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[Continuous infusion of recombinant activated factor VII during and after elbow arthroplasty in a hemophilia A patient with inhibitors].

Recombinant activated factor VII (rFVIIa) is a recently added new agent for the treatment of hemophiliacs with inhibitors. A major drawback to the use of rFVIIa is its short half-life, necessitating frequent and intermittent bolus injections. Continuous infusion of rFVIIa has been reported as a feasible, convenient, safe and cost-effective alternative to intermittent bolus injections. We report the use of continuous rFVIIa infusion during and after left elbow arthroplasty in a hemophiliac with a high titer of inhibitor to factor VIII. rFVIIa was administered as a bolus injection (100 micrograms/kg) at the start of the operation, after which continuous infusion (10-30 micrograms/kg/h) was immediately started and continued for 6 days. Tranexamic acid (50 mg/kg/day, p.o.) was also administered as an antifibrinolytic treatment. Laboratory monitoring of hemostatic efficacy was performed in this case using prothrombin time and the thrombelastogram. Finally, effective intra- and postoperative hemostasis and normal healing of the surgical incisions were achieved, except for local thrombophlebitis. Although the optimal maintenance or target level of rFVIIa has been a matter of debate, we consider continuous infusion of rFVIIa to be a feasible, convenient, safe and cost-effective alternative to intermittent bolus injections.

Antibodies↗

[Familial study of factor XI deficiency. Presurgical prophylactic treatment with desmopressin plus antifibrinolytics].

Factor XI deficiency is a rare inherited coagulation disorder. It rarely produces spontaneous bleeding although patients with this disorder are at risk for hemorrhagic complications after trauma or surgery. Because there is no clear correlation between the tendency to bleed and the severity of the disease itself, predicting hemorrhagic complications after surgery in patients with mild disease is difficult. This hereditary deficiency is characterized by prolongation of activated partial thromboplastin time with normal prothrombin time, and the demonstration of selective plasma factor XI deficit. Currently available products in the therapeutic arsenal are transfusion of fresh-frozen plasma, virus-inactivated factor XI concentrates, desmopressin (DDAVP) and antifibrinolytic drugs, whether alone or in combination. We describe a family with two affected children, in which the deficiency was identified as an autosomal recessive trait. Of the two patients, one required prophylactic treatment with desmopressin and tranexamic acid before surgery; the treatment was successful and no related complications were observed. The long-term outcome of individuals with this disease seems to be good with continuous follow up and early control of hemorrhagic episodes. Prophylactic therapy is not required, except when surgery is anticipated.

Antifibrinolytic Agents↗

[Menorrhagia and inherited disorders of coagulation].

Menorrhagia, a common complaint among women, may be a manifestation of an underlying inherited disorder of coagulation. In this review, the most frequent hereditary bleeding disorders associated with menorrhagia are briefly analyzed. Particularly, the epidemiological, clinical and diagnostic characteristics of von Willebrand disease, factor VIII, factor IX and factor XI deficiencies are examined. The influence of external factors (age, phase of menstrual cycle and hormonal therapy) on coagulation factor levels is also analyzed. Finally, the main therapeutic options (such as hormonal therapy, tranexamic acid and desmopressin), for the treatment of menorrhagia in women with hereditary bleeding disorders are reviewed. Since inherited bleeding disorders are frequently associated with menorrhagia, the conclusion is drawn that an underlying congenital bleeding disorder should be ruled out in any woman with menorrhagia.

Blood Coagulation Disorders, Inherited↗

Hypothermic circulatory arrest and retrograde cerebral perfusion for aortic surgery at Siriraj Hospital: a preliminary review of anesthetic management.

OBJECTIVE: To evaluate the anesthetic management in patients undergoing aortic surgery cerebral perfusion; with particular emphasis on under hypothemic circulatory arrest and retrograde intraoperative brain protection, blood salvage and postoperative outcomes. MATERIAL AND METHOD: Retrospective case series. Data on medical conditions, anesthesia, surgery and postoperative care from patients who underwent operation between June 1993 and December 1999 were analyzed. RESULTS: There were 53 patients involved in this study. They all received general balanced anesthesia; 70.6 per cent had single-lumen endotracheal intubation, while the remaining required double-lumen endotracheal intubation. The duration of the anesthetic procedure, aortic cross-clamping and circulatory arrest, were 365.58 +/- 89.21, 126.35 +/- 34.64 and 48.35 +/- 19.47 min respectively. The lowest nasopharyngeal and rectal temperature were 17.42 +/- 1.40 degrees C and 21.26 +/- 2.80 degrees C respectively. Thiopental 804.68 +/- 353.93 mg and dexamethasone 14.41 +/- 7.88 mg were administered for brain protection, in addition to retrograde cerebral perfusion; 82.35 per cent received 785.71 +/- 273.86 mg of tranexamic acid and only 23.52 per cent received aprotinin in order to reduce blood loss. However, massive blood replacement therapy was always necessary. In the postoperative period, the patients were ventilated for 39.18 +/- 59.53 h, the length of hospital stay was 14.58 +/- 5.83 d, and the mortality was 13.2 per cent. CONCLUSION: This preliminary data indicate that hypothermic circulatory arrest in aortic surgery is associated with a high mortality rate, despite attempts to provide adequate cerebral protection as well as intraoperative blood salvage.

Adult↗

[Summary of the standard "Vaginal bleeding" (first revision) of the Dutch College of General Practitioners].

In the first revised version of the Dutch College of General Practitioners' practice guideline 'Vaginal bleeding' a distinction is made between excessive (cyclical), irregular, breakthrough and postmenopausal bleeding. The diagnostic guidelines are aimed at identifying possible causes. However, in a considerable number of patients no underlying cause is found and the bleeding is assumed to be caused by hormonal fluctuations, for instance shortly after the menarche or premenopausal. Other causes can be: myomas, an intra-uterine device (IUD), medication, or endometrial carcinoma. Furthermore, lesions of the perineum, vulva or vagina, a pelvic inflammatory disease, Chlamydia infection, cervical carcinoma, imminent abortion or ectopic pregnancy also have to be excluded. In this practice guideline, the management guidelines are limited to the treatment of bleeding from the endometrium. In most cases bleeding caused by hormonal fluctuations is self-limiting. However, symptomatic treatment with progestogens or sub-50 oral contraceptives is possible. NSAIDs taken during the first three days of menstruation are the second-choice treatment in women with excessive bleeding. Tranexamic acid or a levonorgestrel-releasing IUD are other possibilities. Postmenopausal women with vaginal bleeding, first of all have to be examined by means of a cervical smear and transvaginal ultrasonography, to exclude an endometrial carcinoma. They can initially be reassured if the ultrasonography reveals an endometrial thickness of 4 mm or less. In the case of persistent or recurrent vaginal bleeding, they should still be referred to a gynaecologist.

Female↗

[Treatment of chronic idiopathic urticaria unresponsive to type 1 antihistamines in monotherapy].

The chronic idiopathic urticaria treatment is a difficult and often frustrating problem for physicians. Due to the lack of definitive medical therapeutic programs to relieve the symptoms and prevent from their recurrence, several pharmacologic approaches to the management of chronic idiopathic urticaria are proposed. The chronic urticaria pharmacologic therapy is therefore fit to abrogate effects of histamine and other mediators on cutaneous vasculature and inflammatory cells that participate in the pathogenesis of the urticaria. The most common approach is to avoid all aggravating factors and to block histamine. The mainstay therapy is the H1 antihistamines. A significant number of patients may remain unresponsive even after an increase in the dose or a change in the type of H1 antihistaminic drug. In these cases, several therapies can be associated: combinations of H1 antihistamines, nonsedating one tablet (morning) and one sedating (evening), this approach is very usual but no study has confirmed it rational; addition an H2 antagonist to the previous treatment for some patients may improve control of their symptoms; alternatively, the tricyclic antidepressant, Doxepin is usually prescribed. The results of other drugs reported in the literature is unpredictable, to include them in a strategy therapy. The results with Badrenergic agents, nifedipine, ketotifen, leukotriene antagonists and tranexamic acid are variable and don't appear better than those with H1 antagonists. The efficiency of danazol has to be confirmed by other controlled studies. Warfarin, sulfasalazine and ultraviolet radiation have been used apparently successfully, but no controlled study has been published. Only when the above treatments have failed then immunosuppresive therapies, intravenous immunoglobulin and plasmapheresis can be proposed for chronic idiopathic urticaria.

Adrenergic beta-Agonists↗

Oral anticoagulant therapy in patients undergoing dental surgery.

The literature on dental surgery in patients receiving oral anticoagulants is reviewed, and methods of managing anticoagulant therapy to minimize the risk of complications are discussed. Although blood loss during and after oral surgery in patients receiving oral anticoagulant drugs can be substantial, research indicates that most bleeding incidents are not serious and can be controlled by local measures. Studies of 241 anticoagulant-treated patients undergoing more than 500 dental extractions during the 1950s and 1960s showed that only 9 had postoperative bleeding. More recent studies indicate that continued anticoagulation can increase the frequency of prolonged bleeding and delay wound healing. An antifibrinolytic mouthwash containing tranexamic acid can effectively suppress postoperative bleeding. Gelatin sponges, oxidized cellulose, and microcrystalline collagen are other useful hemostatic agents. A reduction in the intensity of anticoagulation therapy has been recommended; the prothrombin time should be measured shortly before the procedure in such patients. In many patients the duration of subtherapeutic anticoagulation must be minimized to reduce the possibility of thromboembolism. An option for high-risk patients is to switch them to heparin. Each patient must be evaluated individually, and the level of risk of the dental procedure and the risk of thromboembolism should be taken into account. In patients taking oral anticoagulants who must undergo dental surgery, careful control of the intensity of anticoagulation and improved methods of local hemostasis can minimize the risk of hemorrhagic complications and thromboembolism.

Administration, Oral↗

Mechanisms involved in enhancement of plasma fibrinolytic activity by chloroform.

The effects of a single 1-min extraction with chloroform (CHCl3) on plasma fibrinolytic activity has been examined by 125I-fibrin solid phase assay, using normal plasma and plasma depleted of plasminogen (PLG) by lysine-Sepharose affinity chromatography. Fibrinolytic activity of normal plasma is increased (40%-175%), and more than 95% of antiplasmin activity is removed. The increase is demonstrable in PLG-depleted plasma, and is not inhibited by tranexamic acid (0.01 M). Purified PLG is not activated to plasmin by ChCl3 treatment. Bio-Gel A 0.5 m fractionation of CHCl3-extracted, PLG-depleted plasma reveals fractions with the following activities: (1) streptokinase-activatable, PLG-independent fibrinolytic activities; (2) PLG activator activities; and (3) plasmin-stimulated but PLG-independent fibrinolytic activities, which include activities inhibited by hexadimethrine bromide and which cofractionate in part with plasmin-stimulated procoagulant activities. In addition, similar fractionation of nonextracted plasma reveals two non-plasmin fibrinolytic activities (approximately 30,000 and 13,000 daltons) activated by streptokinase and plasmin, respectively. The findings indicate that the enhanced fibrinolytic activity resulting from CHCl3 treatment is independent of plasmin as the ultimate fibrinolytic enzyme, although activities stimulated by plasmin may contribute, and that such treatment is a useful maneuver for study of PLG-dependent and PLG-independent fibrinolytic mechanisms, and their interactions.

Blood Coagulation↗

Experience of desmopressin (DDAVP) administration in patients with congenital and acquired bleeding disorders.

Desmopressin (DDAVP) 0.3 micrograms/kg was administered intravenously to three normal volunteers and 12 patients with von Willebrand's disease (vWD), congenital or acquired platelet function defect, or uremic bleeding to assess its effects and side effects. DDAVP significantly shortened the bleeding time as compared with basal values. The mean peak post-DDAVP level of factor VIII coagulant activity increased 5.9 +/- 0.5 (mean +/- SEM) fold, von Willebrand factor antigen increased 3.7 +/- 0.3 fold, von Willebrand factor ristocetin cofactor activity increased 4.6 +/- 0.6 fold and the tissue-type plasminogen activator antigen increased 3.4 +/- 0.6 fold. Analysis of the multimeric structure of the von Willebrand factor revealed that type I vWD had complete correction after DDAVP infusion transiently. Except for a mild drop in both systolic and diastolic blood pressures, few side effects were noted. By concomitant intravenous infusion of DDAVP and oral administration of tranexamic acid, we successfully treated two cases of type I vWD undergoing tooth extraction, and one case of acquired bleeding disorder undergoing a biopsy of a mandibular mass, and a uremic patient complicated by intractable traumatic hematuria. Our experiences confirmed that most patients with vWD and some patients with congenital or acquired bleeding disorders can be treated effectively by DDAVP infusion without the need for plasma product replacement. In this study we found that a patient with a variant form of type I vWD had prolongation of the bleeding time, thrombocytopenia and platelet aggregation after DDAVP infusion.

Adolescent↗

[Treatment of gynecologic bleeding disorders].

Conclusions reached at an expert meeting arranged by the Medical Products Agency (Läkemedelsverket) in Sweden on the treatment of gynaecological bleeding disorders are presented. An active approach to endometrial diagnosis is recommended when bleeding is protracted and does not respond to medication, and when bleeding occurs more than one year after menopause. A period of expectation is permissible in women younger than 45 years. Exfoliative endometrial diagnosis is highly sensitive and specific and, in recent years, the traditional curettage has been reappraised as the first method of choice. Bleeding during anovulatory cycles is usually managed by treatment with progestagens. Menorrhagia may be diminished by oral contraception, tranexamic acid or NSAID. Endometrial resection offers a promising alternative to hysterectomy. Genital infection is another common cause of irregular bleeding in sexually active women and must be treated before invasive procedures are undertaken. Abnormal bleeding in patients with endometriosis often improves as a result of the treatment given to alleviate other symptoms such as pain. Bleeding irregularities caused by gynaecological malignancy, particularly contact bleeding in cancer of the cervix, are seen during the reproductive years and are accessible for diagnosis. The authors also discuss irregular bleeding caused by coagulopathia or treatment with hormones, as well as the effect of antifibrinolytic drugs.

Adult↗

[Dental extractions in patients taking anticoagulants: is alteration of the anticoagulant regime necessary?].

A major concern in the management of patients under anticoagulants is the potential for excessive bleeding after dental procedures. Recommendations for the administration of oral anticoagulants in conjunction with oral surgery range from complete withdrawal of anticoagulants to the maintenance of an unchanged therapy. Rising evidences show that the alteration of anticoagulation is not necessary for patients with INR of 4 or less previous to tooth extractions. Topical antifibrinolytics as tranexamic acid control successfully alveolar bleeding. It is time to stop interrupting anticoagulant therapy for oral surgery. A theoretical risk of hemorrhage after dental surgery in patients at therapeutic levels of anticoagulation exists but it is minimal and is greatly overweighed by the risk of thromboembolism after alteration of the anticoagulant therapy.

Anticoagulants↗

[Anesthetic management of coagulation factor V deficiency].

Factor V deficiency, or Owren's disease, is a rare inherited recessive autonomic disorder that is congenital. The bleeding in patients with this disease depends on plasma levels of factor V. Anesthetic management is similar to that used for patients with other coagulation disorders. On the one hand, it is useful to initiate infusion of plasma if purified concentrates are not available. On the other hand, it is important to monitor hemostasis carefully so that bleeding during postoperative recovery can be prevented. Plasma and antifibrinolytic drugs such as tranexamic acid should continue to be administered in the first few days after surgery. We report the case of a man with homozygotic factor V deficiency who underwent surgery for colon cancer. This article reviews the main aspects of anesthetic management of this coagulation disorder.

Anesthesia, General↗

Minor oral surgery in anticoagulated patients: local measures alone are sufficient for haemostasis.

Minor oral surgery in warfarinized patients can be performed without stopping or altering the dose of the drug. Thirty patients underwent various types of oral surgical procedures without interruption of their anticoagulant therapy and their therapeutic international normalized ratio maintained. Local measures such as pressure, packing the sockets with oxidized regenerated cellulose, and suturing were applied. In some patients, tranexamic acid mouthwashes were prescribed to further enhance haemostasis. Four patients had minimal postoperative bleeding in the form of bloodstained saliva, which lasted for 24 hours. This study highlights the importance of local measures in controlling postoperative bleeding in warfarinized patients undergoing minor oral surgical procedures.

Adult↗

[Serious bleeding in systemic lupus erythematosus complicated by lupus anticoagulant-hypoprothrombinaemia syndrome].

Severe hemorrhagic diathesis due to lupus anticoagulant complicated by hypoprothrombinaemia resulting from prothrombin autoantibodies is a rare disorder and is often associated with systemic lupus erythematosus (SLE). We report a case in which a 15-year-old girl with SLE developed marked haemorrhagic manifestations due to menorrhagia and nosebleeds. The acute bleeding episode was treated with SAGM, tranexamic acid and recombinant factor VIIa. Lupus anticoagulant, cardiolipin antibodies and antiprothrombin antibodies were successfully depressed within weeks after corticosteroid therapy was begun.

Adolescent↗

[Episodes of angioedema in children with C1 esterase inhibitor deficiency].

A 6-year-old boy and a 3.5-year-old girl presented with unexplained episodes of angioedema without urticaria. Low serum C1 esterase inhibitor activity was found in both children. Family history revealed autosomal dominant inheritance in the girl. The boy had a negative family history for angioedema. C1 esterase inhibitor deficiency is a rare but serious condition that may cause oedema of the upper respiratory tract and death by asphyxiation. Episodes of angioedema occur spontaneously, usually subsiding within 48-72 h. Between episodes, the patients are symptom free. Treatment consists of substitution of synthetic C1 esterase inhibitor during episodes of edema carrying a risk of upper airway obstruction. In patients who have more than one episode of severe angioedema per month, daily treatment with tranexamic acid should be considered. Both of these patients were not receiving daily treatment.

Airway Obstruction↗

Acute gastrointestinal bleeding: Part II.

OBJECTIVE: To review the management of acute gastrointestinal bleeding in the critically ill patient in a two part presentation. DATA SOURCES: Articles and a review of studies reported from 1991 to 2001 and identified through a MEDLINE search of the English language literature on acute gastrointestinal bleeding. SUMMARY OF REVIEW: Oesophageal varices are a common source of upper gastrointestinal bleeding in patients who have portal hypertension. Management requires resuscitation and treatment of associated coagulation disturbances along with intravenous octreotide (50 microg followed by 50 microg/hr for 48 hr) before endoscopy is performed. Octreotide is more effective than vasopressin in controlling acute variceal suppressant and has fewer side effects compared with glypressin. To provide haemostasis, endoscopic variceal sclerosis has largely been replaced by variceal ligation using an overtube and small elastic 'o' rings to band the bleeding variceal channels. If bleeding continues then Balloon tamponade and intravenous fibrinolytic inhibitors (e.g. tranexamic acid 3-6 g i.v. daily) are used for 24 hr before endoscopy (with variceal ligation) is repeated. If the variceal bleeding is resistant to repeated banding, portal decompression using transjugular intrahepatic portosystemic shunt or surgical shunt should be considered. While beta adrenergic blockers (e.g. propranalol) are indicated to reduce the incidence of rebleeding, they are contraindicated in a patient with actively bleeding oesophageal varices. CONCLUSIONS: Acute oesophageal variceal bleeding can often be managed successfully using octreotide and variceal ligation. If bleeding continues then transjugular intrahepatic portosystemic shunt or surgical shunt should be considered.

Journal Article↗

Platelet-rich plasma treatment and hemostasis in patients with hemorrhagic risk.

AIM: Our research aimed to evaluate the risk of haemorrhage following oral surgical operations, in patients who were undergoing an anticoagulant therapy, and to test the usefulness of the autologous platelet gel in order to control haemostasis. METHODS: A total of 208 patients (84 males/124 females) undergoing an anticoagulant therapy and submitted to oral surgery, were divided at random into 4 groups (A, B, C, D) consisting of 52 patients each, using as criterion of differentiation the kind of treatment we adopted in order to get haemostasis. The patients belonging to the first 3 groups (A, B, C), underwent a surgical operation without discontinuing the dicumarol therapy. In order to get haemostasis, we used: platelet-rich plasma (PRP) and suture, in group A; PRP, haemostatic sponges and suture, in group B; haemostatic sponges, suture and compression by means of gauzes soaked in tranexamic acid in group C. Group D, instead, consisted of patients who underwent a surgical operation, before which the dicumarol therapy had been suspended and replaced by heparincalcium. RESULTS: Patients belonging to the groups A and B showed a very good haemostasis like the patients of group D (control group). As the coumarin therapy didn't need to be discontinued some days before the surgical operation, so the days of hospital stay were reduced and there wasn't the risk of thromboembolism. As to group C (19 males), 6 patients (i.e. 11.5%) showed a good haemostasis, both at once and in the long term, so that they could be discharged on day 2 after surgery. CONCLUSIONS: The results obtained during our research, highly encourage using PRP regularly when carrying out surgical treatments on patients who are undergoing a coumarin therapy.

Aged↗

[Desmopressin in hemophilia A and Von Willebrand's disease].

The treatment with desmopressin prior to surgery of patients with mild haemophilia A (HA) and Von Willebrand's disease (VWD) was retrospectively evaluated in a general hospital, from 1978 until 1987. From a group of 87 treated patients, 40 patients are reported (21 VWD, 19 HA) of which plasma factor VIII (FVIII) and Von Willebrand factor (VWF) concentrations were determined before, and twice after desmopressin treatment. Desmopressin was administered intravenously at a dose of 0.4 micrograms/kg body weight. Tranexamic acid was used only when surgery in the mouth cavity was performed, at a dose of 1 gram three times a day. Side effects were seen only in 5 patients (3 VWD, 2 HA). No significant difference between both groups was seen in bleeding tendency, transfusion necessity and side effects (chi 2 test). In both groups, FVIII and VWF concentrations increased significantly after 20 and 60 minutes following DDAVP administration (paired t-test). After 360 minutes, the FVIII concentration increased significantly in both groups, however, only in the VWD patients did VWF increase significantly. In neither group did initial FVIII concentrations correlate with the increase in FVIII (linear regression analysis). One female patient reacted differently to DDAVP, with a decrease in FVIII and VWF values. Desmopressin is a safe and effective agent in the management and prophylaxis of bleeding tendency in patients with mild HA and mild VWD.

Deamino Arginine Vasopressin↗