Hugh C. Kim

Randomized controlled trial of tissue plasminogen activator in proximal deep venous thrombosis

PURPOSE To compare the efficacy and safety of recombinant human tissue-type plasminogen activator (rt-PA, supplied as Activase) with heparin alone or rt-PA plus heparin in the treatment of venographically documented proximal deep venous thrombosis (DVT) of the leg. PATIENTS AND METHODS Sixty-four patients underwent 65 randomizations to rt-PA alone (n = 36), rt-PA plus heparin (n = 17), or heparin alone (n = 12) in a prospective, multicenter, randomized, open-label trial, with efficacy assessed by a radiology panel unaware of treatment assignment. Patients randomly assigned to rt-PA received 0.05 mg/kg/hour for 24 hours via a peripheral vein, with a maximum dose of 150 mg. All patients then received heparin and warfarin for the remainder of the hospitalization. Follow-up venography was performed 24 to 36 hours after initiation of therapy. RESULTS Complete or more than 50% lysis occurred in 10 (28%) patients treated with rt-PA, five (29%) patients with rt-PA plus heparin, and no patient treated with heparin. No lysis occurred in 16 (44%) patients treated with rt-PA plus heparin, and 10 (83%) patients who received heparin alone (p = 0.04). There was one major complication, a nonfatal intracranial hemorrhage in a patient who received rt-PA alone. At 7 to 10 days after initiation of treatment, the level of serum glutamic oxaloacetic transaminase nearly doubled among all patients, including those assigned to receive heparin alone. CONCLUSION (1) rt-PA and rt-PA plus heparin cause more clot lysis than heparin alone; (2) the addition of heparin to rt-PA does not improve the lysis rate; (3) DVT treated with heparin is commonly associated with a rise in the transaminase level; (4) heparin does not increase the risk of bleeding from rt-PA therapy; and (5) alternative dosing regimens and modes of administration of rt-PA should be investigated to improve further its efficacy and safety in the treatment of acute DVT.

Effect of Recombinant Human Erythropoietin on Transfusion Risk in Coronary Bypass Patients

BACKGROUND Patients having a cardiac operation frequently require allogeneic blood transfusions despite surgical blood-conservation techniques. Recombinant human erythropoietin (Epoetin alfa) may augment this conservation by stimulating erythropoiesis. The safety and efficacy of perioperative use of Epoetin alfa to reduce the need of allogeneic transfusion was studied. METHODS A multicenter double-blind, placebo-controlled, parallel-group study involved 182 patients having coronary artery bypass grafting and randomized to receive Epoetin alfa (300 or 150 IU/kg) or placebo subcutaneously for 5 days before, on the day of, and for 2 days after operation. RESULTS Perioperative Epoetin alfa resulted in greater increases in baseline to preoperative hemoglobin levels and hematocrit (300 IU/kg) and in presurgery to postsurgical day 1 reticulocyte counts versus placebo (p < or = 0.05). However, there was no significant difference in transfusion requirements. Incidences of adverse events were similar in all study groups. CONCLUSIONS Lower incidences of allogeneic blood exposure were observed in both Epoetin alfa-treated groups; however, the differences between all treatment groups were not significant. This was probably due to the relatively short 5-day preoperative course of Epoetin alfa therapy. There were no significant differences between the three groups relative to safety. Epoetin alfa was well tolerated in this population.

The Treatment of Lead Poisoning from Gunshot Wounds with Succimer (DMSA)

Lead poisoning is an unusual complication of gunshot wounds that occurs when retained lead bullet fragments are in contact with body fluids capable of solubilizing lead. The epidemic of violence by gunfire may result in increasing numbers of lead poisoning cases from this exposure. The use of oral chelation for toxicity resulting from this mode of exposure has not been previously discussed. Cases of lead poisoning arising from bullet lead in the synovial cavity of the hip, synovial cavity of the chest, and pleural space are reported. A combination of surgical debridement and chelation therapy with oral succimer produced a satisfactory outcome in all three cases. Oral succimer may be a safe and effective chelation agent for treating lead toxicity in adults with high lead levels secondary to gun shot wounds.

Association of hemostatic factors with peripheral vascular disease.

Hemostatic risk factors have been well established in coronary artery disease but less well studied in peripheral vascular disease. The relationship of coagulation and fibrinolytic proteins to lower limb arterial occlusive disease and other vascular risk factors remains poorly defined. Fibrinogen, factor VII coagulant activity, von Willebrand factor (vWf) antigen, and plasminogen activator inhibitor-1 (PAI-1) activity were measured in 46 adult participants in the Arterial Disease Multiple Intervention Trial (ADMIT) and in 76 control subjects and related to ankle-brachial systolic pressure index (ABI), a measure of lower limb arterial stenosis. The primary inclusion criterion for the ADMIT study population was an average of two ABIs <0.85. Fibrinogen and PAI-1 in ADMIT subjects were significantly higher than in control subjects (331 +/- 52 mg/dl vs 273 +/- 46 mg/dl, p < 0.0001; 18.7 +/- 10 units/ml vs 13.5 +/- 8.9 units/ml, p < 0.04). There were significant correlations of fibrinogen with ABI, factor VII coagulant activity, and systolic and diastolic blood pressures; PAI-1 with body mass index and age; and factor VII coagulant activity with cholesterol levels. Logistic regression analysis, considering hemostatic variables and several known nonhemostatic risk factors of peripheral arterial disease, showed that fibrinogen and systolic blood pressure were independently associated with ABI status in this population. The results demonstrate a strong independent correlation between fibrinogen levels and the presence of lower limb arterial stenosis. PAI-1 levels were elevated in ADMIT participants, but multivariate analysis did not demonstrate an independent relationship between PAI-1 and ABI.

Long term follow-up of arthroscopic synovectomy for chronic hemophilic synovitis

Recurrent hemarthrosis of the knee in hemophiliac patients leads to chronic synovitis, predisposing the joint to further hemarthroses and degeneration. Open synovectomy controls bleeding, however, significant loss of motion frequently results. We are reporting on seven patients who underwent arthroscopic synovectomy and had decreased bleeding episodes while maintaining range of motion. The seven patients had frequent recurrent hemarthroses despite medical management. All had had signs of degenerative arthritis preoperatively. Five of the seven had loss of motion. Length of follow-up averaged 4 years. Six of the seven had reduced bleeding episodes with an average of 0.22 hemarthroses per week. The seventh patient required significantly less Factor to control bleeding. No patient lost more than 10 degrees of motion. Three patients had increases in motion; two were unchanged. Radiographic progression of degenerative changes was noted in five patients, the other two were unchanged. We recommend early arthroscopic synovectomy in the treatment of recurrent hemarthrosis in hemophiliac patients.

Cystic degeneration of thymic Hodgkin's disease following radiation therapy

A case of thymic Hodgkins disease presenting with an anterior mediastinal mass is reported. The mass progressively expanded in size on plain chest radiography during and following a mantle radiation therapy. A repeat computed tomographic (CT) scan of the chest in this patient revealed a cystic component to the mass, and thin‐needle aspiration of the cyst led to a shrinkage of the mass. An experience in this case and review of literature suggest Hodgkins disease involving the thymus gland frequently predisposes to cystic degeneration especially following radiotherapy, leaving a stable or progressively enlarging residual mass. A precise diagnosis of such a progressively expanding mass despite the adequate radiation therapy is crucial. CT scan of the chest in such cases and a thin‐needle aspiration of the cystic mass offer precise diagnosis and may obviate the need for an open thoracotomy procedure.

Human immunodeficiency virus infection in sexually active wives of infected hemophilic men

PURPOSE Because of past multiple exposures to contaminated coagulation factor concentrates, the prevalence of human immunodeficiency virus (HIV) infection among adult hemophilic men in the United States is reported to range from 75 to 90 percent. The risk of HIV transmission through a long-term monogamous heterosexual contact can be estimated by studying the spouses of hemophilic subjects since these couples generally do not abuse intravenous drugs, usually maintain stable monogamous relationships, and are usually free of other risk factors. Our purpose was to gather data on the risk of heterosexual transmission of HIV infection in the context of long-term monogamous relations according to the duration of HIV antibody seropositivity and of HIV antigenemia in HIV-infected hemophilic men, and their sexual habits. SUBJECTS AND METHODS Infection with HIV was studied in 14 sexually active spouses of infected hemophilic men who had been HIV antibody reactive for a mean of 46 +/- 23 (SD) months. One half of the hemophilic men studied had overt HIV antigenemia for a mean duration of 27 +/- 23 (SD) months; six of the men studied fulfilled clinical criteria for the diagnosis of acquired immunodeficiency syndrome (AIDS). All 14 couples were sexually active in a strictly monogamous fashion, in marriages of 13.5 +/- 10.5 (SD) years with an average reported frequency of four sexual encounters per month (range: one to 12). Plasma samples of the hemophilic husbands were retrospectively analyzed for HIV and hepatitis B virus markers. Blood samples were obtained from female spouses on at least two occasions, six months apart. Comprehensive questionnaires regarding sexual habits and other risk factors were filled out by each couple; during this interview, the couple was counseled about safe sexual practices. None of the couples studied used condoms prior to January 1986. RESULTS Antibodies to HIV developed in only one of the 14 wives. At the time when this seroconversion was detected, her husband, in whom AIDS developed, had been reactive for HIV antibody for 49 months, and showed positive findings for HIV antigen for 26 months. No additional risk factors were identified for this couple. The infected female spouse, however, has a 14-year history of multiple sclerosis, and had been treated with immunosuppressant intermittently. Despite a significantly reduced number of CD4 lymphocytes, she has remained clinically asymptomatic for 17 months since seroconversion. HIV antibodies did not develop in any of the 13 remaining wives, despite the frequent practice of oral sex by six couples and reports of occasional anal intercourse by another couple.(ABSTRACT TRUNCATED AT 400 WORDS)

“Superwarfarin” ingestion: A new problem in covert anticoagulant overdose

For the attention of psychiatric consultants, brodifacoum, a new longer-acting, warfarin-like oral anticoagulant rodenticide, has been used for suicide attempts. The overdose potential with brodifacoum is serious since it is readily available without prescription, and bleeding complications last for weeks to months after a single ingestion. This article reports a case of ingestion and reviews four similar cases from medical literature. Also reviewed are details about mechanism of action, procedures for diagnosis, and treatment requirements. Also, characteristics of persons who ingest long-acting anticoagulants appear to differ from those who ingest short-acting anticoagulants reported from earlier literature.

Efficacy and safety of monoclonal antibody purified factor IX concentrate in haemophilia B patients undergoing surgical procedures

The present study summarizes results of the efficacy and safety of monoclonal antibody (MAb) purified factor IX concentrate [Mononine® Coagulation Factor IX (Human), Centeon L.L.C., King of Prussia, PA, USA] for surgical prophylaxis in 74 patients with mild, moderate or severe haemophilia B who underwent a total of 81 different operative interventions. Surgical procedures included joint replacement/arthroplasty (n= 12), gastrointestinal (GI) or rectal surgery (n= 6), synovectomy/osteotomy (n= 8), hernia repair (n= 4), central catheter insertion (n= 3), ENT surgery (n= 4), dental procedures (n= 14), biopsies (n= 2), gynaecological procedures (n= 4), ophthalmological surgery (n= 4), spinal surgery (n= 4), urogenital surgery (n= 2), other orthopaedic surgery (n= 4) or other miscellaneous procedures (n= 10). All patients demonstrated haemostasis rated as ‘excellent’ by the investigators. No patients experienced clinically evident thromboembolic complications during treatment with MAb factor IX. These results, from a large and varied random group of patients, demonstrate that this highly purified factor IX concentrate is safe and effective for surgical prophylaxis in patients with haemophilia B, including those patients who have experienced thromboembolic complications during prior treatment with prothrombin complex concentrates.

DDAVP in the Treatment of Bleeding Disorders

Hemophilia A and von Willebrands disease are hereditary disorders associated with qualitative and quantitative abnormalities of clotting factor VIII. A major clinical feature is excessive or abnormal bleeding often necessitating the use of transfusions of pooled blood products to achieve hemostasis. Exposure to blood products places the recipient at risk for infection by the hepatitis B virus or the human immunodeficiency virus. A synthetic analog of arginine vasopressin, 1‐desamino‐8‐d‐arginine vasopressin, has been shown to increase the plasma levels of factor VIII coagulant activity and von Willebrands factor, and clinically to improve abnormal bleeding, obviating the need to use blood products.