Psychosocial correlates of physical activity in adolescents with haemophilia.

Boys with haemophilia are now encouraged to exercise and take part in physical activities, but actual measures of time spent in active participation is lacking. The aim of this study was to obtain an objective measure of daily physical activity in boys with haemophilia as compared with healthy controls. The study also aimed to ascertain the social and cognitive factors associated with exercise in this population. Seventeen patients (aged 11-18 years) with haemophilia were studied and compared with 44 healthy controls (aged 10-16.5 years). Physical activity was measured by accelerometry. Psychosocial correlates were assessed using validated questionnaires. Measured physical activity levels in subjects with haemophilia were slightly higher than for the control group. Both groups spent 70% of the day inactive, with similar proportions of time in moderate and vigorous activity. Subjects with haemophilia had a favourable self-image and similar levels of anxiety as peers without a bleeding disorder. Self-efficacy scores were lower than for controls suggesting increased sensitivity to barriers and lack of acceptance of alternatives. Health beliefs did not influence physical activity, but a negative correlation of time spent in high or vigorous activity with scores for support-seeking was observed. The data demonstrate that in the appropriate social environment and with medical support, patients with haemophilia may be as physically active as their peers without a bleeding disorder. Further investigation into the psychosocial barriers of physical activity in patients with haemophilia is needed to more effectively encourage healthy behaviours.

Laboratory response to intranasal desmopressin in women with menorrhagia and platelet dysfunction.

Intranasal desmopressin (IN-DDAVP) is used for home treatment of menorrhagia in women with inherited bleeding disorders. The effect of IN-DDAVP on laboratory haemostatic parameters in women with menorrhagia related to platelet dysfunction is unknown. We evaluated the effects of IN-DDAVP on haemostatic parameters in women with menorrhagia and platelet dysfunction and correlated them with menstrual flow. Eleven women (aged 18-45) with menorrhagia and haemostatic abnormalities had determination of von Willebrand factor antigen (VWF:Ag), von Willebrand factor ristocetin cofactor (VWF:RCo) activity, factor VIII coagulant activity (FVIII:C), platelet aggregation and platelet adenosine tri-phosphate (ATP) release pre-IN-DDAVP and 60-min post-IN-DDAVP. Eight of eleven women underwent platelet function analyzer (PFA-100) closure time determination with collagen/adrenaline and collagen/adenosine diphosphate cartridges pretreatment and post-treatment. IN-DDAVP was administered during two consecutive menstrual cycles. Menstrual flow was assessed during each cycle using a pictorial blood assessment chart. Treatment with IN-DDAVP resulted in elevated VWF levels and shortened PFA-100 closure time with significant inverse correlation between shortening of PFA-100 closure times and increases in VWF levels. There were also significant inverse correlations between changes in menstrual flow and changes in VWF:Ag (P = 0.02), VWF:RCo (P = 0.04) and FVIII:C (P = 0.006), following treatment. In vitro platelet aggregation and platelet ATP release response did not correct and did not correlate with changes in menstrual flow. Our results demonstrate a correlation between haemostatic parameters and menstrual flow following IN-DDAVP in women with menorrhagia and platelet dysfunction.

Immune thrombocytopenia in hemophiliacs infected with human immunodeficiency virus and their response to splenectomy.

We studied five patients with hemophilia A in the age range of 18 to 64 years who were infected with human immunodeficiency virus and who developed immune thrombocytopenia. The clinical course of immune thrombocytopenia in relation to human immunodeficiency virus infection and the patients' responses to splenectomy and immune variables were determined. All five patients developed antibody to human immunodeficiency virus 6 to 60 months (median, 24 months) before the onset of thrombocytopenia, and two patients became human immunodeficiency virus antigenemic (one patient at the onset of immune thrombocytopenia and the other 60 months after the onset of immune thrombocytopenia [24 months after splenectomy]). All five patients had a strong platelet-associated immunoglobulin G and three patients also had a weak platelet-associated immunoglobulin M on their platelets. In four of five patients danazol therapy failed, and three patients required moderate doses of prednisone. Because of the progression of immune thrombocytopenia, four of the five patients underwent splenectomy with preoperative high-dose intravenous immune globulin. All four had an excellent immediate response to splenectomy, with a rise in platelet count to more than 300 x 10(9)/L and sustained remission during postsplenectomy follow-up of 6 to 45 months. There was no significant drop in CD4 and CD8 counts after splenectomy, and all four patients remained clinically well.

Diffusion-controlled growth rate of stepped interfaces.

For many materials, the structure of crystalline surfaces or solid-solid interphase boundaries is characterized by an array of mobile steps separated by immobile terraces. Despite the prevalence of step-terraced interfaces a theoretical description of the growth rate has not been completely solved. In this work the boundary element method (BEM) has been utilized to numerically compute the concentration profile in a fluid phase in contact with an infinite array of equally spaced surface steps and, under the assumption that step motion is controlled by diffusion through the fluid phase, the growth rate is computed. It is also assumed that a boundary layer exists between the growing surface and a point in the liquid where complete convective mixing occurs. The BEM results are presented for varying step spacing, supersaturation, and boundary layer width. BEM calculations were also used to study the phenomenon of step bunching during crystal growth, and it is found that, in the absence of elastic strain energy, a sufficiently large perturbation in the position of a step from its regular spacing will lead to a step bunching instability. Finally, an approximate analytic solution using a matched asymptotic expansion technique is presented for the case of a stagnant liquid or equivalently a solid-solid stepped interface.

Clinical experience of a new monoclonal antibody purified factor IX: half-life, recovery, and safety in patients with hemophilia B.

Highly purified factor IX, produced by a monoclonal antibody immunoaffinity technique, contains a high concentration of factor IX with negligible amounts of other vitamin K-dependent coagulation factors. When infused in patients with hemophilia B, monoclonal factor IX concentrate yielded a mean half-life of 34.6 +/- 13.1 (+/- SD) hours and in vivo recovery of 0.67 +/- 0.14 U/dL rise per each U/kg of factor IX infused. Unlike prothrombin complex concentrate (PCC) infusion, monoclonal IX infusion was not associated with rises in factors II, VII, and X, but achieved in vivo recovery and half-life at least comparable to PCC. Long-term use of monoclonal IX as a home-care product provided excellent response in the control of bleeding episodes and was equivalent to previous patient experience with PCC. The results indicate that monoclonal IX concentrate raises factor IX levels effectively, while avoiding extraneous thrombogenic components.

Platelet functional defects in women with unexplained menorrhagia.

Menorrhagia is a common clinical problem and is unexplained in more than 50% of women. Although studies suggest that von Willebrand's Disease (VWD) is found in a substantial number of women with unexplained menorrhagia, the prevalence of platelet defects in women with menorrhagia is unknown. To determine the prevalence of platelet and other hemostatic defects, we evaluated women ages 17-55 diagnosed with unexplained menorrhagia. Seventy-four women (52 white, 16 black, six other) were studied. Bleeding time was prolonged in 23 women (31.5%). Maximal percent platelet aggregation was decreased with one or more agonists in 35 (47.3%) women. The most commonly found platelet function defects were reduced aggregation responses to ristocetin in 22 women and to epinephrine in 16 women. Sixteen of 22 women with reduced ristocetin aggregation had von Willebrand ristocetin cofactor (VWF:RCo) and von Willebrand factor antigen (VWF:Ag) > 60%. Platelet ATP release was decreased with one or more agonists in 43 (58.1%) women. Of the black women studied, 11/16 (69%) had abnormal platelet aggregation studies compared with 20/52 white women (39%) (P = 0.06). Black women with menorrhagia had a higher prevalence of decreased platelet aggregation in response to ristocetin and epinephrine than did white women (P = 0.0075, P = 0.02). Ten women (13.5%) had VWF:RCo and/or VWF:Ag < 60%. Using race and blood group specific ranges, 5 (6.8%) women had decreased VWF:RCo, VWF:Ag and/or collagen binding (VWF:CB). Mild factor XI deficiency was found in two women and one woman with mild factor V deficiency and one hemophilia A carrier were identified. We conclude that the prevalence of platelet function defects and other inherited bleeding disorders is substantial in a multiracial US population of women with unexplained menorrhagia.

Methamphetamine intoxication. A speedy new treatment.

This communication describes the use of droperidol in methamphetamine poisoning. Droperidol antagonizes the central stimulatory effects of amphetamines producing a person who is indifferent to environmental stimuli, calm and cooperative. Coupled with an acid diuresis, causing a fivefold increase in the urinary concentration of methamphetamine and recovery of 66% of the ingested drug, a seriously intoxicated patient showed rapid improvement.

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)

Effect of factor XII deficiency on pregnancy and parturition.

The clotting parameter of a primigravida with factor XII deficiency was studied during her third trimester of pregnancy, labor and post-partum; and compared with those of her newborn male infant. Sharp increases in factors VII, VIII, IX, X and moderate increases in factors II and XI were documented during pregnancy and at labor. All factors had returned to normal or near normal levels 24 hours after delivery. Factor XII remained at 0.0 level throughout. In the infant the clotting factor levels reflected depression of vitamins K-dependent factors II, IX, and X and a factor XII level of 40.0%. No undue bleeding was noted in the mother at delivery or placental separation, and no bleeding manifestation was apparent in the infant. These findings suggest that factor XII does not play a major role in triggering or modulating the course of normal labor, nor is its absence necessarily associated with bleeding complications during parturition or placental separation.

Deletion polymorphism in the angiotensin-converting enzyme gene as a thrombophilic risk factor after hip arthroplasty.

Despite thromboprophylaxis, deep vein thrombosis is a common complication of major orthopedic surgery. Predisposing genetic risk factors are unknown. In this case-control study, we investigated the association of the insertion (I)/deletion (D) angiotensin converting enzyme (ACE) gene polymorphism, Factor V Leiden (R506Q) mutation, and 5,10 methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with post-operative venous thrombosis in 85 patients who underwent elective total hip arthroplasty. The odds of a thrombotic event following hip surgery among subjects with the DD genotype of the ACE gene was increased more than 10-fold compared to subjects with the II genotype (odds ratio 11.7 [95% confidence interval 2.3-84.5]); it was increased 5-fold in subjects with the ID genotype compared to the II genotype (odds ratio 5.0 [95% confidence interval 1.1-34.9]). Mean plasma ACE level in control subjects not on ACE inhibitors at the time of study (n=43) was lowest in persons homozygous for the I allele (18.9+/-7.95 U/l), intermediate in patients with the ID genotype (31.6+/-10.8 U/l) and highest in subjects homozygous for the D allele (44.0+/-7.14 U/l). Mean plasma ACE level among cases was higher (33.0 U/l, n=25) than among controls (29.4 U/l, n=43) but this difference was not statistically significant. Neither the Factor V Leiden mutation nor MTHFR gene polymorphism increased the risk of thrombosis following hip replacement. These results demonstrate that the I/D ACE gene polymorphism is a potent risk factor for thrombosis in subjects undergoing total hip arthroplasty.

Patients with prolonged bleeding time of undefined etiology, and their response to desmopressin.

Between 1981 and 1986, we evaluated 59 patients who presented with isolated prolongation of bleeding time with normal platelet counts, platelet aggregation and coagulation parameters (including von Willebrand's factor), and without evidence of liver or kidney disease, or exposure to anti-platelet agents. These patients, termed as vascular fragility syndrome (VFS), were analyzed to further characterize their bleeding patterns. The pattern of bleeding manifestations was similar to that of patients with platelet dysfunction, such as mucocutaneous bleeding or excessive post-operative bleeding. In 16 patients, desmopressin (1-desamino-8-d-arginine vasopressin, DDAVP) was infused to control active bleeding or as a part of pre-surgical evaluation. Bleeding time improved (pre-DDAVP bleeding time 15.3 +/- 3.4 min, mean +/- S.D.; post-DDAVP bleeding time 10.7 +/- 3.9 min; p less than 0.01) within 30 minutes following the DDAVP infusion with either satisfactory arrest of acute bleeding or good control of subsequent hemostasis with surgery. Side effects with DDAVP were transient and minor, i.e. facial flushing, or conjunctival erythema. These findings indicate that VFS with isolated prolongation of bleeding time is a frequently encountered bleeding disorder and that DDAVP is effective in achieving hemostasis for the management of acute bleeding and may be useful prior to surgical procedures.

Effect of niacin supplementation on fibrinogen levels in patients with peripheral vascular disease.

This study demonstrates that niacin supplementation decreases plasma fibrinogen and low-density lipoprotein cholesterol in subjects with peripheral vascular disease randomized to receive niacin, warfarin, antioxidants, or placebo. Changes in fibrinogen levels are highly correlated with changes in low-density lipoprotein cholesterol (r = 0.61; p < 0.009) in subjects taking niacin.

Reduced erythrocytic deformability in megaloblastic anemia.

Ten patients with megaloblastic anemia had erythrocytes with reduced deformability. The mean half-life for erythrocyte filtration was 9.89 minutes in these patients, compared with 5,20 minutes in controls. The half-life was inversely related to the hemoglobin concentration. After adequate vitamin replacement therapy filtrability improved significantly. Two patients had thromboembolic disease, It is proposed that the reduced erythrocytic deformability reflects membrane rigidity that might ultimately lead to hemolysis.

Clinical trial of a new disposable bleeding-time device.

A new disposable bleeding time device (Hemalet) was tested in 20 normal individuals and 11 patients with various bleeding disorders. The results were compared with those of Simplate II. The mean bleeding time for normal individuals was 5.4 +/- 1.5 (mean +/- 1 SD) minutes by Hemalet and 5.8 +/- 1.4 (mean +/- 1 SD) minutes by Simplate II, with good correlation between the results by the two devices (r = 0.81). The bleeding time in patients with various bleeding disorders were also comparably prolonged between the two devices. The new disposable bleeding time device with a disposable blade has quick release (penetration) into skin and retraction, and offers an alternative means of a bleeding time test.

Acute promyelocytic leukemia in pregnancy: all-trans retinoic acid as a newer therapeutic option.

BACKGROUND: Acute promyelocytic leukemia is a unique subset of acute myelogenous leukemia, characterized by a neoplastic proliferation of promyelocytes and a prompt response to all-trans retinoic acid (tretinoin), which induces differentiation of immature leukemic promyelocytes into mature neutrophils. Because of the high incidence of disseminated intravascular coagulation (DIC) associated with acute promyelocytic leukemia and the danger of exacerbation of DIC with pregnancy, management of acute promyelocytic leukemia during pregnancy requires prompt and careful attention. CASE: A 29-year-old woman in her third trimester was diagnosed with acute promyelocytic leukemia and DIC. The infant was delivered by cesarean and the mother was successfully treated with tretinoin, inducing the leukemic promyelocytes to differentiate into mature granulocytes and possibly reversing the DIC. CONCLUSION: If the fetus can be delivered safely, tretinoin as a single agent is an option for the initial treatment of maternal acute promyelocytic leukemia because it does not suppress the bone marrow and may ameliorate DIC. Because of the danger of hyperleukocytosis, chemotherapy should be added initially if the white blood cell count is greater than 5000/microL. If the fetus cannot be delivered at a viable stage, conventional cytotoxic chemotherapy is the alternative option.

Blood: use and abuse of whole blood and fractions.

Guidelines for the replacement of blood and various components of blood in cases of hemorrhage, anemia, thrombocytopenia, granulocytopenia, and coagulation disorders are presented. Complications of various therapies, such as the transmission of hepatitis B in the transfusion of pooled plasma, and methods of calculating the number of units of a particular component needed in a particular patient are considered.

"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.

Reconstructive plastic surgery in hemophiliacs.

Major surgery can be safely performed in hemophiliacs when adequate factor activity is provided, i.e., 100 percent activity perioperatively and 50 percent activity thereafter. These patients require complete hemostatic evaluation in order to properly titrate perioperative needs. The extreme cost of surgery and hospitalization mandates that, when possible, patients needing multiple procedures have them performed at the same time. A case is presented in which a paraplegic hemophiliac with extensive pressure sores underwent quadruple flaps following these tenets.

Musculoskeletal problems in hemophilia.

Spontaneous deep muscle and joint bleeding is a common characteristic of severe hemophilia, often causing damage to the musculoskeletal system. The development of concentrated replacement factors, however, has made home care programs possible, helped prevent deformity, and improved surgical management.