. The infection was accompanied by a polydermatomal rash with typical morphologic characteristics, followed by cutaneous dissemination and the syndrome of inappropriate antidiuretic hormone (SIADH), as well as myotomal paresis. The diagnosis was supported by cytology and by culture of the virus from the CSF. The isolation of the virus from the CSF, coupled with abnormalities of the patient's mental status and CSF, indicate that meningoencephalitis occurred and probably accounted for the SIADH. The patient had a spontaneous and complete recovery. To our knowledge, this is the first report of SIADH associated with herpes zoster infection.

Effects of anticoagulation on markers of activation of clotting following major orthopedic surgery.

INTRODUCTION: This study examines makers of activation of clotting following three chemoprophylactic regimens used for prevention of postoperative venous thromboembolic disease (TED) following high-risk surgery for TED. METHODS: Patients having elective primary knee or hip replacement surgery received variable dose warfarin (target international normalized ratios 2.0-2.5), 1 mg warfarin daily starting 7 days preoperatively or aspirin 325 mg daily starting on the day of surgery. Twelve patients in each group were treated for 28 ± 2 days. Thrombin-antithrombin (T-AT) and prothrombin fragment F1 + 2 were measured at baseline and postoperative days 3 and 28 ± 2. RESULTS: Thrombin-antithrombin and F1 + 2 on postoperative day 3 were equal for the study groups. By days 28 ± 2, variable dose warfarin therapy group suppressed production of F1 + 2 (P = 0.002) with no difference in the T-AT accumulation. F1 + 2 for other patients overlapped the normal range. CONCLUSION: The signals of activated clotting following surgery did not differentiate the three regimens on postoperative day 3. Variable dose warfarin was associated with suppression of F1 + 2 after 1 month of therapy, with no effect on accumulation of T-AT. Fixed low-dose warfarin started 7 days prior to surgery and aspirin are not inferior on postoperative day 3, but appear to be inferior over a longer treatment.

Bleomycin-induced fatal hyperpyrexia.

Bleomycin is a frequently used antitumor agent with adverse effects usually involving the lungs, skin, and bone marrow. An acute hyperpyrexic reaction has also been noted with this agent, usually after the initial injection. Thus a test dose is recommended before therapy is begun. A case of fulminant hyperpyrexia and death in a patient with lymphoma who had previously received multiple courses of bleomycin without prior hyperpyrexia is reported. Fever was associated with the patient's lymphoma and may have effectively reduced the patient's "margin" for tolerating the additional drug-induced pyrexia. It is suggested that attempts be made to lower fevers before therapy with this agent is initiated.

Variable response of activated partial thromboplastin time to heparin therapy during hemodialysis.

The consistency of the anticoagulant effect of intravenously administered heparin was studied. The activated partial thromboplastin time (APTT) was measured for six patients hourly during three consecutive hemodialysis sessions each. Cephaloplastin was the plasma-activating agent. The time required to form a clot was measured by a light-sensitive electronic timer and confirmed within +/- 5% by the tilt tube method. Results are reported in second relative to units of heparin given to patients per kilogram body weight. The range of APTT's measured 55 minutes after each heparin dose greatly exceeded the range of technical variability of the assay method. The probably mechanisms and consequences for this variability after a constant heparin dose are discussed. The anticoagulation effect of heparin during hemodialysis in an otherwise stable clinical situation is not constant. The risks of having too much or too little anticoagulation are not eliminated by having determined a therapeutic heparin dose during one dialysis rung.

Prophylaxis against central vein thrombosis with low-dose warfarin.

Low-dose warfarin was given to patients to prevent venous thrombosis. Patients at greatest risk for having thrombi adjacent to central venous catheters were detected by the von Kaulla assay. Patients with normal von Kaulla assays had one thrombus per 1844 days at risk while those with accelerated von Kaulla assays had one thrombus per 500 days at risk. Low-dose warfarin therapy given to patients at high risk reduced the incidence of venous thrombosis from one thrombus per 251 days to one thrombus per 1617 days. Thus low doses of warfarin that do not prolong the prothrombin time appear to offer prophylaxis against venous thrombosis in patients at high risk for developing venous thrombosis adjacent to the central venous catheters.

Effects of low-dose warfarin on antithrombin III levels in morbidly obese patients.

Morbid obesity has been associated with increased risks for thrombotic diseases. Patients with morbid obesity are shown to have decreased activity and decreased concentration of antithrombin (AT) III. This deficit can be corrected by giving the patients low doses of the oral anticoagulant warfarin. The same beneficial effect was not observed in normal lean control volunteers in whom the levels of AT III were normal at all times. Thus, it may be possible to offer prophylactic protection against the effects of having depressed levels of AT III in patients at increased risk for thrombotic diseases without using full anticoagulant doses of warfarin, including morbidly obese patients.

Insulin resistance and monoclonal gammopathy.

Two maturity-onset diabetic patients developed severe insulin resistance during the course of monoclonal gammopathies. One patient had Waldenström macroglobulinemia and the other had multiple myeloma with IgA gammopathy. The maximum insulin binding capacity (MIBC) was 121 U/liter and 54.7 U/liter, respectively, during insulin resistance. The clinical courses of insulin resistance paralleled the activity of the monoclonal gammopathies (MG) with the insulin resistance disappearing after the monoclonal gammopathies were controlled. Six other diabetic patients with concurrent insulin resistance and monoclonal gammopathies are reviewed.

Thrombocytopenia complicating preeclampsia: data to support a new model.

Thrombocytopenia can be associated with preeclampsia without evidence of consumptive coagulopathy and may contribute to placental insufficiency. In the case reported here, the patient's platelets agglutinated in vitro in the presence of her serum when the serum had been preincubated with her placental cells. The reaction was calcium and, probably, complement dependent. Mixtures of sera and placentas from normal APO-matched control pregnancies caused no agglutination of the patient's platelets. The capacity of her serum and placental cells to agglutinate her own platelets was not found in the sera obtained 60 days post partum. These findings suggest that in some cases of preeclampsia the platelets may be involved in an immune-mediated phenomenon that can induce platelet agglutination and is probably accentuated in the placenta, thus attenuating placental blood flow.

Physiological changes in hemostasis associated with acute exercise.

Acute exercise enhances fibrinolytic (FA), factor VIII coagulant and factor VIII ristocetin cofactor activities, and increases the concentration of factor VIII-related antigen. Little is known concerning the mechanisms of these changes. To investigate possible relationships between exercise-induced changes in blood lactate, 2,3-diphosphoglycerate (DPG), and the hemostatic variables, a branching multistage treadmill protocol was used to exercise male volunteers to a maximum effort. Blood samples were drawn before, immediately post-, and 8 min postexercise. All hemostatic variables were significantly (P less than 0.05) increased postexercise. Highest values for factor VIII coagulant, factor VIII-related antigens and factor VIII ristocetin cofactor were observed at 8 min postexercise. Significant (P less than 0.001) correlations were found postexercise for lactate with factor VIII coagulant (r = 0.64), while no association between pre-, post-, or 8 min postexercise. Postexercise lactate demonstrated a significant correlation (r = +0.81), which was strengthened by including the preexercise high-density lipoprotein (HDL) concentrations (r = +0.87). Consequently, the expected postexercise FA may be calculated from the observed values for postexercise lactate and preexercise HDL. The correlations of lactate with postexercise FA and with postexercise factor VIII coagulant may reflect a common stimulus for these exercise-induced changes.

Plasma levels and effects of sulfinpyrazone in patients requiring chronic hemodialysis.

Sulfinpyrazone (Anturane), which inhibits platelet synthesis of prostaglandins and platelet release of serotonin, was given to patients with chronic renal failure requiring hemodialysis. Patients were mateched in double-blind fashion to receive either placebo or sulfinpyrazone at 200 mg orally three times a day. Peak plasma levels of sulfinpyrazone after the first 200-mg dose ranged from 6.7 to 11.4 micrograms/ml (mean : 8.7 micrograms/ml). The plasma concentration showed a monoexponential disappearance pattern with an apparent half-life of 4 hours. At steady state, sulfinpyrazone peak plasma levels were 10.7 to 30.1 micrograms/ml. Residual plasma levels 12 hours after a final dose while in steady state were 3.7 and 4.3 micrograms/ml. Sulfinpyrazone protected against falls of platelet counts normally encountered during hemodialysis. Sulfinpyrazone blocked the increased platelet aggregability and the platelet uptake and release of serotonin normally seen following dialysis. Sulfinpyrazone prevented the consumption of antithyrombin III which is normally seen with hemodialysis, without having changed the anticoagulant efficacy of heparin. Sulfinpyrazone can be given to patients with chronic renal failure. It prevents platelet consumption during hemodialysis and protects against the decrement of antithyrombin III normally seen during hemodialysis.

Four patients with myelodysplastic syndrome with translocation (1;7)(p11;p11) including one patient with independent clones del(7)q22) [corrected] and t(1;7)(q21;q11)

A translocation involving the short arm of chromosome #1 and the short arm of chromosome #7, [t(1;7)(p11;p11)] was present in four patients with myelodysplastic syndrome (MDS). Two of these patients had prior lymphoproliferative disorders and developed MDS following prolonged therapy with alkylating agents. One of the patients with prior therapy history has two additional independent abnormal clones: one with a partial deletion of the long arm of #7 and the other with t(1;7)(q21;q11). A third patient had a family history of leukemia in both the father and a brother, both of whom developed acute nonlymphocytic leukemia following an MDS phase. The last patient was an elderly woman with no predisposing features.

Considerations for using lower doses of warfarin.

Warfarin is a very effective anticoagulant when used in the standard dose; however, the definition of standard dose has become ambiguous as the importance of the thromboplastin used in the measure of the prothrombin times has been demonstrated. Full or "standard" anticoagulation with warfarin imposes a hemorrhagic risk that can be avoided using lower doses. The premise has now been established that less than standard doses are efficacious. What is yet to be determined, however, is how low the dose of warfarin may be while maintaining efficacy and in which clinical settings. These conclusions must be established cautiously in clinical settings before being advocated generally. More complete discussions of this topic as well as safer means of using warfarin in general are available.

Effect of sulfinpyrazone upon antithrombin III and platelet factor 4 in chronic renal failure.

Despite the suppressive effects of uremia upon platelet function, patients with chronic renal failure are at increased risk for thrombotic diseases. This increased risk is linked to lowered concentrations of antithrombin III (AT III) and increased platelet release in vivo, as indicated by increased plasma concentrations of platelet factor 4 (PF4). Sulfinpyrazone, a drug capable of reducing the frequency of thrombotic events in uremic patients, allows return toward normal of the AT III while reducing to normal the plasma concentration of PF4. Thus, suppression of platelet function by sulfinpyrazone appears to reduce in vivo clotting, and thus reduces consumption of AT III.

Effect on platelet function of hypoalbuminemia in peritoneal dialysis.

Chronic renal failure is associated with functional platelet defects. Peritoneal dialysis is associated with improvement in platelet function. This study demonstrates that the hypoalbuminemia resulting from peritoneal dialysis may account for part of the improvement. Platelet aggregation was measured when plasma albumin was less than 3 g/dl and again when the albumin level was raised to greater than 4 g/dl. Normal albumin levels were associated with decreased platelet function when the slope of aggregation to ADP and epinephrine were used as the study parameters. Patients with peritoneal dialysis given albumin to correct their plasma albumin level also acquired reduced platelet aggregation.

Factor VIII complex in chronic renal failure: influence of protein C, fibrinolysis and diabetes mellitus.

Chronic renal failure causes elevations of factor VIII coagulant activity and Factor VIII-related antigen even before the patients enter chronic hemodialysis. The change from control of Factor VIII ristocetin cofactor does not reach significance. The elevations are not effected by entering onto hemodialysis. These parameters are the same for non-diabetic and diabetic patients. Protein C, plasminogen and total fibrinolytic capacity are normal in diabetic and non-diabetic patients, with or without hemodialysis for chronic renal failure. However, before entering onto hemodialysis some of these parameters had negative correlation coefficients with parts of the factor VIII complex among the diabetic and non-diabetic patients. These negative correlates turned positive after hemodialysis. Thus, there are differences in these catabolic mechanisms for factor VIII when hemodialysis is used for diabetic and non-diabetic patients with chronic renal failure.

Response of protein C and protein C inhibitor to warfarin therapy in patient with combined deficiency of Factors V and VIII.

The role of Protein C in combined factor V/VIII deficiency was examined by reducing the Protein C concentration using warfarin therapy in a patient with the combined deficiency. The factor VIII deficiency was like Hemophilia-A, with deficiency of VIII:C and VIII:C(Ag), but normal VIIIR:Ag and VIIIR:cof. The factor V deficiency was due to loss of the V antigen. During warfarin therapy the Protein C level was reduced, but concentrations of factors V and VIII did not change. Protein C Inhibitor was normal throughout. Thus combined factor V/VIII deficiency is not related to Protein C levels.

Noncirrhotic portal hypertension in adults.

Of 366 cases of portal hypertension in adult patients referred for evaluation and management in the past 15 years, the cause was not related to cirrhosis or hemochromatosis in 41. No specific cause was demonstrated for portal hypertension in four cases, which were excluded from further evaluation. Of the remaining 37 patients, 26 had a presinusoidal block characterized primarily by bleeding from esophagogastric varices, and 9 had a postsinusoidal block characterized by the rapid development of intractable ascites. In two cases an arteriovenous fistula was the cause of portal hypertension. Treatment was operative or nonoperative depending on the nature and prognosis of the basic disease. The various approaches to therapy include shunting procedures for the control of ascites or esophagogastric varices, the use of a type of portal-azygous disconnection and a direct approach to a valve or a fistula. In the absence of a rapidly fatal primary disease, portal hypertension is not a threatening problem and may be controlled with minimal mortality by appropriate surgical management.

Open heart surgery in patients with cold-reactive proteins.

The presence of cold-reactive proteins may pose special hazards to the patient about to undergo hypothermic cardiopulmonary bypass, topical myocardial cooling, and cold potassium cardioplegic arrest. The detection and characterization of such proteins, their potential adverse effects, and a proposed management protocol are discussed.